Impact of Fertility Concerns With Tamoxifen Use
Background: Adjuvant tamoxifen reduces breast cancer recurrence risk and mortality; however, initiation and treatment persistence are poor for younger patients. We hypothesized that a unique set of factors, including fertility concerns, would contribute to the poor tamoxifen use among premenopausal patients.
Methods: From 2007 to 2012, 515 premenopausal patients younger than age 45 years, with stage 0 to III hormone receptor–positive breast cancer, for whom tamoxifen was recommended, were identified. Clinical and pathologic tumor characteristics, treatment regimens, and fertility concerns were recorded. Clinical factors associated with tamoxifen noninitiation and discontinuation were identified using univariate and multivariable analysis. After the recommendation for tamoxifen, patient reasons for tamoxifen noninitiation or discontinuation were also documented. All statistical tests were two-sided.
Results: Based on multivariable analysis, fertility concerns were statistically associated with both noninitiation (odds ratio = 5.04, 95% confidence interval (CI) = 2.29 to 11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09 to 3.38) of tamoxifen. 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. Primary patient reasons for noninitiation and early discontinuation included concerns about side effects and fertility.
Conclusion: This study provided 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. Interventions to optimize treatment initiation and persistence for young cancer patients should include access to fertility preservation options.
Approximately 25 000 women under age 45 years are diagnosed with invasive or in situ breast cancer annually. As advances in cancer care have improved life expectancy, young survivors can prioritize both cancer treatment and survivorship goals. Fertility is a vital survivorship issue, with many cancer treatments involving chemotherapy, radiation, and hormonal modulation, all of which may impair ovarian function. For women of childbearing age, fertility concerns can have an important role in treatment decision-making. A survey of young breast cancer patients showed that more than half had concerns about treatment-related infertility, and 29% stated that fertility concerns influenced treatment decisions.
Hormonal modulation with tamoxifen is recommended for patients with hormone receptor–positive disease, representing approximately 70% of breast cancers. Five years of tamoxifen treatment reduces recurrence risk by 47% and mortality by 26%; recent data suggest continuing tamoxifen for up to ten years may also be beneficial. Despite these benefits, tamoxifen adherence is poor, particularly among young women. Many reproductive-aged patients who would benefit from tamoxifen have plans for future pregnancy; however, tamoxifen is teratogenic and pregnancy is contraindicated during treatment. As fertility declines with age, length of therapy may deter premenopausal patients. Although tamoxifen may not directly damage the ovaries, several studies report a higher rate of treatment-related amenorrhea, particularly after age 40 years. Additionally, recent data suggest that examestane, used in conjunction with ovarian suppression, may result in improved disease-free survival when compared with tamoxifen for premenopausal estrogen receptor–positive patients. This approach would also pose substantial challenges to young patients regarding childbearing and anti-estrogenic side effects.
Despite poor tamoxifen utilization among younger patients, no study has evaluated predictors of noninitiation or early discontinuation unique to this population or examined fertility concerns as a possible causative factor. Given the importance of fertility to young patients and its effect on treatment decisions, we hypothesized that fertility concerns negatively impacted tamoxifen initiation and continuation. Examination of the impact of fertility concerns on tamoxifen use is highly timely, serving as primary data supporting the rationale for the actively accruing International Breast Cancer Study Group POSITIVE trial for hormone receptor–positive, premenopausal breast cancer patients planning a pregnancy. Outcomes of the POSITIVE study, regarding the safety of taking a hiatus from tamoxifen as well as pregnancy outcomes, will provide critical information for young breast cancer suvivors with fertility concerns. The goal of the current study was to investigate the potential association between fertility concerns and noninitiation or early discontinuation of tamoxifen in a cohort of premenopausal breast cancer patients, while taking into account additional factors that might also have a role in treatment implementation.
Abstract and Introduction
Abstract
Background: Adjuvant tamoxifen reduces breast cancer recurrence risk and mortality; however, initiation and treatment persistence are poor for younger patients. We hypothesized that a unique set of factors, including fertility concerns, would contribute to the poor tamoxifen use among premenopausal patients.
Methods: From 2007 to 2012, 515 premenopausal patients younger than age 45 years, with stage 0 to III hormone receptor–positive breast cancer, for whom tamoxifen was recommended, were identified. Clinical and pathologic tumor characteristics, treatment regimens, and fertility concerns were recorded. Clinical factors associated with tamoxifen noninitiation and discontinuation were identified using univariate and multivariable analysis. After the recommendation for tamoxifen, patient reasons for tamoxifen noninitiation or discontinuation were also documented. All statistical tests were two-sided.
Results: Based on multivariable analysis, fertility concerns were statistically associated with both noninitiation (odds ratio = 5.04, 95% confidence interval (CI) = 2.29 to 11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09 to 3.38) of tamoxifen. 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. Primary patient reasons for noninitiation and early discontinuation included concerns about side effects and fertility.
Conclusion: This study provided 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. Interventions to optimize treatment initiation and persistence for young cancer patients should include access to fertility preservation options.
Introduction
Approximately 25 000 women under age 45 years are diagnosed with invasive or in situ breast cancer annually. As advances in cancer care have improved life expectancy, young survivors can prioritize both cancer treatment and survivorship goals. Fertility is a vital survivorship issue, with many cancer treatments involving chemotherapy, radiation, and hormonal modulation, all of which may impair ovarian function. For women of childbearing age, fertility concerns can have an important role in treatment decision-making. A survey of young breast cancer patients showed that more than half had concerns about treatment-related infertility, and 29% stated that fertility concerns influenced treatment decisions.
Hormonal modulation with tamoxifen is recommended for patients with hormone receptor–positive disease, representing approximately 70% of breast cancers. Five years of tamoxifen treatment reduces recurrence risk by 47% and mortality by 26%; recent data suggest continuing tamoxifen for up to ten years may also be beneficial. Despite these benefits, tamoxifen adherence is poor, particularly among young women. Many reproductive-aged patients who would benefit from tamoxifen have plans for future pregnancy; however, tamoxifen is teratogenic and pregnancy is contraindicated during treatment. As fertility declines with age, length of therapy may deter premenopausal patients. Although tamoxifen may not directly damage the ovaries, several studies report a higher rate of treatment-related amenorrhea, particularly after age 40 years. Additionally, recent data suggest that examestane, used in conjunction with ovarian suppression, may result in improved disease-free survival when compared with tamoxifen for premenopausal estrogen receptor–positive patients. This approach would also pose substantial challenges to young patients regarding childbearing and anti-estrogenic side effects.
Despite poor tamoxifen utilization among younger patients, no study has evaluated predictors of noninitiation or early discontinuation unique to this population or examined fertility concerns as a possible causative factor. Given the importance of fertility to young patients and its effect on treatment decisions, we hypothesized that fertility concerns negatively impacted tamoxifen initiation and continuation. Examination of the impact of fertility concerns on tamoxifen use is highly timely, serving as primary data supporting the rationale for the actively accruing International Breast Cancer Study Group POSITIVE trial for hormone receptor–positive, premenopausal breast cancer patients planning a pregnancy. Outcomes of the POSITIVE study, regarding the safety of taking a hiatus from tamoxifen as well as pregnancy outcomes, will provide critical information for young breast cancer suvivors with fertility concerns. The goal of the current study was to investigate the potential association between fertility concerns and noninitiation or early discontinuation of tamoxifen in a cohort of premenopausal breast cancer patients, while taking into account additional factors that might also have a role in treatment implementation.
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