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

Abstract

Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events. Keywords: synchronous bilateral breast carcinoma; molecular pathology; LOH Contralateral breast carcinoma is the most common second malignancy for breast carcinoma patients, with an incidence as high as 12%.1-3 Bilateral breast carcinomas exist in two forms, synchronous, in which both tumors occur at the same time, or metachronous, in which the carcinomas occur at different times. Synchronous bilateral breast carcinoma is uncommon, reported to range from 0.3 to 8% in the literature. [4][5][6][7] This wide range of reported incidence rates for synchronous bilateral breast carcinoma is a result of different time cutoff. Although some authors require both breast carcinomas to be diagnosed simultaneously or within less than 1 month, 7-10 others used up to 12 months as a cutoff time to differentiate synchronous from metachronous bilateral breast carcinomas.11-13 Using criteria of less than 1 month, the incidence of synchronous bilateral breast is less than 2%. 7,14 When cancer is detected in the opposite breast, the question arises whether this tumor is a second cancer (polyclonal origin) or a metastatic spread from the first breast cancer (monoclonal origin). The answer to this question is critical as both tumor staging and management will be different depending upon the results.11 Currently, this distinction is attempted using histopathologic features. Different histologic types, a better histologic diff...

Bilateral breast cancer following augmentation mammaplasty with polyacrylamide hydrogel injection: A case report

“…A current topic in the field of cancer treatment involves detecting the expression levels of genes in tumor tissues to screen out patients sensitive to specific chemotherapeutic agents, to thus determine the most appropriate type of neoadjuvant and adjuvant chemotherapy on an individual basis (26)(27)(28). Two such genes determined in the present case were TUBB3 and TOP2A.…”

“…However, it has also been reported that distinct, characteristic genetic alterations could not be detected using the comparative genomic hybridization method (32). By performing loss of heterozygosity studies, Saad et al (26) identified discordant mutations in synchronous bilateral breast carcinoma patients, supporting the diagnosis of de novo bilateral primary breast carcinoma. This indicated that the application of molecular technology may be important in the differential diagnosis of dual primary carcinoma versus metastatic breast cancer from the contralateral breast.…”

“…Furthermore, a number of cases exist that have been verified as bilateral primary cancer despite exhibiting the same pathology as the initial breast cancer (25) or the metastatic carcinoma of an axillary lymph node. This indicates that a reevaluation of the histological criteria commonly used to differentiate between primary and metastatic lesions is required (26).…”

Molecular Profiling of Synchronous and Metachronous Cancers of the Pancreas Reveal Molecular Mimicry Between Samples from the Same Patient

“…There are several tests to assess clonality in neoplasms, including loss of heterozygosity (LOH), microsatellite instability (MSI), and methylation-related X chromosome inactivation [4][5][6]. These techniques have been widely used to profile the genotype of synchronous tumors from the lung, breast, and colon, where multicentric lesions frequently occur [7][8][9]. In contrast, PDA typically occurs as a solitary neoplasm, and multiple autonomous lesions are rare [10].…”

Synchronous Bilateral Breast Cancer (SBBC): Report of a Case with Review of Literature

“…In SBBC patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary BCs. In patients with lymph node metastases, the primary BC and metastases shared the same mutations, revealing a metastatic lesion [7]. Contradictory data exists concerning the prognosis of patients with SBBC.…”