Hormones May Protect Ovaries, Preserve Fertility in Breast Cancer

Chemotherapy in young women can damage ovaries and result in premature menopause, but new research shows that the addition of hormonal treatment may preserve ovarian function and fertility in patients with breast cancer and may increase the chances of pregnancy after treatment.

Chemotherapy in young women can damage ovaries and result in premature menopause, but new research shows that the addition of hormonal treatment may preserve ovarian function and fertility in patients with breast cancer and may increase the chances of pregnancy after breast cancer treatment.

The research, published in Annals of Oncology1 and presented September 28 at the 2015 European Cancer Congress2, found that using luteinizing hormone-releasing hormone analogue (LHRHa) during chemotherapy is effective in preventing premature ovarian failure (POF) and may increase chances of pregnancy after breast cancer.

“We found that temporary suppression of ovarian function with LHRHa 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,” Matteo Lambertini, MD, medical oncologist at the IRCCS AOU San Martino-IST, Genoa, Italy, said in a statement.

The meta-analysis included 12 randomized trials and involving 1231 premenopausal patients with breast cancer receiving chemotherapy, with or without LHRHa.

An initial calculation found that rates of POF were reduced by 64% in patients who received LHRHa (Odds Ratio [OR] = 0.36; 95% CI, 0.23-0.57; P < .001). However, the studies used different definitions of POF, and results ranged widely.

The analysis was then restricted to eight studies that included specific data on whether a woman’s periods had restarted 1 year after chemotherapy. In the eight relevant trials, rates of POF with the addition of LHRHa were reduced by 45% (OR = 0.55; 95% CI, 0.41-0.73; P < .001), and there was close agreement in results from all studies.

The use of LHRHa was originally developed to preserve ovarian function rather than fertility, and only five of the studies reported pregnancies after breast cancer treatment. In these studies, overall there were 33 patients with pregnancies among those who received LHRHa alongside chemotherapy, and 19 among those who did not. This was an 83% increase in the chance of becoming pregnant (OR = 1.83; 95% CI, 1.02-3.28, P = .041). Rates were similar across the five studies.

LHRHa treatment for breast cancers driven by hormones remains controversial, as previous work has implied that resumption of a woman’s periods after treatment could have a detrimental impact on long-term health.

“Major international guidelines from ASCO and ESMO consider the administration of LHRHa 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 trial3 and the updated results of the PROMISE-GIM6 study4,” Lambertini said.

Both studies examined disease-free survival (DFS). The POEMS-SWOG S0230 trial looked at women whose cancers were HR—negative, and found that women had improved DFS if they received LHRHa. The PROMISE-GIM6 study found that adding LHRHa made no difference to DFS, even within the subgroup of women with HR–positive breast cancer—the majority of the patients enrolled in the study.

“These data suggest that this strategy could be useful and safe not only in women with hormone receptor—negative breast cancer, but also in those with hormone receptor–positive tumors who account for two-thirds of new cases of breast cancer in young women,” Lambertini said.

The researchers concluded that current guidelines on fertility preservation for patients with breast cancer should consider using LHRHa during chemotherapy to increase the likelihood of patients’ resuming their periods and eventually becoming pregnant after treatment.

“Pharmacological protection of the ovaries with LHRHa 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,” Lambertini said. “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.”

References

1. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a systematic review and meta- analysis of randomized studies [published online ahead of print September 7, 2015] Ann Oncol.

2. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a systematic review and meta- analysis of randomized studies. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract 1957.

3. Moore HCF, Unger JM, Albain KS. Ovarian protection during adjuvant chemotherapy. N Engl J Med. 2015;372(23):2269—2270.

4. Lambertini M, Boni L, Michelotti A, et al. Long-term outcome results of the phase III PROMISE-GIM6 study evaluating the role of LHRH analog (LHRHa) during chemotherapy (CT) as a strategy to reduce ovarian failure in early breast cancer (BC) patients. J Clin Oncol. 2014;32(suppl 26): abstr 105.