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Expert Analysis Highlights:
For breast cancer women who carry the BRAC-I or BRAC-II mutations, there is continued evidence that prophylactic removal of the breast and ovaries decreases mortality rate. Prophylactic removal simply refers to surgically removing the breast or ovary that is not known to contain cancer for the purpose of reducing the patient’s risk. For your reference, below are relevant summary abstracts from professional medical journals. This subject is not without controversy. Removing healthy tissue, for example the breast that may otherwise never develop cancerous cells despite having cancer in the opposite breast, is a difficult choice that’s not for everyone. Talk to your doctor about your options.
A recent report from Dr Domchek and colleagues from the University of Pennsylvania in the Journal of American Medical Association showed that prophylactic mastectomy (breast removal) and removal of the ovaries significantly reduce mortality in this select group of women. They examined the survival outcome in a group of 2,482 BRAC-I or BRAC-II mutation carriers identified at 22 medical centers in North America and Europe who were participating in the prospective clinical trial. Approximately 10% of these women underwent prophylactic mastectomies and 40% underwent prophylactic removal of their ovaries.
The results were impressive. No breast cancers developed in mutation carriers who underwent prophylactic mastectomy whereas breast cancer did develop in 7% of those who declined prophylactic mastectomy. The results were even more impressive in preventing ovarian cancer which is much more lethal at the time of diagnosis. Among women who underwent prophylactic removal of their ovaries, only 1% subsequently developed ovarian cancer and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic removal of their ovaries, about 6% subsequently developed ovarian cancer and 19% subsequently developed breast cancer. Thus, prophylactic removal of the ovaries in this select group of mutation carriers can cut the risk of ovarian cancer by 70% in those women who did not have prior breast cancer and decrease it even further, by 85%, in those who did have prior breast cancer.
These findings illustrate why breast cancer patients may want to know about their BRCA genetic status even if they have undergone bilateral mastectomy because prophylactic removal of their ovaries, even in this group of patients, may protect them from developing a new primary malignancy. Among women with no prior breast cancer, prophylactic removal of the ovaries reduced the breast cancer by 37% in carriers of the BRCA-I mutation and by 64% in carriers of BRCA-II mutation.
Another related medical study was reported in the November, 2010 issue of the ASCO Post on women who carried the BRCA mutation. This study by Dr Metcalfe and colleagues from the University of Toronto demonstrated that women younger than 50 years with BRCA-mutated breast cancers can have a 38% risk of developing breast cancer in the opposite breast within the next 15 years. In addition, there is a 68% risk in a woman diagnosed before age 50 who chooses to keep her ovaries and has two first degree relatives diagnosed with breast cancer before the age of 50. Thus, women with a younger age at onset of their breast cancer are at significant risk for developing an opposite breast cancer or ovarian cancer during follow-up over the next 10-15 years.
The results in women who are BRCA-mutant carriers who undergo prophylactic removal of their ovaries are similar to the results reported in the previous studies. In this circumstance the object of the study was to examine the development of opposite breast cancer in mutant carriers who had a diagnosis of cancer in the opposite breast. In this study, women who underwent prophylactic removal of their ovaries and who were younger than 50 years of age at diagnosis have a 60% risk of developing opposite breast cancer within 15 years compared to 20% of those older than 50 years of age. Women younger than 50 who underwent prophylactic removal of their ovaries had a subsequent reduction in their risk for opposite breast cancer by more than one-third. The authors concluded that “women with early-onset breast cancer have the highest risk and get the most protection from prophylactic removal of their ovaries”.
Dr. Metcalfe emphasized how these risk factors can be used in counseling women. For example, while the 15-year risk for a woman diagnosed before age 50 is 37.6% it greatly increases if she decided against prophylactic removal of their ovaries and nearly doubles if she has two or more 1st degree relatives diagnosed with breast cancer at an early age.
KEY REFERENCES BELOW:
JAMA. 2010 Sep 1;304(9):967-75.
Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t’veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR.
Abramson Cancer Center and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
CONTEXT: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.
OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and prior cancer status.
DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.
MAIN OUTCOMES MEASURES: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.
RESULTS: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).
CONCLUSIONS: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
J Natl Cancer Inst. 2010 Nov 23. [Epub ahead of print]
Family History of Cancer and Cancer Risks in Women with BRCA1 or BRCA2 Mutations.
Metcalfe K, Lubinski J, Lynch HT, Ghadirian P, Foulkes WD, Kim-Sing C, Neuhausen S, Tung N, Rosen B, Gronwald J, Ainsworth P, Sweet K, Eisen A, Sun P, Narod SA; for the Hereditary Breast Cancer Clinical Study Group.
Affiliations of authors: Women’s College Research Institute, Toronto, ON, Canada (KM, PS, SAN); Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada (KM); Center for Hereditary Breast Cancers, Pomeranian Medical University, Szczecin, Poland (JL, JG); Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE (HTL); Department of Cancer Genetics, Department of Medicine, and Department of Genetics, Epidemiology Research Unit, CHUM Hôtel-Dieu, University of Montreal, Montreal, QC, Canada (PG); Department of Genetics and Department of Medical Oncology, McGill University, Montreal, QC, Canada (WDF); BC Cancer Agency, Vancouver; BC, Canada (CK-S); Department of Population Sciences, City of Hope, Duarte, CA (SN); Beth Israel Deaconess Hospital, Boston, MA (NT); Department of Gynecology Oncology, University Health Network, University of Toronto, Toronto, ON, Canada (BR); London Regional Cancer Program, London, ON, Canada (PA); Department of Medical Genetics, Ohio State University, Columbus, OH (KS); Sunnybrook Regional Cancer Centre, Department of Medical Oncology, Toronto, ON, Canada (AE).
Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07).
Clin Genet. 2009 Mar;75(3):220-4.
Breast and ovarian cancer risk perception after prophylactic salpingo-oophorectomy due to an inherited mutation in the BRCA1 or BRCA2 gene.
Women’s College Research Institute, Toronto, ON, Canada.
It is often recommended that women who carry a mutation in the BRCA1 or BRCA2 gene have their ovaries and fallopian tubes removed to reduce their risk of gynecologic cancer. The aim of this study was to evaluate women’s perception of their risk of breast and ovarian cancer before and after prophylactic salpingo-oophorectomy. We surveyed 127 women who carry a BRCA1 or BRCA2 mutation and who underwent prophylactic salpingo-oophorectomy at the University Health Network, Toronto. Subjects were asked to estimate their risks of breast and ovarian cancer before and after surgery. Their perceived risks of cancers were then compared with published risks, based on their mutation status. BRCA1 carriers estimated their risk of breast cancer risk to be, on average, 69% before surgery and 41% after surgery. They estimated their risk of ovarian cancer to be 55% before surgery and 11% after surgery. BRCA2 carriers estimated their risk of breast cancer to be 69% prior to surgery and 45% after surgery and their perceived risk of ovarian cancer to be 43% before surgery and 8% after surgery. Compared with published risk figures, the perceived risk of ovarian cancer before prophylactic salpingo-oophorectomy was overestimated by 47% of BRCA1 mutation carriers and by 61% of BRCA2 mutation carriers. Most women who have undergone genetic counseling and subsequently choose prophylactic salpingo-oophorectomy accurately perceive their risk of breast cancer. However, in this study, many women overestimated their risk of ovarian cancer, particularly women who carry a BRCA2 mutation.