Young Women Refuse Tamoxifen Because of Fertility Concerns

Fran Lowry

August 28, 2015

Women of childbearing age who have breast cancer appear to be refusing to take tamoxifen, a potentially lifesaving drug, out of concern that it will affect their chance of having children, according to a study published online August 25 in the Journal of the National Cancer Institute.

"This study provides insight into factors associated with tamoxifen use for reproductive-aged breast cancer survivors, with a new focus on fertility. Fertility concerns negatively impacted tamoxifen initiation and continuation among premenopausal patients," said senior investigator Jacqueline S. Jeruss, MD, PhD, from the University of Michigan School of Medicine in Ann Arbor.

"Tamoxifen therapy has a significant beneficial impact on both the reduction in breast cancer recurrence and breast cancer mortality, yet it is a teratogen and cannot be taken safely during pregnancy," she told Medscape Medical News.

The initiation and continuation of tamoxifen has been poor in young breast cancer survivors, but the issues surrounding their reluctance have not been adequately studied, Dr Jeruss said.

This unique patient population "is contending with survivorship issues that are distinct from the more routinely studied postmenopausal population. Despite the poor tamoxifen utilization among younger patients, and the fact that tamoxifen is a teratogen, no study had evaluated predictors of noninitiation or early discontinuation unique to this population, or examined fertility concerns as a possible causative factor," she explained. "We felt this was an important untested issue to explore."

Reasons for Reluctance to Take Tamoxifen

For their study, Dr Jeruss and her colleagues identified 515 premenopausal women younger than 45 years who were diagnosed with stage 0 to III hormone-receptor-positive breast cancer from 2007 to 2012.

Tamoxifen was recommended for all of the women. At the time they were diagnosed, 112 (22%) of the women expressed a desire to bear children in the future.

Table. Use of Tamoxifen in the Study Cohort

Tamoxifen USe n %
Continued treatment 366 71.1
Declined initiation 69 13.4
Discontinued before 5 years 80 15.5


In addition to fertility concerns, the women were assessed for demographic, disease, and treatment characteristics, and these findings were linked with tamoxifen initiation and continuation.

Fertility concerns significantly influenced a woman's decision to continue or not to start tamoxifen treatment, the investigators report.

On multivariable analysis, fertility concerns were statistically associated with 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).

Other factors that predicted noninitiation included a diagnosis of ductal carcinoma in situ (P < .001), declining radiation therapy (P < .001), not receiving chemotherapy (for patients with invasive disease) (P = .012), being a current smoker (P = .041), being nulliparous (P = .038), and having a lumpectomy (P = .049).

Of the 69 patients who did not initiate tamoxifen treatment, nine (13%) thought there would be little benefit from the treatment, 24 (34%) planned to become pregnant, and 25 (36%) had concerns about adverse effects, the most common of which were uterine cancer (24%), thromboembolism (20%), and hot flashes (12%).

The investigators interviewed 88 women who had not initiated or had discontinued tamoxifen. Of these women, 10 (11.4%) said they thought tamoxifen had little benefit, 31 (35.2%) stated that fertility concerns primarily influenced their decision, and 47 (53.4%) were primarily concerned about adverse effects.

Although 31% of the women who attempted pregnancy reported initiating or resuming tamoxifen, 28% were unaware of the potential benefits of tamoxifen after a delay or hiatus.

Additionally, 9% of women felt that they had been inadequately informed about fertility preservation, and 3% faced financial constraints related to fertility preservation.

Include Fertility Preservation Options for These Women

"Interventions to optimize tamoxifen treatment initiation and persistence for young breast cancer patients should include access to fertility preservation options," Dr Jeruss said.

Fertility preservation is not being discussed as much as it should be for a number of reasons, she explained.

"Changing practice patterns to incorporate new treatment guidelines can take time. Fertility preservation counseling should be made available to young patients with cancer at the earliest possible time point after a patient's diagnosis. This will afford newly diagnosed patients with the greatest chance for the integration of fertility preservation options into the multidisciplinary treatment plan," Dr Jeruss said.

She added that studies have shown that 5 years of tamoxifen treatment reduces breast cancer recurrence by 47% and mortality by 26%, and that recent data suggest that continuing for up to 10 years might be even more beneficial.

"Modifiable risk factors associated with poor tamoxifen use should be addressed to help improve the implementation of this important cancer therapy for young patients," Dr Jeruss said.

"Oncologists should work toward a dialogue where patients can discuss the survivorship issues that are important to them. By creating such a dialogue, more patients may be identified who are willing to complete the recommended course of tamoxifen therapy, though this may involve a treatment delay or hiatus to allow for a pregnancy," she said. "Currently, the appropriateness of a delay or break in tamoxifen treatment should be evaluated on a patient-specific basis, with consideration given to physician recommendations and patient survivorship goals."

Treatment Decisions Complex

Adherence to endocrine treatment is especially critical to ensure optimal survival outcomes in young women, who are at higher risk for recurrence and death from breast cancer, write Shoshana M. Rosenberg, ScD, MPH, and Ann H. Partridge, MD, MPH, from the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

These findings "not only shed new light on the role of side effects," the pair explains, they also "draw attention to the impact of fertility concerns on adjuvant endocrine therapy decision-making,"

"Making the right choice about treatment is particularly complex for younger women who may want to have their own, biological children after their therapy," the editorialists note.

"Because of the increased risk of infertility with age alone, even if a woman remains premenopausal, achieving pregnancy after completion of even 5 years of adjuvant [endocrine treatment] may be particularly challenging for older premenopausal women with hormone-receptor-positive breast cancer," they write.

For young women deciding to whether to discontinue or not initiate endocrine therapy, this study "highlights the importance of understanding how issues unique to young women with breast cancer affect treatment decisions. In turn, accounting for their concerns and identifying effective strategies to manage them may enhance quality of care, quality of life, and survival," the editorialists conclude.

This study was supported by the Center for Reproductive Health After Disease 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. Dr Jeruss, Dr Rosenberg, and Dr Partridge have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online August 25, 2015. Abstract, Editorial


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