A large Irish study of women who were prescribed tamoxifen showed that 22.1% had stopped taking the drug within a year (Cancer 2007 Jan 27, doi: 10.1002/cncr.22486). Within 3.5 years, the number who had stopped had risen to 35.2%.
Thomas Barron and colleagues from Trinity College and St James's Hospital, Dublin, warn that the study raises concerns about patients failing to persist with oral hormonal treatments for breast cancer and oral antineoplastic agents in general.
“Five years of adjuvant tamoxifen is the recommended treatment and results in a reduction in the relative breast cancer recurrence risk of 46% and the relative risk of death of 26%,” the authors wrote.
Women who receive fewer than five years of tamoxifen have significantly higher rates of recurrence and death, they say. Not adhering to treatment or, particularly, stopping it early are “likely to result in significantly worse outcomes.”
About 75% of breast cancers are hormone receptor positive, and, therefore, the women are candidates for treatment with tamoxifen or other hormonal agents.
Using the pharmacy database of the Irish Health Service's Executive Primary Care Reimbursement Service, the investigators identified all women older than 35 years who began taking tamoxifen between January 2001 and January 2004. The service provides free health care, including prescription drugs, to 1.15 million people, about a third of the total population. Elderly and disadvantaged people are over-represented. A third of the women in the cohort were older than 75 years.
Of the study cohort of 2816 women, 16.7% were lost to follow-up (because of death, loss of eligibility for the health insurance, and other factors). Another 25.4% stopped tamoxifen and switched to a different hormonal treatment within 180 days. About 26% were “considered non-persistent with therapy” because they either stopped tamoxifen and did not take another hormonal therapy until after 180 days; or stopped tamoxifen for at least 180 days before restarting it; or stopped it entirely, without restarting it or changing to another hormonal therapy. Only 31.4% persisted with tamoxifen to the end of follow-up at 3.5 years.
“This is the largest study of tamoxifen persistence to date … The results demonstrate that persistence with tamoxifen in clinical practice is lower than previously reported and must be considered a barrier to the use of oral hormonal therapies in breast cancer patients,” the authors wrote.
Women older than 75 and aged 35-44 years were more likely to stop taking tamoxifen than women in other age groups. In elderly people, this might be because of decreased social support and increasing physical and mental impairment. The reason in younger women is unclear; the authors say it may be because of difficulties in accepting the diagnosis.
Women who persisted with treatment often received more prescription drugs, such as antidepressants and tranquillisers. Depression is often a reason for poor adherence to treatment and lower survival in breast cancer, the authors say. Use of tamoxifen together with a selective serotonin reuptake inhibitor or a selective serotonin-noradrenaline reuptake inhibitor might reduce the severity of vasomotor symptoms associated with tamoxifen, they say.