Prognostic significance of synchronous and metachronous bilateral breast cancer

Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast, but the clinical significance of this development is unclear. The purpose of this study was to assess the impact of synchronous bilateral breast cancer or the development of a metachronous contralateral breast primary on the prognosis. In a series of 3210 women age ≤70 years treated between 1975 and 1995 for primary operable breast cancer, 106 were identified to have bilateral breast cancer. Of these women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and 80 developed a contralateral breast cancer after treatment for an initial primary breast cancer. Using life-tables analysis, there was a significant difference in survival between women with unilateral breast cancer, those with synchronous bilateral breast cancers, and those with metachronous contralateral breast with survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p<0.0001), from the date of the diagnosis of the first primary tumor. There was no difference in survival seen between the three groups when survival was calculated from the date of diagnosis of the second primary in cases of metachronous contralateral breast cancer (p=0.31). When contralateral breast cancer was incorporated as a time-dependent covariate in a Cox multivariate model together with the three factors used to determine the Nottingham Prognostic Index (invasive tumor size, grade, and lymph node stage), contralateral breast cancer continued to be a significant prognostic determinant (p=0.02). The survival of women with synchronous bilateral breast cancer or metachronous breast cancers diagnosed within 2 years of the original primary was worse than those with unilateral disease. However, the time duration to metachronous contralateral breast cancer did not have prognostic significance in a multivariate model compared with the prognostic features of the original primary.