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      Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations

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          Abstract

          Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10–20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3–152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers ( P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

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          Triple-negative breast cancer.

          Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.
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            Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

            The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates.
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              Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

              To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and has been published jointly by invitation and consent in both Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine. Copyright © 2013 American Society of Clinical Oncology and College of American Pathologists.

                Author and article information

                Contributors
                sheol1981@naver.com
                Journal
                NPJ Precis Oncol
                NPJ Precis Oncol
                NPJ Precision Oncology
                Nature Publishing Group UK (London )
                2397-768X
                30 April 2024
                30 April 2024
                2024
                : 8
                : 96
                Affiliations
                [1 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Division of Breast Surgery, Department of Surgery, Samsung Medical Center, , Sungkyunkwan University School of Medicine, ; Seoul, South Korea
                [2 ]Sungkyunkwan University School of Medicine, ( https://ror.org/04q78tk20) Seoul, South Korea
                [3 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, Department of Laboratory Medicine and Genetics, Samsung Medical Center, , Sungkyunkwan University School of Medicine, ; Seoul, South Korea
                [4 ]GRID grid.414966.8, ISNI 0000 0004 0647 5752, Department of Surgery, The Breast Care Center, , Daerim St. Mary’s Hospital, ; Seoul, South Korea
                Author information
                http://orcid.org/0000-0002-0750-5824
                http://orcid.org/0000-0002-0708-9242
                http://orcid.org/0000-0001-5405-7385
                Article
                559
                10.1038/s41698-024-00559-0
                11061194
                38689097
                b55242d4-148b-4044-97f6-dfb98d8b5e33
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 September 2023
                : 22 February 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003625, Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs);
                Award ID: HA23C0144
                Award Recipient :
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                © Springer Nature Limited 2024

                breast cancer,surgical oncology
                breast cancer, surgical oncology

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