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Predicting Benefit from Ovarian Suppression in Young Women with High-Risk Breast Cancer
Genomic assays are used to determine which patients with early stage, estrogen-receptor–positive (ER+) breast cancer can avoid chemotherapy and to inform the duration of adjuvant endocrine therapy. One such tool, the Breast Cancer Index (BCI), is composed of two biomarker panels: the HOXB13/IL17BR (H/I) gene ratio, which is a measure of estrogen signaling, and the 5-gene Molecular Grade Index, which is a measure of tumor proliferation. Clinical trials have shown that patients with BCI(H/I)-high tumors benefit significantly from extended duration of endocrine therapy after 5 years, while those with BCI(H/I)-low tumors do not.
Another issue, particularly in young, premenopausal women with early-stage breast cancer at high risk for recurrence, is whether to consider ovarian function suppression (OFS) in addition to adjuvant endocrine therapy. For young patients who continue to menstruate after chemotherapy, early onset menopausal symptoms associated with OFS can be challenging.
The previously reported Suppression of Ovarian Function Trial (SOFT) demonstrated that compared to tamoxifen alone, exemestane or tamoxifen in combination with OFS improved both disease-free survival (DFS) and overall survival at 12 years in premenopausal women (NEJM JW Oncol Hematol Jan 20 2015 and N Engl J Med 2015; 372:436). In the current study, researchers performed the BCI test using RNA extracted from tumor samples available for 1687 of the 3047 SOFT participants. Of these patients, 53% remained premenopausal after chemotherapy, and 66% were node negative.
The investigators postulated that patients with BCI(H/I)-high tumors would be most likely to benefit from OFS. However, patients with BCI(H/I)-high tumors (n=715) gained no benefit from OFS, while those with BCI(H/I)-low tumors (n=972) had significant benefit. The 12-year absolute benefit in breast cancer–free interval with OFS plus tamoxifen or exemestane versus tamoxifen alone was as follows:
- BCI(H/I)-high: tamoxifen/OFS, −1.2%; exemestane/OFS, −0.4%
- BCI(H/I)-low: tamoxifen/OFS, 7.3%; exemestane/OFS, 11.6%
Comment
These results suggest — contrary to the initial hypothesis — that OFS will be of benefit in young, high-risk patients with BCI(H/I)-low tumors, but not in those with BCI(H/I)-high tumors.
Citation(s)
Author:
O'Regan RM et al.
Title:
Breast cancer index in premenopausal women with early-stage hormone receptor–positive breast cancer.
Source:
JAMA Oncol
2024
Aug
15; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
William J. Gradishar, MD