MORPHOLOGIC EFFECTS OF NEOADJUVANT CHEMOTHERAPY IN LOCALLY ADVANCED BREAST-CANCER

The use of chemotherapy as primary treatment in early and locally adva nced breast cancer is rising. As a result, many resected tumors were e xposed to cytotoxic drugs in vivo. To study resulting histopathologic changes, we examined 61 patients with locally advanced stage III breas t cancer who had been treated with a standardized neoadjuvant polychem otherapy regimen before undergoing surgical resection 3 months later. Matched pairs of pre- and posttherapy breast tissue were evaluated for morphologic changes in the residual malignant and benign breast tissu e compartment. A potential correlation between changes and the origina l p53 immunophenotype was examined as well. In 11 cases (18%), complet e pathologic remission with no residual tumor in the mastectomy specim en was achieved. This response was not correlated to the original p53 status. The remaining 50 cases showed residual tumor. The most promine nt histologic change was an increase in nuclear atypia of tumor cells (51% of the cases). This effect was independent of the presence or abs ence of nuclear p53 accumulation in the pre-treatment specimens. Nucle ar atypia was frequently accompanied by tumor cell enlargement (in 49% of the cases). Most commonly, a tumor with relatively small cells pre sented with large epithelioid apocrine features after treatment. In 6 cases (13%), the mitotic rate decreased significantly, while in 12 cas es (26%) the mitotic rate increased after chemotherapy. Elston histogr ades remained unchanged in 70% of the cases but increased in 17% and d ecreased in 13%, mainly due to changes in mitotic rates. Extensive tum or cell vacuolization, a common change seen after radiotherapy, was a minor finding but was seen focally. Within the non-malignant compartme nt, lobular atrophy with hyalinization and minimal epithelial atypia o f lobules and ducts were common. We conclude that changes in residual tumor and normal breast are common following systemic cytotoxic therap y. As neoadjuvant chemotherapy becomes mainstream management for local ly advanced breast cancer, pathologists are required to recognize trea tment induced changes. For correct histopathologic assessment, therapy induced morphologic alterations need to be distinguished from tumor-i ntrinsic morphologic features.