By Shira Klapper, Senior Writer/Editor

Why do some women with breast cancer discontinue adjuvant hormone therapy, such as tamoxifen and aromatase inhibitors? That’s the question at the heart of a study carried out by researchers at the Karolinska Institute in Stockholm, Sweden and the University of Maryland, Baltimore. The study, “Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer,” found that women at higher risk of stopping treatment were more likely to have a family history of ovarian cancer, to be younger than 40, to be age 65 and older, and to use analgesics and hypnotics/sedatives, among other factors. The study was published in the Journal of Clinical Oncology (JCO), online, ahead of print, June 1, 2015.

The study’s first author, Wei He, PhD, explained the clinical importance of understanding the factors associated with discontinuing adjuvant hormone therapy.

“Previous studies have found that adjuvant hormone therapy can reduce the risk of breast cancer recurrence by 41% and cancer specific mortality by 31%,” said Dr. He. “However, over half of patients will discontinue treatment, and only a few factors have been found to predict this discontinuation. For example, according to a recent review, only two factors—[hepatic enzyme] CYP2D6 activity and switching therapy between tamoxifen and aromatase inhibitors—were consistently and significantly identified as predictors for discontinuation. We felt it was important to identify additional factors.”

Other major known reasons for discontinuing adjuvant hormone therapy include treatment-related side effects, such as pain, depression, sleep disorders, and GI reactions such as nausea and vomiting. These side effects are often treated with symptom-relieving drugs.

Risk factors at baseline and during treatment with adjuvant hormonal therapy

The researchers sought to answer two questions: First, are there baseline characteristics, such as age and use of hormone replacement therapy (HRT), that predict who will be at increased risk of discontinuing adjuvant hormone therapy? And second, in the first year of treatment—once treatment with adjuvant hormone therapy has already begun—is the risk of discontinuing treatment higher among patients who use symptom-relieving drugs or who switch therapy between tamoxifen and aromatase inhibitors?

To answer these questions, the researchers looked at 3,395 women with breast cancer in Sweden who had been diagnosed between 2005 and 2008, and followed them for five years, from the point of patients’ first prescription of adjuvant hormone therapy and onward. Data on the women was gathered from Swedish breast cancer and drug registries and a self-reported questionnaire.  

Analysis of the data showed that over half of the women discontinued adjuvant hormonal therapy during the five-year follow up period, and that among those who discontinued treatment, 74% stopped after the first year.

Age, use of analgesics, and hormone replacement therapy, among risk factors

The study found that women at higher risk of stopping treatment were more likely to have the following baseline characteristics: a family history of ovarian cancer, age younger than 40, age 65 or older, use of analgesics and hypnotics/sedatives, and use of GI drugs. Women who used hormone replacement therapy one year before diagnosis of breast cancer had a higher risk of discontinuation in the first year of adjuvant hormonal therapy (HRT), but not afterwards. The JCO article stated that the increased risk found among women under age 40 is concerning since women in this age-group have a worse prognosis, particularly if they discontinue adjuvant hormonal therapy.

Commenting on these findings, Dr. He said, “Our study added at least two points to the literature. First, drugs for pain, depression, sleep disorders, and gastrointestinal disorders used in the first year can predict discontinuation in the following four years, meaning that for those who had side effects, simply prescribing symptom-relieving drugs is not enough. Second, hormone replacement therapy in postmenopausal women can predict discontinuation in the first year, but not afterwards, meaning that early and later discontinuation may have different causes, and different interventions may be needed to prevent early and later discontinuation.”

As for the study’s second question, the data found that women at higher risk of stopping treatment were more likely to switch between tamoxifen  and aromatase inhibitors and to fill at least one prescription of symptom-relieving drugs during the first year of adjuvant hormonal therapy.

Dr. He said the findings from the JCO study can lay the groundwork for an intervention.

“Clinicians can now use our results to identify factors that predict which patients will stop using adjuvant hormone therapy. And this can provide a basis for interventions to prevent discontinuation and to improve outcomes of patients with breast cancer.”

Wei He, PhD, is a postdoctoral fellow in the department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden.

Abstract of the original JCO article.

PDF of the original JCO article.

He W, Fang F, Varnum C, et al. Predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. J Clin Oncol. Epub 2015 June 1.

The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology