Investigation on the Benefit of PMRT in Women With High Risk N0 Breast Cancer

Abstract

Prior studies have shown that there are subsets of women with node-negative breast cancer with tumor-defined risk factors that portend a higher rate of locoregional recurrence (LR). These factors include lymph vascular invasion, tumor size, young age, close margins, or high tumor grade. Women who have ≥2 of these factors may benefit from post-mastectomy radiation therapy (PMRT). The general use of PMRT for women with node-negative (N0) breast cancer has been shown to be associated with decreased survival. However, providing PMRT to women at high risk of LR may result in a survival advantage. This study evaluates whether a survival benefit of PMRT can be observed in women under age 50 with high-risk N0 disease. The Surveillance, Epidemiology, and End Results database was searched for women age 20-49 diagnosed from 1990-2008 with N0 invasive breast cancer and treated with mastectomy. Multivariable proportional hazards survival analysis (MVA) assessed the association between cause specific survival (CSS) and the following factors: age, estrogen receptor (ER) or progesterone receptor (PR) expression, race, tumor size, histology, number of axillary lymph nodes removed, risk group, PMRT, and tumor grade. Risk groups were defined a priori according to number of factors associated with decreased survival on MVA as follows: high risk (tumor size >5.0cm, grade III-IV, and ER-negative and/or PR-negative, intermediate risk (1 or 2 high risk factors), and low risk (size ≤5cm, grade I-II, and ER- and PR-positive) groups. Interaction of PMRT and risk group was analyzed. A total of 7,226 patients were identified in the CSS analysis, of which 191 (2.6%) were high risk, 4,150 (57.4%) were intermediate risk, and 2,885 (40%) were low risk. Receipt of PMRT was 51.3%, 12.1%, and 7.8% in the risk groups, respectively. In the MVA, ER-negative (Hazard ratio [HR] = 1.31 [1.02-1.67] p = 0.03), PR-negative* (HR = 1.96[1.23-3.14] p = 0.005), black race (HR = 1.40 [1.10-1.78] p = 0.006) tumor size 2.1-5cm vs. ≤2cm (HR = 1.76 [1.46-2.11] p < 0.0001), tumor size >5cm vs. ≤2cm (HR = 2.00 [1.15-3.48] p = 0.01), and grade* (HR = 2.29 [1.32-3.98] p = 0.003) were associated with lower CSS (*PR-negative and grade were only associated with lower CSS after 2 years). In the interaction analysis of hazard ratios for risk, there is a lower survival for patients who had PMRT if they were intermediate risk (HR = 0.73 [0.55-0.97]). Patients in the low risk group had a trend toward lower survival with PMRT (HR = 0.59 [0.32-1.08]). Patients in the high-risk group had a trend toward improved survival with PMRT (HR = 2.13 [0.91-4.99]). Young women with N0 breast cancer who have large, high-grade tumors that do not express hormone receptors may benefit from PMRT.