Contralateral Breast Cancer: Molecular Differentiation Between Metastasis and Second Primary Cancer

Abstract

Previous cancer in one breast is a strong known risk factor for cancer in the contralateral breast. Differences in tumor histology and nuclear grading are applied to distinguish between a metastatic spread and a second primary cancer, although cancers of the breast often share the same histological features. Comparison of genetic alterations in paired tumors may provide the most reliable approach for discerning clonal relationships, hence uncovering 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 within paired tumors in 13 patients. The paired tumors of two patients shared the same mutation, revealing the second lesion in one case as a contralateral metachronous lymph node metastasis appearing 29 months after first surgery, and in the other as a spread to the opposite breast. In 11 patients, mutations were either discordant or solely present in one of the lesions, confirming the diagnosis of bilateral breast cancer. Histopathological evaluation had failed to provide firm diagnosis in nine out of 11 instances on account of concordances in pathological parameters such as histological type and grading. In our study, we could show that bilateral breast malignancies most frequently represent two primary breast cancers. We could also demonstrate that contralateral breast cancer spread does occur. Standard pathological assessment allowed a firm diagnosis only in the presence of different histological types.

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

“…show some CBC to have features similar enough to BC1 that a metastatic spread is possible (11)(12)(13)(14)(15).…”

Diagnostic and Prognostic Utility of Molecular Markers in Synchronous Bilateral Breast Carcinoma

“…29,30,31 Although some studies showed that synchronous carcinoma behaves more aggressively than metachronous carcinomas, 8 other investigators have concluded that patients with synchronous bilateral breast carcinoma have the same or a favorable prognosis as their unilateral counterpart breast carcinoma when adjusted for maximum stage. 6,21,29,30,[31][32][33][34][35] Similar to Intra et al, 30 11/24 (46%) of our patients were classified as grade 2, while high-grade tumors (grade 3) were infrequent in synchronous bilateral carcinoma. 36 Moreover, patients with synchronous bilateral carcinoma have a higher rate of ER and PgR positivity than that in patients with unilateral breast cancer, suggesting less aggressive biologic behavior.…”

The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

“…In general, these studies have shown that clonality is quite common for mucosal cancers of the head and neck (23) and bladder (24). However, for sites with paired organs, such as breast (25)(26)(27)(28) and lung (29)(30)(31), the vast majority of new contralateral primaries seem to be biologically independent. The issue does not seem to have been studied in melanoma, but the wide anatomic distribution of melanomas and the absence of a plausible mechanism for the seeding of clonal cells in distant parts of the skin argue against the frequent clonality of multiple primaries in this disease.…”