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Ovarian suppression plus tamoxifen reduced breast cancer recurrence in high-risk young women
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The addition of ovarian suppression to tamoxifen reduced breast cancer recurrence among young women with early-stage, HR-positive disease who did not reach menopause after chemotherapy, according to results of a randomized phase 3 study presented at the San Antonio Breast Cancer Symposium.
A secondary analysis showed ovarian suppression in combination with the aromatase inhibitor exemestane further reduced recurrence.
“I believe this is a practice-changing trial,” Prudence Francis, MD, head of breast medical oncology at Peter MacCallum Cancer Centre in Melbourne, Australia, said during a press conference. “It doesn’t answer every question that we have in premenopausal women, but if I see a woman under age 35 with hormone-sensitive breast cancer, I will know what to advise that woman.
“For women who have not reached menopause and have hormone receptor-positive breast cancer that carries sufficient risk of recurrence that they receive chemotherapy, physicians are likely to discuss the option of treatment with ovarian suppression plus an aromatase inhibitor,” Francis added.
Tamoxifen is the standard adjuvant hormonal treatment for premenopausal women with hormone receptor-positive early breast cancer, but the benefit of adding ovarian function suppression to adjuvant treatment has been unclear.
In the SOFT trial, Francis and colleagues assessed the benefit of adding ovarian function suppression treatment to adjuvant tamoxifen in premenopausal women with hormone receptor-positive early breast cancer. As a secondary component of the study, the investigators evaluated the effect of ovarian suppression plus exemestane in this patient population.
Researchers evaluated 3,047 premenopausal women with ER-positive and/or PR-positive early breast cancer.
A little more than half of patients in the cohort underwent chemotherapy and remained premenopausal after completion. They entered the trial within 8 months of chemotherapy completion. The cohort also included women who were chemotherapy-naive, and they entered the trial within 12 weeks of surgery.
Researchers divided patients into three groups: 1,018 received 5 years of tamoxifen alone; 1,015 received tamoxifen plus ovarian suppression; and 1,014 received ovarian suppression plus exemestane.
The primary analysis compared DFS between those assigned to tamoxifen plus ovarian suppression vs. those assigned tamoxifen alone. Median follow-up was 5.6 years.
In the overall cohort, the addition of ovarian suppression to tamoxifen did not produce a significant DFS benefit (HR=0.83; 95% CI, 0.66-1.04).
Researchers then evaluated outcomes in all three treatment arms and stratified results based on whether patients had received chemotherapy.
Among those who underwent prior chemotherapy (mean age, 40 years), researchers observed a 22% (HR=0.78; 95% CI, 0.6-1.02) reduction in relative risk for recurrence among those who received tamoxifen plus ovarian suppression compared with those who received tamoxifen alone. The decrease — which was not statistically significant — equated to four or five fewer patients out of 100 developing recurrence within 5 years.
Researchers observed a 35% (HR=0.65; 95% CI, 0.49-0.87) reduction in relative risk for recurrence among those who received ovarian suppression plus exemestane compared with those who received tamoxifen alone. The decrease translated to seven or eight fewer patients out of 100 developing recurrence within 5 years.
Among all women aged younger than 35 years, the rate of 5-year breast cancer-free interval was higher among those who received ovarian suppression plus exemestane (83.4%; 95% CI, 74.9-89.3) compared with those who received tamoxifen plus ovarian suppression (78.9%; 95% CI, 69.8-85.5) or tamoxifen alone (67.7%; 95% CI, 57.3-76).
One in six women aged <35 years="" assigned="" exemestane="" and="" ovarian="" suppression="" developed="" further="" breast="" cancer="" within="" 5="" years,="" compared="" with="" one="" in="" three="" women="" who="" received="" tamoxifen="" alone.="">
The chemotherapy-naive cohort (mean age, 46 years) demonstrated high rates of 5-year breast cancer-free interval with all three treatment regimens: tamoxifen alone, 95.8%; tamoxifen plus ovarian suppression, 95.1% (HR=0.95; 95% CI, 0.54-1.69); and ovarian suppression plus exemestane, 97.1% (HR=0.59; 95% CI, 0.31-1.14).
Ovarian suppression increased menopausal symptoms, particularly in the first 2 years, but overall quality of life was not reduced, according to researchers. The combination of exemestane plus ovarian suppression affected sexual functioning.
Francis and colleagues intend to continue following patients enrolled in SOFT to monitor recurrence rates, late side effects and OS.
“It is crucial that we get longer follow-up in the SOFT study because we don’t have mature survival data,” Francis said.
Disclosure: The researchers report no relevant financial disclosures.