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.

Authors

null

Richard G. Gray

University of Oxford, Oxford, United Kingdom

Richard G. Gray , Rosie Bradley , Jeremy Braybrooke , Mike Clarke , Robert Kerrin Hills , Richard Peto , Jonas C. S. Bergh , Sandra M. Swain , Nancy E. Davidson , Prudence A. Francis , Meredith M. Regan

Organizations

University of Oxford, Oxford, United Kingdom, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom, Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom, Karolinska Institutet, Stockholm, Sweden, Georgetown University Medical Center, Washington, DC, Fred Hutchinson Cancer Research Center, Seattle, WA, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, Dana-Farber Cancer Institute, Boston, MA

Research Funding

Other
Cancer Research UK medical charity, NDPH, University of Oxford

Background: Suppressing ovarian function of women with breast cancer may improve outcome by preventing estrogenic stimulation of any residual cancer, particularly for pre-menopausal women with estrogen receptor (ER)-positive tumors. We report a collaborative meta-analysis of individual participant data from randomized trials of ovarian ablation or suppression. Methods: Data were sought from randomized trials that compared ovarian ablation or suppression versus not. Primary analyses included only premenopausal women age < 55 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. Standard log-rank methods estimated ER-weighted annual event rate ratios (RR). Results: Individual patient data were provided for 25 of 27 relevant trials, comprising 14,993 (98.7%) of 15,195 women randomized. Overall, fewer breast cancer recurrences were seen with ovarian ablation/suppression than control (RR = 0·82, 95%CI 0·77–0·88; p < 0·0001). Recurrence reductions were significantly (p = 0.0003) larger among women (n = 7,213) known to be premenopausal prior to ovarian suppression (RR = 0·70, 0·63–0·78; p = 0·0003) than among those (n = 7,786) whose menopausal status was uncertain after chemotherapy (RR = 0·91, 0·83–0·99; p = 0·03). For known premenopausal women, 15-year risk of recurrence was improved by 12·1% (28·9% vs 41·0%; p < 0·0001. 15-year breast cancer and all-cause mortality were improved by 8·0% (20·9% vs 28·9%; RR 0·69, 0·60–0·80; p < 0·0001) and 7.2% (26·0% vs 33·1%; RR = 0·73, 0·64–0·82; p < 0·0001), respectively, with no increase in deaths without recurrence (RR = 0·88, 0·67–1·14; p = 0·33). Recurrence reductions were significantly (p = 0·003) larger among premenopausal women aged under 45 (RR = 0·63, 0·55–0·72; p < 0·0001) than among those aged 45-54 (RR = 0·84, 0·70–1.00; p = 0·045), but did not differ significantly by other recorded patient or tumor characteristics. Conclusions: For pre-menopausal women aged under 45, ovarian ablation or suppression substantially reduces the 15-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Adjuvant Therapy

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 503)

DOI

10.1200/JCO.2023.41.16_suppl.503

Abstract #

503

Abstract Disclosures

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