Revisiting the impact of age and molecular subtype on overall survival after radiotherapy in breast cancer patients

Abstract

Adjuvant radiotherapy (RT) in breast cancer (BC) is often used to eradicate remaining tumor cells following surgery with the goal of maximizing local control and increasing overall survival. The current study investigated the impact of age and BC molecular subtype on overall survival after RT using a meta-analysis of the METABRIC and TCGA BC patient cohorts. We found that RT significantly prolonged survival across the whole BC patient population. The survival benefit of RT was predominantly observed in stage II BC patients treated with breast conserving surgery. Patients were then stratified by age and molecular subtype to investigate survival rate associated with RT. An increase in survival for the luminal-A and basal BC molecular subtypes was observed after RT. Stratifying patients based on age revealed that increased survival was restricted to younger patients (≤60 years of age at diagnosis). There was a significant survival benefit of radiotherapy for younger patients with tumors of the luminal A and basal molecular subtypes. Patients with other breast tumor subtypes or older breast cancer patients did not seem to benefit effects of RT. Therefore, alternate local treatment strategies should be considered for older, luminal B, and HER2 driven BC patients.

Figure 1

Clinical stage and surgery significantly influence survival outcome after radiotherapy. (A) Kaplan-Meier overall survival meta-analysis of radiotherapy (RT) benefit in the combined METABRIC and TCGA cohort (N = 2948; p = 2.14E-04). (B) Influence of clinical stage on RT survival benefit. (C) Influence of surgery type (lumpectomy vs mastectomy) on RT survival benefit. (D) Combined effect of clinical stage and surgery type on RT survival benefit.

Figure 2

Interaction between molecular subtype and radiotherapy on overall survival in breast cancer patients by meta-analysis. Kaplan-Meier overall survival curves comparing survival for breast cancer patients who did and did not receive radiotherapy across different molecular subtypes: luminal-A (A), luminal-B (B), HER2 (C), basal (D). P-values were obtained using the log rank (Mantel-Cox) test.

Figure 3

Effect of radiotherapy on overall survival in younger breast cancer patients across different molecular subtypes. Kaplan-Meier overall survival curves comparing survival for breast cancer patients diagnosed at age ≤60 years (“young”) who did and did not receive radiotherapy across different molecular subtypes: luminal-A (A), luminal-B (B), HER2 (C), and basal (D) (METABRIC cohort). P-values were obtained using the log rank (Mantel-Cox) test.

Figure 4

Effect of radiotherapy on overall survival in older breast cancer patients across different molecular subtypes. Kaplan-Meier overall survival curves comparing survival for breast cancer patients diagnosed at age > 60 years (“old”) who did or did not receive radiotherapy across different molecular subtypes: luminal-A (A), luminal-B (B), HER2 (C), basal (D) (METABRIC cohort). P-values were obtained using the log rank (Mantel-Cox) test.