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Kavgaci G, Sahin TK, Muderrisoglu T, Ileri S, Guven DC, Aksoy S. Post-operative serum CEA predicts prognosis in HR-positive/HER2-negative early breast cancer. Expert Rev Anticancer Ther 2024; 24:1319-1326. [PMID: 39673491 DOI: 10.1080/14737140.2024.2443009] [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: 09/10/2024] [Revised: 12/04/2024] [Accepted: 12/06/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND The prognostic role of preoperative carcinoembryonic antigen (CEA) in breast cancer is recognized, but the impact of postoperative CEA levels on survival in early breast cancer is uncertain. RESEARCH DESIGN AND METHODS We conducted a retrospective study of 921 non-metastatic breast cancer patients treated at anonymized. Patients were categorized as normal (CEA ≤3 µg/L) or elevated (CEA >3 µg/L). RESULTS Elevated postoperative CEA levels were associated with shorter disease-free survival (DFS) (median, 174.6 vs. 239.8 months; hazard ratio (HR): 1.80; 95% confidence interval (CI): 1.27-2.56; p < 0.001) and overall survival (OS) (median, 174.6 vs. 261.1 months; HR:2.34; 95% CI: 1.59-3.45; p < 0.001). Elevated CEA was associated with shorter DFS (median, 174.6 months vs. not reached (NR); HR:2.30; 95% CI: 1.03-5.19; p = 0.043) and OS (NR vs. NR; HR: 2.81; 95% CI: 1.06-7.48; p = 0.039) in stage 1, shorter DFS (median, 239. 8 vs. 141.1 months; HR: 1.95; 95% CI: 1.28-2.98; p = 0.002) and OS (median, 169 vs. 261.1 months; HR: 2.56; 95% CI: 1.6-4.12; p < 0.001) in stage 2 and shorter OS (median, 65 vs. 183.1 months; HR: 3.25; 95% CI: 1.19-8.83; p = 0.021) in stage 3. CONCLUSIONS Elevated postoperative CEA indicates worse DFS and OS in patients with HR-positive/HER2-negative early breast cancer.
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Affiliation(s)
- Gozde Kavgaci
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkiye
| | - Taha Koray Sahin
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkiye
| | - Tugcenur Muderrisoglu
- Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkiye
| | - Serez Ileri
- Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkiye
| | - Deniz Can Guven
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkiye
| | - Sercan Aksoy
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkiye
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Nakanishi S, Suda T, Tanaka K, Yonamine T, Numahata K, Sugawa A, Oshiro T, Oshiro Y, Saito S, Inokuchi J. MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration-resistant prostate cancer. Glycoconj J 2024; 41:381-394. [PMID: 39718721 PMCID: PMC11735536 DOI: 10.1007/s10719-024-10173-8] [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: 08/09/2024] [Revised: 11/29/2024] [Accepted: 12/05/2024] [Indexed: 12/25/2024]
Abstract
Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC). However, monitoring the progression status of AR-negative prostate cancer is a challenge because it does not produce prostate-specific antigen. Based on the negative relationship of expression between AR and SSEA-4, we hypothesized that a soluble molecule synchronized with SSEA-4 in expression could be a serum marker candidate for AR-negative prostate cancer. Thus, we investigated the molecular background of SSEA-4 expression by ST3GAL2-knockout in DU145 cells. Here we show that MUC1 is identified as a molecule associated with ST3GAL2 and expressed in AR-negative prostate cancer. A negative correlation of expression between AR and MUC1 was observed in prostate cancer cell lines and CRPC tissues. The average rate of MUC1 expression was nearly 60% in AR-negative prostate cancer cells in CRPC tissues. Level of serum CA15-3 (MUC1) was the highest in mCRPC among various stages and its higher level was associated with faster progression of mCRPC. Our results demonstrate that MUC1 is identified as a ST3GAL2-associated molecule and expressed in AR-negative CRPC cells. Furthermore, level of serum CA15-3 may reflect the progression status of mCRPC.
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Affiliation(s)
- Shotaro Nakanishi
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan
| | - Tetsuji Suda
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan
| | - Kei Tanaka
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan
| | - Tomoko Yonamine
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan
| | - Kenji Numahata
- Department of Urology, Yamagata Prefectural Central Hospital, 1800 Aoyagi, Yamagata, 990-2292, Japan
| | - Ai Sugawa
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan
| | - Takuma Oshiro
- Department of Urology, Naha City Hospital, 2-31-1 Furujima, Naha, 902-8511, Japan
| | - Yoshinori Oshiro
- Department of Urology, Chubu Tokushukai Hospital, 801 Higa, Kitanakagusuku-son, Nakagami-gun, Okinawa, 901-2393, Japan
| | - Seiichi Saito
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan.
- Medical Corporation Yoshinkai, 123 Daido, Naha, Okinawa, 902-0066, Japan.
| | - Junichi Inokuchi
- Department of Urology, University of the Ryukyus Graduate School of Medicine, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan.
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3
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Jung YJ, Lee S, Kang SK, Kim JY, Choo KS, Nam KJ, Joo JH, Kim JJ, Kim HY. Clinicopathological Factors Predicting Pathological Complete Response to Neoadjuvant Anti-HER2 Therapy in HER2-Positive Breast Cancer. Oncology 2024; 103:351-359. [PMID: 39250898 PMCID: PMC12048099 DOI: 10.1159/000541019] [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: 05/22/2024] [Accepted: 08/14/2024] [Indexed: 09/11/2024]
Abstract
INTRODUCTION Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. METHODS We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and preoperative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. RESULTS Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, p = 0.02), preoperative ER positivity (OR: 2.65, CI: 1.25-5.59, p = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, p < 0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, p = 0.01) and strong preoperative HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, p = 0.04) were independent predictors of a higher pCR rate. CONCLUSIONS A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.
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Affiliation(s)
- Youn Joo Jung
- Department of Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Seungju Lee
- Department of Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Seok Kyeong Kang
- Department of Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Jee Yeon Kim
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Ki Seok Choo
- Department of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Kyung Jin Nam
- Department of Radiology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Ji Hyeon Joo
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Jae Joon Kim
- Department of Hematology and Oncology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Hyun Yul Kim
- Department of Surgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
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Ranjan P, Abubakar Sadique M, Yadav S, Khan R, Kumar Srivastava A. Electrochemical Nanobiosensor of Ionic Liquid Functionalized MoO 3-rGO for Sensitive Detection of Carcinoembryonic Antigen. Chempluschem 2024; 89:e202300625. [PMID: 38321835 DOI: 10.1002/cplu.202300625] [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: 10/31/2023] [Revised: 01/29/2024] [Accepted: 02/02/2024] [Indexed: 02/08/2024]
Abstract
Early diagnosis of cancer can be achieved by detecting associated biomarkers before the appearance of symptoms. Herein, we have developed an electrochemical immunosensor of ionic liquid tailored to molybdenum trioxide-reduced graphene oxide (MoO3-rGO-IL) nanocomposite to detect carcinoembryonic antigen (CEA), a cancer biomarker. The MoO3-rGO-IL nanocomposite has been synthesized in situ via the hydrothermal method. The functionalization of 1-butyl-3-methylimidazolium tetrafluoroborate IL with MoO3-rGO synergistically improves the electrochemical and surface properties of the nanocomposite. The characterization studies revealed that the MoO3-rGO-IL nanocomposite is a highly appropriate material for the construction of immunosensors. The material exhibits exceptional electrical conductivity, surface properties, stability, and a large electrochemical effective surface area (13.77×10-2 cm2) making it ideal for fabricating immunosensors. The quantitative outcome showed that the developed immunosensor (BSA/anti-CEA/MoO3-rGO-IL/GCE) possesses excellent sensitivity, broad linearity from 25 fg mL-1 to 100 ng mL-1, and a low detection limit of 1.19 fg mL-1. Moreover, the remarkable selectivity, repeatability, and efficiency of detecting CEA in serum specimens demonstrated the feasibility of the immunosensor. Thus, the projected electrochemical immunosensor can potentially be utilized for the quantification of CEA in clinical specimens.
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Affiliation(s)
- Pushpesh Ranjan
- CSIR -, Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, 462026, Bhopal, India
- Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India
| | - Mohd Abubakar Sadique
- CSIR -, Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, 462026, Bhopal, India
- Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India
| | - Shalu Yadav
- CSIR -, Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, 462026, Bhopal, India
- Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India
| | - Raju Khan
- CSIR -, Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, 462026, Bhopal, India
- Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India
| | - Avanish Kumar Srivastava
- CSIR -, Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, 462026, Bhopal, India
- Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India
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Miyazaki N, Iwasaki T, Sakai H, Watanuki R, Tanizawa Y, Cai Z, Kawaguchi T, Tsurutani J, Nagashima K. Risk factors for recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer in Japan: a systematic literature review and meta-analysis. Curr Med Res Opin 2024; 40:827-837. [PMID: 38597173 DOI: 10.1080/03007995.2024.2332436] [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: 10/19/2023] [Accepted: 03/14/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors. METHODS We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2- early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS). RESULTS Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97-3.88]), large tumor size (1.67 [1.24-2.23]), high histological grade (1.50 [1.04-2.16]), and high nuclear grade (2.02 [1.61-2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28-4.63]), large tumor size (1.80 [1.24-2.62]), and high histological grade (2.02 [1.44-2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10-0.42]). CONCLUSIONS Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2- early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.).
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Affiliation(s)
- Naoki Miyazaki
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Toshiki Iwasaki
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Hitomi Sakai
- Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan
| | - Rurina Watanuki
- Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshinori Tanizawa
- Japan Drug Development and Medical Affairs, Eli Lilly Japan, Kobe, Japan
| | - Zhihong Cai
- Japan Drug Development and Medical Affairs, Eli Lilly Japan, Kobe, Japan
| | - Tsutomu Kawaguchi
- Japan Drug Development and Medical Affairs, Eli Lilly Japan, Kobe, Japan
| | - Junji Tsurutani
- Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan
| | - Kengo Nagashima
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
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6
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Fatima GN, Fatma H, Saraf SK. Vaccines in Breast Cancer: Challenges and Breakthroughs. Diagnostics (Basel) 2023; 13:2175. [PMID: 37443570 DOI: 10.3390/diagnostics13132175] [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: 04/17/2023] [Revised: 06/09/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Breast cancer is a problem for women's health globally. Early detection techniques come in a variety of forms ranging from local to systemic and from non-invasive to invasive. The treatment of cancer has always been challenging despite the availability of a wide range of therapeutics. This is either due to the variable behaviour and heterogeneity of the proliferating cells and/or the individual's response towards the treatment applied. However, advancements in cancer biology and scientific technology have changed the course of the cancer treatment approach. This current review briefly encompasses the diagnostics, the latest and most recent breakthrough strategies and challenges, and the limitations in fighting breast cancer, emphasising the development of breast cancer vaccines. It also includes the filed/granted patents referring to the same aspects.
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Affiliation(s)
- Gul Naz Fatima
- Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow 226028, Uttar Pradesh, India
| | - Hera Fatma
- Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow 226028, Uttar Pradesh, India
| | - Shailendra K Saraf
- Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow 226028, Uttar Pradesh, India
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Meghalatha TS, Muninathan N. Antitumor activity of withaferin-A and propolis in benz (a) pyrene-induced breast cancer. Bioinformation 2022; 18:841-844. [PMID: 37426503 PMCID: PMC10326326 DOI: 10.6026/97320630018841] [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: 09/02/2022] [Revised: 09/30/2022] [Accepted: 09/30/2022] [Indexed: 09/28/2024] Open
Abstract
Female breast cancer is the leading malignancy surpassing lung cancer recently, and its incidence is continued to rise in many countries. The existing anticancer drugs have limitations like drug resistance and adverse effects leading to poor clinical outcomes. The natural compounds withaferin-A and propolis have been individually reported for their anticancer activity in preclinical models. However, the combined effect of these compounds has not been studied especially in breast cancer models. Therefore, it is of interest to evaluate the effect of Withaferin-A and propolis on Benz(a)pyrene-induced breast cancer. Wistar rats of female gender were treated with saline (normal control), Benz(a)pyrene (disease control), Benz(a)pyrene+ Withaferin-A or Propolis, Benz(a)pyrene+ Withaferin-A+ Propolis. At the end of the treatment, the plasma levels of carcino embryonic antigen (CEA) were measured. We observed a decrease in carcino embryonic antigen (CEA) levels in rats received withaferin-A and propolis combination rather than individual compounds indicating their beneficial role in breast cancer. Results of the present study show that propolis, when combined with withaferin A, exhibits better anti tumor activity than its individual effect in Benz (a) pyrene-induced mammary carcinogenesis.
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Affiliation(s)
- Thazhathuputhenpurayil Sadhasivan Meghalatha
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram Tamil Nadu, India – 631552
| | - Natarajan Muninathan
- Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram Tamil Nadu, India – 631552
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Manafi-Farid R, Ataeinia B, Ranjbar S, Jamshidi Araghi Z, Moradi MM, Pirich C, Beheshti M. ImmunoPET: Antibody-Based PET Imaging in Solid Tumors. Front Med (Lausanne) 2022; 9:916693. [PMID: 35836956 PMCID: PMC9273828 DOI: 10.3389/fmed.2022.916693] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 05/24/2022] [Indexed: 12/13/2022] Open
Abstract
Immuno-positron emission tomography (immunoPET) is a molecular imaging modality combining the high sensitivity of PET with the specific targeting ability of monoclonal antibodies. Various radioimmunotracers have been successfully developed to target a broad spectrum of molecules expressed by malignant cells or tumor microenvironments. Only a few are translated into clinical studies and barely into clinical practices. Some drawbacks include slow radioimmunotracer kinetics, high physiologic uptake in lymphoid organs, and heterogeneous activity in tumoral lesions. Measures are taken to overcome the disadvantages, and new tracers are being developed. In this review, we aim to mention the fundamental components of immunoPET imaging, explore the groundbreaking success achieved using this new technique, and review different radioimmunotracers employed in various solid tumors to elaborate on this relatively new imaging modality.
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Affiliation(s)
- Reyhaneh Manafi-Farid
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahar Ataeinia
- Department of Radiology, Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Shaghayegh Ranjbar
- Division of Molecular Imaging and Theranostics, Department of Nuclear Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Zahra Jamshidi Araghi
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mobin Moradi
- Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Christian Pirich
- Division of Molecular Imaging and Theranostics, Department of Nuclear Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Mohsen Beheshti
- Division of Molecular Imaging and Theranostics, Department of Nuclear Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
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9
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Anoop TM, Joseph P R, Soman S, Chacko S, Mathew M. Significance of serum carcinoembryonic antigen in metastatic breast cancer patients: A prospective study. World J Clin Oncol 2022; 13:529-539. [PMID: 35949431 PMCID: PMC9244974 DOI: 10.5306/wjco.v13.i6.529] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 04/16/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is an important serum tumour marker with a substantial role in diagnosis and monitoring of various solid tumours. About 36%-70% of breast cancers have elevated serum CEA. And the available studies show discrepancy in addressing the prognostic significance of CEA in advanced breast cancer.
AIM To estimate the serum CEA level in our metastatic breast cancer patients and correlate it with response to treatment and clinical outcome.
METHODS This was a prospective clinical study conducted on 50 metastatic breast cancer patients treated at breast clinic, with newly diagnosed metastatic breast cancer planned for palliative chemotherapy, targeted therapy, and hormonal treatment. We estimated the proportion of patients with elevated serum CEA level at baseline and after palliative treatment and also studied the association of serum CEA levels with known prognostic factors. The response to treatment was correlated with the serum CEA levels in the context of responders and non-responders.
RESULTS The median pre-treatment and post-treatment CEA levels were 7.9 (1.8-40.7) ng/mL and 4.39 (1.4-12.15) ng/mL, respectively, in the whole study population (P = 0.032). No statistically significant difference was seen in baseline serum CEA between responders and non-responders. Even in the luminal group, pre-treatment serum CEA was not a predictor of response, but post-treatment CEA was a significant predictor of tumour progression. In patients with liver and lung metastases, post-treatment CEA level difference was not statistically significant in both responders and non-responders though the values were higher in non-responders. Among those with bone metastases, 69.5% had elevated post-treatment serum CEA, and only 37.5% had elevated serum CEA in those with no bone metastases.
CONCLUSION Elevated post-treatment serum CEA levels are associated with disease progression and poor response to therapy. Persistently elevated post-treatment serum CEA levels are significantly associated with bone metastases. Elevated serum CEA and hormonal status are significant predictors of treatment response.
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Affiliation(s)
| | - Rona Joseph P
- Department of Medical Oncology, Regional Cancer Center, Trivandrum 695011, Kerala, India
| | - Saikumar Soman
- Department of Medical Oncology, Regional Cancer Center, Trivandrum 695011, Kerala, India
| | - Steffi Chacko
- Department of Medical Oncology, Regional Cancer Center, Trivandrum 695011, Kerala, India
| | - Mintu Mathew
- Department of Medical Oncology, Regional Cancer Center, Trivandrum 695011, Kerala, India
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Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer. DISEASE MARKERS 2021; 2021:5529106. [PMID: 34621407 PMCID: PMC8492280 DOI: 10.1155/2021/5529106] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 09/12/2021] [Indexed: 12/23/2022]
Abstract
Objectives Molecular subtypes are employed as a guide for targeted treatment and important prognostic factors. This study focused on investigating the association of serum levels of CEA, CA15-3, and CA125 with clinicopathological characteristics of breast cancer to find prognostic markers for breast cancer and provide precise targeted therapy. Materials and Methods In this study, 961 breast cancer patients with preoperative serum levels of CEA, CA15-3, and CA125 and molecular subtypes were analyzed. Cut-off values of 5 ng/ml, 25 U/ml, and 35 U/ml were used for CEA, CA15-3, and CA125, respectively. The χ2 test and Fisher exact test along with logistic multivariate regression analysis were performed for investigating the correlation of CEA, CA15-3, and CA125 serum levels with molecular subtypes and associated factors. Results An increase in the serum concentrations of CEA, CA15-3, and CA125 was discovered in 48 (4.99%), 54 (5.62%), and 55 (5.72%) breast cancer patients, respectively. Univariate analysis demonstrated that the levels of CEA (p < 0.01) and CA15-3 (p < 0.05) were significantly linked with molecular types of breast cancer. Moreover, patients having larger tumor size (p < 0.01, p < 0.0001, and p < 0.05, respectively) along with nodal metastasis (p < 0.05, p = 0.0001, and p < 0.05, respectively) exhibited higher rates of elevated CEA, CA15-3, and CA125 levels. Status of Her-2 positive (p < 0.01) had a significant connection with elevated CEA levels. Multivariate analysis further indicated that molecular subtypes were independent factors associated with CEA and CA15-3 levels. Also, Her-2 status was significantly and independently related to CEA levels. Conclusion Preoperative serum levels of CEA and CA15-3 were independently associated with molecular subtypes of breast cancer. CEA and CA15-3 might improve the prognostic prediction for patients with breast cancer and inform the selection of specific therapies. A further biological analysis is needed for investigating the relationship between Her-2 expression and CEA levels.
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11
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Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don't Forget the Thyroid! ACTA ACUST UNITED AC 2021; 28:2987-2992. [PMID: 34436027 PMCID: PMC8395414 DOI: 10.3390/curroncol28040261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/27/2021] [Accepted: 08/04/2021] [Indexed: 11/30/2022]
Abstract
Serum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations.
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12
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Kim JY, Jeon E, Kwon S, Jung H, Joo S, Park Y, Lee SK, Lee JE, Nam SJ, Cho EY, Park YH, Ahn JS, Im YH. Prediction of pathologic complete response to neoadjuvant chemotherapy using machine learning models in patients with breast cancer. Breast Cancer Res Treat 2021; 189:747-757. [PMID: 34224056 DOI: 10.1007/s10549-021-06310-8] [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: 01/20/2021] [Accepted: 06/22/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The aim of this study was to develop a machine learning (ML) based model to accurately predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) using pretreatment clinical and pathological characteristics of electronic medical record (EMR) data in breast cancer (BC). METHODS The EMR data from patients diagnosed with early and locally advanced BC and who received NAC followed by curative surgery were reviewed. A total of 16 clinical and pathological characteristics was selected to develop ML model. We practiced six ML models using default settings for multivariate analysis with extracted variables. RESULTS In total, 2065 patients were included in this analysis. Overall, 30.6% (n = 632) of patients achieved pCR. Among six ML models, the LightGBM had the highest area under the curve (AUC) for pCR prediction. After hyper-parameter tuning with Bayesian optimization, AUC was 0.810. Performance of pCR prediction models in different histology-based subtypes was compared. The AUC was highest in HR+HER2- subgroup and lowest in HR-/HER2- subgroup (HR+/HER2- 0.841, HR+/HER2+ 0.716, HR-/HER2 0.753, HR-/HER2- 0.653). CONCLUSIONS A ML based pCR prediction model using pre-treatment clinical and pathological characteristics provided useful information to predict pCR during NAC. This prediction model would help to determine treatment strategy in patients with BC planned NAC.
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Affiliation(s)
- Ji-Yeon Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Eunjoo Jeon
- Digital Health Business Team, Samsung SDS, Seoul, 05510, South Korea
| | - Soonhwan Kwon
- Digital Health Business Team, Samsung SDS, Seoul, 05510, South Korea
| | - Hyungsik Jung
- Digital Health Business Team, Samsung SDS, Seoul, 05510, South Korea
| | - Sunghoon Joo
- Digital Health Business Team, Samsung SDS, Seoul, 05510, South Korea
| | - Youngmin Park
- Digital Health Business Team, Samsung SDS, Seoul, 05510, South Korea
| | - Se Kyung Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jeong Eon Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Seok Jin Nam
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Eun Yoon Cho
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Yeon Hee Park
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Jin Seok Ahn
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea
| | - Young-Hyuck Im
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
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13
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Bechmann MB, Brydholm AV, Codony VL, Kim J, Villadsen R. Heterogeneity of CEACAM5 in breast cancer. Oncotarget 2020; 11:3886-3899. [PMID: 33196697 PMCID: PMC7597409 DOI: 10.18632/oncotarget.27778] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 09/29/2020] [Indexed: 11/25/2022] Open
Abstract
CEACAM5 is overexpressed in many primary breast carcinomas. However, the exact role of CEACAM5 in breast cancer tumorigenesis remains unresolved. Here, we examined a repository of 110 cryopreserved primary breast carcinomas by immunohistochemistry to assess the distribution of CEACAM5 in tumor subtypes. The majority of estrogen receptor-positive and HER2-overexpressing tumors were CEACAM5-positive, whereas most of Triple-negative tumors were negative. Assessing sample sets of paired primary breast cancers and corresponding lymph node lesions from a total of 59 patients revealed a high correlation between primary tumor and lymph node with regard to CEACAM5-status. However, a notable subset of sample sets demonstrated intratumoral heterogeneity in the primary tumor, the metastatic lesion or both, suggesting that both CEACAM5-positive and –negative cells can play a role in tumor dissemination. When examining the consequence of expression of CEACAM5 in breast cancer cell lines in culture assays we found that CEACAM5-expressing cells were less invasive. In survival analysis, using cohort studies of breast cancer, expression of CEACAM5 predicted different clinical outcomes depending on molecular subtypes. Altogether, our analysis suggests that CEACAM5 plays a context-dependent role in breast cancer that warrants further investigation.
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Affiliation(s)
- Marc B Bechmann
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andreas V Brydholm
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Victoria L Codony
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jiyoung Kim
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Stem Cell Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - René Villadsen
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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14
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Gajdosova V, Lorencova L, Kasak P, Tkac J. Electrochemical Nanobiosensors for Detection of Breast Cancer Biomarkers. SENSORS (BASEL, SWITZERLAND) 2020; 20:E4022. [PMID: 32698389 PMCID: PMC7412172 DOI: 10.3390/s20144022] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 12/16/2022]
Abstract
This comprehensive review paper describes recent advances made in the field of electrochemical nanobiosensors for the detection of breast cancer (BC) biomarkers such as specific genes, microRNA, proteins, circulating tumor cells, BC cell lines, and exosomes or exosome-derived biomarkers. Besides the description of key functional characteristics of electrochemical nanobiosensors, the reader can find basic statistic information about BC incidence and mortality, breast pathology, and current clinically used BC biomarkers. The final part of the review is focused on challenges that need to be addressed in order to apply electrochemical nanobiosensors in a clinical practice.
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Affiliation(s)
- Veronika Gajdosova
- Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia; (V.G.); (L.L.)
| | - Lenka Lorencova
- Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia; (V.G.); (L.L.)
| | - Peter Kasak
- Center for Advanced Materials, Qatar University, Doha 2713, Qatar
| | - Jan Tkac
- Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, 845 38 Bratislava, Slovakia; (V.G.); (L.L.)
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15
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Rigatti SJ, Stout R. Association of Carcinoembryonic Antigen with Mortality in an Insurance Applicant Population. J Insur Med 2020; 48:24-35. [PMID: 31747325 DOI: 10.17849/insm-48-1-24-35.1] [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: 11/20/2022]
Abstract
Objectives.- To quantify the mortality risks associated with elevated levels of carcinoembryonic antigen (CEA). Background.- Carcinoembryonic antigen is cell surface glycoprotein and has been associated with the presence of high grade or metastatic cancers of the colon as well as other malignant and non-malignant disease. Prior publications have demonstrated the utility of CEA levels in the determination of mortality risk in life insurance applicants. The aim of this paper is to further characterize this risk with a larger set of data containing additional person-years of follow-up, more outcomes, and additional variables potentially associated with occult malignancy. Methods.- By use of the Social Security Death Index, mortality was examined in 321,574 insurance applicants age 50 years and older, who submitted blood samples to Clinical Reference Laboratories for testing including CEA. Results were stratified by age group and by CEA level (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), though other thresholds were tested. Mortality comparisons were carried out using Cox models and tabular methods with the 2015 smoker-distinct Valuation Basic Tables as a comparator. Results.- Relative mortality is increased at CEA levels above 4.0 ng/mL in both smokers and non-smokers. This association is persistent in Cox models when albumin, BMI and cholesterol are included as covariates. The strongest association with mortality risk occurred in the first 3-4 durations. The 3-year cumulative mortality ratio when using the 2015 VBT as baseline was 6.51 when comparing the group with CEA levels of 10+ ng/mL, compared to those with levels below 5.0 ng/mL. Conclusion.- This study shows that CEA is strongly associated with the risk of early excess mortality in life insurance applicants, and this risk appears not to be mitigated by consideration of other markers thought to be associated with occult malignancy.
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Affiliation(s)
- Steven J Rigatti
- Rigatti - Founder, Rigatti Risk Analytics, LLC, Consultant Medical Director, Clinical Reference Laboratories, Lenexa KS. Stout - Chief Scientific Officer/Laboratory Director, Clinical Reference Laboratories, Lenexa KS
| | - Robert Stout
- Rigatti - Founder, Rigatti Risk Analytics, LLC, Consultant Medical Director, Clinical Reference Laboratories, Lenexa KS. Stout - Chief Scientific Officer/Laboratory Director, Clinical Reference Laboratories, Lenexa KS
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16
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Rousseau C, Goldenberg DM, Colombié M, Sébille JC, Meingan P, Ferrer L, Baumgartner P, Cerato E, Masson D, Campone M, Rauscher A, Fleury V, Labbe C, Chauvet AF, Fresnel JS, Toquet C, Barbet J, Sharkey RM, Campion L, Kraeber-Bodéré F. Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer. J Nucl Med 2020; 61:1205-1211. [PMID: 32169921 DOI: 10.2967/jnumed.119.236000] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 12/04/2019] [Indexed: 12/21/2022] Open
Abstract
This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)-negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and 18F-FDG PET. Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of 68Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUVmax and SUVmean) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. Results: The total lesion sensitivity of immuno-PET and 18F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or 18F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or 18F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to 18F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUVmax, SUVmean, and total tumor volume, total lesion activity was significantly higher with immuno-PET than with 18F-FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.
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Affiliation(s)
- Caroline Rousseau
- Nuclear Medicine, ICO Cancer Center, Nantes, France .,CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France
| | - David M Goldenberg
- Immunomedics, Inc., Morris Plains, New Jersey.,IBC Pharmaceuticals, Inc., Morris Plains, New Jersey
| | | | | | | | - Ludovic Ferrer
- CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France.,Physics, ICO Cancer Center, Nantes, France
| | | | | | - Damien Masson
- Biology Department, University Hospital, Nantes, France
| | | | | | | | | | | | | | - Claire Toquet
- Pathology Department, University Hospital, Nantes, France
| | | | | | - Loic Campion
- CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France.,Biometrics, ICO Cancer Center, Nantes, France
| | - Françoise Kraeber-Bodéré
- Nuclear Medicine, ICO Cancer Center, Nantes, France.,CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France.,Nuclear Medicine, University Hospital, Nantes, France
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17
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The impact of DNA methylation on the cancer proteome. PLoS Comput Biol 2019; 15:e1007245. [PMID: 31356589 PMCID: PMC6695193 DOI: 10.1371/journal.pcbi.1007245] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 08/15/2019] [Accepted: 07/02/2019] [Indexed: 12/29/2022] Open
Abstract
Aberrant DNA methylation disrupts normal gene expression in cancer and broadly contributes to oncogenesis. We previously developed MethylMix, a model-based algorithmic approach to identify epigenetically regulated driver genes. MethylMix identifies genes where methylation likely executes a functional role by using transcriptomic data to select only methylation events that can be linked to changes in gene expression. However, given that proteins more closely link genotype to phenotype recent high-throughput proteomic data provides an opportunity to more accurately identify functionally relevant abnormal methylation events. Here we present a MethylMix analysis that refines nominations for epigenetic driver genes by leveraging quantitative high-throughput proteomic data to select only genes where DNA methylation is predictive of protein abundance. Applying our algorithm across three cancer cohorts we find that using protein abundance data narrows candidate nominations, where the effect of DNA methylation is often buffered at the protein level. Next, we find that MethylMix genes predictive of protein abundance are enriched for biological processes involved in cancer including functions involved in epithelial and mesenchymal transition. Moreover, our results are also enriched for tumor markers which are predictive of clinical features like tumor stage and we find clustering using MethylMix genes predictive of protein abundance captures cancer subtypes. To elucidate the molecular basis of cancer we examine the variation and dynamics characterizing the flow of information from epigenome to the transcriptome and proteome. Conducting the first genome wide analysis of epigenome-proteome associations, we present a MethylMix analysis that leverages protein abundance data taking advantage of recent high-throughput proteomic data generated using mass-spectrometry technology to elucidate the role of DNA methylation in cancer. By integrating across molecular data types, we confirm the benefit of using protein abundance data to provide additional insights into pathways and processes involved in oncogenesis and how they manifest as clinical phenotypes. Applying our method across three large cancer cohorts including breast cancer, ovarian cancer and colorectal cancer, MethylMix identifies key genes and describes molecular features and subtypes in these cancers.
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18
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Lian M, Zhang C, Zhang D, Chen P, Yang H, Yang Y, Chen S, Hong G. The association of five preoperative serum tumor markers and pathological features in patients with breast cancer. J Clin Lab Anal 2019; 33:e22875. [PMID: 30843272 PMCID: PMC6595372 DOI: 10.1002/jcla.22875] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/03/2018] [Accepted: 02/10/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The utility of frequently used serum tumor markers in breast cancer remains controversial. The study aimed to investigate the role of preoperative carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), and ferritin (FER) in the management of breast cancer and their relationships with pathological features. METHODS A total of 804 patients with breast mass who underwent breast surgery and 305 healthy volunteers were enrolled. Preoperative serum levels of CEA, CA125, CA153, CA724, and FER were measured. And the pathological features of all the patients were recorded. The association of preoperative serum tumor markers and pathological features was analyzed. RESULTS Among the 804 patients, 355 were identified as malignant cases and 449 as benign cases. CEA, CA153, and FER of patients with breast cancer were higher than those of healthy volunteer group and patients with benign breast diseases. The area under curve (AUC) of CEA, CA153, and FER for distinguishing patients with breast cancer and subjects with non-breast cancer was 0.688 (95% CI: 0.656-0.721), 0.609 (95% CI: 0.574-0.645), and 0.623 (95% CI: 0.586-0.660), respectively. CA153 correlated with tumor size, node status, and TNM stage, whereas CA125 with node status. No statistic differences of the five markers were observed among the four molecular subtypes. CONCLUSION Preoperative levels of CEA, CA153, and FER exhibit low diagnostic accuracy for breast cancer (stage I-III). CA153 correlates with tumor burden, suggesting its prognostic value. The five serum markers do not correlate with molecular subtypes.
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Affiliation(s)
- Mingjian Lian
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Cuixia Zhang
- Department of Pathology, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Dongdong Zhang
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Ping Chen
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Huijing Yang
- Medical Department, Fujian Medical University, Fuzhou, China
| | - Yuanyuan Yang
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Shidong Chen
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Guolin Hong
- Department of Clinical Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China.,Medical Department, Fujian Medical University, Fuzhou, China
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Wang XM, Zhang Z, Pan LH, Cao XC, Xiao C. KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients. Breast Cancer Res Treat 2018; 174:375-385. [PMID: 30535933 DOI: 10.1007/s10549-018-05069-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 11/23/2018] [Indexed: 02/06/2023]
Abstract
AIM To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk. METHODS The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTCKRT19, CTCCEACAM5 and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed. RESULTS In different pathological stages of breast cancer, the rates of CTCKRT19-pos and CTCCEACAM5-pos increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTCKRT19-pos in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTCCEACAM5 and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047). CONCLUSION Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.
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Affiliation(s)
- Xi-Mei Wang
- First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.,Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Zhen Zhang
- First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.,Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Li-Hui Pan
- First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.,Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Xu-Chen Cao
- First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.,Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People's Republic of China
| | - Chunhua Xiao
- First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China. .,Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China. .,Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University, Tianjin, 300060, People's Republic of China.
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20
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Fujimoto Y, Higuchi T, Nishimukai A, Miyagawa Y, Kira A, Ozawa H, Bun A, Imamura M, Miyoshi Y. High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy. J Surg Oncol 2018; 118:228-237. [PMID: 29936704 DOI: 10.1002/jso.25125] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 05/19/2018] [Indexed: 11/06/2022]
Abstract
BACKGROUND AND OBJECTIVES To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on the serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both before and after NAC. METHODS A total of 185 breast cancer patients treated with NAC were recruited. Serum carcinoembryonic antigen and CA15-3 were measured at baseline and at completion of NAC. RESULTS Among the non-pCR cancers (n = 142), the disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = .0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio: 3.31, 95% confidence interval: 1.28-10.23; P = .0122) and residual invasive size (hazard ratio: 4.47, 1.26-28.39; P = .0171) were significant independent factors for DFS. The combination of these factors proved to be an accurate predictor for DFS regardless of breast cancer subtypes. CONCLUSIONS The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments.
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Affiliation(s)
- Yukie Fujimoto
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Tomoko Higuchi
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Arisa Nishimukai
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Yoshimasa Miyagawa
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Ayako Kira
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Hiromi Ozawa
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Ayako Bun
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Michiko Imamura
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Yasuo Miyoshi
- Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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