Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study

Abstract

Background Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge. Methods From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02). Conclusion In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor’s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy

“…This classification stratifies BCA into various intrinsic subtypes through immunohistochemistry: Luminal A (ER and/or PR positive, Her-2 negative), Luminal B (ER and/or PR positive, Her-2 positive), Her-2 enriched (ER and PR negative, Her-2 positive), and TNBC (ER negative, PR negative, Her-2/neu negative) [43]. These subtypes exhibit unique gene expression profiles, dictating divergent clinical outcomes [44,45]. Her-2 positive and TNBC subtypes account for 20% and 25% of invasive breast cancers, respectively.…”

“…Conversely, TNBC patients, lacking ER, PR, and Her-2 expression, do not benefit from receptor-targeted therapies [52]. Comparative clinical analyses reveal that luminal subtype patients generally experience more favorable prognoses and overall survival compared to those with Her-2-positive and TNBC subtypes [44,45]. TNBC and Her-2-positive subtypes collectively constitute approximately 15-20% of all BCA cases [53,54].…”

“…CAR T-cell therapy emerges as a compelling therapeutic strategy, especially for patients with Her-2 enriched and TNBC, who typically face high metastasis rates, early recurrence, and poorer prognoses [44,45,91,92]. The receptors EphA-2 and IL-13Rα2 are notably overexpressed on tumor cells in these subtypes compared to normal epithelial cells, suggesting their potential as targets for CAR T-cell therapy [3,13,16,29,33,[93][94][95][96][97].…”