Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

Joanne Kotsopoulos^{1

2}, Jacek Gronwald³, Tomasz Huzarski³, Amber Aeilts⁴, Susan Randall Armel^{5

6}, Beth Karlan⁷, Christian F Singer⁸, Andrea Eisen⁹, Nadine Tung¹⁰, Olufunmilayo Olopade¹¹, Louise Bordeleau¹², Charis Eng¹³, William D Foulkes¹⁴, Susan L Neuhausen¹⁵, Carey A Cullinane¹⁶, Tuya Pal¹⁷, Robert Fruscio¹⁸, Jan Lubinski³, Kelly Metcalfe^{1

19}, Ping Sun¹, Steven A Narod^{20

21

22}; and the Hereditary Breast Cancer Clinical Study Group

Collaborators, Affiliations

Collaborators

and the Hereditary Breast Cancer Clinical Study Group:
Georgia Wiesner, Aletta Poll, Raymond Kim, Jeanna McCuaig, Dana Zakalik, Fergus Couch, Linda Steele, Howard Saal, Edmond Lemire, Kim Serfas, Kevin Sweet, Seema Panchal, Christine Elser, Robert E Reilly, Joanne L Blum, Cezary Cybulski, Daniel Rayson, Teresa Y Cajal Ramón, Jeffrey Dungan, Stefania Zovato, Antonella Rastelli, Pal Moller, Stephanie Cohen

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
⁵ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, Canada.
⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁷ David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
⁸ Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁹ Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
¹⁰ Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹¹ Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA.
¹² Department of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada.
¹³ Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, USA.
¹⁴ Department of Oncology, McGill Program in Cancer Genetics, McGill University, Montreal, QC, Canada.
¹⁵ Division of Biomarkers of Early Detection and Prevention, City of Hope, Duarte, USA.
¹⁶ Todd Cancer Institute, Long Beach Memorial Hospital, Long Beach, CA, USA.
¹⁷ Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁸ Clinic of Obstetrics and Gynecology, Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
¹⁹ Bloomberg School of Nursing, University of Toronto, Toronto, ON, Canada.
²⁰ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
²¹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.
²² Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6Th Floor, Toronto, ON, M5S 1B2, Canada. steven.narod@wchospital.ca.

PMID: 37432545
DOI: 10.1007/s10549-023-06991-3

Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

Joanne Kotsopoulos et al. Breast Cancer Res Treat. 2023 Sep.

. 2023 Sep;201(2):257-264.

doi: 10.1007/s10549-023-06991-3. Epub 2023 Jul 11.

Authors

Collaborators

and the Hereditary Breast Cancer Clinical Study Group:
Georgia Wiesner, Aletta Poll, Raymond Kim, Jeanna McCuaig, Dana Zakalik, Fergus Couch, Linda Steele, Howard Saal, Edmond Lemire, Kim Serfas, Kevin Sweet, Seema Panchal, Christine Elser, Robert E Reilly, Joanne L Blum, Cezary Cybulski, Daniel Rayson, Teresa Y Cajal Ramón, Jeffrey Dungan, Stefania Zovato, Antonella Rastelli, Pal Moller, Stephanie Cohen

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
⁵ Bhalwani Familial Cancer Clinic, Princess Margaret Cancer Centre, Toronto, Canada.
⁶ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁷ David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
⁸ Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁹ Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
¹⁰ Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹¹ Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA.
¹² Department of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada.
¹³ Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, USA.
¹⁴ Department of Oncology, McGill Program in Cancer Genetics, McGill University, Montreal, QC, Canada.
¹⁵ Division of Biomarkers of Early Detection and Prevention, City of Hope, Duarte, USA.
¹⁶ Todd Cancer Institute, Long Beach Memorial Hospital, Long Beach, CA, USA.
¹⁷ Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁸ Clinic of Obstetrics and Gynecology, Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy.
¹⁹ Bloomberg School of Nursing, University of Toronto, Toronto, ON, Canada.
²⁰ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. steven.narod@wchospital.ca.
²¹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.
²² Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6Th Floor, Toronto, ON, M5S 1B2, Canada. steven.narod@wchospital.ca.

PMID: 37432545
DOI: 10.1007/s10549-023-06991-3

Abstract

Purpose: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation.

Methods: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.

Results: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07).

Conclusion: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

Keywords: BRCA1; BRCA2; Breast cancer; Chemoprevention; Raloxifene; Tamoxifen.

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References

1. Kuchenbaecker KB, Hopper JL, Barnes DR et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416. https://doi.org/10.1001/jama.2017.7112 - DOI - PubMed
1. Daly MB, Pal T, Berry MP et al (2021) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 19(1):77–102. https://doi.org/10.6004/jnccn.2021.0001 - DOI - PubMed
1. Metcalfe K, Eisen A, Senter L et al (2019) International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer 121(1):15–21. https://doi.org/10.1038/s41416-019-0446-1 - DOI - PubMed - PMC
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Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

Collaborators

Affiliations

Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

Authors

Collaborators

Affiliations

Abstract

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous