Hormonal Therapy May Prevent Ovarian Failure and Preserve Fertility in Patients With Breast Cancer

VIENNA, AUSTRIA—Young women undergoing chemotherapy for breast cancer may be more likely to remain fertile if they also receive hormonal treatment, according to new research presented at the European Cancer Congress 2015 (ECC2015) and published simultaneously in Annals of Oncology (2015; doi:10.1093/annonc/mdv374 ).

Adding a luteinizing hormone-releasing hormone analogue (LHRHa) during chemotherapy could protect women's ovaries. The approach may increase the chances of pregnancy after breast cancer treatment by preventing premature ovarian failure (POF).

"Chemotherapy can damage the ovaries and push young women into the 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,” said Matteo Lambertini, MD, a medical oncologist at the IRCCS AOU San Martino-IST, Genoa, Italy.

The research suggests that temporarily suppressing ovarian function with LHRHa significantly reduces the risk of chemotherapy-related ROF. It may also be associated with a higher pregnancy rate in young patients with breast cancer.

Lambertini and his colleagues pooled the best available data. Their meta-analysis included 12 randomized trials and a total of 1,231 patients with breast cancer who are receiving chemotherapy, with or without LHRHa. An initial calculation found that POF incidence was reduced by 64%, approximately two-thirds, in patients who received LHRHa. However, the studies used different definitions of POF, 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 POF with the addition of LHRHa was still striking. Incidence was reduced by 45% with LHRHa, and this time there was close agreement in results from all studies.

The use of LHRHa was originally conceived to preserve ovarian function rather than fertility, and only five of the studies reported on pregnancies after breast cancer treatment. In these studies, overall 33 patients achieved pregnancies among those who received LHRHa alongside chemotherapy, and 19 patients achieved pregnancies among those who did not. This was an 83% increase in the chance of becoming pregnant. Rates were similar across the five studies.

"In breast cancer patients, we believe there is now sufficient evidence to suggest that the administration of LHRHa 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," said Lambertini.

Concerns about the safety of LHRHa treatment have been raised, particularly for breast cancers 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.

Lambertini said that results from the two recent, large studies are reassuring. Both looked at the length of time women remained free of cancer after treatment (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 LHRHa. Furthermore, the PROMISE-GIM6 study found that adding LHRHa 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 the patients enrolled in the study.

Lambertini 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."

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