Hormone lowering treatment linked to reduced recurrence of breast cancer in premenopausal women

A recent study published in the Journal of Clinical Oncology shows that in estrogen receptor-positive premenopausal individuals 2 years of adjuvant endocrine therapy demonstrates a 20-year benefit and hypothesizes variable treatment benefits based on tumor genetic features.

After tumor removal, hormonal therapies (endocrine therapies) have long been used to lower the chance of cancer cells spreading, although it is unknown how long this protection lasts. A short-term risk of recurrence, often within a few years, exists for many malignancies. However, the risk of recurrence is frequently prolonged over a number of decades for women with hormone-driven breast cancer. Thus, this study was carried out by Annelie Johansson and colleagues to evaluate the long-term (20-year) benefit of endocrine treatment in premenopausal breast cancer patients.

Randomly assigning 924 premenopausal patients to 2 years of goserelin, tamoxifen, combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is done in a secondary analysis of the Stockholm trial (STO-5, 1990-1997). Lymph node status was classified during random assignment, and patients with positive lymph nodes (n = 459) were given conventional treatment. 2020 saw the completion of primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586). Patients with genetic low-risk and high-risk were identified by the 70-gene signature. The long-term distant recurrence-free interval was evaluated using Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling (DRFI). High-quality Swedish registries enabled a 20-year full follow-up.

The key findings of this study were:

1. Tamoxifen, goserelin, and the combination significantly increased the long-term distant recurrence-free interval compared to control in estrogen receptor-positive patients (n = 584; median age 47 years).

2. Tamoxifen and goserelin were shown to interact significantly (P =.016).

3. Patients with low genetic risk (n = 305) and high genomic risk (n = 158) both significantly benefited by tamoxifen and goserelin, respectively.

4. In patients with high genetic risk, the addition of tamoxifen to goserelin was associated with an increased risk.

5. Additionally, individuals with low genetic risk saw a 20-year tamoxifen advantage, whereas those with high genomic risk experienced an early goserelin benefit.

Reference: 

Johansson, A., Dar, H., van 't Veer, L. J., Tobin, N. P., Perez-Tenorio, G., Nordenskjöld, A., Johansson, U., Hartman, J., Skoog, L., Yau, C., Benz, C. C., Esserman, L. J., Stål, O., Nordenskjöld, B., Fornander, T., & Lindström, L. S. (2022). Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial. In Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.21.02844