In the Journals

Patients with luminal A breast cancer may not benefit from radiation therapy

Patients with low-risk luminal A breast cancer may not need radiation therapy following breast-conserving surgery due to their low risk for ipsilateral breast relapse, according to retrospective study results.

There has been uncertainty as to whether patients with the lowest risk of local disease recurrence should undergo radiotherapy postoperatively, and, thus, most women still receive the additional treatment, according to study background.

Anthony W. Fyles, MD, FRCPC, a professor in both the department of radiation oncology and the department of obstetrics and gynecology at the University of Toronto and a staff physician at Princes Margaret Cancer Center, and colleagues sought to determine the prognostic and predictive value of subtyping using certain biomarkers for ipsilateral breast relapse. The goal was to identify the need for radiation therapy in a cohort of women with breast cancer who had a low risk for relapse.

Researchers conducted immunohistochemical biomarker analyses for ER, PR, HER-2, cytokeratin 5/6, EGFR and Ki-67 expression in 501 subtyped patients enrolled on the Toronto-British Columbia Trial between 1992 and 2000 who received tamoxifen with or without radiation therapy.

Based on these data, researchers then reclassified patients as luminal A (n = 265); luminal B (n = 165); or the high-risk subtypes luminal HER-2 (n = 22), HER-2 enriched (n = 13), basal like (n = 30), or triple-negative nonbasal (n = 6).

Median follow-up was 10 years.

Overall, these disease classifications predicted the risk for ipsilateral breast relapse. Ten-year ipsilateral breast relapse estimates were 5.2% for luminal A, 10.5% for luminal B and 21.3% for high-risk subtypes (P < .001).

Fyles and colleagues noted that the luminal subtypes derived a lesser benefit from radiation therapy (HR = 0.4 for luminal A; 95% CI, 0.12-1.29; HR = 0.51 for luminal B; 95% CI, 0.19-1.36) than the high risk subtypes (HR = 0.13; 95% CI, 0.03-0.54). However, the overall interaction was not significant.

In an exploratory analysis of 151 women with clinically low-risk luminal A breast cancer aged 60 years or older with T1 and grade 1 or grade 2 tumors, the 10-year rate for ipsilateral breast relapse was 3.1% (95% CI, 1.2-8.2) compared with 11.8% (95% CI, 8.6-16.1) in the high-risk group (n = 341; P = .0063).

Patients with clinically low-risk luminal A treated with tamoxifen demonstrated a 10-year ipsilateral breast relapse rate of 1.3% (95% CI, 0.2-9.1), whereas women who received tamoxifen and radiation demonstrated a 5% (95% CI, 1.6-15.0) relapse rate.

Results of a multivariable analysis indicated ipsilateral breast relapse had a clinically significant association with radiotherapy (HR = 0.31; P < .001), clinical risk group (HR = 2.2; P = .025) and luminal A subtype (HR = 0.25; P < .001).

“We validated the prognostic impact of immunohistochemical subtyping on breast cancer relapse,” Fyles and colleagues wrote. “However, we did not confirm that intrinsic subtyping was predictive for radiotherapy response, because the treatment-subtype interaction term was not significant. This suggests that the low absolute benefit from breast radiotherapy in the luminal subtypes was likely a result of the smaller number of relapses in this group.”

The researchers identified low event rates in patients with early-stage disease as a study limitation that limited the strength of the study conclusions. Further, patients did not undergo anti–HER-2 therapy, which, if used, could have affected the data outcomes.

In an accompanying editorial, Jennifer R. Bellon, MD, senior physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of radiation oncology at Harvard Medical School in Boston, wrote that the study conducted by Fyles and colleagues is a “positive step forward” in answering the question about omitting radiotherapy in a certain cohort of patients.  

“This study … paves the way for other prospective initiatives using the tumor’s biologic identity to select patients with such low risk of local recurrence that radiation therapy can be avoided without adversely affecting survival,” Bellon wrote. “Overtreatment remains a significant issue in the adjuvant management of treatment for women with early-stage breast cancer. Ideally, increasingly sophisticated characterization of each individual tumor will permit tailoring of treatment more closely to each patient; in doing so, it may allow for the omission of radiation therapy in those who are unlikely to benefit. The new frontier of personalized radiation oncology for breast cancer is in sight.” – by Anthony SanFilippo

Disclosure: Fyles reported consultant/advisory roles with Genomic Health. The other researchers reported stock ownership in, research funding and travel expenses from Bioclassifier, Johnson & Johnson and NanoString Technologies. Bellon reports no relevant financial disclosures.

Patients with low-risk luminal A breast cancer may not need radiation therapy following breast-conserving surgery due to their low risk for ipsilateral breast relapse, according to retrospective study results.

There has been uncertainty as to whether patients with the lowest risk of local disease recurrence should undergo radiotherapy postoperatively, and, thus, most women still receive the additional treatment, according to study background.

Anthony W. Fyles, MD, FRCPC, a professor in both the department of radiation oncology and the department of obstetrics and gynecology at the University of Toronto and a staff physician at Princes Margaret Cancer Center, and colleagues sought to determine the prognostic and predictive value of subtyping using certain biomarkers for ipsilateral breast relapse. The goal was to identify the need for radiation therapy in a cohort of women with breast cancer who had a low risk for relapse.

Researchers conducted immunohistochemical biomarker analyses for ER, PR, HER-2, cytokeratin 5/6, EGFR and Ki-67 expression in 501 subtyped patients enrolled on the Toronto-British Columbia Trial between 1992 and 2000 who received tamoxifen with or without radiation therapy.

Based on these data, researchers then reclassified patients as luminal A (n = 265); luminal B (n = 165); or the high-risk subtypes luminal HER-2 (n = 22), HER-2 enriched (n = 13), basal like (n = 30), or triple-negative nonbasal (n = 6).

Median follow-up was 10 years.

Overall, these disease classifications predicted the risk for ipsilateral breast relapse. Ten-year ipsilateral breast relapse estimates were 5.2% for luminal A, 10.5% for luminal B and 21.3% for high-risk subtypes (P < .001).

Fyles and colleagues noted that the luminal subtypes derived a lesser benefit from radiation therapy (HR = 0.4 for luminal A; 95% CI, 0.12-1.29; HR = 0.51 for luminal B; 95% CI, 0.19-1.36) than the high risk subtypes (HR = 0.13; 95% CI, 0.03-0.54). However, the overall interaction was not significant.

In an exploratory analysis of 151 women with clinically low-risk luminal A breast cancer aged 60 years or older with T1 and grade 1 or grade 2 tumors, the 10-year rate for ipsilateral breast relapse was 3.1% (95% CI, 1.2-8.2) compared with 11.8% (95% CI, 8.6-16.1) in the high-risk group (n = 341; P = .0063).

Patients with clinically low-risk luminal A treated with tamoxifen demonstrated a 10-year ipsilateral breast relapse rate of 1.3% (95% CI, 0.2-9.1), whereas women who received tamoxifen and radiation demonstrated a 5% (95% CI, 1.6-15.0) relapse rate.

Results of a multivariable analysis indicated ipsilateral breast relapse had a clinically significant association with radiotherapy (HR = 0.31; P < .001), clinical risk group (HR = 2.2; P = .025) and luminal A subtype (HR = 0.25; P < .001).

“We validated the prognostic impact of immunohistochemical subtyping on breast cancer relapse,” Fyles and colleagues wrote. “However, we did not confirm that intrinsic subtyping was predictive for radiotherapy response, because the treatment-subtype interaction term was not significant. This suggests that the low absolute benefit from breast radiotherapy in the luminal subtypes was likely a result of the smaller number of relapses in this group.”

The researchers identified low event rates in patients with early-stage disease as a study limitation that limited the strength of the study conclusions. Further, patients did not undergo anti–HER-2 therapy, which, if used, could have affected the data outcomes.

In an accompanying editorial, Jennifer R. Bellon, MD, senior physician at Dana-Farber Cancer Institute and Brigham and Women’s Hospital and an assistant professor of radiation oncology at Harvard Medical School in Boston, wrote that the study conducted by Fyles and colleagues is a “positive step forward” in answering the question about omitting radiotherapy in a certain cohort of patients.  

“This study … paves the way for other prospective initiatives using the tumor’s biologic identity to select patients with such low risk of local recurrence that radiation therapy can be avoided without adversely affecting survival,” Bellon wrote. “Overtreatment remains a significant issue in the adjuvant management of treatment for women with early-stage breast cancer. Ideally, increasingly sophisticated characterization of each individual tumor will permit tailoring of treatment more closely to each patient; in doing so, it may allow for the omission of radiation therapy in those who are unlikely to benefit. The new frontier of personalized radiation oncology for breast cancer is in sight.” – by Anthony SanFilippo

Disclosure: Fyles reported consultant/advisory roles with Genomic Health. The other researchers reported stock ownership in, research funding and travel expenses from Bioclassifier, Johnson & Johnson and NanoString Technologies. Bellon reports no relevant financial disclosures.