The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype

Abstract

The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2−/HR+), HER2-positive (HER2+)/HR+, and HER2−/HR-negative (HR−) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034–0.379; p < 0.001), 0.159 (95% CI 0.038–0.671; p = 0.017), and 0.243 (95% CI 0.088–0.676; p = 0.007), respectively, but not for the HER2+/HR− subtype (p = 0.468). We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.