One in six premenopausal women with early breast cancer do not adhere to adjuvant tamoxifen

Issue: November 25, 2018

MUNICH — Approximately one in six premenopausal women with early-stage breast cancer failed to adequately adhere to adjuvant tamoxifen therapy 1 year after starting treatment, according to prospective study results presented at European Society for Medical Oncology Congress.

Perspective from Helena Earl, MD

“This issue is important because nonadherence [to] hormonal therapy — meaning taking less than 80% of prescribed treatment — can be associated with higher risk of mortality and shorter time to recurrence of breast cancer,” study author Barbara Pistilli, MD, medical oncologist at Institut Gustave Roussy in Villejuif, France, said in a press release.

Patients with hormone receptor-positive breast cancer are urged to undergo hormonal therapy such as tamoxifen for 5 to 10 years.

Prior research showed many patients discontinue hormonal therapy before reaching the recommended cessation point, and that younger women tend to be more nonadherent.

The analysis included 1,177 premenopausal women prescribed adjuvant hormonal therapy for stage I to stage III breast cancer.

All women were enrolled in the CANTO cohort, a French prospective study designed to evaluate the long-term impact of side effects from breast cancer treatment, as well as the clinical and social characteristics that affect adherence to endocrine therapy.

Researchers measured tamoxifen serum levels to assess adherence at 1, 3 and 5 years, and compared results with patients’ self-reported adherence.

Serum assessment results showed 16% of the premenopausal women prescribed tamoxifen did not adhere adequately at 1 year, meaning tests showed tamoxifen levels less than 60 ng/mL.

Results showed 10.7% were nonadherent, meaning they had undetectable tamoxifen levels. Another 5.3% were poorly adherent, meaning they had tamoxifen levels below the steady-state concentration expected after 3 months of treatment.

“I was surprised at the high rate of nonadherence, which was considerably higher than reported previously,” Pistilli said in a press release. “Women with breast cancer should be encouraged to discuss their treatment and any side effects they experience with their doctor to obtain help to take their therapy.”

At least half of the women with low or undetectable tamoxifen levels failed to report that they were not adhering to treatment as prescribed, according to researchers.

“We should take time to explore with patients if they are experiencing side effects that can affect their adherence and support them to be open about nonadherence so that we can discuss options to help,” Pistilli said. “We need to understand the patients most at risk of being nonadherent early in their treatment, and provide targeted interventions aiming to improve their self-efficacy and self-management of side effects.”

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The researchers intend to develop an intervention to help improve hormonal therapy adherence among premenopausal women.

Researchers acknowledged study limitations. Because the results were based only on a French cohort, findings may not apply to other populations. Also, serum assessments reflected tamoxifen levels only during the month before testing, not the entire preceding year.

Pistilli and colleagues intend to continue measuring patients’ tamoxifen serum levels at 3 years and 5 years after treatment initiation, and to measure the effect of nonadherence on breast cancer recurrence and mortality.

The 1-year results suggest noncompliance with adjuvant hormonal therapy is “underappreciated and underreported,” according to Giuseppe Curigliano, MD, PhD, head of the early drug development division at European Institute of Oncology at University of Milan.

“Taking into account that many high-risk premenopausal women worldwide are receiving aromatase inhibitors plus ovarian suppression, both inducing more side effects than tamoxifen, we are underreporting the nonadherence rate in real life,” Curigliano, who was not involved with the study, said in the release. “We need also to identify factors that are associated with poor adherence.”

Physician-patient communication also is key, he said.

“It is important for physicians to have a good relationship with their patients and get a feel for the patient’s personality to be able to orient discussions positively and potentially counteract any misunderstandings in order to reduce poor compliance with treatment,” Curigliano said. – by Mark Leiser

Reference: Pistilli B, et al. Abstract 185O_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosure: UNICANCER provided funding for this study. The authors report no relevant financial disclosures.

Perspective

Helena Earl, MD

One of the biggest questions regarding adjuvant endocrine therapy is how long hormonal treatment should last. One crucial piece of information is how much of the prescribed treatment patients take. There is significant literature to show that adherence to hormonal therapy is poor and that adherence of 80% or less can affect outcomes.

Pistilli and colleagues sought to identify how to best measure adherence to endocrine therapy in this particular patient population. We must applaud this fantastic effort, which focused on cancer toxicities involving nearly 12,000 patients across 26 comprehensive cancer centers. The whole concept of focusing hard on what patients report as their toxicities and the known toxicities of our treatments is vitally important.

Part of the study included patient-reported outcomes after initial treatment with chemotherapy before tamoxifen therapy started. The researchers saw severe life-altering toxicities from treatment. In addition, many patients reported anxiety and depression. This shows how important it is for patients to report outcomes. Fifty-five percent of patients who were serum non-adherent had self-reported as adherent. This is a large number. If we simply ask patients about adherence, then this would wrongfully suggest that many are adhering to their treatments when they actually are not.

It appears that serum assessment is a more accurate assessment of adherence and that nonadherence is a significant issue, particularly among premenopausal women. This multidisciplinary team of researchers should be applauded for their clear focus on toxicities as it applies to treatment adherence for long-term therapies.

Helena Earl, MD

University of Cambridge

United Kingdom

Disclosures: