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Lymph node status predicted 10-year mortality in BRCA1 mutation carriers with small, stage I-III breast cancers


 

FROM THE JOURNAL OF CLINICAL ONCOLOGY

Overall survival rates at 10 years after diagnosis were similarly good in women with and without BRCA1 mutations if they had stage I-III node-negative breast cancers that were smaller than 2 cm, based on a retrospective study of Polish women who were under age 50 years at diagnosis.

Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted hazard ratio, 4.1; 95% confidence interval, 1.8-8.9). Among BRCA1 carriers with 2 cm or smaller breast tumors, the 10-year survival rate was 84.1%, compared with 89.9% for the node-negative patients and 68.6% for the node-positive patients, according to Dr. Tomasz Huzarski of Pomeranian Medical University, Szczecin, Poland, and the members of the Polish Hereditary Breast Cancer Consortium.

Their study also showed that mortality rates were lower in BRCA1 carriers who had prophylactic oophorectomies. Compared with BRCA1 carriers who had intact ovaries, carriers who had an oophorectomy had a mortality reduction of 70% (adjusted HR, 0.30; 95% CI, 0.12-0.75).

The findings were gleaned from the medical records of 3,345 Polish women who were age 50 years or less when diagnosed from 1996 to 2006 with stage I-III breast cancer. In Poland, three founder mutations (5382insC, C61G, 4153delA) represent over 90% of the BRCA1 mutations, and young women diagnosed with breast cancers at one of 17 affiliated clinical centers there are screened for those BRCA1 mutations. The records indicated that 233 (7%) of the women with a first cancer diagnosis of stage I-III breast cancer had a BRCA1 mutation.

Based on BRCA1 status alone, the 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4%-86.4%); for noncarriers, it was 82.2% (95% CI, 80.5%-83.7%). The difference was not statistically significant, the authors wrote in an article published online in the Journal of Clinical Oncology (J. Clin. Oncol. 2013 Aug. 12 [doi:10.1200/JCO.2012.45.3571]).

In a multivariate analysis, however, mortality differed significantly for BRCA1 carriers and noncarriers (HR, 1.81; 95% CI, 1.26-2.61; P = .002). Of the 233 BRCA1-positive patients, 101 (43.6%) comprised a high-risk group who had cancers that were node positive and/or at least 5 cm or more in size. Their 10-year survival was 68.2% (95% CI, 58.2%-78.6%).

"The effect of oophorectomy on survival was profound and was statistically significant for BRCA1 carriers," the Dr. Huzarski and his coworkers wrote. A preventive oophorectomy was performed in 115 of the 233 carriers. There were 13 deaths, all resulting from breast cancer, in the 115 women. Among the 113 women (data were missing for 5 women) who did not have an oophorectomy, there were 28 deaths: 22 from breast cancer and 6 from breast or ovarian cancer. Overall, 28 (68%) of the 41 deaths occurred in women with intact ovaries.

As the study was limited to women in Poland, the authors cautioned that the results may not generalizable to women with other BRCA1 mutations or ethnicities. Additionally, these were early-onset cases only and the survival rates may not accurately reflect those of women diagnosed with cancer at a later age.

"It is important that these observations be replicated in other populations; if they are, oophorectomy should be considered a standard of care for women with breast cancer and a BRCA1 mutation," they wrote.

Dr. Huzarski and his associates reported having no financial conflicts of interest.

mdales@frontlinemedcom.com

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