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

Jian-Hua Mao,Paul J Van Diest,Antoine M Snijders,Jesus Perez-Losada

doi:10.1038/s41598-017-12949-5

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.

Highlights

Breast cancer (BC) is the leading female malignancy and the second leading cause of cancer deaths in U.S women, with tumor metastasis being the underlying cause in most of these breast cancer related death[1,2]
We first investigated the demographic differences between patients that received radiotherapy versus those that did not using the METABRIC and TCGA data (Table 1)
Overall we found that patients who receive radiotherapy survive significantly longer compared to those who did not receive radiotherapy in both datasets (Figure S1; METABRIC: p = 0.007; TCGA: p = 1.12E-04)

Summary

Introduction

Breast cancer (BC) is the leading female malignancy and the second leading cause of cancer deaths in U.S women, with tumor metastasis being the underlying cause in most of these breast cancer related death[1,2]. Gene expression profiling has been used to classify breast cancers into different molecular subtypes[3,4,5,6]. Radiotherapy is a well-established adjuvant treatment modality following breast cancer surgery. Separating patients who benefit from those who do not benefit from radiotherapy remains challenging, and current clinical practice considers radiotherapy for all patients undergoing breast cancer surgery. The availability of large cancer genomic data sets in combination with clinical data allows for exploring unbiased approaches to identify patients that do and do not benefit from radiotherapy and biomarkers that can predict the response to radiotherapy. We combined two large breast cancer databases to address the impact of age at diagnosis and breast cancer molecular subtype on response to radiotherapy

Methods

Results

Conclusion