SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. It is estimated that approximately 300,590 new cases of breast cancer will be diagnosed in 2023 and about 43,700 individuals will die of the disease, largely due to metastatic recurrence. Breast cancer is the second leading cause of cancer death in women, in the U.S. About 70% of breast tumors express Estrogen Receptors and/or Progesterone Receptors, and HR-positive/HER2-negative breast cancer is the most frequently diagnosed molecular subtype. About 90% of all breast cancers are detected at an early stage, and these patients are often cured with a combination of surgery, radiotherapy, chemotherapy, and hormone therapy.
It has been hypothesized that estrogen in breast cancer acts as a catalyst/promoter for cancer growth, by stimulating the division and proliferation of breast tissue and increasing the risk for cancer causing mutations. A recently published study (Nature 2023;618:1024–1032) suggests that estrogen might be involved in the genomic reshuffling that gave rise to cancer-gene activation in breast cancer, acting as an initiator as well.
The researchers in this study postulated that suppressing ovarian function of women with breast cancer may improve outcome by preventing estrogenic stimulation of any residual/microscopic cancer, particularly among pre-menopausal women with Estrogen Receptor (ER)-positive tumors. To further clarify this benefit, the researchers from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials, that compared ovarian ablation or suppression with no ovarian ablation or suppression. Primary analyses included only premenopausal women age less than 55 years, with ER-positive or unknown tumors, stratified into those who received no chemotherapy, or remained premenopausal following chemotherapy, and those whose menopausal status following chemotherapy was not ascertained.
The following observations were noted from this meta-analysis:
–Fewer breast cancer recurrences were seen overall with ovarian ablation/suppression than control (RR=0.82, P< 0.0001).
• Among women receiving no chemotherapy or remaining premenopausal after chemotherapy (N=7,213), similar benefits were seen and the reduction in recurrent breast cancer was significant with ovarian ablation/suppression than control. The breast cancer recurrence rate at 15 years was 39.3% in the control group versus 29.5% in the ovarian ablation or suppression group, with an absolute benefit of 9.8% and a Rate Ratio (RR) of 0.71 (P<0.0001).
• Breast cancer mortality and all-cause mortality in the ovarian ablation or suppression group at 15 years, were improved by 8.0% (20.9% versus 28.9%; RR 0.69, P<0.0001) and 7.2% (26.0% versus 33.1%; RR = 0.73, P< 0.0001), respectively, with no increase in deaths without recurrence (RR = 0•88, P=0.33).
• Among those women who were premenopausal before chemotherapy and whose menopausal status was uncertain after chemotherapy (N=7,786), the rate of recurrence at 15 years was 43.1% in those who received ovarian ablation/suppression and 44.4% in the control group (RR=0.91; P =0.03).
• Recurrence reductions were significantly larger among premenopausal women under 45 years, than among those 45-54 years, and did not differ significantly by tumor characteristics. Among premenopausal women under 45 years (N=4,437), the recurrence rate was 41.3% in the control group and 30.4% with ovarian ablation or suppression, representing a 15-year benefit of 10.9% and a Rate Ratio of 0.66 (P<0.00001). Among those women 45-54 years (N=2,776), the recurrence rate was 36.1% in the control group and 28.6% with ovarian ablation or suppression, suggesting a 15-year benefit of 7.5% and Rate Ratio of 0.82 (P=0.02).
• Among those taking Tamoxifen, the benefit with ovarian ablation or suppression was less, and was only 4.5% (RR = 0.80; P =0.002).
The authors concluded that ovarian ablation or suppression in pre-menopausal women less than 45 years with ER-positive breast cancer, substantially reduces the 15-year risk of recurrence and death from breast cancer, without increasing mortality from other causes.
Effects of ovarian ablation or suppression on breast cancer recurrence and survival: Patient-level meta-analysis of 14,993 pre-menopausal women in 25 randomized trials. Gray RG, Bradley R, Braybrooke J, et al. J Clin Oncol 41, 2023 (suppl 16; abstr 503)
