Antidepressants and Breast Cancer Treatment Interactions
| Institution: | Kaiser Foundation Research Institute | ||
| Investigator(s): |
Reina Haque , Ph.D. -
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| Award Cycle: | 2008 (Cycle 14) | Grant #: 14IB-0086 | Award: $125,607 |
| Award Type: | IDEA | ||
| Research Priorities | |||
| Etiology>Environment and gene/environment interactions: nature vs. nurture | |||
Initial Award Abstract (2008)
Thousands of American women with breast cancer are taking tamoxifen to reduce their chances of developing a recurrence or a second primary cancer. Tamoxifen has been on the market for nearly 25 years and the manufacturer claims an exposure history of 10 million patient years. Despite its success in reducing cancer risk and recurrence, tamoxifen's serious side effects include stroke and venous thrombosis. Non-fatal but notable side effects that diminish a woman's quality of life and quality of sleep include vasomotor effects (hot flashes and night sweats) and depression. Because hormone replacement therapy commonly used to alleviate these symptoms is contraindicated for women with breast cancer, antidepressants increasingly have been used to relieve clinical depression and the hot flashes caused by tamoxifen. Our interest is in the relationship between combined tamoxifen and antidepressant medication use and breast cancer recurrence. A few recent laboratory-based studies suggest that certain common antidepressants, such as Paxil, may interfere with tamoxifen’s effectiveness in preventing breast cancer recurrence. Some recent reports caution physicians not to prescribe common antidepressant medications with tamoxifen. Nevertheless, no compelling studies on health outcomes have been published to demonstrate the ability of antidepressant drugs to diminish tamoxifen’s effectiveness. To address whether women are at an elevated risk for subsequent breast cancer (recurrence or second primary) when using certain antidepressants, we will assemble a large group of women with diverse ages, incomes, and racial/ethnic backgrounds from the membership of Kaiser Permanente Southern California (KPSC) health plan who were diagnosed with their first breast cancer lesion from 1996 to 2006. We will follow them over time to determine how many of these patients developed subsequent breast cancer. We plan to examine breast cancer risk in two main groups of women: (1) those who were treated with both antidepressants and tamoxifen after their initial disease, and (2) women who were exposed to tamoxifen only (this will be the comparison group). We will analyze whether breast cancer recurrence varies by types of antidepressants, and identify factors that may confound or modify this association such as demographics, tumor characteristics, comorbidities (additional disorders or diseases), or the use of other medications. As both depression and hot flashes are extremely common in breast cancer patients, information about the safety or the adverse effects of combined tamoxifen and antidepressant use is crucial. Given the new concerns of this potential adverse drug interaction, this study is well-timed.
Progress Report 1 (2009)
This study will determine whether concurrent use of antidepressant medications (including SSRIs or other types) and tamoxifen poses serious health threats among breast cancer survivors by elevating subsequent breast cancer risks compared with women who were exposed only to tamoxifen. To date, we have assembled a cohort of over 12,000 early stage breast cancer survivors of diverse racial/ethnic backgrounds, ages, and incomes from the membership of the Kaiser Permanente Southern California health plan. These women were diagnosed with breast cancer between 1996 and 2006 and exposed to tamoxifen therapy. They will be followed through 2008. Given our access to one of the finest clinical data bases in California, we were able to retrieve comprehensive health information on these women including tumor characteristics, primary and adjuvant therapy, demographics, healthcare utilization, and pharmacy prescriptions. Further, we have developed an automated data algorithm that identifies the primary outcome (breast cancer recurrence and second primaries). Our preliminary data show that nearly half of the breast cancer survivors were exposed to both tamoxifen and antidepressants. Of those exposed, nearly 40% were specifically exposed to SSRIs. Roughly 23% of the survivors were of minority backgrounds. Additional analyses examining the association of combined use of antidepressants and tamoxifen on subsequent breast cancer are underway. We anticipate completing the analyses of the primary aims by December 2009 and manuscripts by July 2010. Antidepression medications are commonly used to treat both depression and hot flashes due to tamoxifen use among breast cancer patients. Information about the safety or the adverse effects of combined tamoxifen and antidepressant use would have far reaching clinical implications in treating the depression and hot flashes many women experience after a diagnosis of breast cancer. If an association is not found, this would provide reassurance to continue prescribing certain antidepressant medications to women diagnosed with breast cancer.
Symposium Abstract (2010)
Reina Haque (PI), Chantal Avila, Jiaxiao Shi, Joanie Chung, Craig Cheetham, Virginia P. Quinn
Kaiser Permanente Southern California
Overview of the research topic and relevance to breast cancer: Thousands of women diagnosed with breast cancer (BCa) are taking tamoxifen to improve their chances of survival. Despite its success in reducing the risk of future BCa, tamoxifen's side effects include stroke and blood clots, hot flashes, and night sweats. Increasingly, antidepressants have been used to relieve some of these symptoms. Of concern, a few recent laboratory-based studies suggest that certain common antidepressants called selective serotonin re-uptake inhibitors (SSRIs) interfere with tamoxifen's effectiveness. Recent reports even caution physicians not to prescribe these antidepressant medications with tamoxifen. Very few studies have attempted to assess the effect of the interaction between antidepressants with tamoxifen on long-term outcomes.
The research question: The overarching goal of the study is to determine whether women are at an elevated risk for overall death or BCa death when they use antidepressants while receiving tamoxifen therapy.
General methods: We assembled a large group of socioeconomically diverse women from the membership of the Kaiser Permanente Southern California health plan who were diagnosed with their first BCa in 1996-2006 and followed through 12/31/07 to determine how many of these patients died. We then compared the mortality rates among mutually exclusive groups of antidepressant users: (1) paroxetine, (2) fluoxetine, (3) other SSRIs (sertaline & citalopram), (4) tricyclics, (5) other types, (6) multiple types, and (7) a comparison group of non-users of antidepressants (i.e., only tamoxifen).
Preliminary results: We identified 12,835 ER+ early stage (0-II) BCa survivors from the SEER-affiliated tumor registry. After excluding ineligibles (not continuously enrolled (n=1343) or no exposure to tamoxifen (n=3944)), we had 7,548 women. Cause of death through 12/31/07 included BCa (n=394, 5.2%); cardiovascular disease (n=183, 2.4%); other causes (n=408, 5.4%); and unknown causes (n=268, 3.6%); leaving 6,295 (83.4%) women alive by end of follow-up. We examined crude and adjusted rates of Bca and overall mortality using Cox proportional hazards modeling. We adjusted for age at diagnosis, year, race/ethnicity, income, medical utilization, comorbidity, stage, primary and adjuvant cancer therapy, and other tumor characteristics (histology, grade, lymph nodes, PR). We did not observe a significant association between paroxetine use and mortality (HR=1.29, 95% CI: 0.91-1.82). However, we did find significant associations between fluoxetine (HR=1.47, 95% CI: 1.15-1.89) and other SSRIs (HR=2.36, 95% CI: 1.39-4.01) with overall mortality. Among women with good adherence to tamoxifen (80% medication possession ratio), the association between fluoxetine and other SSRIs with all cause mortality became stronger. Of note, these estimates were based on small numbers of deaths and need to be interpreted with caution.
Impact & next steps: Our results suggest that concomitant use of tamixofen and some antidepressants may affect survival. Although we were able to adjust for a numerous potential confounders, these preliminary data need to be evaluated in larger samples of BCa survivors.
