Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12–109 months). At 5 years, in-field LC was 99.2% (95% CI: 98–99.7); out-field LC 98.9% (95% CI: 97.4–99.6); DFS 96.2% (95% CI: 94.2–97.6); OS 98.6% (95% CI: 97.2–99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Management Strategies for Older Patients with Low-Risk Early-Stage Breast Cancer: A Physician Survey

When managing older patients with lower-risk hormone-receptor-positive (HR+), HER2 negative (HER2−) early-stage breast cancer (EBC), the harms and benefits of adjuvant therapies should be taken into consideration. A survey was conducted among Canadian oncologists on the definitions of “low risk” and “older”, practice patterns, and future trial designs. We contacted 254 physicians and 21% completed the survey (50/242). Most respondents (68%, 34/50) agreed with the definition of “low risk” HR+/HER2− EBC being node-negative and either: ≤3 cm and low histological grade, ≤2 cm and intermediate grade, or ≤1 cm and high grade. The most popular chronological and biological age definition for older patients was ≥70 (45%, 22/49; 45% 21/47). In patients ≥ 70 with low risk EBC, most radiation and medical oncologists would recommend post-lumpectomy radiotherapy (RT) and endocrine therapy (ET). Seventy-eight percent (38/49) felt that trials are needed to evaluate RT and ET’s role in patients ≥ 70. The favored design was ET alone, vs. RT plus ET (39%, 15/38). The preferred primary and secondary endpoints were disease-free survival and quality of life, respectively. Although oncologists recommended both RT and ET, there is interest in performing de-escalation trials in patients ≥ 70.

Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

Objective To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Scopus to 1 December 2020. Eligibility criteria for study selection Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors. Data extraction and synthesis Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival. Methods A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R 2 ) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes v breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival. Results 54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R 2 =0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R 2 =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms. Conclusion A lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

Cardiotoxicity among Patients Using Pertuzumab, Trastuzumab and Taxane with HER2-Positive Early-Stage Breast Cancer: A Single-Centre Experience

Aim: In this study, we aimed to investigate the incidence rate, risk factors, and mortality rates in patients with early-stage breast cancer using anti-HER2 (Human epidermal growth factor receptor-2) treatment. Patients and Methods: A total of 106 patients diagnosed with human epidermal growth factor 2 (HER2)-positive early-stage breast cancer and receiving anti-HER2 treatment at King Abdulaziz Medical City (KAMC) from 2015 to 2019 were included in the analysis to assess the incidence of cardiotoxicity was collected as a retrospective study. Univariate and multivariate analyses as well as multiple exact logistic regression analysis were conducted to understand the relationships between the left ventricular ejection fraction (LVEF) and treatment combinations and comorbidities Results: The LVEF measurements using an echocardiography method at the baseline (before any treatment) and during the anti-HER2 therapy were assessed. The results suggest that the higher the drug combination, the higher the odds ratio for the declined ejection fraction (EF) patient group. Further, patients treated with the pertuzumab and trastuzumab combination were four times more likely to have a decline in their EF than those who did not use the pertuzumab and trastuzumab drug combination (OR 4.28, 95% CI [1.68–10.91]). Conclusion: This study demonstrated that the drug combination considered here is associated with reduced LVEF and, similarly, comorbidities were also related to EF. However, a larger study in a global patient population will confirm the present observations.