Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.
The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.
The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.
Recently published research has supported hormone therapy targeting the ovaries in this population.
“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
Study methods and results
For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.
Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).
Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).
The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”
Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
Tamoxifen on its own seems to have powerful positive effect
The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.
The meta-analysis didn’t examine cost or cost-effectiveness.
Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.
Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.
“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”
According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”
It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.
No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.