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Mini Oral session 2

LBA1 - 20-year benefit of endocrine therapy in premenopausal breast cancer patients by the 70-gene risk signature


08 May 2021


Mini Oral session 2


Tumour Site

Breast Cancer


Annelie Johansson


Annals of Oncology (2021) 32 (suppl_2): S21-S36. 10.1016/annonc/annonc503


A. Johansson

Author affiliations

  • Karolinska Institute, 171 77 - Stockholm/SE


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Abstract LBA1


Premenopausal breast cancer patients have an increased long-term risk for fatal disease, and endocrine therapy benefit including ovarian suppression is unexplored. Here for the first time, we assessed the 20-year benefit of goserelin and tamoxifen stratified by the molecular 70-gene signature risk prediction in premenopausal women in a randomized trial.


In 1990-1997, n=924 premenopausal patients (age range 26-57, median 46) were randomized into 4 well-balanced trial arms; 2 years of goserelin, tamoxifen, the combination of goserelin and tamoxifen, or no endocrine therapy. Lymph-node positive women (n=459) received standard chemotherapy. Swedish high-quality National registries allowed long-term (20 years) complete follow-up after randomization. Immunohistochemistry of the clinically used breast cancer markers was performed in 2020 (n=729) together with Agilent microarray profiling (n=589). The 70-gene signature classified patients into low or high risk of recurrence. Kaplan-Meier analysis and multivariable Cox proportional hazard regression were used to assess the endocrine therapy benefit.


Adjusted multivariable analyses show that in estrogen receptor (ER)-positive patients (n=610) goserelin, tamoxifen, and the combination of goserelin and tamoxifen reduced the 20-year risk of distant recurrence compared to no endocrine therapy, see table. Stratification by the 70-gene signature showed a significant benefit in low risk patients (n=306) from tamoxifen therapy (Hazard Ratio [HR]=0.38, 95% Confidence Interval [CI]: 0.18-0.82), whereas high risk patients (n=159) had a significant benefit from goserelin therapy (HR=0.22, 95% CI: 0.10-0.49). Similar findings were seen when using breast cancer-specific survival as the end-point. Table: LBA1

Long-term (20 year) risk of distant recurrence adjusted for tumour size, grade, lymph-node status, PR, HER2, Ki-67, chemotherapy, and radiotherapy

Premenopausal ER-positive breast cancer patients Treatment Adjusted HR (95%CI)
All patients Goserelin 0.48 (0.32-0.72)
Tamoxifen 0.59 (0.39-0.88)
Goserelin + Tamoxifen 0.67 (0.46-0.97)
No endocrine therapy 1.00 (Ref)
70-gene signature low risk patients Goserelin 0.80 (0.42-1.52)
Tamoxifen 0.38 (0.18-0.82)
Goserelin + Tamoxifen 0.72 (0.39-1.32)
No endocrine therapy 1.00 (Ref)
70-gene signature high risk patients Goserelin 0.22 (0.10-0.49)
Tamoxifen 0.69 (0.33-1.46)
Goserelin + Tamoxifen 0.64 (0.32-1.27)
No endocrine therapy 1.00 (Ref)


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.

Legal entity responsible for the study

The authors.


The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare (FORTE), and The Swedish Cancer Society (Cancerfonden).


L. van 'T Veer: Shareholder/Stockholder/Stock options, Full/Part-time employment, Dr van't Veer is one of the inventors of the MammaPrint 70-gene risk signature (patent no WO2002103320): Agendia.

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