The effects of hormonal and chemotherapy on tumoral and nonneoplastic breast tissue.

One hundred four sequential pretherapy and posttherapy breast tissue specimens from 57 patients with locally advanced and metastatic breast cancer were evaluated in an attempt to define the effects of systemic chemotherapeutic agents on the tumors and residual nonneoplastic breast tissue. The patients were treated uniformly at the National Cancer Institute on an experimental protocol combining systemic chemotherapy with attempted hormonal synchronization. Tumors were sampled prior to and following several cycles of chemotherapy to a maximum objective clinical response (average number of cycles, 7). In 38 cases, the posttreatment biopsy was positive for tumor. The most striking histologic change was extreme vacuolization of tumor cells that often resembled histiocytes. Atrophy of the terminal duct lobular unit (TDLU) and atypia of epithelial cells in TDLU and large ducts were also seen. Severe degrees of epithelial atypia occasionally proved to be difficult to distinguish from residual intraductal carcinoma. Breast biopsies were stained with antibodies to cytokeratin, epithelial membrane antigen (EMA), B72.3, lactalbumin, and SP1 using immunoperoxidase techniques. The number of cases showing immunoreactivity with antibodies to cytokeratin, EMA, and B72.3 remained approximately the same before and after therapy, while SP1 expression decreased and lactalbumin expression increased after therapy. Recognition of chemotherapeutic changes in breast tissue is important since systemic chemotherapy plays an important role in the management of breast cancer.