Contralateral breast cancer: molecular differentiation between metastasis and second primary cancer

Previous cancer in one breast is a strong known risk factor for cancer in t he contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primar y cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide th e most reliable approach for discerning clonal relationships, hence uncover ing the presence or absence of multiple primary cancers. We compared tumors from 33 patients with cancer in both breasts for mutations in the p53 gene . With this molecular approach, we were able to define the relationship wit hin paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralater al metachronous lymph node metastasis appearing 29 months after first surge ry, and in the other as a spread to the opposite breast. In 11 patients, mu tations were either discordant or solely present in one of the lesions, con firming the diagnosis of bilateral breast cancer. Histopathological evaluat ion had failed to provide firm diagnosis in nine out of 11 instances on acc ount of concordances in pathological parameters such as histological type a nd grading. In our study, we could show that bilateral breast malignancies most frequen tly represent two primary breast cancers. We could also demonstrate that co ntralateral breast cancer spread does occur. Standard pathological assessme nt allowed a firm diagnosis only in the presence of different histological types.