Influence of the subtype on local recurrence risk of breast cancer with or without radiation therapy.

PURPOSE: To investigate if intrinsic subtypes of breast cancer predict different risks of ipsilateral breast tumor recurrence (IBTR) following breast-conserving surgery (BCS) with and without postoperative radiation therapy.

PATIENTS AND METHODS: We randomized 381 women with a unifocal T1N0M0 breast cancer to BCS alone (197 women) or BCS plus postoperative radiation therapy (XRT) (184 women). All available histopathological material was re-analyzed with modern immunohistochemical methods (223 women). After 20 years of complete follow-up we analyzed the risk of IBTR by intrinsic breast cancer subtypes (luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2-positive and triple negative). We used Cox regression analyses to estimate hazard ratios (HR) with 95% confidence intervals (CI).

RESULTS: In a multivariate analysis the luminal B/HER2-negative subtype, compared with the luminal A subtype, was associated with a higher risk of IBTR overall (HR 3.04; 95% CI 1.38-6.71) and in both the XRT-group (HR 5.08 95% CI 1.31-19.7) and the non-XRT-group (HR 2.58 95%CI 1.07-6.20); (p for interaction = 0.37). The risk of IBTR in the XRT- and non-XRT group, stratified by intrinsic subtype, revealed an absolute risk difference at 20 years to the benefit of XRT of 14% (95% CI 1.0%-26%) for luminal A, 17% (95% CI -6.0% to 39%) for luminal B/HER2 negative and 22% (95% CI -7.0-51%) for the high-risk group.

CONCLUSIONS: Among breast cancer patients treated with BCS, the luminal B/HER2-negative subtype predicts an about 3-fold higher risk for IBTR compared to other intrinsic subtypes independent of postoperative radiation therapy.