Systemic treatment for locally advanced breast cancer: what we still need to learn after a decade of multimodality clinical trials.

Multimodality therapy of locally advanced breast cancer with initial chemo-(hormono)-therapy followed by locoregional treatment has become increasingly popular during the past decade. A paucity of large randomised clinical trials leaves the following unanswered questions: does systemic treatment impact on long-term control of distant metastases? What is the best treatment sequence? The most effective drug combination? The optimum treatment duration? Future prospects in the treatment of locally advanced breast cancer include the use of haematopoietic growth factors to increase the dose-intensity of neoadjuvant chemotherapy, the investigation of autologous bone marrow transplantation with high dose chemotherapy on a larger scale, the development of new approaches designed at interrupting the "autocrine loop" of breast cancer local growth factors and the introduction of diphosphonates in the adjuvant systemic therapy.