Hormone therapy is controversial, but can protect young breast cancer patients from chemotherapy-induced ovarian failure and infertility
Results of a meta-analysis presented at the 2015 European Cancer Congress demonstrate that young women who undergo chemotherapy in the treatment of their breast cancer have a higher probability to remain fertile if they also receive hormonal therapy. The meta-analysis included data from 1,231 breast cancer patients who received chemotherapy alone, or in combination with a luteinizing hormone-releasing hormone (LHRH) agonist. However, the use of LHRH agonists (LHRHa) in this setting remains controversial, especially in women with hormone-receptor sensitive (HR+) tumors.
It is generally appreciated that chemotherapy has detrimental effects on the fertility of young breast cancer patients. Chemotherapy damages the ovaries of these women and pushes them prematurely into menopause resulting in infertility, sleeping problems, a disturbed sexual function and an increased risk of developing osteoporosis. This is very disturbing for cancer patients and may influence their treatment choice. In order to assess whether temporary suppression of the ovarian function with LHRHa has a protective effect on the ovaries of young breast cancer patients undergoing chemotherapy, Lambertini et al. performed a meta-analysis including data from 1,231 breast cancer patients.
In the initial analysis, including the entire data set, the rate of premature ovarian failure (POF) was found to be significantly lower in patients who received an LHRHa while they were under chemotherapy (reduction in POF incidence of 64%). In addition to this, the investigators also noted an association between LHRHa use and a higher rate of pregnancies. However, the different studies in this analysis used different definitions of POF and the results in the different studies varied significantly.
In a second part of the study, the analysis was therefore limited to the studies reporting data on the resumption of periods in patients 12 months after the start of the chemotherapy. In this second part, including 8 studies, the effect of a LHRHa on the incidence of POF was impressive. In fact, the incidence of POF was reduced by 45% when patients received LHRHa while on chemotherapy and this finding was consistent in the 8 studies. Only 5 studies reported data with respect to pregnancies. In total, 33 pregnancies were reported in the cohort of women receiving LHRHa as compared to 19 in the women who did not receive hormonal therapy together with chemotherapy. This translates into an increase of 83% in the chance of becoming pregnant when LHRHa is given.
However, there are concerns about the safety of LHRHa treatment, particularly for breast cancers that are driven by hormones. The standard treatment of these breast cancers includes anti-estrogen therapy alongside chemotherapy. Previous work has implied that resumption of a woman’s periods after treatment could have a detrimental impact on long-term health. According to the authors, 2 recent large studies offer some reassurance in this respect. In the POEMS-SWOG S0230 trial, including HR- breast cancer patients, women receiving LHRHa did not have a worse disease-free survival than women who did not receive LHRHa. In addition to this, the PROMISE-GIM6 study demonstrated that the addition of LHRHa to chemotherapy did not affect the disease-free survival in women with HR+ tumors, who accounted for the majority of patients enrolled in this study.
Earlier this year, the 2015 St Gallen International Expert Consensus panel and the NCCN guidelines have been updated to acknowledge the role of LHRHa in preventing ovarian failure induced by chemotherapy, but only in women with HR- tumors. Other guidelines are hesitating to recommend this technique. As such, the role of LHRHa in safeguarding the fertility of women with breast cancer is still subject to debate and remains controversial, especially in women with HR+ tumors.
Lambertini M, et al. Ovarian suppression with luteinizing hormone-releasing hormone agonists during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients: A systematic review and meta-analysis of randomized studies. Presented at ECC 2015; Abstract #1957.