Timing of adjuvant systemic therapy and radiotherapy after breast-conserving surgery and mastectomy

In the last two decades, systemic adjuvant treatment for breast cancer, in association with radiotherapy, has been shown to prolong disease-free survival and overall survival in patients with operable breast tumors. So far, the optimal sequence of systemic therapy and radiotherapy for breast cancer patients after conservative surgery or mastectomy is unclear. Several retrospective analyses showed a possible detrimental effect on local regional recurrence rates when radiation therapy is delayed after chemotherapy. On the other hand, delaying chemotherapy after radiotherapy may increase the risk of distant failure and affect the survival. Concurrent administration of targeted treatment (e.g. non-anthracycline/taxane containing chemotherapy, trastuzumab, endocrine therapy) with radiotherapy is considered a valid option. A "tailored" approach on sequencing of chemotherapy and radiotherapy which takes into account various variables, such as histological and biological features of the tumor, as well as the patient status and the treatment modality is required in order to optimize the delivery of adjuvant treatments. This review focuses on the effects of timing of chemotherapy-radiotherapy and risks of relapse, in terms of locoregional and distant recurrence in patients with operable breast cancer.