Similar 10-Year Survival in Patients With Early-Onset BRCA1-Negative and BRCA1-Positive Breast Cancer
In a study reported in Journal of Clinical Oncology, Tomasz Huzarski, MD, PhD, of Pomeranian Medical University, Szczecin, Poland, and colleagues from the Polish Hereditary Breast Cancer Consortium assessed survival among women with early-onset breast cancer with and without BRCA1 mutation and identified prognostic factors among those with BRCA1-positive disease. They found that 10-year overall survival was similar in BRCA1-positive and BRCA1-negative disease. Positive lymph node status was a predictor of increased mortality and oophorectomy a predictor of reduced mortality in women with BRCA1-positive disease.
Study Details
In the study, 3,345 women aged ≤ 50 years with stage I to III invasive breast cancer from 17 affiliated centers in Poland were tested for three founder mutations in BRCA1 (5382insC, C61G, and 4153delA). Dates of diagnosis were between 1996 and 2006. Diagnosis had to be pathologically confirmed by core or fine-needle aspiration biopsy. Patients with a previous diagnosis of contralateral breast cancer or another cancer were excluded from the analysis. Information on tumor characteristics and treatments received was retrieved from medical records, and dates of death were obtained from the vital statistics registry.
Mutation carriers were diagnosed at an earlier age (42 vs 44 years, P < .001) and were less likely to have estrogen receptor (ER)-positive (16% vs 62%, P < .001), progesterone receptor (PR)-positive (20% vs 70%, P < .001), and HER2-positive (6.5% vs 21%, P < .001) disease, more likely to have triple-negative disease (69% vs 13%, P < .001), and more likely to have had oophorectomy (50% vs 14%), with most (108 of 115 mutation carriers) having the procedure after breast cancer diagnosis.
Survival Analysis
Mean follow-up was 7.4 years. The 10-year overall survival rate was 80.9% for mutation carriers vs 82.2% for noncarriers (hazard ratio [HR] on univariate analysis = 1.14, P = .42). After adjustment for other prognostic features, the hazard ratio for mutation carriers became significant (1.81, P = .002). Among the subgroup of 485 women with triple-negative cancer, overall survival for mutation carriers was not inferior to that of noncarriers. Ten-year overall survival was 84.1% among BRCA1 carriers with small (> 2 cm) tumors, 89.9% for node-negative patients, and 68.6% for node-positive patients. Among carriers with tumors ≤ 1 cm, 27.5% were node-positive, and 10-year overall survival was 81.8% in these patients. Patients with cancers that were either node-positive or > 5 cm constituted a high-risk group; 44% of the mutation carriers were in this group and had 10-year overall survival of 68.2%.
Predictive Factors
Among mutation carriers, positive lymph node status was a predictor of poorer survival (adjusted HR = 4.1, P < .001) and oophorectomy was a predictor of improved survival (adjusted HR = 0.30, P = .01). The hazard ratio for oophorectomy was the same when patients receiving the procedure prior to diagnosis were excluded from the analysis. Factors not significantly associated with overall survival for mutation carriers on multivariate analysis included year of birth, age at diagnosis, ER, PR, and HER2 status, tumor size, and receipt of chemotherapy.
The investigators concluded, “The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.”
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