GnRH Analogue Use Preserves Fertility During Chemotherapy

Pam Harrison

December 18, 2017

SAN ANTONIO ― The use of a gonadotropin-releasing hormone analogue (GnRHa) in young women undergoing chemotherapy has again been shown to help preserve ovarian function and fertility, a meta-analysis of five major randomized trials confirms.

"Having a family is one of the most important achievements in a person's life, but for young breast cancer patients, this can be particularly challenging because of the possible development of infertility as a consequence of the use of anticancer treatment, particularly chemotherapy," Matteo Lambertini, MD, medical oncologist, Institut Jules Bordet, Brussels, Belgium, told a press briefing here.

Dr Matteo Lambertini

"We found rates of premature ovarian insufficiency (POI) were more than double in the group who did not receive a GnRHa during chemotherapy, while the number of pregnancies in the GnRHa group was also double the number in controls, so the use of GnRHa during chemotherapy significantly increases a patients' chance of future pregnancy after the end of treatment," he added.

The study was reported here at the San Antonio Breast Cancer Symposium (SABCS) 2017.

The five randomized trials involved 436 women who were assigned to treatment with a GnRHa and another 437 women who served as control patients. Approximately two thirds of women in both groups were aged 40 years and younger.

More women had estrogen receptor–negative breast cancer than estrogen receptor–positive disease, but two trials enrolled estrogen receptor–negative women only, Dr Lambertini pointed out.

Goserelin (Zoladex, AstraZeneca) was used in three trials, and triptorelin (Trelstar, Allergan) was used in the remaining two. Almost all patients were treated with anthracycline-based chemotherapy.

The presence of amenorrhea was used as a marker of POI in some trials; in the others, the presence of amenorrhea plus postmenopausal hormonal status was used to define POI status. POI rates were analyzed in 363 patients in the GnRHa group and in 359 patients in the chemotherapy-alone group.

"Women treated with a GnRHa during chemotherapy were 62% less likely to develop POI as a result of chemotherapy compared with controls," Dr Lambertini reported.

The POI rate was 14.1% in the GnRHa group, compared with 30.9% in the control group (P < .001).

"Importantly, he added, "the effect of treatment was homogeneous across the different subgroups and was seen in patients 40 years of age and under and those over the age of 40, and was independent of estrogen receptor status as well as the type and duration of chemotherapy received," Dr Lambertini observed.

One year following completion of the chemotherapy schedule, rates of amenorrhea were not significantly different between the two groups, at 36.8% for women receiving concurrent GnRHa treatment vs 40.4% for control patients.

However, at 2 years posttreatment, amenorrhea rates were essentially halved among GnRHa recipients compared with control patients, at 18.2% for those who received active treatment during chemotherapy compared with 30% for those who did not (P = .009).

Most importantly, 10.3% of the GnRHa group were able to become pregnant after the end of treatment, compared with 5.5% of those who received chemotherapy alone (P = .30).

Dr Lambertini pointed out that all of the pregnancies occurred in women aged 40 years and younger and that 84% of the pregnancies that did occur in the GnRHa group occurred in women with estrogen receptor–negative disease.

Importantly as well, "over 5 years of follow-up, there were no differences between the two groups in either disease-free or overall survival," Dr Lambertini noted, "attesting to the safety of this approach."

How to Counsel Women

Approached by Medscape Medical News as to how physicians should counsel young women with early breast cancer who are concerned about preserving ovarian function and, possibly, fertility, Dr Lambertini cautioned that giving a GnRHa during chemotherapy clearly does not prevent early menopause in all patients, but it does decrease the risk.

"So patients who are candidates for GnRHa use during chemotherapy are women who are concerned about developing early menopause and who are interested in preserving ovarian function even if they are not interested in becoming pregnant after completion of treatment," he said.

On the other hand, if a woman is interested in having a baby after completion of chemotherapy, "I think they first should be counseled about the use of cryopreservation procedures, because these are the more established techniques, and then the GnRHa can be given after the cryopreservation procedure is done," he added.

Women who do not have access to cryopreservation should proceed directly with GnRHa treatment during chemotherapy, Dr Lambertini suggested.

"For both of these groups of women, I think GnRHa should now be considered standard of care," he concluded.

Asked by Medscape Medical News to comment on the study, Jennifer Litton, MD, associate professor in the Department of Breast Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, said that patients should be encouraged to also seek out other management options.

"I think this is a reasonable option for patients, but I think it is also very important to proceed with a reproductive endocrinology consult when possible for consideration of oocyte retrieval prior to chemotherapy to further improve chances of future pregnancies," Dr Litton said in an email.

"However," she added, "due to cost and timing, that might not always be possible."

Importantly, an ongoing trial, the Pregnancy Outcome and Safety of Interrupting Therapy for Women With Endocrine Responsive Breast Cancer (POSITIVE) trial, is also investigating what happens when patients stop endocrine therapy to become pregnant and then resume it to complete the chemotherapy course.

The aim of the study is to investigate whether temporarily interrupting endocrine therapy in order to permit pregnancy is associated with a higher risk for breast cancer recurrence.

Studies indicate that approximately half of young women with newly diagnosed breast cancer are concerned about developing POI and that about the same percentage of women are interested in becoming pregnant once chemotherapy is completed.

Dr Lambertini has received consultant or advisor fees from Teva and a travel grant from Astellas. Dr Litton has received research funding from EMD Serono, AstraZeneca, Pfizer, Genentech, and GlaxoSmithKline and serves on advisory boards for Pfizer and AstraZeneca.

San Antonio Breast Cancer Symposium (SABCS) 2017: Abstract GS4-01, presented December 7, 2017.

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