For roughly 80% of breast cancer survivors, treatment doesn’t end with surgery, radiation and chemotherapy. Instead, for the next five to 10 years, doctors recommend that they take medication to block sex hormones, which can fuel tumor growth and spark recurrence.

The drugs are life-saving: They've been shown to cut risk of cancer recurrence by as much as half in patients with hormone receptor-positive tumors (HR+) - the most common form of breast cancer. Yet despite their promised benefits, 40% of patients stop taking them early and a third take them less frequently than directed.

New CU Boulder research, published this month in the Journal of Clinical Oncology, sheds light on why that is and what doctors and the health care system can do about it.

It found that, overall, interventions can increase medication adherence by nearly 1.5 times. But some strategies work better than others.

"Our bottom-line finding is that there are strategies that do work in supporting women to take these life-extending medications, and that we as a cancer care community need to do better," said senior author Joanna Arch, a professor in the Department of Psychology and Neuroscience and member of the CU Cancer Center on the Anschutz Medical Campus.

Arch noted these so-called "adjuvant endocrine therapies," like the estrogen-blockers Tamoxifen and aromatase inhibitors, can be costly and come with a host of side effects, including weight gain, sexual side effects, joint pain, depression and sleeplessness.

"Imagine going from your normal estrogen activity to little or no estrogen within days. That's what these medications do," she said. "But the women who take them as prescribed also have lower recurrence rates and live longer. It’s a dilemma."

As more next-generation cancer drugs, including chemotherapy agents, shift from infusions provided in a clinic to oral therapies taken at home, the medical community has grown increasingly interested in developing ways to make sure patients take their pills.

In a sweeping meta-analysis, Arch and her colleagues analyzed 25 studies representing about 368,000 women to gain insight into what works and what doesn’t.

Educational pamphlets are not enough

The study found that cost-cutting policy changes, such as providing generic alternatives or requiring insurance companies to cover pills at the same level as infusions, consistently worked. Such "oral parity laws" have been passed in 43 states in recent years.

In one study, participants were asked to create stickers to put on their pill boxes.

Mobile apps and texts to remind patients to take their medication and psychological/coping strategies also yielded modest improvements.

The study's findings around managing side effects were complicated: Simply educating women on side effects, via pamphlets or verbal explanations, generally failed to increase the likelihood that women took their medication as directed.

But things such as physical therapy, exercise and behavioral counseling aimed at alleviating or managing side effects often worked.

"Education in and of itself is not enough. That is a clear finding," said Arch, suggesting that doctors write referrals to practitioners who specialize in side effects and follow up with appointment reminders. "Most oncologists, I believe, don't realize how low adherence is for these women. They assume that if they write the prescription, it’s being taken."

Addressing mental health is key

One study included in the meta-analysis was Arch's own.

In it, women were asked to identify their primary motivation for taking their medication - whether it was living to see their child or grandchild grow up, pursuing their art or running a marathon someday. Via an online program, they created a sticker with a photo representing that goal, and the words "I take this for..." below it. Then, they stuck it on their pill box.

Participants were more likely to take their pills, at least for the first month, than those who didn't.

"Even just a tiny thing like this can help," said Arch.

Notably, very few studies looked at whether treating depression can help. Arch, aiming to fill this gap, recently launched her own pilot trial.

"One of the most consistent predictors of not adhering to any medication is depression," she said. "Depression taps motivation."

The new Journal of Clinical Oncology study is the first meta-analysis to show that interventions can be helpful, and that’s important, said Arch, because insurance companies need data to make decisions about what to cover.

But the study also showed that the effects are relatively modest and that there is room for improvement.

Arch said she hopes the study will spark more research into novel ways to support survivors: "We have a lot of work to do."

Bright EE, Finkelstein LB, Nealis MS, Genung SR, Wrigley J, Gu HCJ, Schmiege SJ, Arch JJ. A Systematic Review and Meta-Analysis of Interventions to Promote Adjuvant Endocrine Therapy Adherence Among Breast Cancer Survivors. J Clin Oncol. 2023 Aug 2:JCO2300697. doi: 10.1200/JCO.23.00697