Challenges in the treatment of breast cancer brain metastases: evidence, unresolved questions, and a practical algorithm.

Breast cancer is the leading cause of brain metastases in women. Large randomized clinical trials that have evaluated local therapies in patients with brain metastases include patients with brain metastases from a variety of cancer types. The incidence of brain metastases in the breast cancer population continues to grow, which is, aside from the rising breast cancer incidence, mainly attributable to improvements in systemic therapies leading to more durable control of extracranial metastatic disease and prolonged survival. The management of breast cancer brain metastases remains challenging, even more so with the continued advancement of local and highly effective systemic therapies. For most patients, a metastases-directed initial approach (i.e., radiation, surgery) represents the most appropriate initial therapy. Treatment should be based on multidisciplinary team discussions and a shared decision with the patients taking into account the risks and benefits of each therapeutic modality with the goal of prolonging survival while maintaining quality of life. In this narrative review, a multidisciplinary group of experts will address challenging questions in the context of current scientific literature and propose a therapeutic algorithm for breast cancer patients with brain metastases.

Does overall treatment time impact on survival after whole-brain radiotherapy for brain metastases?

PURPOSE To evaluate whether reduced overall treatment time (OTT), i.e., administration of more than 5 fractions per week, or uncompensated treatment interruption resulting in increased OTT influences survival of patients treated with whole-brain radiotherapy (WBRT) for brain metastases. METHODS Retrospective multi-institutional intention-to-treat study including 233 patients treated with primary WBRT (prescribed dose 10 fractions of 3 Gy; no previous SRS or surgery) administered over 10-38 days. Four groups were studied: OTT 10-11 vs. 12 days, 13-15 or >15 days. RESULTS Fourteen patients (6%) failed to complete WBRT and received 3-9 fractions (median 7). Their median survival was 0.5 months as compared to 3 months in patients who completed WBRT. No significant impact of OTT on survival was found. Median survival was 1.5, 2.9, 3.0 and 3.1 months in the four groups mentioned above. CONCLUSIONS Compensation for unintended treatment interruption is generally recommended but might not always be feasible. Depending on histological tumour type or expected repopulation, prognostic factors and neurological status, it might be acceptable to complete an interrupted course of WBRT without compensation in selected patients. While survival might be largely independent from OTT, it should also be evaluated whether this parameter has any impact on quality of life and duration of palliation.