Aromatase inhibitors benefit certain premenopausal women with early breast cancer
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Aromatase inhibitors may reduce breast cancer recurrence compared with tamoxifen for certain premenopausal women with breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
Researchers observed this benefit for women treated with ovarian suppression for ER-positive early-stage disease.
“We know that tamoxifen reduces the 15-year breast cancer mortality rate by one-third in ER-positive disease,” Rosie Bradley, BSc, MSc, medical statistician in the clinical trial service unit at University of Oxford, said during a presentation. “Aromatase inhibitors are even more effective than tamoxifen for postmenopausal women but are ineffective for premenopausal women. However, aromatase inhibitors may benefit premenopausal women if treated with ovarian suppression.”
Bradley and colleagues performed a meta-analysis of data from four randomized trials — ABCSG 12, TEXT, SOFT and HOBOE — that included 7,030 premenopausal women with ER-positive early-stage breast cancer. All women had received ovarian suppression, and 40% of women had node-positive disease.
Researchers randomly assigned the women to an aromatase inhibitor or tamoxifen.
Breast cancer recurrence and cause-specific mortality served as primary outcomes.
Median follow-up for all four trials was 8 years.
Results showed a reduced risk for recurrence among women treated with aromatase inhibitors compared with tamoxifen (14.7% vs. 17.5%). Aromatase inhibitor combined with ovarian suppression reduced the risk for breast cancer recurrence by 21%.
“We observed the main benefit of aromatase inhibitors on recurrence from [baseline] to year 4 of treatment — the period when treatments differed,” Bradley said. “There was either no further benefit or a loss of benefit during years 5 to 9 of treatment and little follow-up beyond year 10.”
Researchers observed a significant reduction in the rate of distant recurrence with aromatase inhibitors (rate ratio = 0.83; 95% CI, 0.71-0.97).
“We did not observe a difference in mortality rates between the treatment groups, but we did observe a trend toward fewer breast cancer deaths from baseline to year 4 with tamoxifen, then fewer breast cancer deaths in years 5 to 9 with aromatase inhibitors,” Bradley said. “This shows the importance of longer-term follow-up in these trials to fully assess the effects of breast cancer mortality.”
Results of subgroup analyses by any recurrence showed proportional reduction in recurrence did not vary by age, BMI, tumor size or grade, histologic subtype, or the presence or absence of chemotherapy.
“We did observe an unexpected trend toward diminishing efficacy with increasing nodal involvement with aromatase inhibitors, with no benefit of aromatase inhibitors among those with N4-positive disease,” Bradley said. “Using aromatase inhibitors rather than tamoxifen in premenopausal women receiving ovarian suppression reduced the risk for breast cancer and reduced the risk for distant recurrence, but there was no effect on breast cancer mortality or OS. Longer follow-up is needed.”
Perspective
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This study raised the question regarding the role of ovarian suppression and/or aromatase inhibitors for women with premenopausal breast cancer. It is important to note that within the four trials included in this study, there were different choices of ovarian suppression, including zoledronic acid. The choice of aromatase inhibitor also differed among the studies. Despite the improvement in breast cancer recurrence with ovarian suppression and an aromatase inhibitor, the combination did not translate into an improvement in breast cancer mortality. It also is important to think about survivorship. For those treated with aromatase inhibitors, there is a risk for increased fractures, and what about future cardiovascular risk? Weighing aspects of survivorship into discussions with patients is essential.
University of Minnesota
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Bradley R, et al. Abstract GS2-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 7-10, 2021; San Antonio.
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