Long-term outcomes of preventing premature menopause during chemotherapy

The majority of young women with invasive breast cancer are candidates to receive both chemotherapy and endocrine therapy. Loss of ovarian function and impaired fertility are possible consequences of anticancer treatments. Fertility concerns can affect treatment decisions of young women with breast cancer. Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy, according to background information in the article.

Lucia Del Mastro, M.D., of the Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy and colleagues randomly assigned 281 premenopausal women (median age, 39 years) with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer to receive chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The trial was conducted at 16 Italian sites. Women were enrolled between October 2003 and January 2008; last annual follow-up was June 2014. Median follow-up was 7.3 years.

The 5-year cumulative incidence estimate of menstrual resumption was 73 percent among the 148 patients in the LHRHa group and 64 percent among the 133 patients in the control group. Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1 percent) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6 percent) in the control group. Five-year disease-free survival was 80.5 percent in the LHRHa group and 84 percent in the control group. This increased but statistically nonsignificant risk appeared specific to the patients with hormone receptor-negative tumors.

The authors write that these results, together with the findings of another study (POEMS-SWOG S0230), "indicate that, in addition to fertility preservation strategies such as embryo and oocyte cryopreservation, temporary ovarian suppression with LHRHa is an option to preserve ovarian function in premenopausal women with early stage breast cancer receiving adjuvant chemotherapy."

Editorial: Prevention of Premature Menopause and Preservation of Fertility in Young Cancer Survivors

"The report by Lambertini et al in this issue of JAMA adds long-term follow-up information to the growing literature regarding the use of LHRHa through chemotherapy for the prevention of premature menopause, a desired outcome for some patients for prevention of associated menopausal symptoms and adverse health effects," writes Ann H. Partridge, M.D., M.P.H., of the Dana-Farber Cancer Institute, Boston, in an accompanying editorial.

"Although the findings suggest modest benefits regarding the potential prevention of treatment-associated infertility, collectively these studies reflect the emerging importance of understanding and improving such critical quality-of-life issues, offering patients new treatment and supportive care options, and ultimately providing hope regarding an issue that is highly valued by many young patients diagnosed with cancer."