Oncologists should take an individualized approach when making decisions about adjuvant endocrine therapies for premenopausal hormone receptor–positive, HER2-negative early breast cancer, suggests an analysis of a pair of randomized phase III trials published online in the Journal of Clinical Oncology.
Investigators led by Meredith M. Regan, Sc.D., of Dana-Farber Cancer Institute in Boston, analyzed data from the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials of adjuvant endocrine therapies, comprising a total of nearly 5,000 women.
Results suggested that the absolute improvement in the 5-year breast cancer–free interval rate with exemestane plus ovarian function suppression (OFS) versus tamoxifen with or without OFS ranged from less than 1% in women with a lowest recurrence risk based on clinicopathologic factors to 10%-15% in women with a highest risk.
“TEXT and SOFT demonstrated that premenopausal women with hormone receptor–positive disease benefit, on average, from exemestane plus OFS versus tamoxifen with or without OFS. However, individualized treatment decisions should weigh the benefits against the adverse effects and costs of these therapy options,” the investigators wrote.
“In the absence of predictive biomarkers, consideration of a patient’s prognosis, as illustrated by STEPP [Subpopulation Treatment Effect Pattern Plot] analysis of a composite measure of recurrence risk in the TEXT and SOFT populations, is integral to this decision making,” they added.
In the SOFT trial, women were randomized to 5 years of tamoxifen alone (as an active comparator), tamoxifen plus OFS, or exemestane (Aromasin) plus OFS. In the TEXT trial, women were randomized to 5 years of exemestane plus OFS or of tamoxifen plus OFS.
Dr. Regan and colleagues based their analyses on a total of 4,891 women. They assessed each patient’s composite recurrence risk from a Cox model that included a set of conventional clinicopathologic factors: age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. And they used STEPP methodology to assess the impact of endocrine therapy across groups having different risk.
The median duration of follow-up was 5.6 years in the SOFT trial and 6 years in the TEXT trial. Results showed that the 5-year breast cancer–free interval rate was 90.8% for the study cohort as a whole. But it ranged considerably from 98.6% for patients with composite risk in the lowest quartile to 77.5% for patients with composite risk in the highest quartiles, the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.3171).
In the SOFT population, patients who remained premenopausal after neoadjuvant or adjuvant chemotherapy had an absolute improvement of 5% or more in the 5-year breast cancer–free interval rate with exemestane plus OFS, compared with tamoxifen plus OFS or tamoxifen alone. The difference was 10%-15% for the subset at intermediate to high risk for recurrence.
In addition, a benefit of tamoxifen plus OFS over tamoxifen alone was evident in patients having the highest composite risk.
Among patients who were not given chemotherapy, who on average had the lowest composite recurrence risk, the 5-year breast cancer–free interval rate was excellent regardless of the endocrine therapy received.
In the TEXT trial population, the benefit of exemestane plus OFS over tamoxifen plus OFS in 5-year breast cancer–free interval rate ranged from 5% to 15%. Again, the patients who were not given chemotherapy, who had the lowest composite recurrence risk, fared well regardless of which endocrine therapy they received.
These findings should help guide clinical decisions in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, both at the extremes of risk and in the scenario of intermediate risk, where factors such as patient preference, tolerance, and cost play a greater role, according to the investigators.
“Further follow-up of TEXT and SOFT patients is essential to guide patient care,” they concluded.