A 20-year follow-up of premenopausal patients with estrogen receptor–positive breast cancer and stratification by the molecular 70-gene risk signature suggested that patients at high risk of distant disease recurrence derive significant benefit from goserelin, while patients at low risk have greater benefit with tamoxifen. These findings were presented at the ESMO Breast Cancer Virtual Congress 2021 by Johansson et al (Abstract LBA1).
Researchers investigated the utility of the 70-gene risk signature in determining the 20-year benefit of endocrine therapy in premenopausal patients with breast cancer. According to the authors, this is the first time an assessment of the 20-year benefit of goserelin and tamoxifen as stratified by the molecular 70-gene signature risk prediction in premenopausal women has ben carried out in a randomized trial.
This study with unique long-term follow-up in premenopausal patients suggests that high-risk patients significantly benefit from goserelin, whereas low-risk patients benefit from tamoxifen.— Johansson et al
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Study Details
The study enrolled 924 premenopausal patients with breast cancer from 1990 to 1997, who were then randomly assigned to one of four cohorts: 2 years of goserelin, tamoxifen, the combination of goserelin and tamoxifen, or no endocrine therapy. In addition, 459 patients with lymph node–positive disease received standard chemotherapy. Patient characteristics were well balanced across treatment arms, and the patients’ median age was 46 years (range = 26–57).
The 20-year follow-up was carried out using the Swedish high-quality National registries following random assignment.
Clinically relevant breast cancer markers were identified by immunohistochemistry in 729 patients; of these samples, Agilent microarray profiling could be done in 589. The 70-gene signature classified patients into groups with low or high risk of disease recurrence. The investigators assessed the benefit of endocrine therapy by Kaplan-Meier analysis and multivariable Cox proportional hazard regression. The long-term 20-year risk of distant recurrence adjusted for tumor size, grade, lymph node status, progesterone receptor, HER2, Ki-67, chemotherapy, and radiotherapy.
Results of Endocrine Therapy Follow-up
Analysis of all 610 estrogen receptor–positive patients demonstrated that endocrine therapy, including goserelin (hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.32–0.72), tamoxifen (HR = 0.59, 95% CI = 0.39–0.88), and goserelin plus tamoxifen (HR = 0.67, 95% CI = 0.46–0.97) reduced the 20-year risk of distant recurrence compared to patients receiving no endocrine therapy (HR = 1.00).
Stratification by the 70-gene signature demonstrated that 306 low-risk patients derived a significant benefit from tamoxifen therapy (HR = 0.38, 95% CI = 0.18–0.82), while goserelin (HR = 0.80), and goserelin/tamoxifen (HR = 0.72) provided less benefit to these patients.
In contrast, 159 patients at high risk showed significant benefit from goserelin therapy (HR = 0.22, 95% CI = 0.10–0.49), while less benefit was observed with tamoxifen (HR = 0.69) or the combination (HR = 0.64).
The investigators indicated that similar findings were seen when using breast cancer–specific survival as the endpoint.
The authors concluded, “This study with unique long-term follow-up in premenopausal patients suggests that high-risk patients significantly benefit from goserelin, whereas low-risk patients benefit from tamoxifen.”
Commentary
Prudence Francis, MD
Prudence Francis, MD, of the Peter MacCallum Cancer Centre in Melbourne, Australia discussed the study results. She commented that short duration of endocrine therapy/tamoxifen (only 2 years), prior chemotherapy in some patients, and the absence of HER2 therapy might influence outcomes. She added that the results should be viewed as hypothesis-generating, and that multigene assay results are not yet available for larger patient cohorts (SOFT and TEXT).
Disclosure: This study was funded by the Swedish Research Council (Vetenskapsrådet), the Swedish Research Council for Health, Working life and Welfare (FORTE), and the Swedish Cancer Society (Cancerfonden). For full disclosures of the study authors, visit oncologypro.esmo.org.
