Evaluation of Cardiotoxicity in HER-2-Positive Breast Cancer Patients Treated With Radiation Therapy and Trastuzumab.

PURPOSE: Trastuzumab is associated with cardiac dysfunction in patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. The current study examines the effect of radiation therapy (RT) on cardiotoxicity in this patient population. METHODS AND MATERIALS: The Herceptin Adjuvant (HERA) trial is a phase 3 prospective, randomized clinical trial that established the efficacy of trastuzumab in HER-2-positive breast cancer. The current study is a retrospective analysis of 3321 trial patients treated with trastuzumab, with or without RT. Cardiac function was closely monitored over a median follow-up period of 11 years. The primary endpoint of the current study was to determine the effect of RT on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events. RESULTS: Patients were divided into 3 groups: 1270 patients received trastuzumab and left-sided RT (group 1); 1271 patients received trastuzumab and right-sided RT (group 2); and 780 patients received trastuzumab with no RT (group 3). The incidence of decline in LVEF documented by echocardiography was 9.18%, 8.99%, and 8.80%, respectively, with no significant differences among the 3 groups (P = .073). The incidence of cardiovascular events was low in all groups, with the lowest incidence noted in group 3 (0.62%) followed by group 2 (0.92%) and group 1 (1.08%) (P = .619). Univariate and multivariate competing-risks regression showed that left-sided and right-sided RT delivery did not significantly increase the risk of LVEF decline or cardiovascular events. CONCLUSIONS: Our analysis of the HERA trial suggests that RT does not significantly increase the risk of cardiotoxicity in HER-2-positive breast cancer patients treated with trastuzumab. Continued monitoring of patients is needed to investigate late effects of contemporary treatments for breast cancer patients.

Post-mastectomy Radiation Therapy in Triple-Negative Breast Cancer Patients: Analysis of the BEATRICE Trial.

PURPOSE: Post-mastectomy radiation therapy (PMRT) improves locoregional control and overall survival in patients with breast cancer. With the evolution of systemic therapy, the benefit of PMRT in patients with triple-negative disease requires further evaluation. PATIENTS AND METHODS: BEATRICE is a phase III randomized clinical trial that examined the efficacy of bevacizumab in patients with triple-negative breast cancer (TNBC). The current study is a retrospective analysis of data on patients enrolled and treated with mastectomy and systemic therapy. The primary endpoint was determining the effect of PMRT on locoregional recurrence rates (LRR). Hazard ratios were estimated using Cox regression, and LRR curves were generated by the Kaplan-Meier method. RESULTS: In total, 940 patients were included in our analysis, of whom 359 (38.2%) received PMRT while 581 (61.8%) did not. At median follow-up of 5 years, no significant difference in LRR was noted between the PMRT and no PMRT groups in node-negative patients (HR = 1.09). Patients with N1 disease had 5-year LRR-free survival of 96% for PMRT versus 91% for no PMRT (HR = 0.46). Most N2 patients received PMRT and had 5-year LRR-free survival of 76%. CONCLUSION: PMRT benefit in TNBC patients treated with modern systemic therapy is lower than historical reports. Delivery of PMRT in patients with N1 disease enrolled in the BEATRICE trial was not shown to improve local control. As this might be due to patient selection for PMRT, future randomized controlled trials are required to assess the role of PMRT in this patient population.

Post-lumpectomy radiation therapy boost in breast cancer patients: evidence revisited.

PURPOSE: Radiation therapy is an integral part in the management of breast cancer after breast conservative surgery. In selected patients at high risk for local recurrence (LR), a boost radiation dose is commonly applied to the tumour bed. METHODS: We performed a review of the English literature using PubMed, Medline and Google Scholar for published manuscripts addressing the effect of boost radiation in breast cancer patients, focusing mainly on LR and overall survival (OS). RESULTS: A total of seven studies were included in our review. Most studies (6/7, 85.7%) showed a significant improvement in local control independent of age (hazard ratios ranging between 0.34 and 0.73), with the largest absolute benefit in younger patients. None of the studies, however, was able to demonstrate an improvement in OS. CONCLUSIONS: With lack of sufficient studies addressing the role of boost radiation, individualised treatment decisions are recommended, taking into account the risk factors for LR, including tumour biology. Real-life data are sorely needed to better assess the role of tumour bed boost in the contemporary era.

De-intensifying Radiation Therapy in HER-2 Positive Breast Cancer: To Boost or Not to Boost?

PURPOSE: Radiation therapy is fundamental in the management of breast cancer. After whole breast irradiation, an additional boost dose is often applied to the primary tumor bed. Here, we analyze the effect of radiation therapy boost on local control in patients with HER-2 positive breast cancer. METHODS AND MATERIALS: We studied 1082 patients with HER-2 positive breast cancer who were originally enrolled in the Herceptin Adjuvant Trial and treated with breast-conserving surgery, radiation therapy, and adjuvant chemotherapy with trastuzumab. The primary endpoint of the study was to determine the effect of a radiation boost on local recurrence. Kaplan-Meier curves were generated, and hazard ratios were estimated using Cox regression. RESULTS: Our analysis included 441 patients (40.8%) who received radiation therapy boost and 641 patients (59.2%) who did not, after completion of whole breast radiation. Patients from both groups had similar baseline characteristics in terms of age, nodal involvement, and grade. At a median follow-up of 11 years, local control was 93% (confidence interval, 90%-95%) in the radiation boost group compared with 91% (confidence interval, 89%-93%) in the no-boost group (P = .33). When analyzing patients by age, patients <40 years of age had a higher risk for local recurrence; however, this was not significantly lowered by the addition of boost. Furthermore, no local control benefit for boost was noted in both hormone receptor (HR) subtypes (HR+: P = .11; HR-: P = .98). CONCLUSIONS: Patients with HER-2 positive breast cancer treated with breast-conserving surgery, whole breast radiation, and trastuzumab have excellent local control. Delivery of an additional radiation boost in this patient population was not shown to improve local control. Future studies are needed to identify subgroups of HER-2 positive patients who derive a clinically relevant benefit from radiation boost.

Post-mastectomy radiation therapy in breast cancer patients with 1-3 positive lymph nodes: No one size fits all.

Post-mastectomy radiation therapy (PMRT) is standard therapy for advanced breast cancer. However, given the lower risk of recurrence, PMRT administration remains controversial in select patients with limited nodal disease. We performed a review of the literature that focuses on the effect of PMRT in breast cancer patients with 1-3 positive lymph nodes, mainly examining loco-regional recurrence (LRR) and overall survival (OS). Most studies, including a large meta-analysis by the EBCTCG, showed a significant improvement in LRR rates among patients receiving PMRT. While most studies demonstrated a trend towards OS improvement, only few studies showed a statistically significant OS or breast cancer-specific survival benefit for PMRT. As such, individualized treatment decisions are recommended, taking into consideration clinicopathological findings. Future studies with large sample sizes and long follow-up times are still needed to better assess the role of PMRT in patients with limited nodal involvement.