Morphologic effects of neoadjuvant chemotherapy in locally advanced breast cancer

The use of chemotherapy as primary treatment in early and locally advanced breast cancer is rising. As a result, many resected tumors were exposed to cytotoxic drugs in vivo. To study resulting histopathologic changes, we examined 61 patients with locally advanced stage III breast cancer who had been treated with a standardized neoadjuvant polychemotherapy 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 tissue compartment. A potential correlation between changes and the original p53 immunophenotype was examined as well. In 11 cases (18%), complete pathologic remission with no residual tumor in the mastectomy specimen was achieved. This response was not correlated to the original p53 status. The remaining 50 cases showed residual tumor. The most prominent histologic change was an increase in nuclear atypia of tumor cells (51% of the cases). This effect was independent of the presence or absence of nuclear p53 accumulation in the pre-treatment specimens. Nuclear atypia was frequently accompanied by tumor cell enlargement (in 49% of the cases). Most commonly, a tumor with relatively small cells presented with large epithelioid apocrine features after treatment. In 6 cases (13%), the mitotic rate decreased significantly, while in 12 cases (26%) the mitotic rate increased after chemotherapy. Elston histogrades remained unchanged in 70% of the cases but increased in 17% and decreased in 13%, mainly due to changes in mitotic rates. Extensive tumor cell vacuolization, a common change seen after radiotherapy, was a minor finding but was seen focally. Within the non-malignant compartment, lobular atrophy with hyalinization and minimal epithelial atypia of lobules and ducts were common. We conclude that changes in residual tumor and normal breast are common following systemic cytotoxic therapy. As neoadjuvant chemotherapy becomes mainstream management for locally advanced breast cancer, pathologists are required to recognize treatment induced changes. For correct histopathologic assessment, therapy induced morphologic alterations need to be distinguished from tumor-intrinsic morphologic features.