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Figure  . Many women stop tamoxifen therapy well before their 5-year course is up. Learning the reasons why is important to developing interventions.

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A significant number of women who begin taking tamoxifen stop taking the drug well before completing the usual 5-year course of therapy, Irish researchers report in the journal CANCER (2007;109:832–839). In their study of pharmacy records for 2,816 women with a new tamoxifen prescription, 22.1% stopped taking the drug within the first year of treatment, and 35.2% had quit by 3.5 years. That could put them at higher risk of breast cancer recurrence, say Thomas I. Barron, MSc, and colleagues from Trinity College and St. James's Hospital in Dublin.

The issue of nonadherence to tamoxifen therapy—and indeed, oral cancer therapy in general—is one that is beginning to generate more interest and concern in the medical community, says Ann Partridge, MD, MPH, a staff member in the Department of Medical Oncology at Dana-Farber Cancer Institute and Assistant Professor in the Department of Medicine at Harvard Medical School who has also studied the topic extensively.

“People are just recognizing on a larger scale the impact of nonadherence,” says Partridge. “There isn't a whole lot of intervention research [on drug adherence] that's done today in the field of cancer, and one of the reasons for that is, conventionally, cancer therapy has been given in doctors' offices. But there's a burgeoning market of oral therapies where patients are taking more things outside the doctors' offices.”

That makes it increasingly important to pinpoint and address the reasons why patients fail to take their medications as prescribed or stop taking them altogether.

Because the Irish study looked only at prescription records and not diagnoses, medical records, or the patients themselves, the researchers could not fully explore why women stopped taking tamoxifen. The study did exclude women who began a different hormonal therapy within 6 months of stopping tamoxifen (25.4%). But it could not identify the percentages of women who may have quit because of a breast cancer recurrence or new cancer, or because of excessive toxicity.

Women aged 35 to 44 years and those over age 75 years were most likely to quit tamoxifen (hazard ratios [HR] 1.36 and 1.46, respectively). Women who had used antidepressants in the year before starting tamoxifen were also more likely to quit (HR 1.41).

Those findings offer some clues as to why women quit, Barron and his colleagues say. Perhaps older women are more likely to have cognitive impairments that make them forget their medication. Further, older women and their physicians may recognize that the absolute survival benefit of treatment decreases with shorter life expectancy, so the balance of benefits and side effects becomes less favorable for women who are older and/or have life-limiting comorbidities. Younger women may be less willing to accept the menopause-like side effects the drug can cause. But more research is needed to really understand what causes women to stray from their treatment plan, says Partridge.

“There are lots of reasons why people don't take their drugs, some of which are modifiable,” she explains.

For instance, people who often forget their medication may benefit from pill diaries or pill boxes to help them keep track of dosages, Partridge points out. Scheduling refills to coincide with other regular activities (monthly bill paying, quarterly oil changes) is another suggestion she offers patients. Refill reminders from pharmacies and insurance companies can also help women stick with their medication. Financial assistance programs from drug companies and other sources can help women who otherwise might not be able to afford their full course of treatment.

Side effects are another area where effective interventions are available, Partridge says. Hot flashes may be helped by vitamin E or SSRI antidepressants. The musculoskeletal complaints common to aromatase inhibitors can be addressed with NSAID pain relievers. Vaginal dryness can be ameliorated with over-the-counter remedies.

But patients and doctors need to talk about these issues if they hope to address them, Partridge says. Patients need to mention such problems to their doctor, and doctors should ask patients, too.

“I think on an individual level, the best thing a physician can do is consider the possibility of nonadherence and ask patients in a nonjudgmental way, ‘How's it going, are you remembering to take it, is it causing problems?’” she says. “The more communication there is, the better we are able to identify problems with adherence and intervene.”