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To Optimize Tamoxifen Use Among Premenopausal Women With Breast Cancer, Include Access to Fertility-Preservation Options

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Key Points

  • Fertility preservation is a significant factor for premenopausal women with hormone receptor–positive breast cancer declining, delaying, or discontinuing use of tamoxifen.
  • Other predictors of noninitiation include a diagnosis of ductal carcinoma in situ, declining radiation, and not receiving chemotherapy.
  • Significant predictors of early discontinuance are smoking and not receiving radiation therapy.

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,” Llarena et al reported in the Journal of the National Cancer Institute.

The researchers identified 515 premenopausal patients younger than 45 years of year 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.

Fourteen Factors Considered

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 (56%) agreed to participate and 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.

Multivariable analysis indicated that fertility concerns were statistically associated with both noninitiation (odds ratio = 5.04, 95% confidence interval [CI] = 2.29–11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09–3.38) of tamoxifen, 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.”

Fertility-Preservation Options

Patients who are likely to not 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 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 (GNRHa) are also being investigated to help preserve ovarian function during exposure to chemotherapy,” the authors added. While recent results “were encouraging,” the authors noted that prior studies with GNHRa “failed to show benefit” and both ASCO and National Comprehensive Cancer Network “guidelines currently state this treatment to be ‘unproven or inconclusive,’ until additional data is 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 wrote.  

Jacqueline S. Jeruss, MD, PhD, of the University of Michigan, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the Center for Reproductive Health After Disease (P50HD076188) from the National Institutes of Health National Center for Translational Research in Reproduction and Infertility and by Northwestern University’s Medical Student Summer Research Program.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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