Combination of Modern Radiotherapy and New Targeted Treatments for Breast Cancer Management

SIMPLE SUMMARY: Since the introduction of hormone therapy for the treatment of breast cancer (BC) three decades ago, many new targeted therapies have been developed. Some of them are currently used, such as HER2 inhibitors, while others are still under development, such as cell cycle (CDK) inhibitors, immune checkpoint (PD1/PDL1) inhibitors, or molecules acting on DNA damage (PARP) repair. Besides this, radiation therapy (RT) is commonly used either as adjuvant treatment for early BC after breast conservative surgery or in palliative intent for the treatment of metastatic sites. Our research has shown that the combinations of the most commonly used targeted treatments and RT were feasible with a few toxicities. Nevertheless, most of the knowledge on this subject is based on retrospective studies and a small number of patients and care should be taken in this setting until these results would be confirmed in prospective randomized studies. ABSTRACT: Background: The objective of the present study was to review the essential knowledge about the combinations of the most commonly used or under development targeted treatments and radiation therapy (RT). Methods: Preclinical and clinical studies investigating this combination were extensively reviewed. Results: Several studies showed that the combination of RT and tamoxifen increased the risk of radiation-induced pulmonary toxicity; therefore, both modalities should not be given concomitantly. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and RT seems to be safe. However, trastuzumab emtansine (T-DM1) should not be administered concurrently with brain RT since this combination could increase the risk of brain radionecrosis. The combination of RT and other new target treatments such as selective estrogen receptor degradants, lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but was essentially evaluated on retrospective or prospective studies with a small number of patients. Furthermore, there is considerable heterogeneity among these studies regarding the dose and fractionation of radiation, the dosage of drugs, and the sequence of treatments used. Conclusions: The combination of RT with most targeted therapies for BC appears to be well-tolerated, but these results need to be confirmed in prospective randomized studies.