Radiotherapy Benefit in Young Women With Node-Positive Breast Cancer May Vary by Intrinsic Subtypes


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Tinne Laurberg, MD

Radiation therapy appears to significantly decrease local recurrence in premenopausal women with node-positive and luminal A tumors, based on an analysis of two small but independent randomized series reported at the 2013 European Cancer Congress in Amsterdam.1

“Though not definitive, our study suggests that these biologically slow-growing luminal A tumors may obtain the greatest benefit from regional radiotherapy. Thus, radiation should not be omitted in young patients with high-risk tumors,” said Tinne Laurberg, MD, of Aarhus University Hospital, Denmark.

Study Design

Luminal A tumors are associated with good prognosis but carry substantial risk for late locoregional relapse. The study tested the predictive value of intrinsic subtypes (as defined by the PAM50 classifier) for benefit from adjuvant radiation therapy among premenopausal women with node-positive tumors. Tumors were classified as luminal A, luminal B, HER2-enriched, basal-like, and normal-like.

Tumor samples (n = 232) were derived from two independent postmastectomy randomized adjuvant radiation trials with more than 20 years of follow-up—the British Columbia Randomized Radiation Trial (1979–1986)2 and the Danish Breast Cancer Group protocol 82b (1982–1989).3 In both trials, patients received adjuvant CMF (cyclophosphamide, methotrexate, fluorouracil) and were randomly assigned to postmastectomy radiation therapy or no radiotherapy. In the British Columbia trial, patients with estrogen receptor–positive tumors were re-randomized to receive oophorectomy, and 42 of them were included in this correlative study.

Both trials showed that radiation therapy lowered the incidence of locoregional recurrence and improved overall survival, in comparison to adjuvant chemotherapy alone.

In the current analysis by intrinsic subtypes, patients with luminal A tumors had the greatest benefit for local control. Basal-like tumors appeared to derive some benefit, which warranted further investigation. Luminal B and HER2-enriched subtypes had few patients, and therefore limited power excluded the potential benefit, Dr. ­Laurberg reported.

In patients with luminal A tumors, locoregional recurrence-free rates were 90% with radiotherapy and 59% without (P = .04) in the British Columbia trial and 92% vs 50%, respectively
(P = .01), in the Danish trial. In patients with basal-like tumors, locoregional recurrence-free rates were 86% vs 36% (P = .03) and 60% vs 51%, respectively (P = .35), in the two trials.

Differences between the treatment arms were not statistically significant for the other subtypes. No differences in overall survival were observed in any of the comparisons.

“Intrinsic subtype based on PAM50 is predictive for radiation therapy benefit among premenopausal high-risk patients, with radiation therapy lowering the incidence of locoregional recurrence among luminal A patients,” Dr. Laurberg concluded. “In this subanalysis within each subtype, the effect is clear, especially in luminal A tumors and maybe also in basal-like tumors. Radiotherapy is protective in luminal A tumors, with survival free of locoregional relapse in 90% of patients after 20 years, but for luminal B tumors there were no statistical significant differences observed for locoregional recurrence after radiotherapy compared to the control arm. For basal-like breast cancer, the protective effect of radiotherapy was seen only in the British Columbia cohort,” she added.

“Depending on confirmation, intrinsic subtyping may be useful to predict patients who may benefit from adjuvant radiation therapy,” Dr. Laurberg suggested. ■

Disclosure: Dr. Laurberg reported no potential conflicts of interest.

References

1. Laurberg T, Tramm T, Gelmon K, et al: 2013 European Cancer Congress. Abstract 1850. Presented September 28, 2013.

2. Ragaz J, Jackson SM, Le N, et al: N Engl J Med 337:956-962, 1997.

3. Marie Overgaard M, Hansen PS, Overgaard J, et al: N Engl J Med 337:949-955, 1997


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