Ovarian cancer after breast cancer in women with a BRCA1 or BRCA2 pathogenic variant

Adriana I Apostol; Joanne Kotsopoulos; Jacek Gronwald; Raymond H Kim; Beth Y Karlan; Amber Aeilts; Teresa Ramón Y Cajal; Tuya Pal; Andrea Eisen; Louise Bordeleau; William D Foulkes; Fergus Couch; Dana Zakalik; Robert Fruscio; Ping Sun; Jan Lubinski; Nadine Tung; Christian F Singer; Pal Moller; Mev Dominguez-Valentin; Steven A Narod; Kelly Metcalfe; Hereditary Breast Cancer Clinical Study Group

doi:10.1016/j.ygyno.2025.07.030

Ovarian cancer after breast cancer in women with a BRCA1 or BRCA2 pathogenic variant

Gynecol Oncol. 2025 Oct:201:44-52. doi: 10.1016/j.ygyno.2025.07.030. Epub 2025 Aug 9.

Authors

Adriana I Apostol¹, Joanne Kotsopoulos², Jacek Gronwald³, Raymond H Kim⁴, Beth Y Karlan⁵, Amber Aeilts⁶, Teresa Ramón Y Cajal⁷, Tuya Pal⁸, Andrea Eisen⁹, Louise Bordeleau¹⁰, William D Foulkes¹¹, Fergus Couch¹², Dana Zakalik¹³, Robert Fruscio¹⁴, Ping Sun¹⁵, Jan Lubinski³, Nadine Tung¹⁶, Christian F Singer¹⁷, Pal Moller¹⁸, Mev Dominguez-Valentin¹⁸, Steven A Narod¹⁹, Kelly Metcalfe²⁰; Hereditary Breast Cancer Clinical Study Group

Collaborators

Hereditary Breast Cancer Clinical Study Group:
Kevin Sweet, Christine Elser, Seema Panchal, Aletta Poll, Georgia Wiesner, Susan Armel, Linda Steele, Howard Saal, Kim Serfas, Carey A Cullinane, Robert E Reilly, Daniel Rayson, Leanne Mercer, Jeffrey Dungan, Stephanie Cohen, Susan Neuhausen, Sophie Sun, Leigha Senter, Joanne L Blum, Klaudia Stempa, Tracy Graham, Intan Schrader, Marta Seca, Martina Delle Marchette, Serena Negri, Cristina Dell'Oro, Alessandra Inzoli, Rosa Alfonso, Consol Lopez, Francesco Cusco, Olufunmilayo Olopade, Cezary Cybulski, Tomasz Huzarski

Affiliations

¹ Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada; Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
² Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³ Departament of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
⁴ Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
⁵ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁶ Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
⁷ Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁸ Vanderbilt-Ingram Cancer Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹ Department of Medical Oncology, Sunnybrook Odette Cancer Center, and University of Toronto, ON, Canada.
¹⁰ Department of Oncology, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada.
¹¹ Department of Human Genetics, McGill University, Montreal, QC, Canada.
¹² Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MI, USA.
¹³ Cancer Genetics Program, Beaumont Hospital, Royal Oak, MI, USA.
¹⁴ Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
¹⁵ Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada.
¹⁶ Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁷ Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.
¹⁸ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
¹⁹ Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. Electronic address: Steven.narod@wchospital.ca.
²⁰ Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada; Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada.

PMID: 40784323
DOI: 10.1016/j.ygyno.2025.07.030

Abstract

Objective: Inherited BRCA1/2 pathogenic variants (mutations) confer high lifetime risks of breast and ovarian cancers. Estimating the cumulative ovarian cancer risk following a breast cancer diagnosis in these women will help guide decisions regarding preventive salpingo-oophorectomy.

Methods: Women carrying a BRCA1 or BRCA2 mutation were followed after breast cancer and completed follow-up questionnaires every two years. The 15-year cumulative risk of ovarian cancer was estimated for women with a prior history of breast cancer and for matched control women without breast cancer.

Results: A total of 2084 BRCA carriers with breast cancer (1515 BRCA1, 569 BRCA2) were included. During a mean follow-up of 3.9 years, 71 ovarian/fallopian carcinomas were diagnosed (66 BRCA1, 5 BRCA2). The 15-year cumulative ovarian cancer risk was 14.9 % in BRCA1 and 5.1 % in BRCA2 carriers. Women with breast cancer were compared to those without; 1378 matched pairs were included. The 15-year cumulative risk of ovarian/fallopian cancer was 10.8 % in women with a history of breast cancer versus 25.9 % in those without. Among BRCA1 carriers, the risk was 12.2 % in women with breast cancer and 32.0 % in those without. Among BRCA2 carriers, the 15-year ovarian cancer risk was 2.0 % in both groups.

Conclusions: Ovarian cancer risk remains high in BRCA1/2 carriers following breast cancer diagnosis. For BRCA1 mutation carriers, the risk is lower than in women without breast cancer. However, for both BRCA1 and BRCA2 the ovarian cancer risk is elevated, and considering the poor prognosis associated with ovarian cancer, risk-reducing salpingo-oophorectomy is strongly recommended for women with BRCA-associated breast cancer.

Keywords: BRCA mutation; Breast cancer; Ovarian after breast cancer; Ovarian cancer.

MeSH terms

Adult
Aged
BRCA1 Protein* / genetics
BRCA2 Protein* / genetics
Breast Neoplasms* / epidemiology
Breast Neoplasms* / genetics
Case-Control Studies
Fallopian Tube Neoplasms / epidemiology
Fallopian Tube Neoplasms / genetics
Female
Follow-Up Studies
Genes, BRCA1*
Genes, BRCA2*
Genetic Predisposition to Disease
Humans
Middle Aged
Mutation
Ovarian Neoplasms* / epidemiology
Ovarian Neoplasms* / genetics
Salpingo-oophorectomy

Substances

BRCA2 protein, human
BRCA1 protein, human
BRCA2 Protein
BRCA1 Protein