Breast cancer subtype does not predict response to radiotherapy

Breast cancer subtype failed to predict response to radiotherapy after breast conservation surgery, according to an analysis of data from the Swedish Breast Cancer Group 91 Radiotherapy trial.

However, subtypes showed a trend toward certain effects. Radiation reduced risk for breast cancer death among triple-negative tumors, whereas HER-2-positive tumors appeared the most radioresistant.

Literature is discordant on how different breast cancer subtypes respond to radiation therapy. Further, studies have only evaluated the risk for recurrence after radiation, but not the effect of radiation, according to Martin Sjöström, MD, PhD student in the division of oncology and pathology at Lund University in Sweden, and colleagues.

“The addition of radiation primarily prevents ipsilateral breast tumor recurrences, but also reduced breast cancer deaths, as demonstrated in meta-analyses by the Early Breast Cancer Trialists’ Collaborative Group, where one breast cancer death was prevented at 15 years for every four recurrences avoided by year 10; however, the meta-analysis also suggests that approximately 70% of node-negative patients will suffer an ipsilateral breast tumor recurrence within 10 years with surgery alone, whereas approximately 10% suffer an ipsilateral breast tumor recurrence despite radiation therapy, thus implying overtreatment and undertreatment of patients,” the researchers wrote.

To evaluate the effect of adjuvant radiotherapy in different breast cancer subtypes, Sjöström and colleagues evaluated tumor tissue collected from 1,003 patients with node-negative, stage I and stage II breast cancer from the Swedish Breast Cancer Group 91 Radiotherapy trial, which assigned patients to breast conservation surgery with or without radiation between 1991 and 1997.

Ipsilateral breast tumor recurrence as the first event within 10 years served as the study’s primary endpoint.

In total, 958 patients had data available for subtyping; researchers classified these as luminal A like (n = 554), luminal B like (n = 259), triple negative (n = 81) and HER-2 positive (ER negative, n = 20; ER positive, n = 44).

Radiation therapy reduced the cumulative incidence of ipsilateral breast tumor recurrence as the first event after 10 years for luminal A-like tumors (19% vs. 9%; HR = 0.46; 95% CI, 0.29-0.74), luminal B-like tumors (24% vs. 8%; HR = 0.33; 95% CI, 0.16-0.65) and triple-negative tumors (21% vs. 6%; HR = 0.25; 95% CI, 0.05-1.12), but not HER-2-positive tumors (15% vs. 9%; HR = 1.29; 95% CI, 0.38-4.4).

However, researchers could not determine an overall difference in radiation effect between subtypes.

Radiation therapy reduced risk for breast cancer death among patients with triple-negative tumors (HR = 0.35; 0.12-1.05), but for no other subtype.

Because previous research showed radiation reduced the risk for ipsilateral breast tumor recurrence in a low-risk cohort — defined as ER positive, N0, and age 65 years or older — researchers evaluated whether subtyping enhanced this classification.

They found this group did not have a low risk for ipsilateral breast tumor recurrence. Radiation reduced the cumulative incidence of ipsilateral breast tumor recurrence at 10 years as the first event (20% vs. 6%; HR = 0.3; 95% CI, 0.11-0.81), but had no effect on breast cancer death (HR = 0.85; 95% CI, 0.41-1.76) or death from any cause (HR = 0.94; 95% CI, 0.67-1.34).

Researchers noted the low use of systemic adjuvant treatment might be a limitation of this analysis, in addition to the fact that the absolute effect of radiation may be smaller with modern treatment.

Although the study was large, it was not powered to detect differences in response between subgroups.

“Whereas we can see indications of variable radiation therapy effect on ipsilateral breast tumor recurrence between subtypes, this could not be statistically confirmed by an interaction test, and confirmatory studies are needed,” they wrote.

“Although additional large studies are needed to differentiate subgroups within triple-negative tumors and the luminal vs. nonluminal HER-2-positive tumors, our study indicates that subgroups of high-risk tumors respond differently to radiation therapy and that at least triple-negative and HER-2-postiive tumors should be analyzed separately,” they added. – by Alexandra Todak

Disclosures: Sjöström reports he has no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.