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Zhang Y, An W, Wang C, Liu X, Zhang Q, Zhang Y, Cheng S. Novel models based on machine learning to predict the prognosis of metaplastic breast cancer. Breast 2025; 79:103858. [PMID: 39675092 PMCID: PMC11699302 DOI: 10.1016/j.breast.2024.103858] [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: 08/26/2024] [Revised: 12/09/2024] [Accepted: 12/10/2024] [Indexed: 12/17/2024] Open
Abstract
BACKGROUND Metaplastic breast cancer (MBC) is a rare and highly aggressive histological subtype of breast cancer. There remains a significant lack of precise predictive models available for use in clinical practice. METHODS This study utilized patient data from the SEER database (2010-2018) for data analysis. We utilized prognostic factors to develop a novel machine learning model (CatBoost) for predicting patient survival rates. Simultaneously, our hospital's cohort of MBC patients was utilized to validate our model. We compared the benefits of radiotherapy among the three groups of patients. RESULTS The CatBoost model we developed exhibits high accuracy and correctness, making it the best-performing model for predicting survival outcomes in patients with MBC (1-year AUC = 0.833, 3-year AUC = 0.806; 5-year AUC = 0.810). Furthermore, the CatBoost model maintains strong performance in an external independent dataset, with AUC values of 0.937 for 1-year survival, 0.907 for 3-year survival, and 0.890 for 5-year survival, respectively. Radiotherapy is more suitable for patients undergoing breast-conserving surgery with M0 stage [group1: (OS:HR = 0.499, 95%CI 0.320-0.777 p < 0.001; BCSS: HR = 0.519, 95%CI 0.290-0.929 p = 0.008)] and those with T3-4/N2-3M0 stage undergoing mastectomy [group2: (OS:HR = 0.595, 95%CI 0.437-0.810 p < 0.001; BCSS: HR = 0.607, 95%CI 0.427-0.862 p = 0.003)], compared to patients with stage T1-2/N0-1M0 undergoing mastectomy [group3: (OS:HR = 1.090, 95%CI 0.673-1.750 p = 0.730; BCSS: HR = 1.909, 95%CI 1.036-3.515 p = 0.038)]. CONCLUSION We developed three machine learning prognostic models to predict survival rates in patients with MBC. Radiotherapy is considered more appropriate for patients who have undergone breast-conserving surgery with M0 stage as well as those in stage T3-4/N2-3M0 undergoing mastectomy.
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Affiliation(s)
- Yinghui Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wenxin An
- Department of Urology Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Cong Wang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiaolei Liu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Qihong Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yue Zhang
- Department of Breast Medicine, Harbin Medical University Cancer Hospital, Harbin, China.
| | - Shaoqiang Cheng
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
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Miao Z, Ba F, Wen Z, Chen K, Shen X, Gen F, Yang Y. Survival trends of patients with metaplastic breast carcinoma with different hormone receptor statuses: a SEER-based retrospective cohort study. BMC Womens Health 2024; 24:628. [PMID: 39593066 PMCID: PMC11590209 DOI: 10.1186/s12905-024-03470-9] [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: 12/03/2023] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Metaplastic breast carcinoma (MpBC) is a rare histological subtype of breast cancer, and its prognosis is relatively poor. The survival trend of MpBC with different hormone receptor statuses has remained unclear over the past two decades. METHODS MpBC patient data were collected from the Surveillance, Epidemiology, and End Results database from 2000 to 2019. Patients were divided into two groups according to their hormone receptor status (negative and positive). The survival probabilities were calculated via Kaplan‒Meier curves. Logistic regression analysis was used to obtain odds ratios for treatment and demographic characteristics. Multivariate Cox regression was used to identify prognostic factors. RESULTS A total of 3,076 patients were enrolled, and a significant improvement in survival was observed over the last 10 years. For HR-negative MpBC patients, both overall survival and breast cancer-specific survival improved, whereas no survival improvement was observed for HR-positive patients. Compared with those in the time period from 2000 to 2009, the proportion of negative nodes and the likelihood of receiving chemotherapy increased for HR-negative patients from 2010 to 2019. In the HR-negative subgroup, the survival of Whites improved significantly, whereas the survival of Blacks improved in the HR-positive subgroup. CONCLUSIONS The survival of HR-negative MpBC patients has improved significantly in the past 20 years, which may be related to early diagnosis, increased adjuvant therapy and medical development, but no trend towards improvement has been observed in HR-positive patients. Racial disparities in different HR statuses also need to be addressed.
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Affiliation(s)
- Zhiming Miao
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Futing Ba
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Zechao Wen
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Kai Chen
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Xiang Shen
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Feng Gen
- Department of Breast and Thyroid Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Jiangsu, China
| | - Yinlong Yang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Püsküllüoğlu M, Konieczna A, Świderska K, Streb J, Pieniążek M, Grela-Wojewoda A, Pacholczak-Madej R, Mucha-Małecka A, Mituś JW, Szpor J, Kunkiel M, Rudzińska A, Jarząb M, Ziobro M. Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study. Acta Oncol 2024; 63:620-635. [PMID: 39099323 PMCID: PMC11332538 DOI: 10.2340/1651-226x.2024.40413] [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: 03/26/2024] [Accepted: 06/28/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND AND PURPOSE Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. MATERIALS AND METHODS In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. RESULTS Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. INTERPRETATION Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.
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Affiliation(s)
- Mirosława Püsküllüoğlu
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland.
| | - Aleksandra Konieczna
- Breast Cancer Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
| | - Katarzyna Świderska
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, 02-781 Warsaw, Poland
| | - Joanna Streb
- Department of Oncology, Jagiellonian University Medical College, 31-008 Krakow, Poland; Department of Oncology, University Hospital, 30-688 Krakow, Poland
| | - Małgorzata Pieniążek
- Department of Oncology, Wrocław Medical University, 50-367 Wrocław, Poland; Lower Silesian Comprehensive Cancer Center, 53-413 Wrocław, Poland
| | - Aleksandra Grela-Wojewoda
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Renata Pacholczak-Madej
- Department of Anatomy, Jagiellonian University Medical College, 31-008 Krakow, Poland; Department of Gynaecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland; Department of Chemotherapy, The District Hospital, 34-200 Sucha Beskidzka, Poland
| | - Anna Mucha-Małecka
- Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Jerzy W Mituś
- Department of Anatomy, Jagiellonian University Medical College, 31-008 Krakow, Poland; Department of Surgical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Joanna Szpor
- Department of Pathomorphology, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Michał Kunkiel
- Department of Oncology. Grochowski Hospital, 04-073 Warsaw, Poland
| | - Agnieszka Rudzińska
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Michał Jarząb
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, 02-781 Warsaw, Poland
| | - Marek Ziobro
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
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Püsküllüoğlu M, Swiderska K, Konieczna A, Streb J, Grela-Wojewoda A, Rudzinska A, Dobrzańska J, Pacholczak-Madej R, Mucha-Malecka A, Kunkiel M, Mitus JW, Jarząb M, Ziobro M. Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi‑centre experience. Oncol Lett 2024; 27:198. [PMID: 38516685 PMCID: PMC10955678 DOI: 10.3892/ol.2024.14331] [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: 12/20/2023] [Accepted: 02/09/2024] [Indexed: 03/23/2024] Open
Abstract
Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.
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Affiliation(s)
- Mirosława Püsküllüoğlu
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Katarzyna Swiderska
- Breast Cancer Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
| | - Aleksandra Konieczna
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, 02-781 Warsaw, Poland
| | - Joanna Streb
- Department of Oncology, Jagiellonian University Medical College, 31-008 Krakow, Poland
- Department of Oncology, University Hospital, 30-688 Krakow, Poland
| | - Aleksandra Grela-Wojewoda
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Agnieszka Rudzinska
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | | | - Renata Pacholczak-Madej
- Department of Anatomy, Jagiellonian University Medical College, 31-008 Krakow, Poland
- Department of Gynaecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
- Department of Chemotherapy, The District Hospital, 34-200 Sucha Beskidzka, Poland
| | - Anna Mucha-Malecka
- Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Michał Kunkiel
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, 02-781 Warsaw, Poland
| | - Jerzy W. Mitus
- Department of Anatomy, Jagiellonian University Medical College, 31-008 Krakow, Poland
- Department of Surgical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
| | - Michał Jarząb
- Breast Cancer Unit, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland
| | - Marek Ziobro
- Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, 31-115 Krakow, Poland
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Barrientos-Toro EN, Ding Q, Raso MG. Translational Aspects in Metaplastic Breast Carcinoma. Cancers (Basel) 2024; 16:1433. [PMID: 38611109 PMCID: PMC11011105 DOI: 10.3390/cancers16071433] [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: 02/06/2024] [Revised: 03/18/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial-mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC.
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Affiliation(s)
- Elizve Nairoby Barrientos-Toro
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Qingqing Ding
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Maria Gabriela Raso
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
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Wei Y, Jiao Z, Sun T, Lai Z, Wang X. Molecular Mechanisms Behind Vascular Mimicry as the Target for Improved Breast Cancer Management. Int J Womens Health 2023; 15:1027-1038. [PMID: 37465721 PMCID: PMC10350405 DOI: 10.2147/ijwh.s406327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 06/20/2023] [Indexed: 07/20/2023] Open
Abstract
Introduction Breast cancer has a high incidence and mortality rate in women due to metastasis and drug resistance which is associated with vasculogenic mimicry (VM). We purposed to explore VM formulation in breast cancer and mechanism of which is involved in EphA2/PIK3R1/CTNNB1 in the present study. Methods The expression of EphA2/PIK3R1/CTNNB1 and breast cancer patient prognosis was analyzed from TCGA data, both gene and protein expression as well as VM were measured in human breast cancer tissue samples collected in our study. The relationship between EphA2/PIK3R1/CTNNB1 and the formation of VM in breast cancer and its possible regulatory mechanism was explored. Results The results of the bioinformatics analysis based on TCGA showed that the expression of PIK3R1/ CTNNB1/ PECAM1 (CD31) in tumor tissues was significantly lower than that in normal tissues. EphA2 was positively correlated with PIK3R1, PIK3R1 with CTNNB1, and CTNNB1 with PECAM1 expression in breast cancer tissues. The results of detection in breast cancer and adjacent tissues indicated that the expression of EphA2/PIK3R1/CTNNB1 in cancer tissues was significantly lower than that in adjacent tissues. The expression of PIK3R1 was positively correlated with EphA2 and CTNNB1 expression, respectively, as well as EphA2 expression correlated with CTNNB1 expression positively. VM formation was significantly increased in breast cancer tissues compared with adjacent tissues. Conclusion Our results suggested that the formation of VM in breast cancer may be related to the EphA2/PIK3R1/CTNNB1 molecular signaling pathway.
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Affiliation(s)
- Yali Wei
- Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei Province, People’s Republic of China
| | - Zheng Jiao
- Department of Neurosurgery, Youanmen Hospital, Beijing, People’s Republic of China
| | - Tianpei Sun
- Clinical School of Medicine, Hebei University, Baoding, Hebei Province, People’s Republic of China
| | - Zhiwei Lai
- Department of Thoracic Surgery, Shanghai Sixth People’s Hospital Fujian Campus, Jinjiang, Fujian Province, People’s Republic of China
| | - Xiaochun Wang
- Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei Province, People’s Republic of China
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Ismail Y, Kamal A, Allam R, Zakaria AS. The conundrum of metaplastic breast cancer: a single Egyptian institution retrospective 10-year experience (2011-2020). J Egypt Natl Canc Inst 2023; 35:16. [PMID: 37271778 DOI: 10.1186/s43046-023-00178-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 05/14/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Metaplastic breast cancer (MetBC) still represents a conundrum owing to its peculiar histogenesis and molecular drivers that render it extremely resistant to standard chemotherapy with ultimate dismal survival. AIM Describe the Egyptian National Cancer Institute's (NCI-E) experience with MetBC regarding its clinicopathologic features, treatment, and survival outcomes. PATIENTS AND METHODS Between 2011 and 2020, all MetBC patients presented to NCI-E were retrospectively evaluated. Original clinicopathologic data, therapeutic modalities, pathologic response to neoadjuvant chemotherapy (NACT), recurrence, and date of last follow-up/death were obtained from archived charts. RESULTS A cohort of 135 females, the median age was 52 years, and median follow-up period was 40 months (range: 2.6-130.8). Two-thirds were triple negative (TN). Squamous carcinoma was prevalent in 74.8% followed by carcinoma with osseous/chondroid differentiation, spindle cell, and low-grade adenosquamous carcinoma encountered in 13.3, 7.4, and 4.5%, respectively. Modified radical mastectomy was done in 59.3%, and positive nodes (pN+) were depicted in 37.7%. Median Ki-67 was 45% (range: 10-88); grade III and lymphovascular invasion (LVI) were observed in 83.7 and 43.7%, respectively. Stage II was the most common (49%), whereas initial stage IV was encountered in 8.1%. Anthracyclines/taxane combinations were rampant in adjuvant/neoadjuvant settings. The latter was employed in 41 patients, with only 3 cases (7.3%) achieving pathologic complete response (pCR), while moderate/significant residual tumor burden was found in 83%. The 5-year DFS and OS were 56.4 and 57.6%, respectively. Spindle cell carcinoma showed the worst survival parameters in univariate analysis. On the multivariate level, higher tumor stage (pT3 & 4), Ki-67 ≥ 45%, and TN subtype were independent variables for worse DFS and OS; age ≥ 52 years and the presence of LVI were independent features for worse DFS, whereas pN+ was an independent parameter for worse OS. CONCLUSIONS This study further solidifies the dreadful response of MetBC to conventional chemotherapy regimens employed in common non-metaplastic pathologies. A radical shift in treatment standards tailored to combat the molecular landscape of this distinctive tumor is urgently needed. Immunotherapy and molecularly targeted agents demonstrated promising results in phase I and II trials with hopeful sooner implementation in phase III studies.
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Affiliation(s)
- Yahia Ismail
- Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt.
| | - Amr Kamal
- Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
| | - Rasha Allam
- Cancer Epidemiology & Biostatistics Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
| | - Al-Shimaa Zakaria
- Pathology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt
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Hu J, Lang R, Zhao W, Jia Y, Tong Z, Shi Y. The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer. Breast Cancer Res Treat 2023; 200:23-36. [PMID: 37160814 DOI: 10.1007/s10549-023-06945-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 04/05/2023] [Indexed: 05/11/2023]
Abstract
OBJECTIVE Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. METHODS We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. RESULTS A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171-2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357-3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. CONCLUSIONS MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.
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Affiliation(s)
- Jiayue Hu
- Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Ronggang Lang
- Department of Breast Pathology and Lab, Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Breast Cancer of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Weipeng Zhao
- Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Yongsheng Jia
- Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Zhongsheng Tong
- Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Yehui Shi
- Department of Breast Oncology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
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Chartier S, Brochard C, Martinat C, Coussy F, Feron JG, Kirova Y, Cottu P, Marchiò C, Vincent-Salomon A. TROP2, androgen receptor, and PD-L1 status in histological subtypes of high-grade metaplastic breast carcinomas. Histopathology 2023; 82:664-671. [PMID: 36527253 DOI: 10.1111/his.14852] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/08/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
AIMS High-grade metaplastic breast carcinoma (HG-MBC) is a rare subtype of invasive breast carcinoma, mostly triple-negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type. METHODS Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG-MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor [ER], progesterone receptor [PR], androgen receptor [AR], human epidermal growth factor receptor 2 [HER2], programmed death ligand-1 [PD-L1], and trophoblast cell surface antigen 2 [TROP2]). RESULTS The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumour-infiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple-negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD-L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour-infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1-negative. Lastly, 21 (32.3%) cases were HER2-low, all being HER2 1+, with no HER2 2+. CONCLUSION Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes.
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Affiliation(s)
- Suzanne Chartier
- Department of Pathology, Hôpital Bicêtre, APHP, Université Paris Saclay, Le Kremlin-Bicêtre, France.,Department of Pathology, Institut Curie, Paris, France
| | | | | | - Florence Coussy
- Department of Medical Oncology, Institut Curie, Paris, France
| | | | - Youlia Kirova
- Department of Radiotherapy, Institut Curie, Paris, France
| | - Paul Cottu
- Department of Medical Oncology, Institut Curie, Paris, France
| | - Caterina Marchiò
- Department of Medical Sciences, University of Turin, Italy.,Pathology Unit, Candiolo Cancer Institute FPO-IRCCS, Candiolo, Italy
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Thomas HR, Hu B, Boyraz B, Johnson A, Bossuyt VI, Spring L, Jimenez RB. Metaplastic breast cancer: A review. Crit Rev Oncol Hematol 2023; 182:103924. [PMID: 36696934 DOI: 10.1016/j.critrevonc.2023.103924] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 12/19/2022] [Accepted: 01/20/2023] [Indexed: 01/23/2023] Open
Abstract
Metaplastic breast cancer (MpBC) is an uncommon aggressive malignancy that is associated with a poor prognosis. Due to its rarity, the relationships between the clinical and pathological features of MpBC, treatment approach, and clinical outcomes remain underexplored. In the following review article, we synthesize the existing data on the clinical, pathological and genomic features, management, and outcomes of MpBC. We also identify potential targets for future clinical trials.
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Affiliation(s)
- Horatio R Thomas
- Department of Radiation Oncology, University of California, San Francisco, United States.
| | - Bonnie Hu
- Department of Radiation Oncology, Massachusetts General Hospital, United States
| | - Baris Boyraz
- Department of Pathology, Massachusetts General Hospital, United States
| | - Andrew Johnson
- Department of Radiation Oncology, Massachusetts General Hospital, United States
| | - Veerle I Bossuyt
- Department of Pathology, Massachusetts General Hospital, United States
| | - Laura Spring
- Department of Medicine, Division of Medical Oncology, Massachusetts General Hospital, United States
| | - Rachel B Jimenez
- Department of Radiation Oncology, Massachusetts General Hospital, United States
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Zheng C, Fu C, Wen Y, Liu J, Lin S, Han H, Han Z, Xu C. Clinical characteristics and overall survival prognostic nomogram for metaplastic breast cancer. Front Oncol 2023; 13:1030124. [PMID: 36937402 PMCID: PMC10018193 DOI: 10.3389/fonc.2023.1030124] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 02/09/2023] [Indexed: 03/06/2023] Open
Abstract
Background Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC. Methods We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA). Results MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram's C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model's (0.700 95% CI 0.644 -0.756). Nomogram's great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869). Conclusions Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses.
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Affiliation(s)
- Caihong Zheng
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, China
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chengbin Fu
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China
| | - Yahui Wen
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, China
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jiameng Liu
- Department of Breast Surgery, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Shunguo Lin
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China
| | - Hui Han
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China
| | - Zhonghua Han
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China
- *Correspondence: Zhonghua Han, ; Chunsen Xu,
| | - Chunsen Xu
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China
- *Correspondence: Zhonghua Han, ; Chunsen Xu,
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Malignant breast myoepithelioma: A systematic review. J Gynecol Obstet Hum Reprod 2022; 51:102481. [DOI: 10.1016/j.jogoh.2022.102481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 09/25/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022]
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13
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Thapa B, Arobelidze S, Clark BA, Xuefei J, Daw H, Cheng YC, Patel M, Spiro TPP, Haddad A. Metaplastic Breast Cancer: Characteristics and Survival Outcomes. Cureus 2022; 14:e28551. [PMID: 36185859 PMCID: PMC9517584 DOI: 10.7759/cureus.28551] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2022] [Indexed: 11/30/2022] Open
Abstract
Objectives Metaplastic breast cancer (MBC) is a rare neoplasm accounting for <1% of all breast cancer. We evaluated the clinical characteristics and survival outcomes of MBC. Methods Patients diagnosed with pathologically proven MBC were reviewed from the institutional breast cancer database from 2000 to 2017. Results A total of 136 patients diagnosed with MBC were included in the study. The median age of the diagnosis was 60 years, and 60% of patients were stage II at diagnosis, and 22% were stage III. About two-thirds of the patients were triple-negative; 93% had nuclear grade III, and 25% had a lymphovascular invasion. Squamous differentiation (29%) was the most common histologic subtype, followed by the spindle subtype (21%). The most common distant metastases were lung (22%), followed by bone (13%). Moreover, 60% had a mastectomy, 19% had endocrine therapy, 58% had radiation, 51% received anthracycline-based chemotherapy, 26% had non-anthracycline chemotherapy, and 22% received no chemotherapy. In the entire cohort, the two-year overall survival (OS) and five-year OS were 79% and 69%, respectively, and the two-year progression-free survival (PFS) and five-year PFS were 72% and 61%, respectively. On multivariable analysis, the stage of MBC (stage III: hazard ratio (HR), 5.065 (95% confidence interval (CI), 1.02-25.27) (p=0.048)), poor functional status (Eastern Cooperative Oncology Group (ECOG) score, 2; HR, 24.736 (95% CI, 1.92-318.73) (p=0.014)), and distant metastasis to the brain (HR, 8.453 (95% CI, 1.88-38.04) (p=0.005)) and lung (HR, 42.102 (95% CI, 7.20-246.36) (p<0.001)) were significant predictors of decreased OS. Conclusions MBC demonstrated early disease progression and poor overall survival. The stage of MBC, decreased performance status, and metastasis to the lung and brain were independent poor prognostic factors.
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Liu N, Zhang GD, Bai P, Su L, Tian H, He M. Eight hub genes as potential biomarkers for breast cancer diagnosis and prognosis: A TCGA-based study. World J Clin Oncol 2022; 13:675-687. [PMID: 36160462 PMCID: PMC9476610 DOI: 10.5306/wjco.v13.i8.675] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 12/23/2021] [Accepted: 07/26/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Breast cancer (BC) is the most common malignant tumor in women.
AIM To investigate BC-associated hub genes to obtain a better understanding of BC tumorigenesis.
METHODS In total, 1203 BC samples were downloaded from The Cancer Genome Atlas database, which included 113 normal samples and 1090 tumor samples. The limma package of R software was used to analyze the differentially expressed genes (DEGs) in tumor tissues compared with normal tissues. The cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of upregulated and downregulated genes. Univariate Cox regression was conducted to explore the DEGs with statistical significance. Protein-protein interaction (PPI) network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape software. Survival analyses of the hub genes were carried out using the Kaplan-Meier method. The expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database.
RESULTS A total of 1317 DEGs (fold change > 2; P < 0.01) were confirmed through bioinformatics analysis, which included 744 upregulated and 573 downregulated genes in BC samples. KEGG enrichment analysis indicated that the upregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, cell cycle, and the p53 signaling pathway (P < 0.01); and the downregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor signaling pathway, and AMP-activated protein kinase signaling pathway (P < 0.01).
CONCLUSION In view of the results of PPI analysis, which were verified by survival and expression analyses, we conclude that MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.
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Affiliation(s)
- Nan Liu
- Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
| | - Guo-Duo Zhang
- Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
| | - Ping Bai
- Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
| | - Li Su
- Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
| | - Hao Tian
- Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China
| | - Miao He
- Department of Hematology and Oncology, Chongqing Traditional Chinese Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chongqing 400011, China
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Zhu K, Chen Y, Guo R, Dai L, Wang J, Tang Y, Zhou S, Chen D, Huang S. Prognostic Factor Analysis and Model Construction of Triple-Negative Metaplastic Breast Carcinoma After Surgery. Front Oncol 2022; 12:924342. [PMID: 35814407 PMCID: PMC9261478 DOI: 10.3389/fonc.2022.924342] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 05/24/2022] [Indexed: 11/13/2022] Open
Abstract
Objective The study aimed to analyze the prognostic factors of patients with triple-negative (TN) metaplastic breast carcinoma (MpBC) after surgery and to construct a nomogram for forecasting the 3-, 5-, and 8-year overall survival (OS). Methods A total of 998 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database were assigned to either the training or validation group at random in a ratio of 7:3. The clinical characteristics of patients in the training and validation sets were compared, and multivariate Cox regression analysis was used to identify the independent risk variables for the OS of patients with TN MpBC after surgery. These selected parameters were estimated through the Kaplan–Meier (KM) curves using the log-rank test. The nomogram for predicting the OS was constructed and validated by performing the concordance index (C-index), receiver operating characteristics (ROC) curves with area under the receiver operating characteristic curves (AUC), calibration curves, and decision curve analyses (DCAs). Patients were then stratified as high-risk and low-risk, and KM curves were performed. Results Multivariate Cox regression analysis indicated that factors including age, marital status, clinical stage at diagnosis, chemotherapy, and regional node status were independent predictors of prognosis in patients with MpBC after surgery. Separate KM curves for the screened variables revealed the same statistical results as with Cox regression analysis. A prediction model was created and virtualized via nomogram based on these findings. For the training and validation cohorts, the C-index of the nomogram was 0.730 and 0.719, respectively. The AUC values of the 3-, 5-, and 8-year OS were 0.758, 0.757, and 0.785 in the training group, and 0.736, 0.735, and 0.736 for 3, 5, and 8 years in the validation group, respectively. The difference in the OS between the real observation and the forecast was quite constant according to the calibration curves. The generated clinical applicability of the nomogram was further demonstrated by the DCA analysis. In all the training and validation sets, the KM curves for the different risk subgroups revealed substantial differences in survival probabilities (P <0.001). Conclusion The study showed a nomogram that was built from a parametric survival model based on the SEER database, which can be used to make an accurate prediction of the prognosis of patients with TN MpBC after surgery.
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Affiliation(s)
| | | | | | | | | | | | | | - Dedian Chen
- *Correspondence: Sheng Huang, ; Dedian Chen,
| | - Sheng Huang
- *Correspondence: Sheng Huang, ; Dedian Chen,
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Unique clinicopathological characteristic and survival rate of metaplastic breast cancer;a special subtype of breast cancer a 5 year cohort study in single referral centre in North Borneo. Ann Med Surg (Lond) 2022; 78:103822. [PMID: 35734649 PMCID: PMC9207046 DOI: 10.1016/j.amsu.2022.103822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/15/2022] [Accepted: 05/16/2022] [Indexed: 11/24/2022] Open
Abstract
Introduction Metaplastic Breast Cancer (MBC) of the breast is a rare entity of breast cancer, with a very poor prognosis, and whose pathophysiology is still unwell established. Therapeutic management is very heterogeneous due to its incomplete understanding. The aim of this study is to describe the demographic, clinical, and therapeutic characteristics of our MBC patient. Material and methods A cross-sectional study was conducted to evaluate the demographic and clinicopathological features of these patients. Data of patients diagnosed with metaplastic breast cancer were retrieved from our breast cancer database in Queen Elizabeth Hospital II from January 2015 to May 2021. Results 14 patients were diagnosed with metaplastic breast cancer during this period of study. All of them were female, with the average age of 52 years old. The patients were predominantly Bajau and Kadazan Dusun, each comprising of 35%(n = 5). 57% (n = 8) of patients were postmenopausal. 85% (n = 12) of patients were presented with breast lump of an average largest diameter of 69.23 mm. BIRADS staging of the affected breast revealed that most of the patients were BIRADS 5.57% (n = 8) patients underwent mastectomy, 4 went for either breast conserving surgery of the breast. The most common histopathological type is squamous cell carcinoma, which accounts for 42% (n = 6) of the patients. 71% (n = 10) were pathologically triple negative. 7 patients were pathologically node positive. 35% (n = 5) had lung metastasis, and one of the patients had concurrent lung and liver metastasis. Conclusion The prognosis of patients with Metaplastic carcinoma of breast remains poor because most of it detected late and histologically triple negative type. Till date, there is no specific management guideline which warrant a multi institutional studies evaluating role of new therapies such as Anti-PD-1 Therapy in combination with chemotherapy to improve patient outcome.
This article highlight the unique clinicopathological characteristic of special type of breast cancer, metaplastic breast cancer from cross sectional study from 2015 until 2021. It is important to know the characteristic of metaplastic breast cancer in order to predict the respond of the treatment and prognosticate the disease. This article also review current treatment guideline regarding metaplastic breast cancer.
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Yoon E, Ding Q, Hunt K, Sahin A. High-Grade Spindle Cell Lesions of the Breast: Key Pathologic and Clinical Updates. Surg Pathol Clin 2022; 15:77-93. [PMID: 35236635 DOI: 10.1016/j.path.2021.11.005] [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] [Indexed: 06/14/2023]
Abstract
Most of the high-grade spindle cell lesions of the breast are malignant phyllodes tumors (MPTs), spindle cell carcinomas (SpCCs), and matrix-producing metaplastic breast carcinomas (MP-MBCs). MPTs have neoplastic spindle stromal cells and a classic leaf-like architecture with subepithelial stromal condensation. MPTs are often positive for CD34, CD117, and bcl-2 and are associated with MED12, TERT, and RARA mutations. SpCCs and MP-MBCs are high-grade metaplastic carcinomas, whereas neoplastic epithelial cells become spindled or show heterologous mesenchymal differentiation, respectively. The expression of epithelial markers must be evaluated to make a diagnosis. SAS, or rare metastatic spindle cell tumors, are seen in the breast, and clinical history is the best supporting evidence. Surgical resection is the standard of care.
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Affiliation(s)
- Esther Yoon
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030-4009, USA.
| | - Qingqing Ding
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030-4009, USA
| | - Kelly Hunt
- Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 85, Room G1.3565C, Houston, TX 77030-4009, USA
| | - Aysegul Sahin
- Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030-4009, USA
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Chen Q, Zhou Q, He H, He Y, Yuan Y, Zou Q, Yi W. Chemotherapy significantly improves long-term survival of small lesion node negative metaplastic breast carcinoma in T1c population rather than T1a and T1b. Sci Rep 2022; 12:871. [PMID: 35042902 PMCID: PMC8766593 DOI: 10.1038/s41598-022-04946-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 12/24/2021] [Indexed: 12/05/2022] Open
Abstract
Metaplastic breast carcinoma (MpBC) is considered a highly aggressive disease, the outcome of chemotherapy on small lesions (T1abcN0M0) MpBC patients remain unclear. We identified 890 female MpBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. After propensity score matching (PSM), 584 patients were matched. Survival probability was compared among T1a, T1b, and T1c patients and between patients with and without chemotherapy using Kaplan-Meier analysis and Cox proportional hazard analysis. Significance was set at two-sided P < 0.05. We classified 49, 166, and 675 patients as T1a, T1b, and T1c MpBC, respectively. The chemotherapy group included 404 patients (45.4%). Following PSM, survival analysis indicated that the patients who underwent chemotherapy had higher OS (P = 0.0002) and BCSS (P = 0.0276) in the T1c substage, but no significant difference was detected in T1a or T1b patients. In this population-based study, small lesion MpBC showed a favorable prognosis. Chemotherapy improved the prognosis of T1c MpBC patients but not T1a and T1b patients to a beneficial extent. Our findings may offer novel insight into a therapeutic strategy for MpBC.
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Affiliation(s)
- Qitong Chen
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Qin Zhou
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Hongye He
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Yeqing He
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Yunchang Yuan
- Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Qiongyan Zou
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.
| | - Wenjun Yi
- Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.
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Vohra P, Chen YY, Krings G. Less Common Triple-Negative Breast Cancers. A COMPREHENSIVE GUIDE TO CORE NEEDLE BIOPSIES OF THE BREAST 2022:463-573. [DOI: 10.1007/978-3-031-05532-4_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Xia LY, Xu WY, Hu QL. The different outcomes between breast-conserving surgery plus radiotherapy and mastectomy in metaplastic breast cancer: A population-based study. PLoS One 2021; 16:e0256893. [PMID: 34473783 PMCID: PMC8412345 DOI: 10.1371/journal.pone.0256893] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 08/17/2021] [Indexed: 12/25/2022] Open
Abstract
Background Metaplastic breast cancer (MBC) are rare. The survival outcomes of MBC patients after breast conserving surgery plus radiotherapy (BCS+RT) or mastectomy have not been established. The study aimed to compare survival outcomes of MBC patients subjected to BCS+RT or mastectomy therapeutic options. Methods Patients who were subjected to BCS+RT or mastectomy between 2004 and 2014 were enrolled in this study through the Surveillance, Epidemiology and End Results (SEER) database. Breast cancer-specific survival (BCSS) and the overall survival (OS) of the participants were determined. Cox proportional hazard model and the Kaplan Meier method were used to determine the correlation between the two surgical methods and survival outcomes. Results A total of 1197 patients were enrolled in this study. Among them, 439 patients were subjected to BCS+RT, while 758 patients were subjected to mastectomy. After propensity score matching (PSM), the BCS+RT and mastectomy groups consisted of 321 patients, respectively. The univariate and multivariate analysis with a 6-month landmark all indicate that patients receiving BCS+RT has higher OS than patients receiving mastectomy (HR = 0.701,95% CI = 0.496–0.990, P = 0.044; HR = 0.684,95% CI = 0.479–0.977, P = 0.037) while the BCSS was no difference between the two groups (HR = 0.739,95% CI = 0.474–1.153, P = 0.183; HR = 0.741,95% CI = 0.468–1.173, P = 0.200). Conclusion The BCS+RT therapeutic option exhibits a higher OS in MBC patients compared to the mastectomy approach.
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Affiliation(s)
- Lin-Yu Xia
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
- * E-mail:
| | - Wei-Yun Xu
- Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Qing-Lin Hu
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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González-Martínez S, Pérez-Mies B, Pizarro D, Caniego-Casas T, Cortés J, Palacios J. Epithelial Mesenchymal Transition and Immune Response in Metaplastic Breast Carcinoma. Int J Mol Sci 2021; 22:ijms22147398. [PMID: 34299016 PMCID: PMC8306902 DOI: 10.3390/ijms22147398] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 01/08/2023] Open
Abstract
Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent triple negative (TN) invasive carcinomas with poor prognosis. MBCs have a different clinical behavior from other types of triple negative breast cancer (TNBC), being more resistant to standard chemotherapy. MBCs are an example of tumors with activation of epithelial–mesenchymal transition (EMT). The mechanisms involved in EMT could be responsible for the increase in the infiltrative and metastatic capacity of MBCs and resistance to treatments. In addition, a relationship between EMT and the immune response has been seen in these tumors. In this sense, MBC differ from other TN tumors showing a lower number of tumor-infiltrating lymphocytes (TILS) and a higher percentage of tumor cells expressing programmed death-ligand 1 (PD-L1). A better understanding of the relationship between the immune system and EMT could provide new therapeutic approaches in MBC.
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Affiliation(s)
| | - Belén Pérez-Mies
- Department of Pathology, Hospital Ramón y Cajal, 28034 Madrid, Spain;
- Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain; (D.P.); (T.C.-C.)
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Faculty of Medicine, University of Alcalá de Henares, Alcalá de Henares, 28801 Madrid, Spain
| | - David Pizarro
- Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain; (D.P.); (T.C.-C.)
| | - Tamara Caniego-Casas
- Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain; (D.P.); (T.C.-C.)
| | - Javier Cortés
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, 28670 Madrid, Spain
- International Breast Cancer Center (IBCC), Quironsalud Group, 08017 Barcelona, Spain
- Medica Scientia Innovation Research, 08007 Barcelona, Spain
- Medica Scientia Innovation Research, Ridgewood, NJ 07450, USA
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain
- Correspondence: (J.C.); (J.P.)
| | - José Palacios
- Department of Pathology, Hospital Ramón y Cajal, 28034 Madrid, Spain;
- Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain; (D.P.); (T.C.-C.)
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Faculty of Medicine, University of Alcalá de Henares, Alcalá de Henares, 28801 Madrid, Spain
- Correspondence: (J.C.); (J.P.)
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22
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Gortman A, Aherne NJ, Westhuyzen J, Amalaseelan JV, Dwyer PM, Hoffmann M, Last AT, Shakespeare TP. Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up. Mol Clin Oncol 2021; 15:178. [PMID: 34276997 DOI: 10.3892/mco.2021.2340] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 02/15/2021] [Indexed: 12/24/2022] Open
Abstract
Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.
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Affiliation(s)
- Aron Gortman
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia
| | - Noel J Aherne
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia.,Rural Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2450, Australia.,School of Health and Human Sciences, Southern Cross University, Coffs Harbour, New South Wales 2450, Australia
| | - Justin Westhuyzen
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia
| | - Julan V Amalaseelan
- Department of Radiation Oncology, North Coast Cancer Institute, Lismore, New South Wales 2480, Australia
| | - Patrick M Dwyer
- Department of Radiation Oncology, North Coast Cancer Institute, Lismore, New South Wales 2480, Australia
| | - Matthew Hoffmann
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Port Macquarie, New South Wales 2444, Australia
| | - Andrew T Last
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Port Macquarie, New South Wales 2444, Australia
| | - Thomas P Shakespeare
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia.,Rural Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2450, Australia
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23
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Lan T, Lu Y, Zheng R, Shao X, Luo H, He J, Yang H, Xu H, Wang X, Hu Z. The Role of Adjuvant Chemotherapy in Metaplastic Breast Carcinoma: A Competing Risk Analysis of the SEER Database. Front Oncol 2021; 11:572230. [PMID: 33981594 PMCID: PMC8107469 DOI: 10.3389/fonc.2021.572230] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 02/19/2021] [Indexed: 01/02/2023] Open
Abstract
Purpose: Chemotherapy is the clinically recommended treatment for patients with operable metaplastic breast carcinoma (MBC); however, its impact remains controversial. This study investigated the possible role of chemotherapy in the treatment of MBC. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify the operable MBC patients. The competing risk analysis along with the propensity score matching (PSM) method was performed to evaluate the effect of chemotherapy. Moreover, a competing risk nomogram was built to identify prognosis in patients with MBC. Results: Of the 1137 patients with MBC, 775 received chemotherapy and 362 did not receive chemotherapy. The 5-year cumulative incidence of breast cancer-specific death (BCSD) showed similar outcomes in both the Chemo and No-Chemo groups (21.1 vs. 24.3%, p = 0.57). Chemotherapy showed no apparent association with BCSD (HR, 1.07; 95% CI, 0.72–1.60; p = 0.72), even after subgroup analysis or PSM. Race, tumor size, lymph node status, and radiation were identified as the significant factors for MBC after a penalized variable selection process. In addition, a competing risk nomogram showed relatively good accuracy of prediction with a C-index of 0.766 (95% CI, 0.700–0.824). Conclusion: Our findings demonstrated that chemotherapy did not improve BCSD for operable MBC patients. Thus, it may indicate the need to reduce exposure to the current chemotherapy strategies for patients with resectable MBC. Additionally, some novel treatment strategies are required urgently to identify and target the potential biomarkers.
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Affiliation(s)
- Tian Lan
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China.,The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yunyan Lu
- Department of Cardiology, The First People's Hospital of Xiaoshan District, Hangzhou, China
| | - Ruzhen Zheng
- Department of Radiotherapy, Hangzhou Cancer Hospital, Hangzhou, China
| | - Xiying Shao
- Department of Medical Oncology (Breast), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
| | - Hua Luo
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Junling He
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Huifen Yang
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Haibin Xu
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Xiaojia Wang
- Department of Medical Oncology (Breast), Zhejiang Cancer Hospital, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
| | - Zujian Hu
- Department of Breast Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
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24
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Erjan A, Almasri H, Abdel-Razeq H, Al-Masri M, Haddad H, Alnsour A, Rahman FA, Dayyat A. Metaplastic Breast Carcinoma: Experience of a Tertiary Cancer Center in the Middle East. Cancer Control 2021; 28:10732748211004889. [PMID: 33827281 PMCID: PMC8204524 DOI: 10.1177/10732748211004889] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background: Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center. Methods: Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS. Results: 81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (<2 mm). Almost all patients received chemotherapy. 75.3% received radiotherapy, 23.5% received hormonal therapy and 6.2% received Trastuzumab. With a median follow-up of 54 months, 18.5% developed loco-regional recurrence and 34.6% relapsed distally. Five-year OS was 66.0%. On multivariate analysis: adjuvant radiotherapy correlated with better OS (P < .0001), and tumor size >5 cm, nodal involvement and LVI correlated with worse OS, (P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype. Conclusion: We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.
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Affiliation(s)
- Ayah Erjan
- Department of Radiation Oncology, 37559King Hussein Cancer Center, Amman, Jordan
| | - Hanan Almasri
- Department of Radiation Oncology, 37559King Hussein Cancer Center, Amman, Jordan
| | | | - Mahmoud Al-Masri
- Department of Surgery, 37559King Hussein Cancer Center, Amman, Jordan
| | - Hussam Haddad
- Department of Pathology, 37559King Hussein Cancer Center, Amman, Jordan
| | - Anoud Alnsour
- Department of Radiation Oncology, 37559King Hussein Cancer Center, Amman, Jordan
| | - Fadwa Abdel Rahman
- Department of Radiation Oncology, 37559King Hussein Cancer Center, Amman, Jordan
| | - Abdulmajeed Dayyat
- Department of Radiation Oncology, 37559King Hussein Cancer Center, Amman, Jordan.,Department of Radiation Oncology, Dalhousie University, Nova Scotia, Canada
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25
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El-Sheikh N, Mousa NO, Tawfeik AM, Saleh AM, Elshikh I, Deyab M, Ragheb F, Moneer MM, Kawashti A, Osman A, Elrefaei M. Assessment of Human Papillomavirus Infection and Risk Factors in Egyptian Women With Breast Cancer. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2021; 15:1178223421996279. [PMID: 33716506 PMCID: PMC7917427 DOI: 10.1177/1178223421996279] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/01/2021] [Indexed: 12/12/2022]
Abstract
Numerous risk factors for breast cancer (BC) have been identified. High-risk human papilloma virus (HR-HPV) is the etiological agent of cervical cancer and in some cases of head and neck cancer, specifically oropharyngeal cancer, but the role of HR-HPV in evoking neoplasia in BC is still unclear. In this study, all women above the age of 18 visiting the oncology clinic at Al-Azhar university hospital and Ain Shams specialized hospital between the period of February 2017 and March 2018 were invited to participate. We determined the prevalence of HR-HPV genotypes 16, 18, and 31 in breast tissue samples from 72 women with treatment-naïve BC and 15 women with benign breast lesions (BBL) by quantitative real-time PCR (qRT-PCR) and primer sets targeting the E6 and E7 regions. High-risk human papilloma virus DNA was detected in 16 of 72 (22.2%) BC cases (viral load range = 0.3-237.8 copies/uL) and 0 of 15 women with BBL. High-risk human papilloma virus was detected in 14 of 16 (87.5%), 2 of 16 (12.5%), and 0 of 16 (0%) for genotypes 16, 18, and 31, respectively. Forty-three age-matched healthy Egyptian women were enrolled as controls for assessment of local risk factors that can be used to initiate a strategy of BC prevention in Egypt. Assessment of the risk factors demonstrated that low education level, passive smoking, lack of physical activity, family history of cancer, and use of oral contraception were significant risk factors for BC. In conclusion, our results lead us to postulate that HR-HPV infection may be implicated in the development of some types of BC in Egyptian women. In addition, identification of local risk factors can support practical prevention strategies for BC in Egypt.
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Affiliation(s)
- Nabila El-Sheikh
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Nahla O Mousa
- Biotechnology Department, Egypt- Japan University of Science and Technology (E-JUST), Basic and Applied Sciences Institute (BAS), Alexandria, Egypt.,Biotechnology Program, Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt
| | - Amany M Tawfeik
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Alaa M Saleh
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Iman Elshikh
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Mohamed Deyab
- Department of Surgery, Faculty Medicine, Al-Azhar University, Cairo, Egypt
| | - Faten Ragheb
- Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Manar M Moneer
- Department of Epidemiology and Statistics, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Ahmed Kawashti
- Department of Surgery, Faculty Medicine, Al-Azhar University, Cairo, Egypt
| | - Ahmed Osman
- Biotechnology Department, Egypt- Japan University of Science and Technology (E-JUST), Basic and Applied Sciences Institute (BAS), Alexandria, Egypt.,Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Mohamed Elrefaei
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
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26
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Tadros AB, Sevilimedu V, Giri DD, Zabor EC, Morrow M, Plitas G. Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype. Ann Surg Oncol 2021; 28:4245-4253. [PMID: 33389291 DOI: 10.1245/s10434-020-09430-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 11/11/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer. METHODS Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method. RESULTS Of 132 MBC patients, those with heterologous mesenchymal MBC (n = 45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78-0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32-0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6-3.3; p < 0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response. CONCLUSIONS Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC's unique biology.
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Affiliation(s)
- Audree B Tadros
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Varadan Sevilimedu
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Dilip D Giri
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Emily C Zabor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - Monica Morrow
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - George Plitas
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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27
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Hodgson A, Turashvili G. Pathology of Hereditary Breast and Ovarian Cancer. Front Oncol 2020; 10:531790. [PMID: 33117676 PMCID: PMC7550871 DOI: 10.3389/fonc.2020.531790] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 09/01/2020] [Indexed: 12/11/2022] Open
Abstract
Hereditary breast and ovarian cancer (HBOC) syndrome is most commonly characterized by deleterious germline mutations in BRCA1 and BRCA2. HBOC patients are prone to the development of malignant neoplasms in multiple organs including the breast, ovary, and fallopian tube. From a pathological perspective, a number of morphological features have been described in BRCA-associated breast and tubo-ovarian cancers. For example, breast cancers diagnosed in BRCA1-mutation carriers are frequently of a high Nottingham grade and display medullary morphology and a triple-negative and/or a basal-like immunophenotype. In contrast, breast cancers in BRCA2-mutation carriers are similar to sporadic luminal-type tumors that are positive for hormone receptors and lack expression of human epidermal growth factor receptor 2. Cancers arising in the fallopian tube and ovary are almost exclusively of a high-grade serous histotype with frequent Solid, pseudo-Endometrioid, and Transitional cell carcinoma-like morphology (“SET features”), marked nuclear atypia, high mitotic index, abundant tumor infiltrating lymphocytes, and necrosis. In addition, pushing or infiltrative micropapillary patterns of invasion have been described in BRCA-associated metastases of tubo-ovarian high-grade serous carcinomas. Besides BRCA1 and BRCA2 mutations, alterations in a number of other homologous recombination genes with moderate penetrance, including PALB2, RAD51C, RAD51D, BRIP1, and others, have also been described in HBOC patients with varying frequency; however, distinct morphological characteristics of these tumors have not been well characterized to date. In this review, the above pathological features are discussed in detail and a focus is placed on how accurate pathologic interpretation plays an important role in allowing HBOC patients to receive the best possible management.
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Affiliation(s)
- Anjelica Hodgson
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gulisa Turashvili
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.,Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
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28
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González-Martínez S, Pérez-Mies B, Carretero-Barrio I, Palacios-Berraquero ML, Perez-García J, Cortés J, Palacios J. Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma. Cancers (Basel) 2020; 12:cancers12071832. [PMID: 32650408 PMCID: PMC7408634 DOI: 10.3390/cancers12071832] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/01/2020] [Accepted: 07/04/2020] [Indexed: 12/12/2022] Open
Abstract
Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent invasive carcinomas that display differentiation of the neoplastic epithelium towards squamous cells and/or mesenchymal-type elements. Most MBC have a triple negative phenotype and poor prognosis. Thus, MBC have worse survival rates than other invasive breast carcinomas, including other triple negative breast carcinomas (TNBC). In this study, we reviewed the molecular features of MBC, pointing out the differences among subtypes. The most frequently mutated genes in MBC were TP53 and PIK3CA. Additionally, mutations in the other genes of the PI3K/AKT pathway indicated its importance in the pathogenesis of MBC. Regarding copy number variations (CNVs), MYC was the most frequently amplified gene, and the most frequent gene loss affected the CDKN2A/CDKN2B locus. Furthermore, the pattern of mutations and CNVs of MBC differed from those reported in other TNBC. However, the molecular profile of MBC was not homogeneous among histological subtypes, being the alterations in the PI3K pathway most frequent in spindle cell carcinomas. Transcriptomic studies have demonstrated an epithelial to mesenchymal program activation and the enrichment of stemness genes in most MBC. In addition, current studies are attempting to define the immune microenvironment of these tumors. In conclusion, due to specific molecular features, MBC have a different clinical behavior from other types of TNBC, being more resistant to standard chemotherapy. For this reason, new therapeutic approaches based on tumor molecular characteristics are needed to treat MBC.
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Affiliation(s)
| | - Belén Pérez-Mies
- Pathology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; (B.P.-M.); (I.C.-B.)
- Instituto Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Faculty of Medicine, University of Alcalá de Henares, Alcalá de Henares, 28801 Madrid, Spain
- Breast Pathology Unit, Hospital Universitario Ramón y Cajal, 28801 Madrid, Spain
| | - Irene Carretero-Barrio
- Pathology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; (B.P.-M.); (I.C.-B.)
| | | | - José Perez-García
- IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, 08023 Barcelona, Spain;
| | - Javier Cortés
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- IOB Institute of Oncology, Quironsalud Group, Hospital Quiron, 08023 Barcelona, Spain;
- IOB Institute of Oncology, Quironsalud Group, 28006 Madrid, Spain
- Medica Scientia Innovation Research, 08018 Barcelona, Spain
- Medica Scientia Innovation Research, Ridgewood, NJ 07450, USA
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain
- Correspondence: (J.C.); (J.P.)
| | - José Palacios
- Pathology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; (B.P.-M.); (I.C.-B.)
- Instituto Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain
- CIBER-ONC, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Faculty of Medicine, University of Alcalá de Henares, Alcalá de Henares, 28801 Madrid, Spain
- Breast Pathology Unit, Hospital Universitario Ramón y Cajal, 28801 Madrid, Spain
- Correspondence: (J.C.); (J.P.)
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29
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Tawfeik AM, Mora A, Osman A, Moneer MM, El-Sheikh N, Elrefaei M. Frequency of CD4+ regulatory T cells, CD8+ T cells, and human papilloma virus infection in Egyptian Women with breast cancer. Int J Immunopathol Pharmacol 2020; 34:2058738420966822. [PMID: 33103515 PMCID: PMC7786412 DOI: 10.1177/2058738420966822] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 09/22/2020] [Indexed: 12/11/2022] Open
Abstract
Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment of breast cancer (BC) patients and may play a role in the progression of BC. High-risk human papilloma virus (HR-HPV) has a causal role in cervical, head, and neck tumors but the role of HR-HPV in evoking neoplasia in BC is still unclear. In this study we assessed the prevalence of CD4+CD25+ FOXP3+ regulatory T cells (CD4+Tregs) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL), and 20 healthy volunteers (HV). HR-HPV genotypes type 16, 18, and 31 were investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HR-HPV was detected in 4/20 (20%) and 0/15 (0%) BC and BBL patients respectively. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (P < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III BC compared to early stage I and II BC (P = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These results lead us to postulate that the association between the frequency of CD4+ Tregs and CD8+ T cells in the peripheral blood may be a prognostic or predictive parameter in Egyptian women with BC. In addition, HR-HPV infection may be implicated in the development of some types of BC in Egyptian women.
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Affiliation(s)
- Amany M Tawfeik
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Ahmed Mora
- Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Ahmed Osman
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
- Biotechnology Program, Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology, Cairo, Egypt
| | - Manar M Moneer
- Department of Epidemiology and Statistics, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Nabila El-Sheikh
- Molecular Immunology Unit for Infectious Diseases, Department of Microbiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Mohamed Elrefaei
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
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Lin S, Liu C, Tao Z, Zhang J, Hu X. Clinicopathological characteristics and survival outcomes in breast carcinosarcoma: A SEER population-based study. Breast 2019; 49:157-164. [PMID: 31812891 PMCID: PMC7375547 DOI: 10.1016/j.breast.2019.11.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/12/2019] [Accepted: 11/13/2019] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVES Carcinosarcoma of the breast is a rare disease. Its clinicopathological features and prognosis are not well defined. The aim of this study was to compare the clinicopathological features and clinical outcome between breast carcinosarcoma and breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS Patients with breast carcinosarcoma and breast IDC were identified through the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Then a comparison was conducted between these two groups. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences. The Cox proportional hazard model was used to identify potential prognostic factors of breast carcinosarcoma. RESULTS In total, we identified 63 patients with breast carcinosarcoma and 200,596 cases with breast IDC. Comparing with IDC, breast carcinosarcoma was significantly correlated with higher grading, higher staging, larger tumor size, lower lymph node involvement, and a higher proportion of triple negative breast cancer (TNBC), suggesting a significantly worse clinical outcome. After adjusting for the uneven clinicopathological variables with PSM, significant differences were still observed between these two histology types. Subgroup analysis further showed that carcinosarcoma-TNBC has an inferior clinical outcome compared with IDC-TNBC. Finally, we identified independent prognostic factors, namely, stage, tumor size, and distant metastasis. CONCLUSION It is concluded that breast carcinosarcoma has distinct clinicopathological features and a significantly worse clinical outcome than common IDC.
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Affiliation(s)
- Shuchen Lin
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China
| | - Chang Liu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China
| | - Zhonghua Tao
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China
| | - Jian Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China
| | - Xichun Hu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai, 200032, China.
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31
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Abdelwahed A, Ahmed M. Rare epithelial breast cancer: surgery and adjuvant therapy. Transl Cancer Res 2019; 8:S479-S492. [PMID: 35117126 PMCID: PMC8797705 DOI: 10.21037/tcr.2019.05.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/10/2019] [Indexed: 01/30/2023]
Abstract
Breast cancer is a heterogenous disease, exhibiting a wide range of morphological phenotypes shaping its prognosis and clinical course. However, optimal management of rarer breast cancer subtypes is often undefined and controversial in literature due to the lack of large studies and randomised trials. This review aims to discuss the treatment of 13 rare epithelial subtypes, focussing on surgery and adjuvant therapies.
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Affiliation(s)
| | - Muneer Ahmed
- King's College London, Division of Cancer, Research Oncology, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK
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Li Y, Chen M, Pardini B, Dragomir MP, Lucci A, Calin GA. The role of radiotherapy in metaplastic breast cancer: a propensity score-matched analysis of the SEER database. J Transl Med 2019; 17:318. [PMID: 31547814 PMCID: PMC6757394 DOI: 10.1186/s12967-019-2069-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 09/17/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Only few studies, with small patient cohorts, have evaluated the effect of radiotherapy (RT) for metaplastic breast cancer (MBC). Hence, it is important to investigate the role of RT in MBC survival using a large population-database. METHODS A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) from 1973 to 2015 was performed. We compared MBC patients with or without RT for overall survival (OS) and breast cancer-specific survival (BCSS) using univariate and multivariate Cox proportional hazard regressions before and after propensity score matching (PSM). RESULTS From a total of 2267 patients diagnosed with MBC between 1998 and 2015, 1086 (47.9%) received RT. In the multivariate analysis before PSM, RT provided a better OS (HR 0.73; 95% CI 0.61-0.88; p = 0.001) and BCSS (HR 0.71; 95% CI 0.58-0.88; p = 0.002). Multivariate analyses after PSM (n = 1066) confirmed that patients receiving RT (n = 506) survived longer than those without RT (OS, HR 0.64; 95% CI 0.51-0.80; p < 0.001 and BCSS, HR 0.64; 95% CI 0.50-0.83; p = 0.001). A longer OS was observed when RT was given to older patients (p = 0.001) and in case of large tumor size (p = 0.002). Intriguingly, patients with N0 stage showed better OS after RT (HR 0.69, P = 0.012). CONCLUSIONS Our findings support the beneficial effect of RT for MBC patients. In particular, older patients or with large tumor size have a greater survival benefit from RT. In conclusion, we have assessed the importance of the use of RT in MBC as survival factor and this could lead to the development of guidelines for this rare sub-type of tumors.
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Affiliation(s)
- Yongfeng Li
- Department of Breast Surgery, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Science; Cancer Hospital of the University of Chinese Academy of Sciences; Zhejiang Cancer Hospital, Hangzhou, 310022 Zhejiang People’s Republic of China
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, South Campus Research Building 4, 1901 East Road, Houston, TX 77054 USA
| | - Meng Chen
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, South Campus Research Building 4, 1901 East Road, Houston, TX 77054 USA
| | - Barbara Pardini
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, South Campus Research Building 4, 1901 East Road, Houston, TX 77054 USA
- Italian Institute for Genomic Medicine, Turin, Italy
| | - Mihnea P. Dragomir
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, South Campus Research Building 4, 1901 East Road, Houston, TX 77054 USA
- Department of Surgery, Fundeni Clinical Hospital, 22328 Bucharest, Romania
- The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania
| | - Anthony Lucci
- Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1484, Houston, TX 77030 USA
| | - George A. Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, South Campus Research Building 4, 1901 East Road, Houston, TX 77054 USA
- Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
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Ditsch N, Untch M, Thill M, Müller V, Janni W, Albert US, Bauerfeind I, Blohmer J, Budach W, Dall P, Diel I, Fasching PA, Fehm T, Friedrich M, Gerber B, Hanf V, Harbeck N, Huober J, Jackisch C, Kolberg-Liedtke C, Kreipe HH, Krug D, Kühn T, Kümmel S, Loibl S, Lüftner D, Lux MP, Maass N, Möbus V, Müller-Schimpfle M, Mundhenke C, Nitz U, Rhiem K, Rody A, Schmidt M, Schneeweiss A, Schütz F, Sinn HP, Solbach C, Solomayer EF, Stickeler E, Thomssen C, Wenz F, Witzel I, Wöckel A. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14:224-245. [PMID: 31558897 PMCID: PMC6751475 DOI: 10.1159/000501000] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 05/16/2019] [Indexed: 12/11/2022] Open
Affiliation(s)
- Nina Ditsch
- Brustzentrum, Klinik für Gynäkologie und Geburtshilfe, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
| | - Michael Untch
- Klinik für Gynäkologie und Geburtshilfe, Helios Klinikum Berlin-Buch, Berlin, Germany
| | - Marc Thill
- Klinik für Gynäkologie und Gynäkologische Onkologie, Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany
| | - Volkmar Müller
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Wolfgang Janni
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
| | - Ute-Susann Albert
- Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Kassel, Kassel, Germany
| | | | - Jens Blohmer
- Klinik für Gynäkologie mit Brustzentrum der Charité, Berlin, Germany
| | - Wilfried Budach
- Strahlentherapie, Radiologie Düsseldorf, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Peter Dall
- Frauenklinik Städtisches Klinikum Lüneburg, Lüneburg, Germany
| | - Ingo Diel
- Praxisklinik am Rosengarten, Mannheim, Germany
| | | | - Tanja Fehm
- Klinik für Gynäkologie und Geburtshilfe Universitätsklinikum Düsseldorf, Düsseldorf, Germany
| | - Michael Friedrich
- Klinik für Frauenheilkunde und Geburtshilfe Helios Klinikum Krefeld, Krefeld, Germany
| | - Bernd Gerber
- Universitätsfrauenklinik am Klinikum Südstadt, Rostock, Germany
| | - Volker Hanf
- Frauenklinik Nathanstift, Klinikum Fürth, Fürth, Germany
| | - Nadia Harbeck
- Brustzentrum, Klinik für Gynäkologie und Geburtshilfe, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany
| | - Jens Huober
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Germany
| | - Christian Jackisch
- Klinik für Gynäkologie und Geburtshilfe, Sana Klinikum Offenbach, Offenbach, Germany
| | | | | | - David Krug
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Thorsten Kühn
- Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Esslingen, Esslingen, Germany
| | - Sherko Kümmel
- Klinik für Senologie, Kliniken Essen Mitte, Essen, Germany
| | - Sibylle Loibl
- German Breast Group Forschungs GmbH, Neu-Isenburg, Germany
| | - Diana Lüftner
- Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité, Berlin, Germany
| | - Michael Patrick Lux
- Klinik für Gynäkologie und Geburtshilfe, St. Vinzenz-Krankenhaus GmbH Paderborn, Paderborn, Germany
| | - Nicolai Maass
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Volker Möbus
- Klinik für Gynäkologie und Geburtshilfe, Klinikum Frankfurt Höchst GmbH, Frankfurt am Main, Germany
| | - Markus Müller-Schimpfle
- Klinik für Radiologie, Neuroradiologie und Nuklearmedizin, Klinikum Frankfurt Höchst GmbH, Frankfurt am Main, Germany
| | - Christoph Mundhenke
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Ulrike Nitz
- Senologie, Evangelisches Krankenhaus Bethesda, Mönchengladbach, Germany
| | - Kerstin Rhiem
- Zentrum Familiärer Brust- und Eierstockkrebs, Universitätsklinikum Köln, Köln, Germany
| | - Achim Rody
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Marcus Schmidt
- Klinik und Poliklinik für Geburtshilfe und Frauengesundheit der Johannes-Gutenberg-Universität Mainz, Mainz, Germany
| | - Andreas Schneeweiss
- Gynäkologische Onkologie, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Florian Schütz
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Hans-Peter Sinn
- Sektion Gynäkopathologie, Pathologisches Institut, Heidelberg, Germany
| | - Christine Solbach
- Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | - Erich-Franz Solomayer
- Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Elmar Stickeler
- Klinik für Gynäkologie und Geburtsmedizin, Universitätsklinikum Aachen, Aachen, Germany
| | - Christoph Thomssen
- Universitätsfrauenklinik, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany
| | | | - Isabell Witzel
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Achim Wöckel
- Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Würzburg, Würzburg, Germany
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Takala S, Heikkilä P, Nevanlinna H, Blomqvist C, Mattson J. Metaplastic carcinoma of the breast: Prognosis and response to systemic treatment in metastatic disease. Breast J 2019; 25:418-424. [PMID: 30925636 DOI: 10.1111/tbj.13234] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/29/2018] [Accepted: 06/18/2018] [Indexed: 01/09/2023]
Abstract
BACKGROUND Metaplastic breast carcinomas (MpBCs) are rare, aggressive breast cancers. Due to the scant literature of this disease most guidelines do not give recommendation for this entity. The aim of the study was to review the clinicopathologic features, treatment, and outcomes of the patients with MpBC treated at our institution. MATERIAL AND METHODS We searched databases for patients with histologically confirmed MpBC from 2002 to 2016. RESULTS A total of 78 patients with MpBC were included in the study. All histological material was reviewed by an experienced breast pathologist. Most tumors were grade 3 (83%) and triple negative (85%). Eighty-two percent were node negative. Sixty-four percent received adjuvant chemotherapy. The 5-year disease free survival was 63% and 5-year breast cancer specific overall survival was 61%. Tumor size and mixed metaplastic histology were associated with worse outcome in this patient group. One third of the patients (n = 28) had metastatic disease at initial presentation or developed metastases at follow-up. The lungs were the most common site of first distant recurrence. Half (n = 14) of these patients received palliative chemotherapy. Of those only 6% (n = 2) had partial response and 18% had stable disease as best response to treatment. The median overall survival time with metastatic disease was only 3.4 months. CONCLUSION MpBC is an aggressive type of breast cancer with poor outcome despite low nodal involvement and aggressive local and systemic therapy. Tumor response to palliative systemic chemotherapy remains poor for MpBC patients.
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Affiliation(s)
- Sari Takala
- Helsinki University Hospital Comprehensive Cancer Centre, Helsinki, Finland
| | - Päivi Heikkilä
- Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Heli Nevanlinna
- Department of Obstetrics and Gynaecology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
| | - Carl Blomqvist
- Helsinki University Hospital Comprehensive Cancer Centre, Helsinki, Finland.,Department of Oncology, Örebro University Hospital, Örebro, Sweden
| | - Johanna Mattson
- Helsinki University Hospital Comprehensive Cancer Centre, Helsinki, Finland
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35
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Samoon Z, Beg M, Idress R, Jabbar A. Survival and treatment outcomes of metaplastic breast carcinoma: Single tertiary care center experience in Pakistan. Indian J Cancer 2019; 56:124-129. [DOI: 10.4103/ijc.ijc_731_18] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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36
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Budzik MP, Patera J, Sobol M, Czerw AI, Deptała A, Badowska-Kozakiewicz AM. Clinicopathological characteristics of metaplastic breast cancer - analysis of the basic immunohistochemical profile and comparison with other invasive breast cancer types. Breast 2018; 43:135-141. [PMID: 30553188 DOI: 10.1016/j.breast.2018.12.004] [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: 12/05/2018] [Accepted: 12/06/2018] [Indexed: 10/27/2022] Open
Abstract
INTRODUCTION Metaplastic breast cancer (MpBC) is a rare but aggressive type of breast cancer accounting for 0.25-1% of all diagnosed invasive breast cancers. Morphologically, it is characterized by differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal-looking tissue. MATERIAL AND METHODS We analyzed 13 MpBCs selected from the group of 1122 invasive breast cancers. Histopathological examination and analysis of estrogen (ER), progesterone (PR) and HER2 receptors expression in MpBC patients and their comparison to other types of invasive breast cancer has been performed. RESULTS 13 MpBC cases represented 1.16% of the 1122 invasive breast cancers. The MpBC group presented with a significantly larger tumor size (≥T2, 69% versus 49%, p < 0.001) and with higher grade of histological malignancy (G1-G3) (p < 0.001). MpBC group had significantly more cases with no hormone receptors (ER, PR) and HER2 overexpression/gene amplification compared with the other invasive breast cancer types group (ER-, 69% versus 23%, p < 0.001; PR-, 69% versus 28%, p < 0.001; HER2 0/1+, 93% versus 82%, p = 0.019). Most MpBCs (62%) were triple-negative. We found a correlation between hormone receptors expression and lymph node metastasis (p < 0.001). The analysis of the HER2 expression allowed us to find correlation between its expression and tumor histological grade (G1-G3) (p < 0.001), tumor size (T1a-T4) (p < 0.001) and lymph node metastasis (pN0-pN4) (p < 0.001) in MpBCs. DISCUSSION MpBCs are usually larger at primary diagnosis and most of MpBCs present with other poor prognostic indicators and show lack of steroid hormone receptors expression as well as HER2. Hormone receptor status and HER2 expression seems to correlate with histological grade of malignancy (G1-G3), tumor size (T1a-T4) and regional lymph node involvement (pN0-pN4) and these features are directly related to MpBC malignancy.
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Affiliation(s)
- M P Budzik
- Department of Biophysics and Human Physiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland
| | - J Patera
- Department of Pathomorphology, Military Institute of Health Services, Szaserow 128, 04-141 Warsaw, Poland
| | - M Sobol
- Department of Biophysics and Human Physiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland
| | - A I Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, Nielubowicza 5, 02-097 Warsaw, Poland; Department of Economic and System Analyses, National Institute of Public Health - NIH, Chocimska 24, 00-791 Warsaw, Poland.
| | - A Deptała
- Department of Cancer Prevention, Medical University of Warsaw, Woloska 137, 02-507 Warsaw, Poland
| | - A M Badowska-Kozakiewicz
- Department of Biophysics and Human Physiology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland
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Genomic profiling of metaplastic breast carcinomas reveals genetic heterogeneity and relationship to ductal carcinoma. Mod Pathol 2018; 31:1661-1674. [PMID: 29946183 DOI: 10.1038/s41379-018-0081-z] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 04/26/2018] [Accepted: 04/26/2018] [Indexed: 12/30/2022]
Abstract
Metaplastic breast carcinomas comprise a histologically heterogenous group of tumors. Although most are triple (estrogen/progesterone receptor, HER2) negative, these rare tumors are clinicopathologically distinct from other triple negative carcinomas and may be aggressive with worse chemotherapy responses. On the other hand, metaplastic carcinomas are histologically diverse, which is reflected in gene expression differences among subtypes. Whether metaplastic carcinomas are genetically distinct from other triple negative cancers and whether genetic differences underlie histologic subtypes remains poorly understood. We sequenced 408 cancer-related genes in 28 metaplastic carcinomas, including chondroid matrix-producing carcinomas (n = 10), spindle cell carcinomas (n = 5), and carcinomas with squamous (n = 5), mixed spindle/squamous (n = 5), and mixed metaplastic (n = 3) differentiation. Metaplastic carcinomas were highly enriched for PIK3CA/PIK3R1 (61%) and Ras-Map kinase (25%) pathway aberrations compared to other triple negative carcinomas (TCGA dataset 14%, p < 0.001 and 7%, p = 0.005, respectively) and harbored a high frequency of TP53 (64%) and TERT promoter (25%) mutations, but this varied among subtypes. Chondroid-matrix producing carcinomas lacked PI-3 kinase and Ras-Map kinase aberrations and TERT promoter mutations, compared to 100%, 39%, and 39% of non-matrix-producing tumors, respectively. TERT promoter mutations were enriched (47%) in spindle cell carcinomas and tumors with squamous or spindle/squamous differentiation. Spindle cell carcinomas lacked TP53 mutations, in contrast to other subtypes (78%, p = 0.003). Separate analysis of paired ductal carcinoma in situ and metaplastic carcinoma revealed shared clonality in all cases (n = 8). Activating PI-3 kinase and Ras pathway mutations were early events, and inactivating mutations in tumor suppressors including RB1, CDKN2A, and TP53 were associated with invasion in individual cases. Metaplastic components of two tumors showed genetic progression from separately sequenced paired invasive ductal carcinoma. The findings suggest that metaplastic carcinomas are genetically distinct from other triple negative breast cancers and highlight genetic heterogeneity that broadly correlates with histologic subtype. Heterologous elements progress from associated ductal carcinoma.
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38
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Tang J, Kong D, Cui Q, Wang K, Zhang D, Gong Y, Wu G. Prognostic Genes of Breast Cancer Identified by Gene Co-expression Network Analysis. Front Oncol 2018; 8:374. [PMID: 30254986 PMCID: PMC6141856 DOI: 10.3389/fonc.2018.00374] [Citation(s) in RCA: 179] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 08/21/2018] [Indexed: 12/11/2022] Open
Abstract
Breast cancer is one of the most common malignancies. The molecular mechanisms of its pathogenesis are still to be investigated. The aim of this study was to identify the potential genes associated with the progression of breast cancer. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify candidate biomarkers. The gene expression profiles of GSE1561 were selected from the Gene Expression Omnibus (GEO) database. RNA-seq data and clinical information of breast cancer from TCGA were used for validation. A total of 18 modules were identified via the average linkage hierarchical clustering. In the significant module (R2 = 0.48), 42 network hub genes were identified. Based on the Cancer Genome Atlas (TCGA) data, 5 hub genes (CCNB2, FBXO5, KIF4A, MCM10, and TPX2) were correlated with poor prognosis. Receiver operating characteristic (ROC) curve validated that the mRNA levels of these 5 genes exhibited excellent diagnostic efficiency for normal and tumor tissues. In addition, the protein levels of these 5 genes were also significantly higher in tumor tissues compared with normal tissues. Among them, CCNB2, KIF4A, and TPX2 were further upregulated in advanced tumor stage. In conclusion, 5 candidate biomarkers were identified for further basic and clinical research on breast cancer with co-expression network analysis.
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Affiliation(s)
- Jianing Tang
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Deguang Kong
- Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiuxia Cui
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Kun Wang
- Department of Thyroid and Breast Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Dan Zhang
- Department of Thyroid and Breast Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Gong
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Gaosong Wu
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
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Murphy BL, Fazzio RT, Hoskin TL, Glazebrook KN, Keeney MG, Habermann EB, Hieken TJ. Management of the axilla in metaplastic breast carcinoma. Gland Surg 2018; 7:200-206. [PMID: 29770313 DOI: 10.21037/gs.2018.01.01] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Background Metaplastic breast cancer (MBC), characterized by admixed epithelial, squamous or mesenchymal elements, constitutes <1% of breast cancers and has a poor prognosis but a paradoxically low reported rate of axillary lymph node (LN) involvement. Due to its rarity, data on appropriate axillary management is lacking, prompting this investigation of LN status and outcomes. Methods We identified 41 MBC patients treated at our institution 2001-2011 who were followed for a median of 66 months. Statistical analyses evaluated axillary ultrasound (AUS), fine needle aspiration (FNA), and sentinel LN biopsy (SLNB) in association with LN status. Results Median tumor size was 2.7 cm and 76% were triple-negative. Twenty-three patients (56%) had preoperative AUS: 9 (39%) showed ≥1 suspicious LN, 6 proceeded to LN FNA and 3 were confirmed positive. Six patients had neoadjuvant chemotherapy, including 2 FNA LN+. Ten patients were LN+ at operation. Among 19 patients undergoing AUS and axillary surgery, AUS ± FNA sensitivity was 100% and specificity was 94%. LN positivity correlated with increasing tumor size, grade and angiolymphatic invasion. 16 patients recurred, 63% with distant disease (10/16) and one with isolated axillary disease after a negative SLNB not preceded by AUS. Overall SLNB accuracy was 96% (23/24), but absent preoperative AUS, 1/7 (14%) of SLNBs were falsely negative. Conclusions Our study is the first to specifically address the performance and utility of AUS/FNA and SLNB for MBC patients. AUS/FNA at diagnosis followed by SLN surgery provided accurate nodal staging and critical prognostic information to inform treatment recommendations. We recommend this approach for axillary management of MBC patients.
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Affiliation(s)
- Brittany L Murphy
- Department of Surgery, Mayo Clinic, Rochester, MN, USA.,The Robert D and Patricia E Kern Center for the Science of Health Care Delivery Surgical Outcomes Program, Mayo Clinic, Rochester, MN, USA
| | | | - Tanya L Hoskin
- Health Sciences Research Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | | | | | - Elizabeth B Habermann
- The Robert D and Patricia E Kern Center for the Science of Health Care Delivery Surgical Outcomes Program, Mayo Clinic, Rochester, MN, USA
| | - Tina J Hieken
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
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40
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Alaoui M'hamdi H, Abbad F, Rais H, Asmouki H, Soumani A, Khouchani M, Belbaraka R. Rare variant of metaplastic carcinoma of the breast: a case report and review of the literature. J Med Case Rep 2018; 12:43. [PMID: 29463294 PMCID: PMC5820794 DOI: 10.1186/s13256-017-1553-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 12/23/2017] [Indexed: 01/03/2023] Open
Abstract
Background Metaplastic carcinoma encompasses a group of neoplasms characterized by differentiation of the neoplastic epithelium into squamous cells and/or mesenchymal-looking elements. Spindle cell carcinoma is a rare variant of this special histological type. Its prognosis remains poor, with a high rate of local recurrence and distant metastasis. To date, only a small number of cases have been described. There is no clear agreement on this histological subtype. Case presentation We report a case of a 53-year-old Moroccan woman who consulted our institution following palpation of a nodule of the left breast. Mammography in combination with breast ultrasonography revealed a lesion classified as Breast Imaging Reporting and Data System 4 with microcalcification. The patient was diagnosed with spindle cell carcinoma of the breast. The diagnosis was based primarily on histological and immunohistochemical studies of the breast biopsy and secondarily on the surgical specimen. No local or distant metastasis was found. The treatment used was total surgical excision followed by radiotherapy. Conclusions We describe the features (epidemiological, clinical, histological, immunohistochemical, and therapeutic outcomes) of our patient’s case and compare them with literature data.
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Affiliation(s)
- H Alaoui M'hamdi
- Department of Medical Oncology of Marrakech, University Hospital of Marrakech, Marrakech, Morocco.
| | - F Abbad
- Department of Pathology, University Hospital of Marrakech, Marrakech, Morocco
| | - H Rais
- Department of Pathology, University Hospital of Marrakech, Marrakech, Morocco
| | - H Asmouki
- Department of Gynecology and Obstetrics, University Hospital of Marrakech, Marrakech, Morocco
| | - A Soumani
- Department of Gynecology and Obstetrics, University Hospital of Marrakech, Marrakech, Morocco
| | - M Khouchani
- Department of Radiotherapy of Marrakech, University Hospital of Marrakech, Marrakech, Morocco
| | - R Belbaraka
- Department of Medical Oncology of Marrakech, University Hospital of Marrakech, Marrakech, Morocco
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41
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Zhao S, Wang Y, Guo T, Yu W, Li J, Tang Z, Yu Z, Zhao L, Zhang Y, Wang Z, Wang P, Li Y, Li F, Sun Z, Xuan Y, Tang R, Deng WG, Guo W, Gu C. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma. Oncotarget 2018; 7:82139-82157. [PMID: 27384875 PMCID: PMC5347681 DOI: 10.18632/oncotarget.10080] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 05/28/2016] [Indexed: 12/21/2022] Open
Abstract
Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma.
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Affiliation(s)
- Shilei Zhao
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yan Wang
- Department of Respiratory Medicine, The People's Hospital of Liaoning Province, Shenyang, China
| | - Tao Guo
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Wendan Yu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Jinxiu Li
- Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Zhipeng Tang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Zhenlong Yu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Lei Zhao
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yixiang Zhang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Ziyi Wang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Peng Wang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yechi Li
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Fengzhou Li
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Zhe Sun
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
| | - Yang Xuan
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Ranran Tang
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Wu-Guo Deng
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.,State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China
| | - Wei Guo
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China
| | - Chundong Gu
- The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.,Lung Cancer Diagnosis and Treatment Center of Dalian, Dalian, China
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42
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Yue Z, Li HT, Yang Y, Hussain S, Zheng CH, Xia J, Chen Y. Identification of breast cancer candidate genes using gene co-expression and protein-protein interaction information. Oncotarget 2017; 7:36092-36100. [PMID: 27150055 PMCID: PMC5094985 DOI: 10.18632/oncotarget.9132] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Accepted: 04/16/2016] [Indexed: 01/18/2023] Open
Abstract
Breast cancer (BC) is one of the most common malignancies that could threaten female health. As the molecular mechanism of BC has not yet been completely discovered, identification of related genes of this disease is an important area of research that could provide new insights into gene function as well as potential treatment targets. Here we used subnetwork extraction algorithms to identify novel BC related genes based on the known BC genes (seed genes), gene co-expression profiles and protein-protein interaction network. We computationally predicted seven key genes (EPHX2, GHRH, PPYR1, ALPP, KNG1, GSK3A and TRIT1) as putative genes of BC. Further analysis shows that six of these have been reported as breast cancer associated genes, and one (PPYR1) as cancer associated gene. Lastly, we developed an expression signature using these seven key genes which significantly stratified 1660 BC patients according to relapse free survival (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.46–0.65; Logrank p = 5.5e−13). The 7-genes signature could be established as a useful predictor of disease prognosis in BC patients. Overall, the identified seven genes might be useful prognostic and predictive molecular markers to predict the clinical outcome of BC patients.
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Affiliation(s)
- Zhenyu Yue
- School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.,Institute of Health Sciences, Anhui University, Hefei, Anhui 230601, China
| | - Hai-Tao Li
- College of Electrical Engineering and Automation, Anhui University, Hefei, Anhui 230601, China
| | - Yabing Yang
- School of Life Sciences, Anhui University, Hefei, Anhui 230601, China
| | - Sajid Hussain
- School of Life Sciences, Anhui University, Hefei, Anhui 230601, China
| | - Chun-Hou Zheng
- College of Electrical Engineering and Automation, Anhui University, Hefei, Anhui 230601, China
| | - Junfeng Xia
- Institute of Health Sciences, Anhui University, Hefei, Anhui 230601, China
| | - Yan Chen
- School of Life Sciences, Anhui University, Hefei, Anhui 230601, China
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43
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Ezzat A, Abdelhamid AO, El Awady MK, Abd El Azeem AS, Mohammed DM. The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer. Biomed Pharmacother 2017; 95:571-576. [PMID: 28869895 DOI: 10.1016/j.biopha.2017.08.099] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Revised: 08/11/2017] [Accepted: 08/23/2017] [Indexed: 01/06/2023] Open
Abstract
The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression.
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Affiliation(s)
- Afaf Ezzat
- Department of Nutrition and Food Science, National Research Centre, Dokki, Cairo 12622, Egypt
| | | | - Mostafa K El Awady
- Microbial Biotechnology Department, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Amal S Abd El Azeem
- Department of Nutrition and Food Science, National Research Centre, Dokki, Cairo 12622, Egypt
| | - Dina Mostafa Mohammed
- Department of Nutrition and Food Science, National Research Centre, Dokki, Cairo 12622, Egypt.
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44
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Predictive factors on outcomes in metaplastic breast cancer. Breast Cancer Res Treat 2017; 165:499-504. [DOI: 10.1007/s10549-017-4367-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 06/27/2017] [Indexed: 02/01/2023]
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45
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Tsilimigras DI, Ntanasis-Stathopoulos I, Schizas D, Bakopoulos A, Moris D, Stanc GM, Tentolouris A, Nassar S, Salla C. Combined Use of Mammography and FNA Eliminates Pitfalls in the Management of Metaplastic Breast Carcinoma. In Vivo 2017; 31:737-740. [PMID: 28652449 PMCID: PMC5566932 DOI: 10.21873/invivo.11123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 04/14/2017] [Accepted: 04/19/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Due to its heterogeneity, metaplastic breast carcinoma (MBC) poses diagnostic dilemmas, leading to delayed treatment, thereby aggravating the prognosis. Over the years, there has been controversy regarding the role of fine-needle aspiration (FNA) cytology in timely diagnosis. CASE REPORT A 54-year-old woman presented with a palpable mass in the upper outer quadrant of her right breast with corresponding mammographic findings and FNA was performed. The smears revealed small- and medium-sized cohesive clusters of malignant cells with atypical nuclei. Sporadically, there was a pleomorphic population of notably large mononuclear cells, with disturbance of nuclear/cytoplasmic ratio, and binucleated or multinucleated malignant cells. The presence of chondromyxoid substance with focally embedded cells in a magenta-colored substrate was predominant in the background. These features, along with the corresponding mammographic findings, allowed for high preoperative suspicion of MBC. Surgical resection followed immediately without neoadjuvant chemotherapy; the pathology report led to the definite diagnosis of MBC. DISCUSSION MBC is a rare clinical entity with unfavorable prognosis, thus early diagnosis is imperative regarding its management. The effectiveness of FNA in the diagnostic algorithm has been questioned, with data from literature being rather contradictory. FNA seems to provide valuable information, which should always be interpreted in correlation with the clinical and mammographic findings. CONCLUSION High preoperative suspicion of MBC with the combination of mammography and FNA cytology necessitated the surgical excision of the lesion as the principal treatment approach. Although the role of FNA in the diagnosis of MBC is debatable, its combination with clinical presentation and corresponding mammographic findings may prevent the administration of neoadjuvant chemotherapy in patients with ambiguous indications, given the poor response rate of this cancer subtype.
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Affiliation(s)
| | | | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anargyros Bakopoulos
- Third Department of Surgery, Attikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Demetrios Moris
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, U.S.A
| | | | - Anastasios Tentolouris
- First Department of Propaedeutic and Internal Medicine, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Soumphi Nassar
- Department of Surgery, Kyanous Stavros Hospital, Athens, Greece
| | - Charitini Salla
- Department of Cytopathology, Hygeia Hospital, Athens, Greece
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46
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Fayaz S, Demian GA, Eissa HES, Amanguno H, Abuzalouf S. Metaplastic breast carcinoma: Analysis of 31 cases from a single institute. J Egypt Natl Canc Inst 2017; 29:141-145. [PMID: 28669452 DOI: 10.1016/j.jnci.2017.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 04/24/2017] [Accepted: 05/08/2017] [Indexed: 10/19/2022] Open
Abstract
PURPOSE Metaplastic carcinoma of the breast (MBC) accounts for less than 1% of all mammary tumors. This study aimed at revision of the clinico-pathological features, treatment strategy and outcome for MBC patients presented to the Kuwait Cancer Control Center to define the clinical behavior and prognostic factors of these neoplasms in our population. PATIENT AND METHODS Thirty-one patients were retrieved from our surgical pathology registry between January 2005 and December 2014. Medical records were revised regarding the clinico-pathological features and treatment outcome. RESULTS MBC represented 1% of our breast cancer patients. The median age was 50years (32-70years). Two patients presented with metastatic disease. Mastectomy was done for 24 patients and 7 had conservative surgery. The median tumor size at the time of surgery was 5.5cm (1.5-12cm). Axillary nodes were negative in 21 patients (N0), 5 patients were N1, 4 patients were N2 and one Nx. Three histological subtypes were presented: carcinosarcoma (7 cases), squamous cell carcinoma/IDC with squamous differentiation (15 cases), high grade IDC with metaplastic differentiation (9 cases). Immunohistochemically, 26 were negative hormone receptors and all were negative for Her2/neu overexpression. Chemotherapy was used in 28 patients, and adjuvant radiotherapy in 24 patients. The median follow-up was 47months (7-126months), six patients lost follow-up. The 5-year OS was 69% and 5-year PFS was 50%. CONCLUSION MBC is a rare entity among breast carcinoma in Kuwait. Most of the cases present with poor prognostic indicators and often show lack of expression of ER, PR and Her2/neu.
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Affiliation(s)
- Salah Fayaz
- Department of Radiation Oncology, Kuwait Cancer Control Center, Kuwait
| | | | | | - Henney Amanguno
- Department Surgical Pathology, Kuwait Cancer Control Center, Kuwait
| | - Sadeq Abuzalouf
- Department of Radiation Oncology, Kuwait Cancer Control Center, Kuwait
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47
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Saad E, Milley K, Al-Khan A, Nimmo J, Bacci B, Tayebi M, Day M, Richardson S, Danks J. Canine Mixed Mammary Tumour as a Model for Human Breast Cancer with Osseous Metaplasia. J Comp Pathol 2017; 156:352-365. [DOI: 10.1016/j.jcpa.2017.03.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 02/17/2017] [Accepted: 03/27/2017] [Indexed: 01/04/2023]
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48
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El Zein D, Hughes M, Kumar S, Peng X, Oyasiji T, Jabbour H, Khoury T. Metaplastic Carcinoma of the Breast Is More Aggressive Than Triple-negative Breast Cancer: A Study From a Single Institution and Review of Literature. Clin Breast Cancer 2017; 17:382-391. [PMID: 28529029 DOI: 10.1016/j.clbc.2017.04.009] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 03/21/2017] [Accepted: 04/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and provide a through and comprehensive review of the literature to date. MATERIALS AND METHODS We reviewed MBC cases (n = 46) from our institution. The following variables were recorded: tumor histologic subtype, Nottingham grade, tumor size, lymph node status, Tumor, Node, Metastases stage, biomarkers profile, patient's age and race, therapy modality (chemotherapy and radiation), and survival (disease-free survival [DFS] and overall survival [OS]). The clinical and pathological data for TNBC (n = 508) cases were extracted from the breast cancer database. To compare the survival between MBC and TNBC, a subgroup of MBC cases (n = 40) were matched with TNBC cases (n = 40) on the basis of known prognostic confounders. RESULTS There were 17 of 46 (37%) cases with mesenchymal differentiation, 12 (26.1%) squamous cell carcinoma, 14 (30.4%) spindle cell carcinoma, and 3 (6.5%) mixed type. MBC presented at a more advanced stage than TNBC (P = .014) and was more likely to recur (34% vs. 15.5%; P = .004). More MBC patients died from disease than TNBC (29% vs. 16%; P = .05). In the multivariate analysis, MBC had approximately twice the risk of local recurrence than TNBC (95% confidence interval, 1.01-3.83; P = .05). MBC patients had worse DFS and OS than the matched TNBC patients (P < .001 and P = .033, respectively). A review of the literature comparing MBC versus TNBC is presented. CONCLUSION Our results suggest that MBC is clinically more aggressive than TNBC. Further studies might help delineate the differences between these 2 entities.
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Affiliation(s)
- Dima El Zein
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY
| | - Melissa Hughes
- Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY
| | - Shicha Kumar
- Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY
| | - Xuan Peng
- Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY
| | - Tolutope Oyasiji
- Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY
| | - Hossam Jabbour
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY
| | - Thaer Khoury
- Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.
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49
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Böler DE, Kara H, Sağlıcan Y, Tokat F, Uras C. Metaplastic carcinoma of the breast: A case series and review of the literature. JOURNAL OF ONCOLOGICAL SCIENCES 2016. [DOI: 10.1016/j.jons.2016.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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50
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Tzanninis IG, Kotteas EA, Ntanasis-Stathopoulos I, Kontogianni P, Fotopoulos G. Management and Outcomes in Metaplastic Breast Cancer. Clin Breast Cancer 2016; 16:437-443. [PMID: 27431460 DOI: 10.1016/j.clbc.2016.06.002] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 05/21/2016] [Accepted: 06/05/2016] [Indexed: 02/07/2023]
Abstract
Metaplastic breast cancer (MBC) constitutes a rare clinical entity with special clinicopathologic, immunohistochemical, and molecular features. Resistance to systemic therapies, whether chemotherapy or hormonal therapy, is among its main characteristics, which in turn explains the poor prognosis and renders its management a challenge. Thus, the scope of the present review is to discuss the current therapeutic strategies for MBC in clinical practice and the corresponding outcomes and to suggest possible directions for future research. Potential novel targeted therapies could provide a hope for better outcomes but limited data are available owing to the rarity of MBC. As knowledge accumulates on the pathogenesis and genetic characteristics of MBC, emphasis should be given to the implementation of more targeted treatments, which will allow more efficient and individualized management of the disease.
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MESH Headings
- Breast Neoplasms/genetics
- Breast Neoplasms/mortality
- Breast Neoplasms/pathology
- Breast Neoplasms/therapy
- Carcinoma, Ductal, Breast/mortality
- Carcinoma, Ductal, Breast/pathology
- Carcinoma, Ductal, Breast/therapy
- Carcinoma, Lobular/mortality
- Carcinoma, Lobular/pathology
- Carcinoma, Lobular/therapy
- Clinical Trials as Topic
- Combined Modality Therapy/methods
- Disease-Free Survival
- Drug Resistance, Neoplasm
- Female
- Humans
- Immunohistochemistry
- Molecular Targeted Therapy/methods
- Precision Medicine/methods
- Prognosis
- Treatment Outcome
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Affiliation(s)
| | - Elias A Kotteas
- Athens Medical School, Athens, Greece; Oncology Unit, Third Department of Internal Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece
| | | | - Panagiota Kontogianni
- First Propaedeutic Surgical Department, Athens Medical School, Hippocration General Hospital, Athens, Greece
| | - George Fotopoulos
- Athens Medical School, Athens, Greece; Oncology Unit, Third Department of Internal Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece.
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