Adjuvant ovarian suppression for resected breast cancer: 2017 critical assessment

Abstract

Currently available data supporting adjuvant ovarian function suppression for resected breast cancer in premenopausal women in addition to standard chemotherapy and tamoxifen are not persuasive, even though an ASCO guideline supports them. Available information from the key trial, called ''SOFT,'' has only 5-year followup in a 15-year disease. It employs breast cancer events as an endpoint, rather than distant metastases, or better still, death from any cause. The small advantages reported to date may disappear when aromatase inhibitors are given after the occurrence of menopause in the control population. Caution should be exercised in recommending ovarian suppression in all but the highest-risk situations.

Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer—A Single-Center Analysis

“…OSA has the advantages of reducing E2 production more extensively and irreversibly, reducing ovarian androgen production and lowering ovarian cancer risk. Vogl et al advised that support for ovarian ablation is derived from studies that have many limitations, and that ovarian ablation should therefore not be performed except in situations with the highest risk [18]. The Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), upon which the American Society of Clinical Oncology (ASCO) guidelines are based, selected post-chemotherapy patients only if they had functional ovaries and tested positive for hormone receptors, overcoming the limitations of previous studies [18].…”

“…One of our study's limitations was the short follow-up time. Most breast cancer-related deaths and systemic relapses take 10-15 years to occur [18]. Trials like SOFT/TEXT used short-term follow-up periods as well, so definitive conclusions cannot be drawn [18].…”

“…Most breast cancer-related deaths and systemic relapses take 10-15 years to occur [18]. Trials like SOFT/TEXT used short-term follow-up periods as well, so definitive conclusions cannot be drawn [18]. In reality, there is a gap in the literature concerning long-term follow-up studies on multiple hormone adjuvant breast cancer therapies, so the literature does not account for long-term consequences and increased mortality risk related to iatrogenic menopause in this context.…”

Hormone Replacement Therapy After Breast Cancer

“…Vogl argued that “overall survival is the definitive endpoint” and that SOFT did not include in their analyses deaths that occurred in their treated population in the absence of distant breast cancer recurrence. “The severity of life-long ‘off target’ toxicities,” he wrote, including non–breast cancer deaths, “argues that we should require a benefit in overall survival that is both large and durable to justify the toxicities and risks of both OFS alone and especially with an aromatase inhibitor.” 113 …”

Imaging Tumor Proliferation in Breast Cancer

“…A pre-surgical window of opportunity study utilized [ 18 F]FLT-PET in postmenopausal women with ER-positive breast cancer at baseline and after 2 weeks of therapy with irosustat to demonstrate proof of concept data that suggest that steroid sulfatase inhibition is effective in reducing tumor proliferation as measured by FLT-PET, in-vivo. They reported significant reduction in FLT uptake and Ki-67 after 2 weeks of treatment 65 .…”