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Randomized Controlled Trial
. 2022 Mar 8;114(3):400-408.
doi: 10.1093/jnci/djab213.

Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients

Matteo Lambertini  1   2 , Luca Boni  3 , Andrea Michelotti  4 , Emanuela Magnolfi  5 , Alessio Aligi Cogoni  6 , Anna Maria Mosconi  7 , Monica Giordano  8 , Ornella Garrone  9 , Grazia Arpino  10 , Francesca Poggio  11 , Paola Cinacchi  4 , Claudia Bighin  11 , Piero Fregatti  12   13 , Paolo Pronzato  11 , Eva Blondeaux  11 , Lucia Del Mastro  1   2 ; GIM study group
Affiliations
Randomized Controlled Trial

Long-Term Outcomes With Pharmacological Ovarian Suppression During Chemotherapy in Premenopausal Early Breast Cancer Patients

Matteo Lambertini et al. J Natl Cancer Inst. .

Abstract

Background: Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor-positive disease. There are controversial data on its fertility preservation potential.

Methods: The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results: Of 281 randomly assigned patients, 80.4% had hormone receptor-positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor-positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92).

Conclusions: Final analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor-positive disease.

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Figures

Figure 1.
Figure 1.
The PROMISE-GIM6 trial profile.
Figure 2.
Figure 2.
Kaplan-Meier curves for disease-free survival according to treatment arm among (A) all randomly assigned patients, (B) patients with hormone receptor–positive breast cancer, and (C) patients with hormone receptor–negative breast cancer. All statistical tests were 2-sided. GnRHa = gonadotropin-releasing hormone agonist.
Figure 3.
Figure 3.
Kaplan-Meier curves for overall survival according to treatment arm among (A) all randomly assigned patients, (B) patients with hormone receptor–positive breast cancer, and (C) patients with hormone receptor–negative breast cancer. All statistical tests were 2-sided. GnRHa = gonadotropin-releasing hormone agonist.
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References

    1. Azim HA, Partridge AH.. Biology of breast cancer in young women. Breast Cancer Res. 2014;16(4):427. doi:10.1186/s13058-014-0427-5. - DOI - PMC - PubMed
    1. Partridge AH, Hughes ME, Warner ET, et al.Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34(27):3308–3314. doi:10.1200/JClin Oncol.2015.65.8013. - PubMed
    1. Sparano JA, Gray RJ, Ravdin PM, et al.Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019;380(25):2395–2405. doi:10.1056/NEJMoa1904819. - DOI - PMC - PubMed
    1. Villarreal-Garza C, Ferrigno AS, De la Garza-Ramos C, Barragan-Carrillo R, Lambertini M, Azim HA.. Clinical utility of genomic signatures in young breast cancer patients: a systematic review. NPJ Breast Cancer. 2020;6:46. doi:10.1038/s41523-020-00188-3. - DOI - PMC - PubMed
    1. Paluch-Shimon S, Cardoso F, Partridge AH, et al.; ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4). Ann Oncol. 2020;31(6):674–696. doi:10.1016/j.annonc.2020.03.284. - DOI - PubMed

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