BRCA mutations and Outcome
Posted 2/6/2012
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ALthough most women who carry a BRCA mutation already know this (I hope), it is reassuring that a new study confirms that, stage for stage, there is not a difference in prognosis for women who carry the gene vs women who do not. What this means is that any one cancer is independent of the fact of the gene when it comes to outcome. This is from Medscape:
Does a BRCA Mutation Influence Breast Cancer Outcomes?
Maurie Markman, MD
Breast Cancer Prognosis in BRCA1 and BRCA2 Mutation Carriers: An International
Perspective Breast Cancer Family Registry Population-Based Cohort Study
Goodwin PJ, Phillips KA, West DW, et al
J Clin Oncol. 2012;30:19-26
Summary
Using survival data from a population of 3220 breast cancer patients in Canada, the United States, and Australia, researchers sought to explore the outcomes of women with breast cancer and known BRCA mutations vs individuals with sporadic disease (ie, no BRCA mutation). Patients had a median age of 45.3 years; 93 patients had a documented BRCA1 mutation, 71 patients had a documented BRCA2 mutation, and 1 patient had both.
After a mean follow-up of nearly 8 years, univariate and multivariate analyses showed no difference in the risk for distant recurrence or death between patients with BRCA1 mutations and those with sporadic breast cancer.
Of note, univariate analysis showed that the risk for both recurrence (hazard ratio, 1.63; P = .04) and death (hazard ratio 1.81; P = .01) was greater for BRCA2 carriers vs those with sporadic disease, although this difference was not observed in a multivariate analysis. Rather, the multivariate analysis suggested that the differences observed between the BRCA2 carriers and those with sporadic breast cancer were related to the presence of more adverse clinical features (eg, greater nodal involvement, higher tumor grade) in the mutation-positive group.
Viewpoint
It is well-established that women with mutations in BRCA1 or BRCA2 have an increased lifetime risk for breast cancer
and, to a lesser degree, ovarian cancer. In addition, considerable research has demonstrated the utility of prophylactic surgery in reducing that risk.[1]
However, although there is a fair amount of data in the medical literature regarding the potential favorable effects of BRCA mutations in women diagnosed with ovarian cancer (possibly due to enhanced sensitivity of the cancer to platinum agents),[2] there is less information on the specific influence of BRCA status on outcome (ie, risk for recurrence and death) in breast cancer.
The current report is important and generally reassuring to women with documented BRCA1 mutations who are found to
have breast cancer. The data show that, as a group, this population does not have a worse outcome than individuals
with sporadic disease.
However, the data also suggest that a BRCA2 mutation may be associated with less favorable clinical features that
result in higher risk for both recurrence and death.
It is important to note the limited sample size on which the conclusions regarding BRCA2 and its association with
adverse prognostic factors have been made. It is also relevant to acknowledge that this analysis suggests that outcome is influenced more by well-established clinical factors (eg, stage, grade, hormonal status, number of lymph nodes involved) rather than by the presence or absence of the BRCA mutation. Additional reports from other groups of investigators with access to BRCA mutation status and data on long-term survival outcomes will be important to confirm or refute the findings in this report.
Posted: 01/19/2012
Medscape Genomic Medicine © 2012 WebMD, LLC
References
Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing
salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80-87. Abstract
1.
Yang D, Khan S, Sun Y, et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy
sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA. 2011;306:1557-1565. Abstract
2.
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