Bilateral carcinomas of the breast with local recurrence: analysis of genetic relationship of the tumors

Abstract

Local recurrence of bilateral breast carcinomas is rare, but of biological interest, since it is unclear as to which tumor the local recurrence is related to, the ipsilateral or the contralateral, or whether it is an independent neoplasm. The aim of this study was to investigate the genetic relationship of bilateral breast carcinomas to each other and to their local recurrences. Eight cases of bilateral breast carcinomas, five with and three without local recurrence were analyzed using a microsatellite assay for 13 microsatellite loci. The presence of loss of heterozygosity and microsatellite instability in the various tumors was used for clonal analysis. All eight bilateral breast carcinomas showed divergent alterations in at least two microsatellite loci, which ruled out a genetic relationship. Four of five local recurrences were genetically related to the ipsilateral tumor and unrelated to the contralateral tumor. Only one local recurrence that occurred 11.8 years after the surgery of an infiltrative lobular carcinoma simultaneously with distant metastases was genetically related to the contralateral breast carcinoma. Although the number of cases in our study is limited, there is evidence that local recurrence of bilateral breast carcinoma frequently arises from the ipsilateral tumor. Keywords: bilateral breast carcinoma; local recurrence; microsatellite analysis; loss of heterozygosity; clonality Epidemiologic data on breast carcinomas show that 2-11% of breast carcinoma patients will develop contralateral breast carcinoma in their lifetime. Women with unilateral breast carcinoma are at a 2-6-fold increased risk of developing contralateral breast carcinoma, compared to the risk in the general population. 1 Bilateral breast carcinomas are of particular interest with respect to their relationship, whether they represent independent neoplasms or occur by metastatic tumor spread. This issue becomes more complex in the setting of local tumor recurrence. In this situation, the question arises whether the local recurrence is related to one of the bilateral tumors or is an independent, de novo arising neoplasm, or whether both of the tumors and the recurrence are metastases of the other tumor. The fact that whether bilateral breast carcinomas and its local recurrence have to be considered a local or a metastatic process has important therapeutic and prognostic implications.A second independently arising breast carcinoma is favored, if the histological tumor types are different. However, if the histological tumor types are identical, the distinction between a subsequently occurred novel tumor and a local recurrence of the original tumor is difficult. Conventional parameters such as the histopathological grade and various immunohistochemical analyses such as estrogen, progesterone and HER-2/neu receptor expression are not reliable to prove the relationship of these tumors.During recent years, several studies using different molecular methods have indicated that bilateral breast carcinomas are most likely genetically u...

Long-Term Patterns of In-Breast Failure in Patients With Early Stage Breast Cancer Treated With Breast-Conserving Therapy

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

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Evaluation of the Clonal Origin of Multiple Primary Melanomas Using Molecular Profiling

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