Author reply


We thank the authors for their interest in our manuscript1 and appreciate the opportunity to respond.

We correlated morphologic features and immunohistochemical expression in a cohort of patients with T1 and T2 multicentric breast carcinomas to investigate whether these tumors represent intramammary spread of a single clone of tumor cells with similar antigenic expression or multiple independent primary tumors with different phenotypes. Our question was more than an academic exercise, as we re-evaluated the current practice in our institution of performing immunohistochemical analysis on patients' individual, separate invasive tumors. We found near identical immunohistochemical results in the early multicentric carcinomas we studied, with the prognostic and predictive breast biomarkers supporting the mechanism of clonal growth and/or intramammary spread of a single carcinoma.

Contrary to Teixeira et al.'s supposition that we are not aware that molecular and genetic analysis has been performed in attempts to further evaluate the pathogenesis and biology of multicentric breast carcinomas, students of this conundrum are faced with a body of disparate molecular literature that supports both clonally derived synchronous tumors and independent primaries. In fact, in their own words, the authors conclude that existing data is limited.2

The suggestion by the authors to use the clinical terminology multicentric only when clonality has been established is not clinically applicable. Various treatment decisions are made daily in patients with multifocal and multicentric breast cancer that could not wait until molecular confirmation of clonality.

We agree with Teixeira et al. that the majority of malignant breast tumors are invasive ductal carcinomas, not otherwise specified, and that is why, in addition to tumor classification, we evaluated traditional histologic parameters, including nuclear grade, presence of in situ carcinoma, lymphovascular invasion, and the tumor's immunohistochemical profile, in attempts to classify whether the tumors in our cohort represented intramammary spread of a clone of tumor cells or multiple independent primaries with different phenotypic expression. These aforementioned morphologic criteria are currently readily available to the practicing pathologist.

Our conclusion remains that further study is necessary, and that is why we are in the process of studying our group of multicentric breast carcinomas using available molecular techniques in the quest to understand the genesis of multifocal and multicentric breast neoplasia.

Lavinia Middleton M.D.*, S. Eva Singletary M.D.†, Aysegul A. Sahin M.D.‡, * Department of Pathology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, † Department of Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, ‡ Department of Pathology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas.