Several breast cancer experts said the findings of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis and the AERAS study are in line with data emerging from other studies of extended treatment with aromatase inhibitors. All of these studies suggest that extended aromatase inhibitor therapy lends a very small benefit except, perhaps, in patients with early breast cancer who have risk factors that increase their risk for recurrence.

Eleftherios (Terry) P. Mamounas, MD

Summing up the findings, Eleftherios (Terry) P. Mamounas, MD, Medical Director of the Comprehensive Breast Program, University of Florida Health Cancer Center, Orlando, said, “After tamoxifen, aromatase inhibitor therapy improves outcomes significantly. However, the benefit for an aromatase inhibitor following an aromatase inhibitor is modest.”

Dr. Mamounas noted that 5 years of letrozole after 5 years of aromatase inhibitor–based therapy also did not significantly prolong disease-free survival in the NRG Oncology/NSABP B-42 study, which he led.¹ NSABP B-42 was also mentioned in an interview with

William Sikov, MD

William Sikov, MD, Associate Director of Clinical Research at the Program in Women’s Oncology, Women and Infants Hospital of Rhode Island and Associate Professor of Medicine, Obstetrics, and Gynecology at the Warren Alpert Medical School, Brown University. “I tell my patients there was a 4% absolute improvement in events in NSABP B-42, but half of that was from reducing contralateral breast cancer, and the other half was from reducing ipsilateral occurrences. Although those things are not unimportant, they do not really affect survival. For a 1% reduction in distant recurrences, we are treating 100 patients with drugs that can cause some substantial toxicity, at least for some patients, to derive this very small benefit.”

Statistical Significance vs Clinical Significance

Dr. Sikov said the studies presented at the 2018 San Antonio Breast Cancer Symposium “shore up what we’ve been seeing in other studies: there is a small but real improvement with extended aromatase inhibitor therapy…. However, just because a difference is statistically significant, that does not mean it has clinical significance.”

Dr. Sikov continued: “For the most common patient—who starts on an aromatase inhibitor—there was no clear benefit to extending therapy beyond 5 years. You might pick and choose certain high-risk patients who might benefit and continue treatment if that patient is tolerating it without contraindications, such as worsening osteoporosis. But for the vast majority of my patients, I am stopping endocrine therapy at 5 years.”

Laura Esserman, MD

Laura Esserman, MD, Director of the University of California, San Francisco, Carol Franc Buck Breast Care Center, at the Mount Zion campus, agreed. “There is clearly a difference between statistical significance and clinical significance.” She finds it “remarkable” that so few women truly benefit from extended therapy and is hoping someday to have evidence to support which patients do, and which do not, benefit from additional therapy “from agents that clearly cause morbidity in many patients.” ■

DISCLOSURE: Dr. Mamounas is a consultant for -Genentech/Roche, Genomic Health, Biotheranostics, and Merck; and is on the speakers bureau for Genentech/Roche and Genomic Health. Dr. Sikov has served on the speakers bureau for Eli Lilly and Eisai. Dr. Esserman is a consultant/advisor for Blue Cross Blue Shield Association, has received research funding from Merck, and has received travel/accommodations/expenses from Blue Cross Blue Shield Association.

REFERENCE

1. Mamounas EP, Bandos H, Lembersky BC, et al: Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20:88-99, 2019.