Effect of Radiotherapy in Breast Cancer Similar Across Subtypes

Breast cancer subtypes generally did not respond differently to radiotherapy (RT) following breast-conserving surgery (BCS), according to long-term follow-up of a randomized trial. There was some indication that HER2-positive tumors were more resistant to RT than others, however.

“The literature is discordant on how different breast cancer subtypes respond to RT, and most prior studies have investigated the risk of recurrence after RT, but not the effect of RT,” wrote study authors led by Martin Sjöström, MD, of Lund University in Sweden.

The Swedish Breast Cancer Group 91 Radiotherapy trial randomized 1,003 patients with node-negative, stage I and II breast cancer to BCS with or without RT, between 1991 and 1997. Immunohistochemistry and in situ hybridization subtyping was performed on 958 tumors; results of the analysis were published online ahead of print in the Journal of Clinical Oncology.

The tumors were classified as either luminal A–like (554 patients), luminal B–like (259 patients), triple negative (81 patients), and HER2 positive (20 of whom were estrogen-receptor negative and 44 estrogen-receptor positive).

RT was effective in reducing the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) after 10 years in most of the subtypes. For luminal A–like tumors, the 10-year incidence of IBTR was 19% with RT and 9% without, for a hazard ratio (HR) of 0.46 (95% CI, 0.29–0.74; P = .001). For luminal B–like tumors, the 10-year incidence was 24% with RT and 8% without it, for an HR of 0.33 (95% CI, 0.16–0.65; P < .001). For triple-negative tumors, the rates were 21% and 6%, respectively, for an HR that did not reach significance of 0.25 (95% CI, 0.05–1.12; P = .083).

For HER2-positive tumors, this effect was not seen. The 10-year cumulative incidence of IBTR was 15% with RT and 19% without it, for an HR of 1.29 (95% CI, 0.38–4.40; P = .6). An overall difference in the effect of RT between subtypes was also not demonstrated (P = .21 for interaction). These results remained similar after adjustment for prognostic factors.

RT reduced the rate of breast cancer death from triple-negative tumors, with an HR of 0.35 (P = .06), but not for the other subtypes. Death from any cause was not significantly affected by RT in any of the subtypes.

The primary limitation of the study, the authors noted, was its power; though it was among the largest studies on this topic, it was not designed to detect differences in response between subgroups.

“Subtype was not predictive of response to RT, although in our study HER2-positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on [death from breast cancer],” they concluded. “The clinically presumed low-risk, luminal A–like tumors demonstrated an excellent effect from RT with sparse use of systemic therapy, and RT may be an alternative to endocrine therapy in selected cases.”