Primary systemic therapy in operable breast cancer: clinical data and biological fall-out.

Primary systemic chemotherapy (PST) was first used in early 1970s for the treatment of locally advanced breast cancer; in this setting primary chemotherapy was administered to allow for radical surgery and the objective response rates were high with a substantial proportion of patients amenable to surgery. On the basis of this activity, PST was subsequently used to treat operable locally advanced or large primary tumors to increase the rate of conservative surgery. First generation clinical trials demonstrated that breast conservation rates were improved, that a proportion of patients experienced a complete pathologic response and that response to PST was a good predictor of long term outcome. Second generation of clinical trials were designed to compare PST to postoperative adjuvant chemotherapy: here again the rate of conservative surgery was significantly improved and the pathologic response rate demonstrated its prognostic value, however no progression free or survival improvement was obtained in comparison with postoperative treatments. Another interesting observation from these trials was that some tumor parameters (histology, grade, hormone receptor status) can predict the likelihood of achieving a pathologic complete response. On the basis of these data, PST can now be considered the standard of care for locally advanced disease, an reasonable option in case of large primary breast tumors not eligible for conservative surgery and an acceptable alternative for all the patients who are candidate to adjuvant treatment. It however clear that PST represents an excellent in vivo model to test new regimens, to evaluate biomarkers with predictive value and to evaluate the treatment induced modifications in tumor biology. Availability of new technologies able to measure the expression of thousands of genes and of new molecularly directed drugs will increase further the interest in this treatment strategy.