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1
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Therkelsen KE, Cao T, Roy-O'Reilly M, Stocksdale B, Nagpal S. Molecular testing and targeting for solid tumors with CNS metastases. J Neurooncol 2025; 173:1-10. [PMID: 40178767 DOI: 10.1007/s11060-025-04947-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 01/17/2025] [Indexed: 04/05/2025]
Abstract
The landscape of molecular testing in solid tumors is rapidly expanding. Understanding testing options and limitations can inform treatment decisions for many patients with metastatic disease to the central nervous system (CNS).
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Affiliation(s)
- Kate E Therkelsen
- Division of Neuro-oncology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Toni Cao
- Division of Neuro-oncology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Meaghan Roy-O'Reilly
- Division of Neuro-oncology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Brian Stocksdale
- Division of Neuro-oncology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Seema Nagpal
- Division of Neuro-oncology, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
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2
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Veeraraghavan J, De Angelis C, Gutierrez C, Liao FT, Sabotta C, Rimawi MF, Osborne CK, Schiff R. HER2-Positive Breast Cancer Treatment and Resistance. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2025; 1464:495-525. [PMID: 39821040 DOI: 10.1007/978-3-031-70875-6_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2025]
Abstract
HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents. Efforts to develop new treatment regimens to treat/overcome resistance is futile without a primary understanding of the mechanistic underpinnings of resistance. Resistance could be attributed to mechanisms that are either specific to the tumor epithelial cells or those that emerge through changes in the tumor microenvironment. Reactivation of the HER receptor layer due to incomplete blockade of the HER receptor layer or due to alterations in the HER receptors is one of the major mechanisms. In other instances, resistance may occur due to deregulations in key downstream signaling such as the PI3K/AKT or RAS/MEK/ERK pathways or due to the emergence of compensatory pathways such as ER, other RTKs, or metabolic pathways. Potent new targeted agents and approaches to target key actionable drivers of resistance have already been identified, many of which are in early clinical development or under preclinical evaluation. Ongoing and future translational research will continue to uncover additional therapeutic vulnerabilities, as well as new targeted agents and approaches to treat and/or overcome anti-HER2 treatment resistance.
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Affiliation(s)
- Jamunarani Veeraraghavan
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Carmine De Angelis
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Carolina Gutierrez
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Fu-Tien Liao
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Caroline Sabotta
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
| | - Mothaffar F Rimawi
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - C Kent Osborne
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
| | - Rachel Schiff
- Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
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3
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Anselmi Relats JM, Roguin LP, Marder M, Cercato MC, Marino J, Blank VC. Synergistic effect of the sphingosine kinase inhibitor safingol in combination with 2'-nitroflavone in breast cancer. J Mol Med (Berl) 2024; 102:1503-1516. [PMID: 39503902 DOI: 10.1007/s00109-024-02497-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 09/27/2024] [Accepted: 10/19/2024] [Indexed: 11/21/2024]
Abstract
Sphingosine kinase-1 (SPHK1), the enzyme that catalyzes the synthesis of the pro-oncogenic molecule sphingosine-1-phosphate, is commonly upregulated in breast cancer cells and has been linked with poor prognosis and progression by promoting cell transformation, proliferation, angiogenesis, and metastasis. Therefore, SPHK1-targeting drugs have been proposed for breast cancer treatment, with better antitumor results when they are combined with chemotherapy. Previously, we demonstrated that the synthetic flavonoid 2'-nitroflavone (2'NF) exerted a potent and selective antiproliferative effect in murine HER2-positive LM3 mammary tumor cells. As we found that these cells overexpress SPHK1, we decided to explore the antitumor action of the combination of SPHK inhibitors (safingol or SKI-II) with 2'NF. In vitro assays showed that the combination induced a synergistic antiproliferative effect in LM3 cells. Similar results were obtained when human HER2-positive MDA-MB-453 breast cancer cells were treated with the combination of 2'NF/safingol. We also found that safingol potentiated the 2'NF apoptotic effect in both cell lines. The synergistic antitumor effect was confirmed in vivo in an LM3 syngeneic breast cancer model. Moreover, western blot analysis of tumor lysates revealed that combined treatment increased PARP cleavage and Bax protein levels and decreased anti-apoptotic Bcl-xL and Bcl-2 protein levels. Additionally, mice treated with both compounds showed no histopathological effects on different organ tissues. In summary, these findings suggest that the combination safingol/2'NF can be proposed as a potential therapeutic strategy for HER2-positive breast cancer treatment. KEY MESSAGES: The combination safingol/2'-nitroflavone exerts a synergic antitumor action in vitro. Safingol potentiates 2'-nitroflavone apoptotic effect in breast cancer cells. Safingol enhances the 2'-nitroflavone antitumor activity in vivo in breast cancer.
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Affiliation(s)
- Juan Manuel Anselmi Relats
- Laboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junin 956, C1113AAD, Buenos Aires, Argentina
| | - Leonor P Roguin
- Laboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junin 956, C1113AAD, Buenos Aires, Argentina
| | - Mariel Marder
- Laboratorio de Neuro-Fito-Farmacología Medicinal, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
| | - Magalí C Cercato
- Laboratorio de Histotecnología y Cultivo Celular, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina
| | - Julieta Marino
- Laboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junin 956, C1113AAD, Buenos Aires, Argentina
| | - Viviana C Blank
- Laboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junin 956, C1113AAD, Buenos Aires, Argentina.
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Sankarapandian V, Rajendran RL, Miruka CO, Sivamani P, Maran BAV, Krishnamoorthy R, Gangadaran P, Ahn BC. A review on tyrosine kinase inhibitors for targeted breast cancer therapy. Pathol Res Pract 2024; 263:155607. [PMID: 39326367 DOI: 10.1016/j.prp.2024.155607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/09/2024] [Accepted: 09/24/2024] [Indexed: 09/28/2024]
Abstract
Breast cancer is a heterogeneous disease with complex molecular pathogenesis. Overexpression of several tyrosine kinase receptors is associated with poor prognosis, therefore, they can be key targets in breast cancer therapy. Tyrosine kinase inhibitors (TKIs) have emerged as leading agents in targeted cancer therapy due to their effectiveness in disrupting key molecular pathways involved in tumor growth. TKIs target various tyrosine kinases, including the human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor receptor (VEGFR), anaplastic lymphoma kinase (ALK), vascular endothelial growth factor receptor (VEGFR)-associated multi-targets, rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), receptor tyrosine kinase-like orphan signal 1 (ROS1), Mitogen-activated protein kinase (MAPK), and tropomyosin receptor kinase (TRK). These drugs target the tyrosine kinase domain of receptor tyrosine kinases and play a vital role in proliferation and migration of breast cancer cells. Several TKIs, including lapatinib, neratinib, and tucatinib, have been developed and are currently used in clinical settings, often in combination with chemotherapy, endocrine therapy, or other targeted agents. TKIs have demonstrated remarkable benefits in enhancing progression-free and overall survival in patients with breast cancer and have become a standard of care for this population. This review provides an overview of TKIs currently being examined in preclinical studies and clinical trials, especially in combination with drugs approved for breast cancer treatment. TKIs have emerged as a promising therapeutic option for patients with breast cancer and hold potential for treating other breast cancer subtypes. The development of new TKIs and their integration into personalized treatment strategies will continue to shape the future of breast cancer therapy.
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Affiliation(s)
- Vidya Sankarapandian
- Department of Microbiology and Immunology, Kampala International University, Western Campus, Box 20000, Uganda
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Conrad Ondieki Miruka
- Department of Biochemistry, Kampala International University, Western Campus, Box 20000, Uganda
| | - Poornima Sivamani
- Department of Pharmacology and Clinical pharmacology, Christian Medical College, Vellore 632004, India
| | - Balu Alagar Venmathi Maran
- Graduate School of Integrated Science and Technology, Nagasaki University, 1-14 Bunkyomachi, Nagasaki 852-8521, Japan
| | - Rajapandiyan Krishnamoorthy
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea..
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea; Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea..
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5
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Manna M, Gelmon KA, Boileau JF, Brezden-Masley C, Cao JQ, Jerzak KJ, Prakash I, Sehdev S, Simmons C, Bouganim N, Brackstone M, Cescon DW, Chia S, Dayes IS, Edwards S, Hilton J, Joy AA, Laing K, Webster M, Henning JW. Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for the Systemic Treatment of Patients with HER2+ Breast Cancer in Both the Early and Metastatic Setting. Curr Oncol 2024; 31:6536-6567. [PMID: 39590115 PMCID: PMC11593131 DOI: 10.3390/curroncol31110484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/18/2024] [Accepted: 10/20/2024] [Indexed: 11/28/2024] Open
Abstract
Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of breast cancer associated with a poor prognosis when sub-optimally treated. Recent advances include new and effective targeted therapies that have significantly improved outcomes for patients. Despite these advances, there are significant gaps across Canada, underscoring the need for evidence-based consensus guidance to inform treatment decisions. Addressing these gaps is crucial to ensuring that effective therapies are integrated into clinical practice, so as to improve the lives of patients affected by this aggressive form of breast cancer. The Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance is a standing nucleus committee of clinical-academic oncologists across Canada and Breast Cancer Canada, a patient organization. The mandate of this group is to provide evidence-based guidance on best practices in the management of patients with breast cancer. These consensus recommendations were developed using a modified Delphi process with up to three rounds of anonymous voting. Consensus was defined a priori as ≥75% of voters agreeing with the recommendation as written. There are 9 recommendations in the early setting; 7 recommendations in the metastatic setting; and 10 recommendations for patients with brain metastases.
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Affiliation(s)
- Mita Manna
- Saskatchewan Cancer Agency, Regina, SK S4W 0G3, Canada;
| | - Karen A. Gelmon
- BC Cancer—Vancouver, Vancouver, BC V5Z 4E6, Canada; (K.A.G.); (C.S.); (S.C.)
| | | | | | - Jeffrey Q. Cao
- Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (J.Q.C.); (M.W.)
| | | | - Ipshita Prakash
- Jewish General Hospital, Montreal, QC H3T 1E2, Canada; (J.-F.B.); (I.P.)
| | - Sandeep Sehdev
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada; (S.S.); (J.H.)
| | - Christine Simmons
- BC Cancer—Vancouver, Vancouver, BC V5Z 4E6, Canada; (K.A.G.); (C.S.); (S.C.)
| | | | | | - David W. Cescon
- Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada;
| | - Stephen Chia
- BC Cancer—Vancouver, Vancouver, BC V5Z 4E6, Canada; (K.A.G.); (C.S.); (S.C.)
| | - Ian S. Dayes
- Juravinski Cancer Centre, Hamilton, ON L8V 5C2, Canada;
| | - Scott Edwards
- Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3V6, Canada; (S.E.); (K.L.)
| | - John Hilton
- The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada; (S.S.); (J.H.)
| | | | - Kara Laing
- Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3V6, Canada; (S.E.); (K.L.)
| | - Marc Webster
- Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada; (J.Q.C.); (M.W.)
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6
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Zhang Q, Yan X, Tian TL, Wu X. Case report: outcome of anlotinib treatment in breast cancer patient with brain metastases. Front Pharmacol 2024; 15:1381478. [PMID: 39224773 PMCID: PMC11366605 DOI: 10.3389/fphar.2024.1381478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 07/17/2024] [Indexed: 09/04/2024] Open
Abstract
Brain metastases (BM) represent a common and severe complication of breast cancer (BC), emerging in approximately 10%-16% of all BC patients. The prevalent approach for treating BC patients with BM encompasses a multimodal strategy, combining surgery, whole brain radiation therapy, and stereotactic radiosurgery. Yet, a concrete guideline for localized treatment strategies remains elusive, while systemic treatments like small-molecule-targeted therapy and immunotherapy are still in the clinical trial phase. This case study presents a significant clinical response to anlotinib treatment in a patient with estrogen receptor-negative, progesterone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, complicated by BM. After the standard first-line treatment including albumin-bound paclitaxel, trastuzumab and pertuzumab, and a second-line treatment involving pyrotinib, capecitabine, and radiotherapy did not produce the desired results, the patient was then administered anlotinib in combination with pyrotinib and letrozole as a third-line treatment, which led to a partial response (PR). The findings suggest that anti-angiogenic therapy, specifically anlotinib, could be regarded as a promising therapeutic option for BC patients with BM.
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Affiliation(s)
- Qiongwen Zhang
- Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Xi Yan
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Ting-Lun Tian
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Wu
- Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
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Poletes C, Amanirad B, Santiago AT, Yan M, Conrad T, Jerzak KJ, Shultz DB. The incidence of brain metastases in breast cancer according to molecular subtype and stage: a 10-year single institution analysis. J Neurooncol 2024; 169:119-127. [PMID: 38740672 DOI: 10.1007/s11060-024-04707-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 05/02/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Breast cancer (BC) is the second most common etiology of brain metastases (BrM). We aimed to examine the incidence of BrM among all BC patients presenting to a large tertiary cancer centre over one decade. METHODS We included all BC patients presenting consecutively between 2009 and 2019 and cross referenced that cohort to a radiotherapy database, identifying patients treated for BrM at any time following their initial presentation. Cumulative incidences (CI) of BrM diagnoses were calculated using death as a competing risk and compared using the Fine-Gray method. Overall survival was estimated using the Kaplan Meier method. RESULTS We identified 12,995 unique patients. The CI of BrM in patients who initially presented with Stage 0-4 disease was 2.1%, 3.7%, 9.4%, 10.6%, and 28.7%, respectively at 10 years. For 8,951 patients with available molecular subtype data, 6,470 (72%), 961 (11%), 1,023 (11%), and 497 (6%) had hormone-receptor (HR)-positive/ERBB2-, HR-negative/ERBB2-, HR-positive/ERBB2 + , and HR-negative/ERBB2 + disease, respectively; the CI of BrM in each was 7.6%, 25.3%, 24.1%, and 26.6%, at 10 years following BC diagnosis, respectively. Median overall survival (OS) following BC diagnosis and BrM diagnosis was 28 years 95% CI [25, 32] and 10 months 95% CI [9, 12], respectively. CONCLUSIONS From a large, registry-based study, we observed that patients with ERBB2 + and triple negative BC have the highest incidence of BrM. Our data supports prospective surveillance brain MRI studies. Given advancements in BrM treatment, clinicians should have a low threshold for brain imaging in BC patients with high risk subtypes.
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Affiliation(s)
- Christopher Poletes
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
- Royal College of Surgeons in Ireland, Dublin, Ireland.
| | - Bardia Amanirad
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Anna T Santiago
- Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada
| | - Michael Yan
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Tatiana Conrad
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Katarzyna J Jerzak
- Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - David B Shultz
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
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Cacho-Díaz B, Valdés-Ferrer SI, Chavez-MacGregor M, Salmerón-Moreno K, Villarreal-Garza C, Reynoso-Noverón N. Brain metastasis risk prediction model in females with hormone receptor-positive breast cancer. Radiother Oncol 2024; 197:110379. [PMID: 38862080 DOI: 10.1016/j.radonc.2024.110379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/23/2024] [Accepted: 06/05/2024] [Indexed: 06/13/2024]
Abstract
BACKGROUND Breast cancer is a leading cause of cancer-related deaths in females, and the hormone receptor-positive subtype is the most frequent. Breast cancer is a common source of brain metastases; therefore, we aimed to generate a brain metastases prediction model in females with hormone receptor-positive breast cancer. METHODS The primary cohort included 3,682 females with hormone receptor-positive breast cancer treated at a single center from May 2009 to May 2020. Patients were randomly divided into a training dataset (n = 2,455) and a validation dataset (n = 1,227). In the training dataset, simple logistic regression analyses were used to measure associations between variables and the diagnosis of brain metastases and to build multivariable models. The model with better calibration and discrimination capacity was tested in the validation dataset to measure its predictive performance. RESULTS The variables incorporated in the model included age, tumor size, axillary lymph node status, clinical stage at diagnosis, HER2 expression, Ki-67 proliferation index, and the modified Scarff-Bloom-Richardson grade. The area under the curve was 0.81 (95 % CI 0.75-0.86), p < 0.001 in the validation dataset. The study presents a guide for the clinical use of the model. CONCLUSION A brain metastases prediction model in females with hormone receptor-positive breast cancer helps assess the individual risk of brain metastases.
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Affiliation(s)
| | - Sergio I Valdés-Ferrer
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Departamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Mariana Chavez-MacGregor
- Breast Medical Oncology Department and Health Services Research Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Cynthia Villarreal-Garza
- Breast Cancer Center, Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, San Pedro Garza García, Mexico; Department of Medical Oncology, Médicos e Investigadores en la Lucha contra el Cáncer de Mama, Mexico City, Mexico
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9
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Rubin E, Shan KS, Dalal S, Vu DUD, Milillo-Naraine AM, Guaqueta D, Ergle A. Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers. Int J Mol Sci 2024; 25:1064. [PMID: 38256137 PMCID: PMC10816365 DOI: 10.3390/ijms25021064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/08/2024] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related to epidermal growth factor receptor (EGFR). These tyrosine kinases are involved in the transmission of cellular signals controlling normal cell growth and differentiation. If this transmission goes awry, it can lead to dysregulated growth of the cell. HER2 specifically can be implicated in the pathogenesis of at least eight malignancies. HER2 positivity quickly became a well-characterized indicator of aggressiveness and poor prognosis, with high rates of disease progression and mortality. After realizing the implication of HER2, it first became investigated as a target for treatment in breast cancer, and later expanded to areas of research in other cancer types. To this day, the most therapeutic advancements of anti-HER2 therapy have been in breast cancer; however, there have been strong advancements made in the incorporation of anti-HER2 therapy in other cancer types as well. This comprehensive review dissects HER2 to its core, incorporating the most up to date information. The topics touched upon are discussed in detail and up to 200 published sources from the most highly recognized journals have been integrated. The importance of knowing about HER2 is exemplified by the groundbreaking advancements that have been made, and the change in treatment plans it has brought to the oncological world in the last twenty years. Since its groundbreaking discovery there have been significant breakthroughs in knowledge regarding the actual receptor, the receptors biology, its mechanism of action, and advancements in tests to detect HER2 and significant strides on how to best incorporate targeted treatment. Due to the success of this field thus far, the review concludes by discussing the future of novel anti-HER2 therapy currently in development that everyone should be aware of.
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Affiliation(s)
- Elizabeth Rubin
- Memorial Cancer Institute, Pembroke Pines, FL 33028, USA; (K.S.S.); (S.D.); (D.U.D.V.); (A.M.M.-N.); (D.G.); (A.E.)
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10
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Liang K, Feliciano JL, Marrone KA, Murray JC, Hann CL, Anagnostou V, Tackett SA, Shin EJ, Hales RK, Voong KR, Battafarano RJ, Yang SC, Broderick SR, Ha JS, Forde PM, Brahmer JR, Lam VK. Clinical features and outcomes of advanced HER2+ esophageal/GEJ cancer with brain metastasis. ESMO Open 2024; 9:102199. [PMID: 38071928 PMCID: PMC10837776 DOI: 10.1016/j.esmoop.2023.102199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 10/30/2023] [Accepted: 11/15/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood. METHODS We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated. RESULTS We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM. CONCLUSION HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation.
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Affiliation(s)
- K Liang
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - J L Feliciano
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - K A Marrone
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - J C Murray
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - C L Hann
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - V Anagnostou
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - S A Tackett
- Department of Medicine, Biostatistics, Epidemiology and Data Management (BEAD) Core, Johns Hopkins University School of Medicine, Baltimore, USA
| | - E J Shin
- Department of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, USA
| | - R K Hales
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, USA
| | - K R Voong
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, USA
| | - R J Battafarano
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - S C Yang
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - S R Broderick
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - J S Ha
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - P M Forde
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - J R Brahmer
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - V K Lam
- The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, USA.
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11
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Cacho-Díaz B, Meneses-García AA, Valdés-Ferrer SI, Reynoso-Noverón N. A brain metastasis prediction model in women with breast cancer. Cancer Epidemiol 2023; 86:102448. [PMID: 37678094 DOI: 10.1016/j.canep.2023.102448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 08/04/2023] [Accepted: 08/23/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Breast cancer (BC) is a leading cause of mortality and the most frequent malignancy in women, and most deaths are due to metastatic disease, particularly brain metastases (BM). Currently, no biomarker or prediction model is used to predict BM accurately. The objective was to generate a BM prediction model from variables obtained at BC diagnosis. METHODS A retrospective cohort of women with BC diagnosed from 2009 to 2020 at a single center was divided into a training dataset (TD) and a validation dataset (VD). The prediction model was generated in the TD, and its performance was measured in the VD using the area under the curve (AUC) and C-statistic. RESULTS The cohort (n = 5009) was divided into a TD (n = 3339) and a VD (n = 1670). In the TD, the model with the best performance (lowest AIC) was built with the following variables: age, estrogen receptor status, tumor size, axillary adenopathy, anatomic clinical stage, Ki-67 expression, and Scarff-Bloom-Richardson score. This model had an AUC of 0.79 (95%CI, 0.76-0.82; p < 0.0001) in the TD. The 10-fold cross-validation showed the good stability of the model. The model displayed an AUC of 0.81 (95%CI, 0.77-0.85; P < 0.0001) in the VD. Four groups, according to the risk of BM, were generated. In the low-risk group, 1.2% were diagnosed with BM (reference); in the medium-risk group, 5.0% [HR 4.01 (95%CI, 1.8 - 8.8); P < 0.0001); in the high-risk group, 8.5% [HR 8.33 (95%CI, 4.1-17.1); P < 0.0001]; and in the very high-risk group, 23.7% [HR 29.72 (95%CI, 14.9 - 59.1); P < 0.0001]. CONCLUSION This prediction model built with clinical and pathological variables at BC diagnosis demonstrated robust performance in determining the individual risk of BM among patients with BC, but external validation in different cohorts is needed.
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Affiliation(s)
- Bernardo Cacho-Díaz
- Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud. Universidad Autónoma de Mexico (UNAM), ZC 04510, Mexico
| | | | - Sergio I Valdés-Ferrer
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA; Departamento de Neurologíay Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición SalvadorZubiran, Mexico City ZC 14080, Mexico
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12
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Id Said B, Soliman H, Moravan V, Myrehaug S, Tseng CL, Detsky J, Sahgal A, Warner E, Jerzak KJ. Patterns of treatment and outcomes of patients with brain-only metastatic breast cancer. J Neurooncol 2023; 164:437-445. [PMID: 37634217 DOI: 10.1007/s11060-023-04421-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 08/09/2023] [Indexed: 08/29/2023]
Abstract
BACKGROUND We characterized the risk factors and survival of metastatic breast cancer (MBC) patients with brain metastases (BrM) as the first and only site of disease in a large, retrospective cohort. METHODS MBC patients treated for BrM with radiation at a quaternary institution between 2005 and 2019 were identified. MBC patients with BrM but without concurrent extracranial metastases (ECM) or leptomeningeal disease (LMD) were classified as brain-only. Factors associated with brain-only MBC, brain-specific progression free survival (bsPFS) and overall survival (OS) were investigated. RESULTS A total of 691 patients with MBC and BrM were analyzed. Among them, 67 patients (9.7%, n = 67/691) presented with brain-only MBC without concurrent ECM/LMD. Within this subgroup, 40 patients (5.8%, n = 40/691) remained free of any ECM or LMD, while 17 patients (2.5%) developed LMD, and 10 patients (1.4%%) developed ECM with a median follow-up of 8 months (IQR 2-35). Patients with brain-only MBC were more likely to have a single BrM [OR 3.41 (1.62-7.19), p = 0.001] and either HER2+ [OR 3.3 (1.13-9.65), p = 0.03] or TNBC [OR 4.09 (1.42-11.74), p = 0.009] subtypes. Patients who presented with brain-only MBC also had significantly longer OS [HR 0.45, (0.22-0.86), p = 0.008] and a trend toward longer bsPFS [HR 0.67 (0.44-1.03), p = 0.05] compared to those with concurrent ECM/LMD. CONCLUSION Patients with brain-only MBC had a longer bsPFS and OS than those with ECM. Patients with HER2+ and TNBC were more likely to have brain-only disease compared to those with HR+/HER2- MBC.
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Affiliation(s)
- Badr Id Said
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | - Hany Soliman
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | | | - Sten Myrehaug
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | - Chia-Lin Tseng
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | - Jay Detsky
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | - Arjun Sahgal
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, ON, Canada
| | - Ellen Warner
- Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada
| | - Katarzyna J Jerzak
- Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
- Department of Medicine, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.
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13
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Cavallaro PA, De Santo M, Belsito EL, Longobucco C, Curcio M, Morelli C, Pasqua L, Leggio A. Peptides Targeting HER2-Positive Breast Cancer Cells and Applications in Tumor Imaging and Delivery of Chemotherapeutics. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:2476. [PMID: 37686984 PMCID: PMC10490457 DOI: 10.3390/nano13172476] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/27/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023]
Abstract
Breast cancer represents the most common cancer type and one of the major leading causes of death in the female worldwide population. Overexpression of HER2, a transmembrane glycoprotein related to the epidermal growth factor receptor, results in a biologically and clinically aggressive breast cancer subtype. It is also the primary driver for tumor detection and progression and, in addition to being an important prognostic factor in women diagnosed with breast cancer, HER2 is a widely known therapeutic target for drug development. The aim of this review is to provide an updated overview of the main approaches for the diagnosis and treatment of HER2-positive breast cancer proposed in the literature over the past decade. We focused on the different targeting strategies involving antibodies and peptides that have been explored with their relative outcomes and current limitations that need to be improved. The review also encompasses a discussion on targeted peptides acting as probes for molecular imaging. By using different types of HER2-targeting strategies, nanotechnology promises to overcome some of the current clinical challenges by developing novel HER2-guided nanosystems suitable as powerful tools in breast cancer imaging, targeting, and therapy.
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Affiliation(s)
- Palmira Alessia Cavallaro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Marzia De Santo
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Emilia Lucia Belsito
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Camilla Longobucco
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Manuela Curcio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Catia Morelli
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
| | - Luigi Pasqua
- Department of Environmental Engineering, University of Calabria, Via P. Bucci, 87036 Rende, Italy
| | - Antonella Leggio
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Rende, Italy; (P.A.C.); (M.D.S.); (E.L.B.); (C.L.); (M.C.); (C.M.)
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14
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Bai Q, Lv H, Bao L, Yang Y, Zhang X, Chang H, Xue T, Ren M, Zhu X, Zhou X, Yang W. Invasive Breast Cancer with HER2 ≥4.0 and <6.0: Risk Classification and Molecular Typing by a 21-Gene Expression Assay and MammaPrint Plus BluePrint Testing. BREAST CANCER (DOVE MEDICAL PRESS) 2023; 15:563-575. [PMID: 37554155 PMCID: PMC10406110 DOI: 10.2147/bctt.s420738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/26/2023] [Indexed: 08/10/2023]
Abstract
PURPOSE To investigate the HER2 status and clinicopathological features in invasive breast cancer with HER2 ≥4.0 and <6.0, which has always been controversial. METHODS Forty breast cancer cases with HER2 ≥4.0 and <6.0 by fluorescence in situ hybridization (FISH) were collected and classified into two groups based on the HRE2/CEP17 ratio (Group A: ≥2.0, n=22; Group B: <2.0, n=18). Clinicopathological characteristics, HER2 status, risk classification, and molecular typing were further analyzed and compared by 21-Gene expression assay and MammaPrint plus BluePrint test. RESULTS The majority of cases in both groups were invasive carcinoma (NOS), with histological grade II, HR+, Ki-67 ≥20%, HER2 2+, and a high risk of recurrence, although younger patients and lymph node metastases were more common in Group A. Surprisingly, all HR+ breast cancers in both groups were classified as luminal-type, HR- cases were all basal-type or unknown, and the index of HER2 in all cases was <0.000 using the BluePrint test, which indicated that HER2 status should be negative. Furthermore, the level of HER2 mRNA expression in all cases of both groups was <10.7, which was defined as HER2 negative by the 21-Gene expression assay. In addition, 10 patients of Group A received anti-HER2 neoadjuvant therapy; only one patient with HR- achieved Grade 5 based on the Miller-Payne system, whereas none of the patients achieved pathological complete response (pCR) based on the Residual Cancer Burden system. CONCLUSION Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.
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Affiliation(s)
- Qianming Bai
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Hong Lv
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Longlong Bao
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Yu Yang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Xin Zhang
- Department of Pathology, Fudan University Zhongshan Hospital, Shanghai, 200032, People’s Republic of China
| | - Heng Chang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Tian Xue
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Min Ren
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Xiaoli Zhu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Xiaoyan Zhou
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
| | - Wentao Yang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China
- Institute of Pathology, Fudan University, Shanghai, 200032, People’s Republic of China
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15
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Wang H, Liu Q, Zhang M, Zhang J, Ran R, Ma Y, Yang J, Wang F, He S, Zhao X, Wang L, Zhang L, Dong D, Yang J. Real-world data of pyrotinib-based therapy for patients with brain metastases of HER2-positive advanced breast cancer: a single-center retrospective analysis and molecular portraits. Front Oncol 2023; 13:1105474. [PMID: 37397372 PMCID: PMC10313114 DOI: 10.3389/fonc.2023.1105474] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 05/31/2023] [Indexed: 07/04/2023] Open
Abstract
Introduction Pyrotinib is a novel irreversible pan-HER tyrosine kinase inhibitor (TKI). However, real-world data of pyrotinib-containing therapy in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and developing brain metastases (BMs) are limited, and the genomic profile of this subpopulation is almost undefined. Methods and materials Patients with BM of HER2-positive MBC (n = 35) treated with pyrotinib-containing therapy were enrolled in this analysis. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) for disease progression were estimated using the Cox proportional hazards models. Targeted next-generation sequencing of 618 cancer-relevant genes was performed on plasma and primary breast tumors from patients with BM and without BM. Results The median PFS time was 8.00 (95% CI, 5.98-10.017) months, and the median OS time was 23 (95% CI, 10.412-35.588) months. The ORR was 45.7%, and the DCR was 74.3%. In the Cox multivariate analysis, prior exposure to brain radiotherapy (HR = 3.268), received pyrotinib as third- or higher-line treatment (HR = 4.949), subtentorial brain metastasis (HR = 6.222), and both supratentorial and subtentorial brain metastases (HR = 5.863) were independently associated with increased risk of progression. The frequent grade 3-4 adverse event was increased direct bilirubin (14.3%), and two patients suffered from grade 3-4 diarrhea. In the exploratory genomic analysis, altered frequencies of FGFR3, CD276, CDC73, and EPHX1 were higher in the BM group. The consistency of mutated profiles of plasma and primary lesion in the BM group was significantly lower (30.4% vs. 65.5%; p = 0.0038). Conclusions Pyrotinib-containing therapy shows favorable effectiveness and tolerable safety in patients with BM of HER2-positive MBC, particularly in a population that is brain radiotherapy-naïve, received pyrotinib as first- or second-line treatment, and developed supratentorial brain metastasis. In the exploratory genomic analysis, patients with BM showed distinct genomic features from patients without BM.
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Affiliation(s)
- Hui Wang
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Qiaoyan Liu
- Department of Oncology, Xi’an Ninth Hospital, Xi’an, China
| | - Mi Zhang
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Juan Zhang
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Ran Ran
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yingying Ma
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jiao Yang
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Fan Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Shujuan He
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xiaoai Zhao
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Le Wang
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Lingxiao Zhang
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Danfeng Dong
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Jin Yang
- Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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16
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Murazawa C, Hashimoto N, Kuraishi K, Motoyama M, Hashimoto SI, Ikeuchi M, Norimura S, Matsunaga T, Teramoto K, Haba R, Abe N, Yajima T, Kontani K. Status and prognostic value of immunological biomarkers of breast cancer. Oncol Lett 2023; 25:164. [PMID: 36960188 PMCID: PMC10028224 DOI: 10.3892/ol.2023.13750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 02/01/2023] [Indexed: 03/25/2023] Open
Abstract
The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of cancer. However, the dominant subtype, luminal human epidermal growth factor receptor-2 (HER2)-negative breast cancer, is less immunogenic. To determine whether luminal HER2-negative cancer reacts to the anticancer immune response, the present study analyzed the status and prognostic value of the principal immunological biomarkers of breast cancer, including tumor-infiltrating lymphocytes (TILs), CD8+ T lymphocytes, the major histocompatibility complex and programmed cell death ligand-1 (PD-L1). The biomarkers were compared between patients with luminal HER2-negative breast cancer and those with immunogenic subtypes including triple-negative and HER2-overexpressed breast cancer. A total of 71 patients with primary breast cancer were classified into the immunogenic non-luminal (n=23) and less immunogenic luminal HER2-negative groups (n=48) based on immunogenicity. In the luminal HER2-negative group, compared with patients with low TIL levels, those with high TIL levels were at an advanced stage of cancer (P=0.024) and showed worse relapse-free survival (P=0.057); however, the remaining biomarkers exhibited no association with cancer progression or prognosis. In the non-luminal group, patients with high TIL levels showed significantly better RFS than those with low TIL levels (P=0.014). Compared with non-luminal patients negative for PD-L1, those positive for PD-L1 exhibited better overall survival (P=0.064). Notably, TIL status was found to exhibit contrasting prognostic predictions based on immunogenicity. In conclusion, TILs are a strong candidate for prognostic prediction in breast cancer, regardless of the subtype. PD-L1 is a potential candidate for prognostic prediction in immunogenic breast cancers, but not in the luminal HER2-negative subtype.
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Affiliation(s)
- Chisa Murazawa
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Nozomi Hashimoto
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Kana Kuraishi
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Mutsumi Motoyama
- Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa 761-0793, Japan
| | - Shin-Ichiro Hashimoto
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Mayumi Ikeuchi
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Shoko Norimura
- Department of Surgery, Takamatsu Red Cross Hospital, Takamatsu, Kagawa 760-0017, Japan
| | - Toru Matsunaga
- Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa 761-0793, Japan
| | - Koji Teramoto
- Department of Medical Oncology, Shiga University of Medical Science, Otsu, Shiga 520-2191, Japan
| | - Reiji Haba
- Department of Diagnostic Pathology, Kagawa University Hospital, Kagawa 761-0793, Japan
| | - Noriko Abe
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Toshiki Yajima
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
| | - Keiichi Kontani
- Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
- Correspondence to: Dr Keiichi Kontani, Department of Thoracic, Breast and Endocrine Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa 761-0793, Japan, E-mail:
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Shen B, Li J, Yang M, Liu K, Zhang J, Li W, Zhang Y, Wang K. Interactive effects of molecular subtypes with tumor size and extracranial metastatic pattern on risk of brain metastasis in breast cancer patients: A population-based study. Cancer Med 2023; 12:6547-6557. [PMID: 36353772 PMCID: PMC10067112 DOI: 10.1002/cam4.5425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 09/09/2022] [Accepted: 10/23/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Early detection of brain metastasis (BM) is essential for prognostic improvement in breast cancer (BC) patients. The aim was to identify predictors of BCBM in different molecular subtypes on a population-based level. METHODS The Surveillance, Epidemiology, and End Results database was used to select BC patients diagnosed from 2010 to 2018. We evaluated the incidence and risk factors of BCBM and tested the interaction effects between molecular subtypes and other risk factors. RESULTS Among the 527,525 selected patients, molecular subtypes significantly interacted with T stage and extracranial metastasis (ECM) patterns on the risk of BM in the whole BC population (interaction p = 0.002, <0.001, respectively) and after excluding patients with unknown states of key factors. BM development was independent of the T stage only in HR-/HER2- patients (trend p = 0.126). We selected BC patients with single-organ ECM and found a significant interaction between molecular subtypes and ECM patterns (interaction p = 0.013). The impact of ECM patterns on the risk of BM was limited to HR-/HER2- patients (trend p < 0.001), for whom using bone metastasis as a reference, lung metastasis increased the risk of BM (OR = 1.936, 95% CI: 1.300-2.882, p = 0.001). CONCLUSION T stage and ECM patterns had different associations with BM in different molecular subtypes. HR-/HER2- BC had distinct features on BM development, manifested as a lack of tumor size effect and is associated with lung metastasis. Close surveillance for BM should be considered for HR-/HER2- BC patients.
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Affiliation(s)
- Bo Shen
- Shantou University Medical College, Shantou, China
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jieqing Li
- Department of Breast Cancer, Cancer CenterGuangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesGuangzhouChina
| | - Mei Yang
- Department of Breast Cancer, Cancer CenterGuangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesGuangzhouChina
| | - Kangkang Liu
- Department of Research Center for MedicineThe Eighth Affiliated Hospital, Sun Yat‐Sen UniversityShenzhenChina
| | - Junsheng Zhang
- State Key Laboratory of Oncology in South China, Collaborative In‐novation Center for Cancer MedicineSun Yat‐sen University Cancer CenterGuangzhouChina
| | - Weiping Li
- The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical UniversityGuangzhouChina
| | - Yi Zhang
- Department of Breast Cancer, Cancer CenterGuangdong Provincial People's Hospital, Guangdong Academy of Medical SciencesGuangzhouChina
| | - Kun Wang
- Shantou University Medical College, Shantou, China
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Sanglier T, Shim J, Lamarre N, Peña-Murillo C, Antao V, Montemurro F. Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study. Breast 2023:S0960-9776(23)00007-3. [PMID: 36709091 DOI: 10.1016/j.breast.2023.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 01/13/2023] [Accepted: 01/14/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Trastuzumab emtansine (T-DM1) has demonstrated improvements in survival and neurological symptoms in patients with breast cancer with brain metastases (BCBM). This real-world study investigated the effectiveness of T-DM1 versus lapatinib plus capecitabine (LC) in patients with BCBM. METHODS This retrospective, observational study evaluated patients with HER2-positive BCBM using a real-world database. Eligible patients had initiated T-DM1 or LC with a prior diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment. The primary endpoint was overall survival (OS); secondary endpoints were time to next relevant treatment or death (TTNT) and real-world progression-free survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach was used to account for differences in potential baseline characteristics between treatment groups. Outcomes were described using the Kaplan-Meier method, and the average treatment effect of initiating T-DM1 versus LC was estimated using weighted Cox proportional hazard models and hazard ratio (HR). RESULTS A total of 214 patients were available for analysis (T-DM1, n = 161; LC, n = 53). Demographics and baseline characteristics were generally well-balanced between treatment groups after weighting. After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34-0.89]; P=0.013). Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI, 0.36-0.85]; P = 0.005). After weighting, median rwPFS was 6.0 (T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36-0.69]; P < 0.001). CONCLUSIONS These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.
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Zhang Q, He P, Tian T, Yan X, Huang J, Zhang Z, Zheng H, Zhong X, Luo T. Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study. Front Pharmacol 2023; 14:1100556. [PMID: 37025489 PMCID: PMC10070865 DOI: 10.3389/fphar.2023.1100556] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/20/2023] [Indexed: 04/08/2023] Open
Abstract
Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.
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Affiliation(s)
- Qiongwen Zhang
- Department of Head and Neck Oncology, Department of Radiation Oncology, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Ping He
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tinglun Tian
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Yan
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Juan Huang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhang Zhang
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Zheng
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- Multi-omics Laboratory of Breast Diseases, State Key Laboratory of Biotherapy, National Collaborative, Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaorong Zhong
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- Multi-omics Laboratory of Breast Diseases, State Key Laboratory of Biotherapy, National Collaborative, Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xiaorong Zhong, ; Ting Luo,
| | - Ting Luo
- Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- Multi-omics Laboratory of Breast Diseases, State Key Laboratory of Biotherapy, National Collaborative, Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xiaorong Zhong, ; Ting Luo,
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Najjar MK, Manore SG, Regua AT, Lo HW. Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer. Genes (Basel) 2022; 13:2065. [PMID: 36360302 PMCID: PMC9691220 DOI: 10.3390/genes13112065] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 11/03/2022] [Accepted: 11/04/2022] [Indexed: 11/09/2022] Open
Abstract
Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20-30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted monoclonal antibodies with the potent cytotoxic effects of various small molecules, such as tubulin inhibitors and topoisomerase inhibitors. To date, two HER2-targeting ADCs have been approved by the FDA for the treatment of HER2-positive breast cancer: Ado-trastuzumab emtansine (T-DM1; Kadcyla®) and fam-trastuzumab deruxtecan-nxki (T-Dxd; Enhertu®). Kadcyla and Enhertu are approved for use as a second-line treatment after trastuzumab-taxane-based therapy in patients with HER2-positive breast cancer. The success of ADCs in the treatment of HER2-positive breast cancer provides novel therapeutic advancements in the management of the disease. In this review, we discuss the basic biology of HER2, its downstream signaling pathways, currently available anti-HER2 therapeutic modalities and their mechanisms of action, and the latest clinical and safety characteristics of ADCs used for the treatment of HER2-positive breast cancer.
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Affiliation(s)
- Mariana K. Najjar
- Wake Forest Graduate School of Biomedical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
| | - Sara G. Manore
- Wake Forest Graduate School of Biomedical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
| | - Angelina T. Regua
- Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, MSE R162, 6431 Fannin Street, Houston, TX 77030, USA
| | - Hui-Wen Lo
- Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, MSE R162, 6431 Fannin Street, Houston, TX 77030, USA
- Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA
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Tsuruoka S, Kataoka M, Uwatsu K, Makita K, Tsuruoka K, Takata N, Ishikawa H, Hamamoto Y, Mochizuki T, Kido T. Prognostic value of human epidermal growth factor receptor 2 status and systemic therapy in breast cancer with brain metastases treated with radiotherapy. Asia Pac J Clin Oncol 2022; 19:347-354. [DOI: 10.1111/ajco.13881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 08/25/2022] [Accepted: 09/25/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Shintaro Tsuruoka
- Department of Radiation Oncology National Hospital Organization Shikoku Cancer Center Matsuyama Japan
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
| | - Masaaki Kataoka
- Department of Radiation Oncology National Hospital Organization Shikoku Cancer Center Matsuyama Japan
- Department of Radiology Saiseikai Imabari Hospital Imabari Japan
| | - Kotaro Uwatsu
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
| | - Kenji Makita
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
| | - Kota Tsuruoka
- Department of Radiology Saiseikai Matsuyama Hospital Matsuyama Japan
| | - Noriko Takata
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
| | - Hirofumi Ishikawa
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
| | - Yasushi Hamamoto
- Department of Radiation Oncology National Hospital Organization Shikoku Cancer Center Matsuyama Japan
| | - Teruhito Mochizuki
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
- Department of Radiology I.M. Sechenov First Moscow State Medical University Moscow Russian Federation
| | - Teruhito Kido
- Department of Radiology Ehime University Graduate School of Medicine Toon Japan
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22
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Jiaxin C, Jinmei Z, Huiqiang Z, Xuexue W, Xiaobo W, Shaohua Z, Yanhong T, Zefei J, Tao W. Conversion of ER, PR, HER2 and Ki-67 and Prognosis in breast cancer metastases to the brain. Front Neurol 2022; 13:1002173. [PMID: 36353124 PMCID: PMC9637832 DOI: 10.3389/fneur.2022.1002173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 10/04/2022] [Indexed: 11/23/2022] Open
Abstract
Objective This study aimed to analyze the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index in the brain metastatic lesions and primary lesions in Chinese patients with breast cancer brain metastasis (BCBM) and determine the correlation between their changes and patients' survival. Methods A retrospective analysis was performed on patients with BCBM. The clinical characteristic of these patients was collected. The differences in the expression levels of the ER, PR, HER-2, and Ki-67 index between the primary lesions and brain lesions were evaluated, and the association between the differences and survival was analyzed. Results The conversion rate of anyone receptor (ER, PR, or HER2) between the primary lesions and brain metastatic lesions was 45.0% (18/40), of which the ER inconsistency rate was 25.0%, the PR inconsistency rate was 22.5%, and the HER-2 inconsistency rate was 15.0%, and the receptor conversion resulted in a subtype conversion of 27.5% (11/40). The patients with HER-2 expression discordance between the primary lesions and the brain metastatic lesions had significantly longer survival times (58.9 vs. 26.4 months, P = 0.04) after diagnosis of brain metastases. Conclusion In this study, 45.0% of breast cancer patients developed biomarker-conversion between the primary lesions and brain metastatic lesions, and the differences in the expression levels of the ER, PR, and HER-2, the change in Ki-67 index between the primary lesions and brain lesions may predict patients' survival.
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Affiliation(s)
- Chen Jiaxin
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, China
| | - Zhou Jinmei
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhang Huiqiang
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wu Xuexue
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wang Xiaobo
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhang Shaohua
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Tai Yanhong
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jiang Zefei
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wang Tao
- Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, China
- Anhui Medical University, Hefei, China
- Southern Medical University, Guangzhou, China
- *Correspondence: Wang Tao
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23
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Zhao M, Liu J, Tang Y, Zhang L, Ge X, Chen M, Wen Q, Zhu L, Ma Q. Hyaluronidase responsive second near-infrared fluorescent nanocomplex for combined HER2 blockade and chemotherapy of HER2+ breast cancer. BIOMATERIALS ADVANCES 2022; 141:213115. [PMID: 36115156 DOI: 10.1016/j.bioadv.2022.213115] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/22/2022] [Accepted: 09/07/2022] [Indexed: 06/15/2023]
Abstract
The human epidermal growth factor receptor-2-positive (HER2+) type is aggressive and has poor prognosis. Although anti-HER2 therapy alone or in combination with other treatment regimens showed significant improvement in survival outcomes, breast cancer patients are still suffering from tumor relapse and severe dose-limiting side effects. Thus, there is still an unmet challenge to develop effective therapeutic agents for HER2+ breast cancer treatment with minimized side effects. Herein, we produced a stimuli-responsive and tumor-targeted hyaluronic acid (HA) nanocomplex that combined HER2 blockade and chemotherapy for effective HER2+ breast cancer therapy. A hydrophobic NIR-II dye, IR1048, was covalently linked with HA to form a spherical HA-IR1048 nanoparticle (HINP), with Herceptin conjugated on the surface and paclitaxel (PTX) encapsulated inside. The fluorescent signals from the yielding Her-HINP/PTX are quenched originally, but a strong NIR-II signal is generated when HINP is degraded by the hyaluronidase that is overexpressed in breast tumors, thus allowing the tracking and visualization of Herceptin and PTX accumulation. Her-HINP/PTX peaked in HER2+ tumors at 24 h post injection as imaged by NIR-II fluorescent imaging. A significantly improved tumor growth inhibition effect was observed after five systemic treatments compared to single PTX (3.71 ± 0.41 times) or Herceptin (5.98 ± 0.51 times) treatment in a HER2-overexpressed breast cancer mouse model with prolonged survival. Collectively, the designed Her-HINP/PTX presents a new hyaluronidase-responsive and HER2 blockade nanoformulation that can visualize the accumulation of nanocomplexes and release drugs inside tumors for combined HER2+ breast cancer therapy with a great promise for translational study. STATEMENT OF SIGNIFICANCE: The high expressions of a protein called human epidermal growth factor receptor 2 (HER2) in breast tumors make this subtype of cancer aggressive. Currently, chemotherapy combined with a HER2 antibody, Herceptin, is a preferred approach for HER2-positive breast cancer therapy. However, these breast cancer patients still suffer from tumor relapse and severe side effects because various therapeutic agents have inherent different biodistributions, resulting in insufficient treatment effects and unfavorable normal organ uptake of these therapeutic agents. Herein, we produced a nanocomplex carrying both Herceptin and chemotherapy drug to simultaneously deliver two drugs into tumors for efficient HER2+ tumor treatment with minimized side effects, providing new insights for designing a combined therapy strategy.
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Affiliation(s)
- Min Zhao
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Junzhi Liu
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Yuting Tang
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Lumeng Zhang
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Xiaoguang Ge
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China; MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, China
| | - Minglong Chen
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Qiang Wen
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
| | - Lei Zhu
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
| | - Qingjie Ma
- Department of Nuclear Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China.
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Fedele P, Sanna V, Santoro AN, Iaia ML, Fancellu A. Tailoring antiHer2 treatment strategies in breast cancer and beyond. Curr Probl Cancer 2022; 46:100892. [DOI: 10.1016/j.currproblcancer.2022.100892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/04/2022] [Accepted: 05/23/2022] [Indexed: 11/03/2022]
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Wang X, Wang S, Yao S, Shi W, Ma K. The clinical characteristics and treatment of ovarian malignant mesoderm mixed tumor: a systematic review. J Ovarian Res 2022; 15:104. [PMID: 36114551 PMCID: PMC9482291 DOI: 10.1186/s13048-022-01037-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/30/2022] [Indexed: 12/02/2022] Open
Abstract
Background Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases. Methods The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines. Results A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents. Conclusion The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-022-01037-6.
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Wang Y, Xu H, Han Y, Wu Y, Wang J. Comparative Efficacy of Tyrosine Kinase Inhibitors and Antibody–Drug Conjugates in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A Systematic Review and Network Meta-Analysis. Cancers (Basel) 2022; 14:cancers14143372. [PMID: 35884431 PMCID: PMC9321046 DOI: 10.3390/cancers14143372] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/08/2022] [Accepted: 07/09/2022] [Indexed: 12/10/2022] Open
Abstract
Simple Summary Comparisons between the efficacy of tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs) in treating HER2-positive breast cancer brain metastasis (BCBM) patients have not previously been conducted. We performed a systematic review and Bayesian-based network meta-analysis to pool the estimates of progression-free survival, overall survival, and incidence of central nervous system (CNS) disease progression. The current study indicated that both T-DXd and T-DM1 presented better efficacy than TKIs regarding survival outcomes. Treatments containing neratinib or T-DM1 tended to rank the best in reducing the recurrent rate of CNS. Our study provides more evidence for the clinical decision making for patients with HER2-positive BCBM. More high-quality studies with standardized entry criteria and comparable CNS-related endpoints are warranted in the future. Abstract HER2-positive breast cancer brain metastasis (BCBM) is an important clinical problem. A systematic review and network meta-analysis were conducted to compare the efficacy of tyrosine kinase inhibitors (TKIs) and antibody–drug conjugates (ADCs), two categories of emerging agents in this field. We implemented a comprehensive literature search of PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences. A network meta-analysis following Bayesian approaches was performed. Pooled hazard ratios (HRs) and odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate progression-free survival (PFS), overall survival (OS), and the incidence of central nervous system (CNS) disease progression. Sixteen studies were included. Pairwise comparisons of PFS showed salient divergency between T-DXd and the physician’s choice of treatment (HR 0.17; 95% CrI 0.03–0.82) or afatinib (HR 0.14; 95% CrI 0.02–1.00). T-DXd and T-DM1 ranked first regarding PFS and OS, respectively, followed by TKI-containing regimens. The incidence of CNS disease progression was analyzed separately according to baseline BCBM status, among which neratinib-containing regimens were most likely to rank the best. In conclusion, ADCs including T-DXd and T-DM1 showed better efficacy than TKIs in the survival outcomes for HER2-positive BCBM patients. Treatments based on neratinib or T-DM1 revealed favorable results in reducing the recurrent rate of CNS.
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Bhogal T, Cameron D, Palmieri C. Central nervous system disease in phase III studies for advanced HER2 positive breast cancer: A review. Breast 2022; 63:85-100. [PMID: 35344688 PMCID: PMC8961215 DOI: 10.1016/j.breast.2022.03.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/18/2022] [Accepted: 03/19/2022] [Indexed: 01/01/2023] Open
Abstract
Importance The introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However, HER2 positive breast cancer has a predilection for the central nervous system (CNS) which is associated with significant morbidity and mortality. Understanding the intracranial activity of novel HER2 directed agents is key to developing treatments as well as possible preventative strategies for HER2-positive CNS disease. Observations Using protocols and data from published phase III clinical trials for locally advanced/metastatic HER2-positive breast cancer since the licensing of single agent trastuzumab for advanced BC we review the central nervous system related aspects. This includes CNS related entry criteria, use of baseline and on study cross-sectional imaging of the CNS and protocol and non-protocol defined CNS end points and reported data. Conclusions and Relevance: This review found heterogeneity between studies with regard to the entry criteria, use of CNS imaging and reported end points within the pivotal phase III studies. Based on these data, a standardisation of both entry criteria and end points with regard to the CNS should be developed and applied to future studies of HER2-positive advanced BC. Such an approach would enable the generation of comparable data and allow a meaningful analysis of different treatment approaches with regard to the CNS. This in turn would allow the development of the most optimal treatment approaches for HER2 positive CNS disease and ultimately the development of preventative strategies.
Heterogeneity exists with respect to the CNS in studies of advanced HER2 positive breast cancer. A standardised approach to the CNS is required in future clinical trials. This would enable the generation of comparable CNS data for meaningful analysis. This would aid the development of treatments for HER2 positive CNS disease.
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Affiliation(s)
- Talvinder Bhogal
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK; The Clatterbridge Cancer Centre NHS Foundation Trust, 65 Pembroke Place, Liverpool, L7 8YA, United Kingdom
| | - David Cameron
- Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, UK
| | - Carlo Palmieri
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK; The Clatterbridge Cancer Centre NHS Foundation Trust, 65 Pembroke Place, Liverpool, L7 8YA, United Kingdom.
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Huang L, Liu X, Li L, Wang L, Wu N, Liu Z. Novel immune subtypes identification of HER2-positive breast cancer based on immunogenomic landscape. Med Oncol 2022; 39:92. [PMID: 35568771 DOI: 10.1007/s12032-022-01690-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/21/2022] [Indexed: 11/28/2022]
Abstract
HER2 positive BC is heterogeneous. But few studies discussed the classification of HER2-positive BC based on immune-related signatures. Using three publicly BC genomics datasets, we classified HER2 positive BC based on 33 immune-related signatures and used unsupervised machine learning methods to predict and perform the classification. We grouped three HER2-positive BC subtypes that we called Immune-High (IM-H), Immune-Medium (IM-M), and Immune-Low (IM-L), and manifested this categorization was predictable, duplicable and reliable by analyzing another dataset. Compared to other subtypes, IM-H had a higher immune cell infiltration level and stronger anti-tumor immune activities, as well as better clinical survival outcome. Besides these signatures, there were some cancer-related pathways which were hyperactivated in IM-H, including cytokine-cytokine receptor interactions, antigen processing and presentation pathways, natural killer cell-mediated cytotoxicity, Th1 and Th2 cell differentiation, chemokine signaling pathway, Th17 cell differentiation, B and T cell receptor signaling, NF-kappa B signaling, PD-L1 expression and PD-1 checkpoint pathway in cancer, TNF signaling, IL-17 signaling, NOD-like receptor signaling and Toll-like receptor signaling. By contrast, IM-L showed depressed immune-related signatures and enhanced activation of lycosylphosphatidylinositol-anchor biosynthesis and mismatch repair. Moreover, we discovered a gene co-expression network focused on eight transcription factor genes (EOMES, TBX21, GFI1, IRF4, POU2AF1, CIITA, FOXP3 and TOX) and one tumor suppress gene (PRF1), which were closely related with tumor immune. We identified three HER2-positive BC subtypes based on immune-related signatures, which had potential clinical implications and promoted the optimal stratification of HER2-positive BC responsive to immunotherapy.
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Affiliation(s)
- Lingli Huang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China
| | - Xin Liu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China
| | - Li Li
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China
| | - Lei Wang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China
| | - Nan Wu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China
| | - Zhixian Liu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, Jiangsu, China.
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Salvage Treatment for Progressive Brain Metastases in Breast Cancer. Cancers (Basel) 2022; 14:cancers14041096. [PMID: 35205844 PMCID: PMC8870695 DOI: 10.3390/cancers14041096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/31/2022] [Accepted: 02/17/2022] [Indexed: 11/24/2022] Open
Abstract
Simple Summary Thirty percent of patients with human epidermal growth factor receptor 2-positive breast cancer and triple-negative breast cancer, and 15% of patients with the remaining subtypes of breast cancer will develop brain metastases. Available treatment methods include surgery and radiotherapy. However, some individuals will experience intracranial progression despite prior local treatment. This situation remains a challenge. In the case of progressing lesions amenable to local therapy, the choice of a treatment method must consider performance status, cancer burden, possible toxicity, and previously applied therapy. Stereotactic radiosurgery or fractionated radiotherapy rather than whole-brain radiotherapy should be used only if feasible. If local therapy is unfeasible, selected patients, especially those with human epidermal growth factor receptor 2-positive breast cancer, may benefit from systemic therapy. Abstract Survival of patients with breast cancer has increased in recent years due to the improvement of systemic treatment options. Nevertheless, the occurrence of brain metastases is associated with a poor prognosis. Moreover, most drugs do not penetrate the central nervous system because of the blood–brain barrier. Thus, confirmed intracranial progression after local therapy is especially challenging. The available methods of salvage treatment include surgery, stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), whole-brain radiotherapy, and systemic therapies. This narrative review discusses possible strategies of salvage treatment for progressive brain metastases in breast cancer. It covers possibilities of repeated local treatment using the same method as applied previously, other methods of local therapy, and options of salvage systemic treatment. Repeated local therapy may provide a significant benefit in intracranial progression-free survival and overall survival. However, it could lead to significant toxicity. Thus, the choice of optimal methods should be carefully discussed within the multidisciplinary tumor board.
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Barańska A, Dolar-Szczasny J, Kanadys W, Kinik W, Ceglarska D, Religioni U, Rejdak R. Oral Contraceptive Use and Breast Cancer Risk According to Molecular Subtypes Status: A Systematic Review and Meta-Analysis of Case-Control Studies. Cancers (Basel) 2022; 14:cancers14030574. [PMID: 35158842 PMCID: PMC8833678 DOI: 10.3390/cancers14030574] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/19/2022] [Accepted: 01/21/2022] [Indexed: 01/10/2023] Open
Abstract
We conducted a systematic review and meta-analysis to investigate the effect of oral contraceptives (OCs) on risk of breast cancer (BrCa) by status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We searched the MEDLINE (PubMed), Embase and the Cochrane Library database and bibliographies of pertinent articles published up to 2020. Therein, we identified nineteen eligible case-control studies which provided data by breast cancer subtypes: ER-positive (ER+), ER-negative (ER−), HER2-positive (HER2+) and Triplet-negative (TN). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CIs) were calculated using fixed/random effects models. The summary meta-analysis showed that over-use of OCs led to significant increased risk of TNBrCa (OR = 1.37, 95% CI; 1.13 to 1.67, p = 0.002), as well as of ER−BrCa (OR = 1.20, 95% CI: 1.03 to 1.40, p = 0.019). There was also a significant reduction in the risk of ER+BrCa (OR = O.92, 95% CI: 0.86 to 0.99, p = 0.026,) and a slight reduction in the risk of HER2+BrCa (OR = 0.95, 95% CI; 0.79 to 1.14, p = 0.561) after taking OCs. Meta-analysis indicated that OC use has different impacts on risk of breast cancer subtypes defined by receptor status. The identified differences between individual subtypes of breast cancer may reflect different mechanisms of carcinogenesis.
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Affiliation(s)
- Agnieszka Barańska
- Department of Medical Informatics and Statistics with E-Learning Lab, Medical University of Lublin, 20-090 Lublin, Poland
- Correspondence:
| | - Joanna Dolar-Szczasny
- Department of General and Pediatric Ophtalmology, Medical University of Lublin, 20-070 Lublin, Poland; (J.D.-S.); (R.R.)
| | | | - Wiktoria Kinik
- Science Popularization Centre, Medical University of Lublin, 20-059 Lublin, Poland;
| | - Dorota Ceglarska
- Subunit, Primary Health Care Center Provita, 20-093 Lublin, Poland;
| | - Urszula Religioni
- School of Public Health, Centre of Postgraduate Medical Education of Warsaw, 01-813 Warsaw, Poland;
- National Institute of Public Health-National Institute of Hygiene, Warsaw School of Economics, 02-554 Warsaw, Poland
| | - Robert Rejdak
- Department of General and Pediatric Ophtalmology, Medical University of Lublin, 20-070 Lublin, Poland; (J.D.-S.); (R.R.)
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Pituitary metastasis in HER-2 positive breast cancer with initial presentation of hypernatremia: Two case reports. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2021. [DOI: 10.1016/j.cpccr.2021.100107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Lin PH, Wang MY, Lo C, Tsai LW, Yen TC, Huang TY, Huang WC, Yang K, Chen CK, Fan SC, Kuo SH, Huang CS. Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy. Front Oncol 2021; 11:736769. [PMID: 34868925 PMCID: PMC8632818 DOI: 10.3389/fonc.2021.736769] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 10/25/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT). METHODS Plasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations. RESULTS A total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 - 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 - 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 - 3, HR 3.753, 95% CI 1.146 - 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 - 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery. CONCLUSIONS This study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.
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Affiliation(s)
- Po-Han Lin
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
- Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Yang Wang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chiao Lo
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Li-Wei Tsai
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzu-Chun Yen
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Thomas Yoyan Huang
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Chih Huang
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Karen Yang
- Department of Molecular Biology, Princeton University, Princeton, NJ, United States
| | - Chih-Kai Chen
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Chih Fan
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Department of Medical Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chiun-Sheng Huang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan
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Vidal GA, Gautam S, Vlahiotis A, Fisher MD, Pulgar S, DeBusk K. Treatment patterns and overall survival in HER2+ metastatic breast cancer at US community oncology practices. Future Oncol 2021; 18:849-858. [PMID: 34756117 DOI: 10.2217/fon-2021-0405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC). Materials & methods: Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed with HER2+ MBC, with and without brain metastases (BMs), between June 1, 2012 and May 31, 2018 using electronic medical records from the Definitive Oncology Dataset. Results: Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line. Conclusion: OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.
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Affiliation(s)
- Gregory A Vidal
- West Cancer Center & Research Institute, 7945 Wolf River Blvd, Germantown, TN 38138, USA, & University of Tennessee Health Sciences Center, 910 Madison Avenue, Memphis TN 38163, USA
| | - Santosh Gautam
- ConcertAI, 6555 Quince Rd, Ste 400, Memphis, TN 38119, USA
| | - Anna Vlahiotis
- ConcertAI, 6555 Quince Rd, Ste 400, Memphis, TN 38119, USA
| | | | - Sonia Pulgar
- Seagen Inc. 21823 30th Dr SE, Bothell, WA 98021, USA
| | - Kendra DeBusk
- Seagen Inc. 21823 30th Dr SE, Bothell, WA 98021, USA
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Giannoudis A, Sartori A, Eastoe L, Zakaria R, Charlton C, Hickson N, Platt-Higgins A, Rudland PS, Irwin D, Jenkinson MD, Palmieri C. Genomic profiling using the UltraSEEK panel identifies discordancy between paired primary and breast cancer brain metastases and an association with brain metastasis-free survival. Breast Cancer Res Treat 2021; 190:241-253. [PMID: 34499316 PMCID: PMC8558178 DOI: 10.1007/s10549-021-06364-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 08/08/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Brain metastases (BM) are an increasing clinical problem. This study aimed to assess paired primary breast cancers (BC) and BM for aberrations within TP53, PIK3CA, ESR1, ERBB2 and AKT utilising the MassARRAY® UltraSEEK® technology (Agena Bioscience, San Diego, USA). METHODS DNA isolated from 32 paired primary BCs and BMs was screened using the custom UltraSEEK® Breast Cancer Panel. Data acquisition and analysis was performed by the Agena Bioscience Typer software v4.0.26.74. RESULTS Mutations were identified in 91% primary BCs and 88% BM cases. TP53, AKT1, ESR1, PIK3CA and ERBB2 genes were mutated in 68.8%, 37.5%, 31.3%, 28.1% and 3.1% respectively of primary BCs and in 59.4%, 37.5%, 28.1%, 28.1% and 3.1% respectively of BMs. Differences in the mutations within the 5 genes between BC and paired BM were identified in 62.5% of paired cases. In primary BCs, ER-positive/HER2-negative cases harboured the most mutations (70%), followed by ER-positive/HER2-positive (15%) and triple-negatives (13.4%), whereas in BMs, the highest number of mutations was observed in triple-negative (52.5%), followed by ER-positive/HER2-negative (35.6%) and ER-negative/HER2-positive (12%). There was a significant association between the number of mutations in the primary BC and breast-to-brain metastasis-free survival (p = 0.0001) but not with overall survival (p = 0.056). CONCLUSION These data demonstrate the discordancy between primary BC and BM, as well as the presence of clinically important, actionable mutations in BCBM. The UltraSEEK® Breast Cancer Panel provides a tool for BCBM that can be utilised to direct more tailored treatment decisions and for clinical studies investigating targeted agents.
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Affiliation(s)
- Athina Giannoudis
- Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | | | | | - Rasheed Zakaria
- Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
- Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK
| | | | - Nicholas Hickson
- Manchester University Hospital NHS Foundation Trust, Manchester, UK
| | - Angela Platt-Higgins
- Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | - Philip S Rudland
- Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK
| | | | - Michael D Jenkinson
- Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK
- Institute of Systems, Molecular and Integrative Biology, Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
| | - Carlo Palmieri
- Institute of Systems, Molecular and Integrative Biology, Molecular and Clinical Cancer Medicine, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, UK.
- The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK.
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Ahirwar R. Recent advances in nanomaterials-based electrochemical immunosensors and aptasensors for HER2 assessment in breast cancer. Mikrochim Acta 2021; 188:317. [PMID: 34476602 DOI: 10.1007/s00604-021-04963-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 08/14/2021] [Indexed: 12/17/2022]
Abstract
Human epidermal growth factor receptor 2 (HER2) is one of the key molecular targets in breast cancer pathogenesis. Overexpression and/or amplification of HER2 in approximately 15-20% of breast cancer patients is associated with high mortality and poor prognosis. Accumulating evidence shows that accurate and sensitive detection of HER2 improves the survival outcomes for HER2-positive breast cancer patients from targeted therapies. The current methods of clinical determination of HER2 expression levels are based on slide-based assays that rely on invasively collected primary tumours. Alternatively, ELISA-based detection of the shredded HER2 extracellular domain (HER2-ECD) of has been suggested as a surrogate method for monitoring disease progress and treatment response in breast cancer patients. In the past decade, biosensors have emerged as an alternative modality for the detection of circulating HER2-ECD in human serum samples. In particular, electrochemical biosensors based on nanomaterials and antibodies and aptamers have been increasingly developed as promising tools for rapid, sensitive, and cost-effective detection of HER2-ECD. These biosensors harness the high affinity and specificity of antibodies and aptamers, and unique conductive properties, biocompatibility, large surface area, and chemical stability of nanomaterials for selective and sensitive assessment of the HER2. This review provides an overview of the recent advances in the application of nanomaterials-based immunosensors and aptasensors for detection of circulating HER2-ECD. In particular, various electrochemical techniques, detection approaches, and nanomaterials are discussed. Further, analytical figures of merit of various HER2 immunosensors and aptasensors are compared. Finally, possible challenges and potential opportunities for biosensor-based detection of HER2-ECD are discussed.
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Affiliation(s)
- Rajesh Ahirwar
- Department of Environmental Biochemistry, ICMR- National Institute for Research in Environmental Health, Bhopal Bypass Road, Bhauri, Bhopal, Madhya Pradesh, 462030, India.
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Abdullah ML, Al-Shabanah O, Hassan ZK, Hafez MM. Eugenol-Induced Autophagy and Apoptosis in Breast Cancer Cells via PI3K/AKT/FOXO3a Pathway Inhibition. Int J Mol Sci 2021; 22:ijms22179243. [PMID: 34502165 PMCID: PMC8430664 DOI: 10.3390/ijms22179243] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/15/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
The use of natural compounds is promising in approaches to prevent and treat cancer. The long-term application of most currently employed chemotherapy techniques has toxic side effects. Eugenol, a phenolic phytochemical extracted from certain essential oils, has an anti-cancer effect. The modulation of autophagy can promote either the survival or apoptosis of cancer cells. Triple-negative (MDA-MB-231) and HER2 positive (SK-BR-3) breast cancer cell lines were treated with different doses of eugenol. Apoptosis was detected by a flow-cytometry technique, while autophagy was detected by acridine orange. Real-time PCR and Western blot assays were applied to investigate the effect of eugenol on the gene and protein expression levels of autophagy and apoptotic genes. Treating cells with different concentrations of eugenol significantly inhibited cell proliferation. The protein levels of AKT serine/threonine kinase 1 (AKT), forkhead box O3 (FOXO3a), cyclin dependent kinase inhibitor 1A (p21), cyclin-dependent kinase inhibitor (p27), and Caspase-3 and -9 increased significantly in Eugenol-treated cells. Eugenol also induced autophagy by upregulating the expression levels of microtubule-associated protein 1 light chain 3 (LC3) and downregulating the expression of nucleoporin 62 (NU p62). Eugenol is a promising natural anti-cancer agent against triple-negative and HER2-positive breast cancer. It appears to work by targeting the caspase pathway and by inducing autophagic cell death.
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Affiliation(s)
- Mashan L. Abdullah
- Experimental Medicine Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, MNGHA, Riyadh 11426, Saudi Arabia
- Pharmacology and Toxicology Department, King Saud University, Riyadh 11426, Saudi Arabia;
- Correspondence: (M.L.A.); (M.M.H.)
| | - Othman Al-Shabanah
- Pharmacology and Toxicology Department, King Saud University, Riyadh 11426, Saudi Arabia;
| | - Zeinab K. Hassan
- Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, Egypt;
| | - Mohamed M. Hafez
- Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 12613, Egypt;
- Correspondence: (M.L.A.); (M.M.H.)
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Izutsu N, Kinoshita M, Ozaki T, Sakai M, Nakanishi K, Nakayama T, Tamaki Y, Kishima H. Cerebellar preference of luminal A and B type and basal ganglial preference of HER2-positive type breast cancer-derived brain metastases. Mol Clin Oncol 2021; 15:175. [PMID: 34276994 PMCID: PMC8278396 DOI: 10.3892/mco.2021.2337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 06/16/2021] [Indexed: 11/20/2022] Open
Abstract
The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes.
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Affiliation(s)
- Nobuyuki Izutsu
- Department of Neurosurgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.,Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Manabu Kinoshita
- Department of Neurosurgery, Osaka International Cancer Institute, Osaka 541-8567, Japan.,Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
| | - Tomohiko Ozaki
- Department of Neurosurgery, Kawachi General Hospital, Higashiosaka, Osaka 578-0954, Japan
| | - Mio Sakai
- Department of Diagnostic and Interventional Radiology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Katsuyuki Nakanishi
- Department of Diagnostic and Interventional Radiology, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Takahiro Nakayama
- Department of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Yasuhiro Tamaki
- Department of Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan
| | - Haruhiko Kishima
- Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
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Kuksis M, Gao Y, Tran W, Hoey C, Kiss A, Komorowski AS, Dhaliwal AJ, Sahgal A, Das S, Chan KK, Jerzak KJ. The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis. Neuro Oncol 2021; 23:894-904. [PMID: 33367836 PMCID: PMC8168821 DOI: 10.1093/neuonc/noaa285] [Citation(s) in RCA: 140] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. METHODS Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models. RESULTS 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC. CONCLUSION There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
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Affiliation(s)
- Markus Kuksis
- Department of Medicine, Queen’s University, Kingston, Ontario, Canada
| | - Yizhuo Gao
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - William Tran
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Christianne Hoey
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Alex Kiss
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Adam S Komorowski
- Division of Medical Microbiology, McMaster University, Hamilton, Ontario, Canada
| | - Aman J Dhaliwal
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Arjun Sahgal
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Sunit Das
- Division of Neurosurgery, St. Michael’s Hospital, Toronto, Ontario, Canada
| | - Kelvin K Chan
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- The Canadian Centre for Applied Research in Cancer Control, Vancouver, British Columbia, Canada
| | - Katarzyna J Jerzak
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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Schwartz NR, DeBusk K, Forero-Torres A, Feliciano J, Anupindi VR, Yeaw J, McBride A. Economic burden of central nervous system metastases in human epidermal growth factor receptor 2-positive breast cancer. Future Oncol 2021; 17:3457-3463. [PMID: 34044579 DOI: 10.2217/fon-2020-1292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: Compare healthcare resource utilization and costs among patients with HER2+ metastatic breast cancer (MBC) with and without central nervous system (CNS) metastases. Methods: Retrospective matched cohort study using IQVIA's PharMetrics® Plus claims database. Results: Patients with CNS metastases (n = 753) experienced more outpatient, emergency room and inpatient visits versus controls (n = 753; all p < 0.05). In the post-index year, median total all-cause healthcare costs were significantly higher among patients with CNS metastases versus controls ($112,402 vs $50,835; p < 0.0001); outpatient costs primarily drove the cost differential. Conclusion: More effective therapies are needed that improve clinical outcomes and reduce economic burden associated with CNS metastases in patients with HER2+ MBC.
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Affiliation(s)
| | | | | | | | | | | | - Ali McBride
- University of Arizona Cancer Center, Phoenix, AZ 85004, USA.,The University of Arizona College of Pharmacy, Phoenix, AZ 85004, USA
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Mills MN, Naz A, Thawani C, Walker C, Figura NB, Kushchayev S, Oliver DE, Etame AB, Yu HHM, Robinson TJ, Liu JKC, Vogelbaum MA, Forsyth PA, Czerniecki BJ, Soliman HH, Han HS, Ahmed KA. Capecitabine and stereotactic radiation in the management of breast cancer brain metastases. BMC Cancer 2021; 21:552. [PMID: 33992087 PMCID: PMC8126143 DOI: 10.1186/s12885-021-08302-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 04/28/2021] [Indexed: 11/10/2022] Open
Abstract
Background Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). Methods Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. Results Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR−/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15–24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24–30 Gy) in a median of 5 fractions (range: 3–5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. Conclusions In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.
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Affiliation(s)
- Matthew N Mills
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA
| | - Afrin Naz
- Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
| | - Chetna Thawani
- Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
| | - Chelsea Walker
- Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
| | - Nicholas B Figura
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA
| | - Sergiy Kushchayev
- Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Daniel E Oliver
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA
| | - Arnold B Etame
- Department of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Hsiang-Hsuan Michael Yu
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA
| | - Timothy J Robinson
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA
| | - James K C Liu
- Department of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Michael A Vogelbaum
- Department of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Peter A Forsyth
- Department of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Brian J Czerniecki
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Hatem H Soliman
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Hyo S Han
- Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA
| | - Kamran A Ahmed
- Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA.
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Torres-Martinez Z, Delgado Y, Ferrer-Acosta Y, Suarez-Arroyo IJ, Joaquín-Ovalle FM, Delinois LJ, Griebenow K. Key genes and drug delivery systems to improve the efficiency of chemotherapy. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2021; 4:163-191. [PMID: 34142021 PMCID: PMC8208690 DOI: 10.20517/cdr.2020.64] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cancer cells can develop resistance to anticancer drugs, thereby becoming tolerant to treatment through different mechanisms. The biological mechanisms leading to the generation of anticancer treatment resistance include alterations in transmembrane proteins, DNA damage and repair mechanisms, alterations in target molecules, and genetic responses, among others. The most common anti-cancer drugs reported to develop resistance to cancer cells include cisplatin, doxorubicin, paclitaxel, and fluorouracil. These anticancer drugs have different mechanisms of action, and specific cancer types can be affected by different genes. The development of drug resistance is a cellular response which uses differential gene expression, to enable adaptation and survival of the cell to diverse threatening environmental agents. In this review, we briefly look at the key regulatory genes, their expression, as well as the responses and regulation of cancer cells when exposed to anticancer drugs, along with the incorporation of alternative nanocarriers as treatments to overcome anticancer drug resistance.
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Affiliation(s)
- Zally Torres-Martinez
- Chemistry Department, University of Puerto Rico- Rio Piedras campus, San Juan, PR 00936, USA
| | - Yamixa Delgado
- Biochemistry & Pharmacology Department, San Juan Bautista School of Medicine, Caguas, PR 00726, USA
| | - Yancy Ferrer-Acosta
- Neuroscience Department, Universidad Central del Caribe, Bayamon, PR 00956, USA
| | | | - Freisa M Joaquín-Ovalle
- Chemistry Department, University of Puerto Rico- Rio Piedras campus, San Juan, PR 00936, USA
| | - Louis J Delinois
- Chemistry Department, University of Puerto Rico- Rio Piedras campus, San Juan, PR 00936, USA
| | - Kai Griebenow
- Chemistry Department, University of Puerto Rico- Rio Piedras campus, San Juan, PR 00936, USA
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Tymon-Rosario J, Zeybek B, Santin AD. Novel antibody-drug conjugates: current and future roles in gynecologic oncology. Curr Opin Obstet Gynecol 2021; 33:26-33. [PMID: 32618744 PMCID: PMC8253558 DOI: 10.1097/gco.0000000000000642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
PURPOSE OF REVIEW Antibody-drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule. This review summarizes the current literature demonstrating their tremendous promise as therapeutic agents in the treatment of aggressive gynecologic malignancies. RECENT FINDINGS Several antigens have proven to be differentially overexpressed in a variety of gynecologic tumors when compared with normal surrounding tissue and serve as novel targets for ADC therapy. In the last few years HER2/neu, folic acid-alpha (FRα) and Trop-2 overexpression have been exploited as excellent targets by novel ADCs such as Trastuzumab emtansine (T-DM1), SYD985, IMGN853 (Mirvetuximab soravtansine) and Sacituzumab govitecan (SG, IMMU-132) in multiple tumors including ovarian, endometrial and cervical cancers. Although the selectivity of ADCs with noncleavable linkers (i.e. T-DM1) has shown negligible effect on surrounding antigen negative cells, those ADCs with cleavable linkers (i.e. SYD985, IMGN853 and SG) may kill both antigen-positive target cells and surrounding antigen-negative cells via the bystander effect. SUMMARY Preclinical data strongly supports these ADCs and ongoing clinical trials will shed further light into the potential of making these drugs part of current standard practice and providing our patients with a higher level of personalized cancer care.
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Affiliation(s)
- Joan Tymon-Rosario
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA
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43
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Cali Daylan AE, Leone JP. Targeted Therapies for Breast Cancer Brain Metastases. Clin Breast Cancer 2021; 21:263-270. [PMID: 33384227 DOI: 10.1016/j.clbc.2020.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 10/17/2020] [Accepted: 11/24/2020] [Indexed: 10/22/2022]
Abstract
The management of breast cancer, the most common cancer in the female population, has changed dramatically over years with the introduction of newer therapies. An increased incidence of brain metastases in recent years has created a challenge for oncologists because this population continues to have a poorer prognosis compared to metastatic breast cancer without central nervous system involvement. Historically, the exclusion of breast cancer patients with brain metastases from clinical trials has made treatment options even more limited. Nonetheless, more recently, this unmet need has been recognized by basic and clinical researchers and has led to the development of targeted therapies with better blood-brain barrier penetration and intracranial efficacy. Here we review targeted therapies directed at human epidermal growth factor receptor type 2 (HER2), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 and 6 (CDK4/6) and poly(ADP-ribose) polymerase (PARP) for breast cancer patients with brain metastases. These therapies aim to be more efficacious and less toxic to represent a paradigm shift in the management of breast cancer brain metastases.
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Affiliation(s)
- Ayse Ece Cali Daylan
- Department of Medicine, St Elizabeth's Medical Center, Boston, MA; Department of Medicine, Tufts University School of Medicine, Boston, MA.
| | - José Pablo Leone
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
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44
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Rohatgi N, Munshi A, Bajpai P, Singh M, Sahai S, Ahmad M, Singh K, Singh H, Parikh PM, Aggarwal S. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets. South Asian J Cancer 2020; 7:118-122. [PMID: 29721477 PMCID: PMC5909288 DOI: 10.4103/sajc.sajc_116_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10-16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.
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Affiliation(s)
- Nitesh Rohatgi
- Department of Medical Oncology, Max Hospital, New Delhi, India
| | - A Munshi
- Department of Radiation Oncology, Fortis Hospital, Gurugram, Haryana, India
| | - P Bajpai
- Department of Medical Oncology, Manipal Super Specialty Hospital, New Delhi, India
| | - M Singh
- Department of Medical Oncology, Mahavir Cancer Sansthan, Patna, Bihar, India
| | - S Sahai
- Department of Radiation Oncology, Fortis Hospital, Gurugram, Haryana, India
| | - M Ahmad
- Department of Radiation Oncology, Jolly Grant Himalayan Institute, Dehradoon, Uttarakhand, India
| | - K Singh
- Department of Radiation Oncology, MAMS, New Delhi, India
| | - H Singh
- Department of Radiaton Oncology, Action Balajee Cancer Center, New Delhi, India
| | - Purvish M Parikh
- Department of Oncology, Shalby Cancer and Research Institute, Mumbai, Maharashtra, India
| | - S Aggarwal
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
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Basade M, Singhal M, Rathi AK, Nandi M, Minhas S, Goswami C, Shinde S, Parikh PM, Aggarwal S. Practical consensus recommendations regarding the management of HER2 neu positive metastatic breast cancer. South Asian J Cancer 2020; 7:146-150. [PMID: 29721483 PMCID: PMC5909294 DOI: 10.4103/sajc.sajc_123_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Metastatic breast cancer (MBC) is cancer that has spread from the breast to another part of the body or has come back in another distant location. Treatment options for MBC depend on several factors, including where the cancer has spread, the patient's overall health, and the levels of hormone receptors and HER2 in the tumour. Over-expression of HER2 is generally considered to be a negative prognostic feature because it accompanies an increase in breast cancer mortality. However, the development of agents that specifically target HER2 has improved the management of patients with these tumours.[7],[8],[9],[10] This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of these agents and the management of HER2 positive MBC for the benefit of community oncologists.
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Affiliation(s)
- M Basade
- Department of Medical Oncology, Saifee Hospital, Mumbai, Maharashtra, India
| | - M Singhal
- Department of Medical Oncology, Indraprastha Apollo Hospital, New Delhi, India
| | - A K Rathi
- Department of Radiation Oncology, MAMC, New Delhi, India
| | - M Nandi
- Department of Medical Oncology, Jaypee Hospital, Noida, Uttar Pradesh, India
| | - S Minhas
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - C Goswami
- Department of Medical Oncology, Jaypee Hospital, Noida, Uttar Pradesh, India
| | - S Shinde
- Department of Radiation Oncology, Medica Superspecialty Hospital, Kolkata, West Bengal, India
| | - P M Parikh
- Department of Oncology, Shalby Cancer and Research Institute, Mumbai, Maharashtra, India
| | - S Aggarwal
- Department of Radiation Oncology, Medica Superspecialty Hospital, Kolkata, West Bengal, India
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Ko HM, Kim JR, Lee JS. The current status of cancer survivorship care and a consideration of appropriate care model in Korea. KOREAN JOURNAL OF CLINICAL ONCOLOGY 2020; 16:110-118. [PMID: 36945714 PMCID: PMC9942731 DOI: 10.14216/kjco.20017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 11/29/2020] [Accepted: 12/08/2020] [Indexed: 11/07/2022]
Abstract
Purpose Breast cancer patients with a human epidermal growth factor receptor 2 (HER2) enriched subtype are known to have higher rates of brain metastases (BM) than other patients. This study aimed to evaluate treatment options and survival outcomes. Methods A total of 115 breast cancer brain metastases (BCBM) patients with nearly complete medical records were retrospectively analyzed. Additionally, 36 patients were HER2 enriched types according to histological subtypes. The BM was found by brain magnetic resonance imaging in patients who had neurologic symptoms or by regular screening. Age, breast tumor size, number of BM, histological subtypes, first treatment of breast cancer, estrogen receptor, and HER2 status, stage, local treatment of BM were analyzed. Median overall survival, 5-year survival were analyzed from the data. Results The median survival time after BM was 6 months, the mean survival time was 16.3 months, and the 5-year survival after BM was only 8.0%. Factors that significantly affect the survival of BCBM patients include histological subtype, number of BM, use of lapatinib in multivariate analysis. A total of 19 out of 36 HER2 enriched patients were treated with lapatinib or capecitabine. For the treatment of HER2 enriched patients, additional use of blood-brain barrier (BBB) crossing substances, as well as local treatment for BM, significantly improve the survival rate in the Kaplan-Meier method (P=0.001). Conclusion A combination of local treatment modality for BCBM and the use of substances that cross the BBB for the HER2 enriched patient improved the survival rate.
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Affiliation(s)
- Hye Mi Ko
- Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University College of Medicine, Daejeon, Korea
| | - Je-Ryong Kim
- Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University College of Medicine, Daejeon, Korea
| | - Jin Sun Lee
- Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University College of Medicine, Daejeon, Korea
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Mishra J, Kumar B, Targhotra M, Sahoo PK. Advanced and futuristic approaches for breast cancer diagnosis. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2020. [DOI: 10.1186/s43094-020-00113-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Breast cancer is the most frequent cancer and one of the most common causes of death in women, impacting almost 2 million women each year. Tenacity or perseverance of breast cancer in women is very high these days with an extensive increasing rate of 3 to 5% every year. Along with hurdles faced during treatment of breast tumor, one of the crucial causes of delay in treatment is invasive and poor diagnostic techniques for breast cancer hence the early diagnosis of breast tumors will help us to improve its management and treatment in the initial stage.
Main body
Present review aims to explore diagnostic techniques for breast cancer that are currently being used, recent advancements that aids in prior detection and evaluation and are extensively focused on techniques that are going to be future of breast cancer detection with better efficiency and lesser pain to patients so that it helps to a physician to prevent delay in treatment of cancer. Here, we have discussed mammography and its advanced forms that are the need of current era, techniques involving radiation such as radionuclide methods, the potential of nanotechnology by using nanoparticle in breast cancer, and how the new inventions such as breath biopsy, and X-ray diffraction of hair can simply use as a prominent method in breast cancer early and easy detection tool.
Conclusion
It is observed significantly that advancement in detection techniques is helping in early diagnosis of breast cancer; however, we have to also focus on techniques that will improve the future of cancer diagnosis in like optical imaging and HER2 testing.
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Gui X, Li H, Yan Y, Zhang R. Efficacy of lapatinib combined with capecitabine in patients with HER2-positive metastatic breast cancer in a real-world study. Oncol Lett 2020; 20:378. [PMID: 33154776 PMCID: PMC7608029 DOI: 10.3892/ol.2020.12241] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 10/08/2020] [Indexed: 11/24/2022] Open
Abstract
The aim of the present study was to determine the efficacy and safety of lapatinib-based treatment for patients with human epidermal growth factor receptor-2-positive (HER2+) metastatic breast cancer (MBC). The aim of the present real-world study was to investigate the medical records and follow-up information of 92 patients with HER2+ MBC who received a lapatinib-based regimen at the recurrent/metastatic stage, 78 of whom had been pretreated with trastuzumab. The results demonstrated that the median progression-free survival (PFS) was 5.8 months and the overall survival (OS) was 21.5 months, with an objective response rate (ORR) of 21.7%, disease control rate (DCR) of 87.0% and clinical benefit rate (CBR) of 47.8%. In the patients receiving a lapatinib-based regimen as first-, second- and third/later-line treatment, the median PFS was 10.4, 5.2 and 5.1 months (P=0.048), the median OS was 32.9, 29.1 and 13.0 months (P<0.001), the ORR was 38.9, 23.3 and 13.60%, and the DCR was 100, 83.3 and 84.1%, respectively. In the trastuzumab-resistant (n=71) and trastuzumab-sensitive (n=21) patients, the median PFS was 5.2 and 9.1 months (P=0.032), and the median OS was 21.4 and 44.3 months (P=0.003), respectively. In the patients who received lapatinib plus chemotherapy (n=68), the median PFS with lapatinib plus capecitabine (n=38) was 8.1 months, as compared with the 5.1 months with lapatinib plus other chemotherapy agents (n=30; P=0.005). The median PFS of 14 patients with brain metastases was 8.4 months, with an ORR of 35.7% and a DCR of 85.7%. Multivariate analysis revealed that the line of lapatinib-based treatment and its combination with capecitabine or a different agent were independent prognostic factors for the median PFS in patients with HER2+ MBC. A limited number of adverse events were observed with the combination of lapatinib and capecitabine. Therefore, the findings of the present study suggested that lapatinib-based treatment is effective in patients with HER2+ MBC (even in trastuzumab-pretreated patients), and the combination of lapatinib with capecitabine may be recommended due to its good efficacy, convenience and tolerability.
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Affiliation(s)
- Xinyu Gui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Huiping Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Ying Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Ruyan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
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Semba R, Horimoto Y, Arakawa A, Edahiro Y, Takaku T, Iijima K, Saito M. Difficulty Diagnosing a Brain Tumor during Clinical Maintenance of a Complete Response to anti-HER2 Treatments for Metastatic Breast Cancer: A Case Report. Case Rep Oncol 2020; 13:1311-1316. [PMID: 33250747 PMCID: PMC7670346 DOI: 10.1159/000511051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 08/18/2020] [Indexed: 12/16/2022] Open
Abstract
A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.
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Affiliation(s)
- Ryoko Semba
- Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshiya Horimoto
- Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.,Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Atsushi Arakawa
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoko Edahiro
- Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tomoiku Takaku
- Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kotaro Iijima
- Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan
| | - Mitsue Saito
- Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan
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Montemurro F, Delaloge S, Barrios C, Wuerstlein R, Anton A, Brain E, Hatschek T, Kelly C, Peña-Murillo C, Yilmaz M, Donica M, Ellis P. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆. Ann Oncol 2020; 31:1350-1358. [DOI: 10.1016/j.annonc.2020.06.020] [Citation(s) in RCA: 230] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 06/04/2020] [Accepted: 06/25/2020] [Indexed: 10/23/2022] Open
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