Nearly one in six premenopausal women being treated for early-stage breast cancer do not adhere adequately to tamoxifen therapy after one year of treatment, potentially putting themselves at increased risk of recurrence and reduced survival, a French prospective study reports at ESMO 2018 Congress.

Hormonal therapy such as tamoxifen is recommended for five to ten years in all patients with hormone receptor-positive breast cancer but previous research has shown that many discontinue long-term therapy.

“This issue is important because non-adherence with 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,” said lead author Barbara Pistilli, a medical oncologist at Institut Gustave Roussy, Villejuif, France.

The French study is the first to assess adherence by measuring serum levels of tamoxifen rather than simply asking patients about how they take their treatment; there has previously been limited information on adherence to hormonal therapy in younger women.

“I was surprised at the high rate of non-adherence, which was considerably higher than reported previously,” said Pistilli. “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.”

The study included patients recently diagnosed with early (stage I-III) breast cancer in the CANTO cohort, which is a French prospective study investigating the long-term impact of side-effects with breast cancer treatments in around 12,000 participants. The researchers focused on the sub-group of 1799 (16%) premenopausal women prescribed adjuvant hormonal therapy, assessing their adherence to tamoxifen by measuring serum levels at one, three and five years and comparing this with patients’ self-reports of adherence.

The study is also exploring clinical and social characteristics that could impact on adherence to endocrine therapy with the aim of identifying patients most at risk of not taking endocrine therapy as recommended.

Results showed that nearly one in five (16.0%; 188/1177) of the premenopausal women prescribed tamoxifen were not adequately adherent at one year based on serum assessment of tamoxifen (defined as <60 ng/ml)

Just over one in ten (10.7%) were non-adherent, with undetectable levels of tamoxifen. A further 5.3% of patients were poorly adherent, with serum levels of tamoxifen below the steady-state concentration expected after 3 months of treatment.

Analysis of patients’ self-reports showed that at least 50% of patients with undetectable/low tamoxifen levels did not declare they were not taking their tamoxifen as prescribed.

Pistilli commented, “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 non-adherence so that we can discuss options to help.” She added, “We need to understand the patients most at risk of being non-adherent early in their treatment and provide targeted interventions aiming to improve their self-efficacy and self-management of side-effects.”

Based on their findings, the researchers now plan to develop an intervention to support improved adherence to hormonal therapy in premenopausal women.

Commenting on the study for ESMO, Giuseppe Curigliano, Head of the Early Drug Development Division at the European Institute of Oncology, University of Milan, Italy, said: “The fact that 16% of patients appeared not adequately adherent to tamoxifen should, in my opinion, suggest strategies to increase adherence.” He warned: “Non-compliance with adjuvant hormonal treatment is an under-appreciated and under-reported problem and places patients at risk of inadequate clinical benefit. 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 under-reporting the non-adherence rate in real life.”

Curigliano suggested, “We need also to identify factors that are associated with poor adherence.” He noted that patients’ beliefs about cancer and their treatment have been shown to be predictive factors for adherence, with fear of recurrence supporting adherence to therapy.

“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,” he said.

Pistilli acknowledged that limitations of the study included the fact that it was based on a French cohort, so may not necessarily apply elsewhere. It was not designed to investigate patients’ fertility concerns and these are going to be investigated in the future. In addition, serum tamoxifen was measured at only one timepoint, reflecting levels over the previous month, and not across the whole year.

The study will continue to measure serum tamoxifen after three and five years of treatment and the impact of non-adherence on mortality and breast cancer recurrence in long-term follow-up.