ECC 2015: Hormone Therapy May Prevent Ovarian Failure and Preserve Fertility in Women With Breast Cancer
Young women undergoing chemotherapy for breast cancer may be more likely to remain fertile if they also receive hormonal treatment, according to new research (Abstract 1957) presented at the 2015 European Cancer Congress in Vienna, Austria, and published simultaneously by Lambertini et al in Annals of Oncology.
Researchers explained that the addition of treatment with a so-called luteinizing hormone–releasing hormone analog during chemotherapy could protect women’s ovaries. The approach may increase the chances of pregnancy after breast cancer treatment.
Matteo Lambertini, MD, a medical oncologist at the IRCCS AOU San Martino-IST, in Genoa, Italy, said, “Chemotherapy can damage the ovaries and push young women into menopause. They may experience infertility, sleep disturbance, sexual dysfunction, and osteoporosis. It is psychologically distressing, harmful to health, and affects the treatment decisions of many young women.”
“We found that temporary suppression of ovarian function with luteinizing hormone–releasing hormone analog significantly reduces the risk of premature ovarian failure caused by chemotherapy. It also seems to be associated with a higher pregnancy rate in young breast cancer patients.”
Study Findings
Dr. Lambertini and his colleagues pooled the best available data. Their meta-analysis included 12 randomized trials and a total of 1,231 breast cancer patients receiving chemotherapy, with or without luteinizing hormone–releasing hormone analog. An initial calculation found that rates of premature ovarian failure were reduced by 64% in patients who received luteinizing hormone–releasing hormone analog. However, the studies used different definitions of premature ovarian failure, and results ranged widely.
The analysis was then restricted to trials that included specific data on whether a woman’s periods had restarted 1 year after chemotherapy. This is in line with the World Health Organization’s definition of menopause. In the eight relevant trials, the overall reduction in premature ovarian failure with the addition of luteinizing hormone–releasing hormone analog was still striking. Rates were reduced by 45% with luteinizing hormone–releasing hormone analog, and this time there was close agreement in results from all studies.
The use of luteinizing hormone–releasing hormone analog was originally developed to preserve ovarian function rather than fertility, and only five of the studies reported on pregnancies after breast cancer treatment. In these studies, overall there were 33 patients with pregnancies among those who received luteinizing hormone–releasing hormone analog alongside chemotherapy, and 19 among those who did not. This was an 83% increase in the chance of becoming pregnant. Rates were similar across the five studies.
Dr. Lambertini said, “Major international guidelines from ASCO and ESMO consider the administration of [luteinizing hormone–releasing hormone analog] during chemotherapy an experimental strategy to preserve ovarian function and fertility. This is mainly because of the lack of data on long-term ovarian function and pregnancies. However, these guidelines were published before two of the larger studies became available, the POEMS-SWOG S0230 trial and the updated results of the PROMISE-GIM6 study.”
“In breast cancer patients, we believe there is now sufficient evidence to suggest that the administration of [luteinizing hormone–releasing hormone analog] could be considered a potential standard strategy to preserve ovarian function and might also play a role in increasing the likelihood of pregnancy after chemotherapy.”
Hormone Receptor–Positive Breast Cancer
Concerns about the safety of luteinizing hormone–releasing hormone analog treatment have been raised, particularly for breast cancers that are driven by hormones. These hormone receptor–positive cancers have receptors on the cell surface that trigger the cancer’s growth in response to circulating hormones. Standard treatment of these breast cancers includes antiestrogen 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.
Dr. Lambertini explained that results from the two recent, large studies are reassuring. Both looked at the length of disease-free survival. The POEMS-SWOG S0230 trial looked at women with hormone receptor–negative breast cancer. The women had improved disease-free survival if they received luteinizing hormone–releasing hormone analog. Furthermore, the PROMISE-GIM6 study found that adding luteinizing hormone–releasing hormone analog made no difference to disease-free survival, even within the subgroup of women with hormone receptor–positive breast cancer, who accounted for the majority of patients enrolled in the study.
The 2015 St. Gallen International Expert Consensus Panel and the National Comprehensive Cancer Network guidelines have been updated to acknowledge the role of luteinizing hormone–releasing hormone analog in preventing ovarian failure induced by chemotherapy but only in hormone receptor–negative cancer.
“Other guidelines are hesitating to recommend this technique,” Dr. Lambertini said. “To date, the role of this approach in fertility preservation remains controversial.”
He stressed the need for new treatment options. “Pregnancy after breast cancer is safe, even in patients with endocrine-sensitive disease. With the rising trend of delaying childbearing, more breast cancer patients are diagnosed without having completed their families, and thus, it is vital to provide reliable fertility preservation methods for these young women.”
Dr. Lambertini concluded, “Pharmacological protection of the ovaries with luteinizing hormone–releasing hormone analog during chemotherapy is an attractive option to preserve ovarian function and fertility. Agents are widely available, do not require any invasive procedure, and cause no delay in the initiation of anticancer therapies. Moreover, it is possible to use this technique in combination with other fertility-preservation options, including cryopreservation strategies, thereby increasing the chance of fertility preservation as well as ovarian function after cancer therapies.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
