Tamoxifen Use and Access to Fertility-Preservation Options Among Premenopausal Women With Breast Cancer

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A multivariable analysis of clinical factors associated with tamoxifen use among premenopausal women with hormone receptor–positive breast cancer showed that fertility preservation was a significant factor and “the only predictor of both noninitiation and early cessation” of tamoxifen. “Among patients who delayed or declined initiation, 34% cited pursuit of fertility as the reason for noninitiation. Furthermore, 25% of patients who discontinued stated they prioritized fertility,” Natalia C. Llarena of Northwestern University Feinberg School of Medicine, Chicago, and colleagues reported in the Journal of the National Cancer Institute.

The researchers identified 515 premenopausal patients younger than 45 years of age with stage 0 to III hormone receptor–positive breast cancer treated at Northwestern Memorial Hospital’s Lynn Sage Comprehensive Breast Center from 2007 to 2012. “The study was restricted to premenopausal patients for whom adjuvant tamoxifen was recommended,” the authors noted.

A total of 366 women (71.1%) were using tamoxifen. Those who did not start or discontinued use of tamoxifen were contacted by telephone “for a semistructured interview to further evaluate reasons for tamoxifen noninitiation and nonpersistence,” the authors explained. Among the 69 patients (13.4%) who delayed or did not start tamoxifen, 39 patients (56%) agreed to participate; among the 80 patients (15.5%) who discontinued tamoxifen before 5 years, 49 (61%) agreed to participate.

Fourteen factors were considered in univariate analyses for potential association with not starting or discontinuing use of tamoxifen: age at diagnosis, race/ethnicity, marital status, smoking status, alcohol use, parity, insurance status, fertility concerns, anxiety/depression, obesity, surgery (mastectomy or lumpectomy), chemotherapy for stage I to III disease, radiation therapy, and stage of disease.

“Based on multivariable analysis, fertility concerns were statistically associated with both noninitiation (odds
ratio = 5.04, 95% confidence interval (CI) = 2.29–11.07) and early discontinuation of tamoxifen (hazard ratio = 1.78, 95% CI = 1.09–3.38),” the researchers reported. Other independent predictors of noninitiation included a diagnosis of ductal carcinoma in situ, declining radiation, and not receiving chemotherapy (stage I-III). Additionally, smoking and not receiving radiation therapy were statistically significant predictors of early withdrawal from therapy.”

Patient Counseling

Patients who are likely not to initiate tamoxifen, including those with early-stage disease and who decline other adjuvant treatments, “may benefit from education about personal recurrence risk and benefits of tamoxifen,” the authors wrote. “Young patients who decline to initiate should also receive focused counseling about side effects. Importantly, 24% of patients cited concerns about tamoxifen and risk of endometrial cancer as a reason for noninitiation.” As the authors noted, however, “premenopausal women treated with tamoxifen have not been found to be at increased risk for endometrial cancer.”

The investigators listed several available options that can be discussed with young patients concerned about preserving their reproductive potential. “Embryo cryopreservation is the most established method, and oocyte cryopreservation is also a viable option. Ovarian tissue cryopreservation remains an experimental procedure, and technologies to expand this technique are evolving,” the researchers wrote.

“Gonadotropin-releasing hormone analogs are also being investigated to help preserve ovarian function during exposure to chemotherapy,” the authors added. Although recent results “were encouraging,” the authors noted that prior studies with gonadotropin-releasing hormone analogs “failed to show benefit,” and both ASCO and National Comprehensive Cancer Network (NCCN) guidelines currently consider this treatment to be “‘unproven or inconclusive’ until additional data are obtained.”

Despite the availability of fertility options and the importance of fertility to young patients, “fertility preservation is often underutilized and underdiscussed in clinical settings,” the authors concluded.  ■

Llarena NC, et al: J Natl Cancer Inst. August 25, 2015 (early release online).