| Abstract: |
BACKGROUND There is no consensus on the usefulness of a breast-conservation approach for BRCA1/2 mutation carriers. OBJECTIVES To compare the outcomes of treatment with breast-conservation therapy (BCT) and radiotherapy in BRCA1/2 mutation carriers with breast cancer compared with matched controls with sporadic breast cancer. The potential impact of oophorectomy and tamoxifen on rates of in-breast tumor recurrence (IBTR) and the development of contralateral breast cancer (CBC) was also studied. DESIGN AND INTERVENTION In this retrospective cohort study conducted in II institutions in the US, Canada and Israel, women with deleterious germline BRCA1/2 mutations treated with BCT for a first primary breast cancer (stage I/II) were matched by age (within 2 years) and date of diagnosis (within 6 months) to controls with sporadic breast cancer (stage I/II). Patients who had a low probability of having a detectable mutation in either gene (< 5%) were defined as having sporadic disease. Clinical data were retrieved through record review. OUTCOME MEASURES Rates of IBTR and CBC were assessed. RESULTS A total of 160 women with a deleterious germline BRCA1/2 mutation and 445 controls were followed for median observation times of 7.9 and 6.7 years, respectively. No significant difference was found between carriers and controls for IBTR: 10-year and 15-year estimates were 12% (95% CI 9-15%) and 24% (95% CI 17-33%) for carriers and 9% ( 95% CI 7-10%) and 17% (95% CI 12 - 21%) for controls, respectively ( hazard ratio [HR] 1.37, P = 0.19). On multivariate analysis, excluding carriers who had undergone oophorectomy, BRCA1/2 mutation status was an independent predictor of IBTR (HR 1.9; P = 0.04). No significant difference was found between carriers who had undergone oophorectomy and sporadic controls for incidence of IBTR (P = 0.37). Rates of CBC were greater in carriers versus controls: 10-year and 15-year estimates were 26% (95% CI 22 - 30%) and 39% (95% CI 31 - 47%) for carriers and 3% (95% CI 2 - 4%) and 7% (95% CI 5 - 10%) for controls, respectively (HR 9.57; P < 0.0001). In mutation carriers who had not undergone oophorectomy, there were no local failures following tamoxifen treatment, in comparison with rates of 8%, 17% and 31% at 5, 10 and 15 years, respectively, without tamoxifen treatment. Tamoxifen use also reduced risk of CBCs in mutation carriers (HR 0.31; P = 0.05). CONCLUSION The authors recommend considering bilateral oophorectomy and tamoxifen use in individuals with the BRCA1 or the BRCA2 mutation who prefer breast conservation, although additional risk reduction interventions are needed in these patients, particularly for long-term prevention of CBC. |
