Chemotherapy-induced histologic changes in mastectomy specimens and their potential significance

The aim was to assess chemotherapy-induced histologic changes in breast cancer and to evaluate their relationship with tumour response, to treatment and patient survival. We examined paired pre- and post-chemotherapy tumour specimens from 57 patients with stages II and III breast cancers. All patients received three to four courses of anthracycline-containing preoperative treatment and subsequently underwent modified radical mastectomy 3-5 months after diagnosis. Histologic parameters evaluated included extent of residual disease and cytologic changes in residual tumour and in non-neoplastic breast tissue and lymph nodes. Correlation of pathologic changes with disease-free and overall survival was evaluated. Clinical evaluation indicated that 24% (n=14) of patients had a complete response, 53% (n=30) had a partial response, and 22% (n=13) had stable disease. Pathologic assessment revealed a complete response in 14% (n=8) of patients. Clinical and histologic complete responses were discordant in 35% of patients. Sixty-eight percent of tumours demonstrated moderate to severe cytologic changes in the cytoplasm and nucleus of neoplastic cells. These were characterized by increased overall cell size, cytoplasmic vacuolization, nuclear enlargement, multinucleation, and vesiculation of chromatin. Chemotherapy-induced histologic changes varied within a tumour and between patients. Tumour cytologic changes were significantly associated with histologic (p=0.03) as well as clinical (p=0.02) tumour response. Pathologic tumour response, but not histologic changes, was also a powerful predictor of overall survival and relapse-free survival. In the non-neoplastic glandular tissue, periductal and perilobular fibrosis and atrophy of lobular acini similar to those seen in postmenopausal breast tissue were noted. Changes in lymph nodes were characterized by lymphoid depletion and fibrosis with and without tumour metastasis. Chemotherapy-induced cytologic changes are frequently seen in neoplastic breast epithelium and correlate with response to treatment. Histologic confirmation of clinical tumour response to preoperative chemotherapy is necessary for accurate characterization of patients', response to treatment.