Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?

Jacob McGee; Vasily Giannakeas; Beth Karlan; Jan Lubinski; Jacek Gronwald; Barry Rosen; John McLaughlin; Harvey Risch; Ping Sun; William D Foulkes; Susan L Neuhausen; Joanne Kotsopoulos; Steven A Narod; Hereditary Ovarian Cancer Clinical Study Group

doi:10.1016/j.ygyno.2017.02.032

Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?

Gynecol Oncol. 2017 May;145(2):346-351. doi: 10.1016/j.ygyno.2017.02.032. Epub 2017 Mar 14.

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Western University, London, ON, Canada.
² Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
³ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
⁴ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁵ Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, Canada; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Main Floor Room 719, 610 University Ave, Toronto, ON, Canada.
⁶ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, Canada; Public Health Ontario, Toronto, ON, Canada.
⁷ Department of Chronic Disease Epidemiology, Yale School of Public Health, 60 College St., New Haven, CT, USA.
⁸ Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada.
⁹ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
¹⁰ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada.
¹¹ Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street Health Science Building, 6th Floor, Toronto, ON, Canada. Electronic address: steven.narod@wchospital.ca.

PMID: 28314588
DOI: 10.1016/j.ygyno.2017.02.032

Abstract

Objective: Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening.

Methods: First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality.

Results: Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer.

Conclusions: Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer.

Keywords: BRCA; Breast cancer; MRI; Mastectomy; Ovarian cancer.

MeSH terms

Aged
Aged, 80 and over
Breast Neoplasms / diagnostic imaging
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Breast Neoplasms / prevention & control*
Cohort Studies
Female
Genes, BRCA1*
Genes, BRCA2*
Genetic Predisposition to Disease
Humans
Magnetic Resonance Imaging
Middle Aged
Mutation*
Neoplasm Staging
Neoplasms, Second Primary / diagnostic imaging
Neoplasms, Second Primary / genetics
Neoplasms, Second Primary / pathology
Neoplasms, Second Primary / prevention & control
Ovarian Neoplasms / diagnosis
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / mortality
Ovarian Neoplasms / pathology
Prophylactic Mastectomy*
Proportional Hazards Models