Multicentric mammary carcinoma: evidence of monoclonal proliferation

Both the widespread use of screening mammography and emphasis on breast conservation have raised many questions regarding the clinical and therapeutic management of multicentric mammary carcinoma (MMC). MMC has been postulated to be either a clonal proliferation of a single mammary carcinoma or multiple independent synchronous primary tumors in the same breast. The goal of the current study was to evaluate the histologic features and immunohistochemical profile of MMC. We also compared the clinical outcomes of the patients in the current study with stage-matched and treatment-matched groups of patients with unicentric mammary carcinoma.

The authors studied 32 patients with T1-T2, N0-1, M0 multicentric invasive mammary carcinomas diagnosed between 1983-1988 and treated at The University of Texas M. D. Anderson Cancer Center. The histologic features of each tumor (including tumor type, nuclear grade, presence of in situ carcinoma, pattern of in situ carcinoma, and lymphovascular invasion) were evaluated. The authors performed immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, and Ki-67 in 25 cases, including 14 from which > 1 tumor was available to perform comparative immunohistochemical analysis. The clinical parameters of each case were compared with those of the unicentric breast carcinoma controls.

The median age of the patients with MMC was 45 years (range, 28-69 years). Twelve patients had a family history of breast carcinoma (37.5%). The maximum tumor dimension ranged from 0.2-3.2 cm in the index lesion (median, 2.0 cm) and 0.1-2.5 cm in the second lesion (median, 0.9 cm). Twelve patients were clinically classified as having Stage I disease and 20 patients were considered to have Stage II disease at the time of presentation. Follow-up data were available for all the patients and follow-up ranged from 4.5-16 years (median, 6 years). The disease-free survival was 84% at 5 years and 73% at 10 years in the MMC patients and 78% and 70%, respectively, in patients with unicentric breast carcinoma (P = 0.4368). Histologically, 24 of the multicentric tumors were found to be infiltrating ductal tumors and 8 were found to be infiltrating lobular carcinomas. The nipple was involved in 10 cases. The histology of the multicentric invasive tumor was nearly identical in 31 cases (97%). Approximately 72% of the cases had in situ carcinoma in both tumors and 44% had lymphovascular invasion. Comparative immunohistochemical analysis of separate tumors was equivalent with regard to ER, PR, and HER-2/neu. The quantitative immunohistochemical staining for the proliferative marker Ki-67 differed between tumors in two cases.

The near-identical morphologic and immunohistochemical patterns in the MMC cases in the current study support the hypothesis that early-stage synchronous tumors are a clonal proliferation of a single mammary carcinoma. Furthermore, the results of the current study support evaluating prognostic markers in only one tumor per MMC patient. There was no appreciable difference in the disease-free survival of patients with unicentric and multicentric breast carcinoma.