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Background: Pathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described., Methods: We performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose., Results: Out of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR., Conclusions: The factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates., (© 2024. The Author(s).)

Purpose/objective(s): It is currently unclear whether patients with low risk breast cancer receiving adjuvant endocrine therapy need adjuvant radiation therapy after breast conserving surgery. The data of randomized trials are available., Materials/methods: In a database search 5 randomized trials including in total 3766 mostly elderly patients with early stage breast cancer treated either with adjuvant endocrine therapy or with endocrine therapy and additional whole breast radiation after breast conserving surgery were identified. Published hazard ratios for time to local recurrence were the basis of our meta-analysis. Meta-analysis of the effect sizes on local recurrence was performed using a random effects model based on parameter estimates of log hazard ratios in Cox models and their standard errors. Furthermore, overall survival was examined., Results: Adjuvant hormone therapy alone in mostly older patients with low risk breast cancer resulted in significantly shorter time to local relapse compared to radiation therapy combined with hormone therapy (Hazard Ratio: 6.8, 95% CI: 4.23-10.93, p < 0.0001) . There was no significant difference for overall survival., Conclusion: Additional radiation therapy to hormone therapy did improve local relapse in breast cancer patients but did not show significant impact on overall survival.

Background: Adjuvant radiotherapy (RT) of regional lymph nodes (LN) in early breast cancer is still a matter of debate. RT increases the Overall survival (OS) rate of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved LN. The contribution of RT to regional LN to this improvement was poorly identified. Recently, the results of three large randomized trials addressing this question were published as full papers., Material and Methods: Published data of the MA.20 (n = 1832), the EORTC22922-10925 (EORTC) (n = 4004) trial and the French trial (n = 1334) were the foundation of this meta-analysis. Major eligibility criteria were positive i) axillary LN (all trials), ii) LN negative disease with high risk for recurrence (MA.20), and iii) medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial analyzed the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS)., Results: Regional RT of MS-LN and IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS [Hazard Ratio (HR) 0.88 (95 % CL 0.78 - 0.99)]. Adding results of the French trial and using a random effects model to respect the different design of the French trial, the effect on OS of regional RT remained significant [HR 0.90 (95 % CL 0.82 - 0.99)]. The absolute benefits in OS were 1 % in the MA.20 trial at 10 years, 1.6 % in the EORTC trial at 10 years, and 3.3 % in the French trial at 10 years (not significant in single trials). Regional RT of MS-LN and IM-LN (MA.20 and EORTC) yielded to a significant improvement of DFS [HR 0.86 (95 % CL 0.78 - 0.95)] and DMFS [HR 0.84 (95 % CL 0.75 - 0.94)]., Conclusion: Additional regional RT to the internal mammary and medial supraclavicular LN statistically significantly improved DFS, DMFS, and OS in stage I-III breast cancer.