Patients' Decision to Stop Tamoxifen: An Under-Appreciated Confounder
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC. Dr. Ershler reports no financial relationship to this field of study.
Synopsis: Using a large pharmacy data base, Irish investigators tracked Tamoxifen use and calculated prescription adherence. By 3.5 years after initial dose, approximately 1/3 of patients had discontinued use. These findings are more dramatic than those observed for women receiving tamoxifen on clinical trial, suggesting the prevalence of non-adherence might be greater in the community than in academic settings.
Source: Barron TI, et al. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007;109:832-839.
It has been well established that a minimum of five years of tamoxifen therapy is optimal for preventing breast cancer recurrence and mortality in women who have been found to be appropriate candidates for hormonal therapy. Previous studies have shown a relative risk reduction in breast cancer recurrence and mortality by 46 and 26 percent respectively in those patients who receive the full 5 year course of adjuvant tamoxifen therapy.1 Yet, it is also clear that not all women complete the prescribed course. In the past, rates of tamoxifen nonpersistence have been reported from clinical trial data. These rates likely underestimate the true discontinuation rates in the community as patients who enter clinical trials usually are more motivated to adhere to prescribed treatment regimens.
The current study uses objective methods to evaluate tamoxifen persistence in patients who are not enrolled in clinical trials. The Irish Health Services Executive Primary Care Reimbursement Services (HSE-PCRS) pharmacy provided the database for the study population. HSE-PCRS provides free medical care and medications to approximately 33 percent of the total population of Ireland. Prescription refill data were available for 2816 women who were prescribed tamoxifen for breast cancer between 2000 and 2005 and the study population was identified to include 2816 women over the age of 35 who received initial hormonal therapy with tamoxifen between January 2001 and January 2004. The nonpersistence rates were found to be 11.1% at 30 days, 14.5% at 90 days, 22.1% at 1 year, 28.4 % at 2 years, and 35.2% at 3.5 years.
Univariate and adjusted models were used to evaluate for potential predictors of nonpersistence. Age greater than 75 years, the use of antidepressants in the year prior to tamoxifen therapy, and the presence of Parkinson's disease or dementia wereeach shown to have correlation with treatment non-compliance.
These are fairly shocking results. The observed nonpersistence rate of 35.2% at 3.5 years is higher than the 5 year rates seen in self reported studies of persistence (31%)2 and in clinical trials of adjuvant tamoxifen.3, 4 Thus, more than 1/3 of community patients had discontinued the drug by 3 years of an intended 5 year course. The number is certainly higher than expected and more than reported from clinical trials. Yet, it is likely to reflect what is happening in the community setting in which the great majority of breast cancer is treated.
Clinicians should take note, make an effort to determine prescription adherence, and develop strategies to enhance compliance. One likely factor is the coexistence of clinical depression and its effect on drug compliance and to the extent that this can be effectively treated, tamoxifen compliance and breast cancer outcomes may follow suit. Additional studies are needed to identify other modifiable factors contributing to lack of adherence of tamoxifen, and presumably other oral chemotherapies.
1. Ryan PD, Goss PE. Adjuvant hormonal therapy in peri- and postmenopausal breast cancer. Oncologist. 2006;11(7):718-731.
2. Lash, TL, et al., Adherence to tamoxifen over the five-year course. Breast Cancer Res Treat. 2006;99(2):215-220.
3. Fisher B, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol. 2002;20:4141-4149.
4. Fyles, AW, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004;351(10):963-970.