Background: A higher incidence of contralateral breast cancer and ipsilateral recurrence has been reported in familial breast cancer than in sporadic cancer. This study investigated the influence of contralateral cancer and tumour stage on survival in patients with familial non-BRCA1/BRCA2- associated breast cancer. Methods: The incidences of contralateral breast cancer, ipsilateral recurrence, distant disease-free and overall survival were assessed in 327 patients from families with three or more breast and/or ovarian cancers, but no BRCA1 or BRCA2 gene mutation (familial non-BRCA1/2), and in 327 control subjects with sporadic breast cancer, matched for year and age at detection. Results: Mean follow-up was 7·3 years for patients with familial-non-BRCA1/2 cancers and 6·5 years for patients with sporadic breast cancer. Tumours were stage T1 or lower in 62·1 per cent of familial non-BRCA1/2 cancers versus 49·9 per cent in sporadic breast cancers (P = 0·003), and node negative in 55·8 versus 52·1 per cent, respectively (P = 0·477). After 10 years the incidence of metachronous contralateral breast cancer was 6·4 per cent for familial non-BRCA1/2 tumours versus 5·4 per cent for sporadic cancers. The rate of ipsilateral recurrence was not significantly increased (17·0 versus 14·2 per cent, respectively, at 10 years; P = 0·132). Tumour size (hazard ratio (HR) 1·02 per mm increase, P = 0·016) and node status (HR 2·6 for three or more involved nodes versus node negative, P = 0·017) were independent predictors of overall survival in the familial non-BRCA1/2 group, and in the whole group, whereas contralateral breast cancer (HR 0·7, P = 0·503) and risk-reducing contralateral mastectomy (HR 0·4, P = 0·163) were not. Conclusion: Stage at detection was a key determinant of prognosis in familial non-BRCA1/2 breast cancer, whereas contralateral cancer was not. Risk-reducing contralateral mastectomy did not significantly improve survival, but early detection can. Decisions on breast-conserving treatment can be made on the same grounds in patients with familial and sporadic breast cancer. Copyright

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Journal British Journal of Surgery
Tilanus-Linthorst, M.M.A, Alves, C, Seynaeve, C.M, Menke-Pluymers, M.B.E, Eggermont, A.M.M, & Brekelmans, C.T. (2006). Contralateral recurrence and prognostic factors in familial non-BRCA1/2-associated breast cancer. British Journal of Surgery, 93(8), 961–968. doi:10.1002/bjs.5344