GnRHa safe, improves fertility in breast cancer patients
Final analysis of the POEMS (Prevention of Early Menopause) study finds that breast cancer (BC) patients treated with the gonadotrophin-releasing hormone agonist (GnRHa) goserelin, in addition to chemotherapy, are more likely to avoid premature menopause and to become pregnant without negatively impacting disease-related outcomes.
“Potential effects of cancer treatment on fertility may, in some cases, result in refusal of adjuvant systemic therapy,” said Professor Prudence Francis of Peter McCallum Cancer Centre in Melbourne, Australia. “Of note, BC presents earlier in Asian women than in their Western counterparts.” [Edinb Scotl 2011;20:S75-S80; Ann Surg Oncol 2011;18:3072-3078]
A meta-analysis of 14 studies, which included 1,244 cases of BC and 18,145 controls, demonstrated that pregnancy in women with a history of BC is safe and does not compromise overall survival (OS). Women who got pregnant following BC diagnosis had a 41 percent reduced risk of death vs women who did not get pregnant (proportional reporting ratio [PRR], 0.59; 90 percent confidence interval [CI], 0.50 to 0.70). [Eur J Cancer 2011;47:74-83]
Furthermore, a multicentre retrospective study of 333 patients who became pregnant any time after BC diagnosis and 874 matched patients without pregnancies following BC found no difference in disease-free survival (DFS) between the two groups, regardless of oestrogen receptor (ER) status (hazard ratio [HR] for ER-positive patients with or without pregnancies, 0.91; 95 percent CI, 0.67 to 1.24; p=0.55; HR for ER-negative patients with or without pregnancies, 0.75; 95 percent CI, 0.51 to 1.08; p=0.12). Interestingly, BC survivors who got pregnant had better OS (HR, 0.72; 95 percent CI, 0.54 to 0.97; p=0.03), with no interaction according to ER status (p=0.11). [J Clin Oncol 2013;31:73-79]
“Preserving fertility is increasingly relevant as BC outcomes are improving. Since age is a risk factor for reduced fertility, a natural decrease in fertility is likely to occur during the 5 to 10 years of endocrine treatment. Therefore, if a patient’s child-bearing is not complete, a fertility consultation should be offered before starting systemic therapy,” advised Francis.
“According to the 2018 American Society of Clinical Oncology [ASCO] guidelines on fertility preservation in patients with cancer, sperm, oocyte and embryo cryopreservation are considered standard practice. When these methods are not feasible, GnRHa may be offered to BC patients to reduce the likelihood of chemotherapy-induced ovarian insufficiency,” said Francis. [J Clin Oncol 2018;36:1994-2001]
The POEMS study randomized 105 premenopausal women with stage I–IIIA ER-negative, progesterone receptor-negative BC to receive standard chemotherapy, and 113 women to receive chemotherapy with goserelin. More patients in the chemotherapy plus goserelin arm reported at least one pregnancy vs the chemotherapy alone arm (5-year cumulative incidence, 23.1 percent vs 12.2 percent; odds ratio, 2.34; p=0.03). [J Natl Cancer Inst 2019;111:210-213]
Five-year DFS rate was 88.1 percent vs 78.6 percent, while 5-year OS rate was 91.7 percent vs 83.1 percent in the chemotherapy plus goserelin vs chemotherapy alone groups, respectively. “Findings of favourable DFS and OS are intriguing and reassuring regarding the safety of GnHRa treatment,” commented Francis.
“POEMS is the first trial to demonstrate improved fertility prospects and a greater number of successful pregnancies in women treated with goserelin in addition to chemotherapy,” said Francis. “Premenopausal women beginning chemotherapy with curative intent should consider goserelin as a new option to prevent premature ovarian failure.”