Site-specific effect of chemotherapy in patients with breast cancer

The efficacy of cytotoxic therapy in different anatomical sites can be studied by analyzing the anatomical distribution of recurrences following adjuvant therapy or the rate of response according to site of metastasis. Cumulated data from 7 adjuvant studies showed that the relative reduction in the rate of recurrence was 37% for local and regional recurrences versus 25% for distant metastases. There are only sparse and inconclusive data concerning the anatomical pattern of recurrence according to type of adjuvant chemotherapy. Thus, the majority of trials have not demonstrated significant differences in distribution of metastases in patients receiving different types of adjuvant systemic therapy. The available data on the rate of response in relation to metastatic site showed higher response rates in soft tissue metastases (55%), compared to visceral and bone metastases (40%). Cumulated data from 12 trials showed no differences in response rates between different soft tissue lesions (skin, subcutaneous tissue, lymph nodes, breast), or between metastases demonstrated by paraclinical tests (lung, liver, bone). However, there was a tendency for soft tissue lesions to have a higher response rate (55-60%) than visceral and bone metastases (31-44%). The reason for the observed differences is unknown. At the time of diagnosis soft tissue lesions may be smaller (with better blood supply) than visceral lesions. This might increase the likelihood of response, since experimental data show that the response rate is inversely correlated with tumour burden and tumour size. Another explanation is based on the hypothesis of site-specific clonal selection of tumour cells, which differ with respect to sensitivity to cytotoxic agents. However, the observed differences can also be ascribed to methodological errors or differences in assessing response of tumours at specific sites. Thus, the false positive response rate in soft tissue lesions, evaluated by physical examination, is approximately 20% compared with less than 10% in lung lesions evaluated by x-rays.