Grant Number:	1R01CA136743-01A2 Interpret this number
Primary Investigator:	Haque, Reina
Organization:	Kaiser Foundation Research Institute
Project Title:	ABC: Antidepressants and Breast Cancer Pharmacoepidemiology
Fiscal Year:	2010

DESCRIPTION (provided by applicant): ABC: Antidepressants & Breast Cancer Treatment Pharmacoepidemiology Tens of thousands of American women with breast cancer are taking tamoxifen to reduce their chances of developing a recurrence or second primary breast cancer. Many of these women also take antidepressants. Because tamoxifen has side effects that diminish a woman's quality of life and quality of sleep including hot flashes, night sweats, and depression, and because hormone replacement therapy is contraindicated for women with breast cancer, antidepressants increasingly have been used to relieve symptoms caused by tamoxifen. In addition, antidepressants are commonly prescribed for approximately 50% of women experiencing depression subsequent to a breast cancer diagnosis. Recent evidence suggests selective serotonin reuptake inhibitor (SSRI) antidepressants may reduce the metabolism of tamoxifen to its active form, which could reduce tamoxifen's protection against recurrent or a second primary breast cancer. This possibility needs investigation. As result of a few small studies, some recent reports caution physicians against prescribing SSRI medications concurrently with tamoxifen. However, findings from two clinical studies are ambiguous. Only one small study reported an association between antidepressants and breast cancer mortality in women taking tamoxifen while another found no association. Importantly, to date no study has adequately measured antidepressant use. Because tens of thousands of women are likely taking both tamoxifen and antidepressants, it is critical to determine if SSRIs indeed decrease the protection of tamoxifen against subsequent breast cancer among breast cancer survivors. The goal of this project is to investigate whether concomitant use of antidepressants and tamoxifen increases the risk of subsequent breast cancer (recurrence or second primary tumor) among women who have been diagnosed with a first primary breast cancer, compared to similar women treated only with tamoxifen. From a SEER-affiliated electronic tumor registry serving over 6 million members, we will assemble a large cohort of over 25,000 women diagnosed with a first early stage estrogen receptor positive breast cancer and treated with tamoxifen (of whom approximately 12,000 were exposed to antidepressants). Using a health plan's comprehensive pharmacy database, we will determine which women were also treated with SSRI or other antidepressants. We will then identify all women who developed a subsequent breast cancer and those who remained breast-cancer free in this cohort to determine if SSRIs or other antidepressant use is associated with an increased risk of subsequent breast cancer. Finally, using a case-control nested study within the cohort, we will determine if certain factors confound or modify the association. This innovative "ABC" (Antidepressants & Breast Cancer) study presents the first real opportunity to determine if women who take both tamoxifen and antidepressants following their initial breast cancer have a greater likelihood of developing subsequent breast cancer than women exposed to tamoxifen who do not take SSRIs or other antidepressants. PUBLIC HEALTH RELEVANCE: This study will determine if combined use of antidepressants (including SSRIs or other types) and tamoxifen poses serious health threats among breast cancer survivors by elevating subsequent breast cancer risks, compared to women who were only exposed to tamoxifen. As both depression and hot flashes are common in 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 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.




Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen.
Authors: Kwan M.L. , Shi J.M. , Habel L.A. , Song J. , Chung J.W. , Avila C.C. , Schottinger J.E. , Cheetham T.C. , Fletcher S.W. , Haque R. .
Source: Breast Cancer Research And Treatment, 2016 Apr; 156(2), p. 379-89.
PMID: 27002508
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Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors.
Authors: Haque R. , Shi J. , Schottinger J.E. , Ahmed S.A. , Cheetham T.C. , Chung J. , Avila C. , Kleinman K. , Habel L.A. , Fletcher S.W. , et al. .
Source: Journal Of The National Cancer Institute, 2016 Mar; 108(3), .
PMID: 26631176
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A hybrid approach to identify subsequent breast cancer using pathology and automated health information data.
Authors: Haque R. , Shi J. , Schottinger J.E. , Ahmed S.A. , Chung J. , Avila C. , Lee V.S. , Cheetham T.C. , Habel L.A. , Fletcher S.W. , et al. .
Source: Medical Care, 2015 Apr; 53(4), p. 380-5.
PMID: 25769058
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Metformin And Breast And Gynecological Cancer Risk Among Women With Diabetes
Authors: Soffer D. , Shi J. , Chung J. , Schottinger J.E. , Wallner L.P. , Chlebowski R.T. , Lentz S.E. , Haque R. .
Source: Bmj Open Diabetes Research & Care, 2015; 3(1), p. e000049.
PMID: 25664181
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Comorbidities and cardiovascular disease risk in older breast cancer survivors.
Authors: Haque R. , Prout M. , Geiger A.M. , Kamineni A. , Thwin S.S. , Avila C. , Silliman R.A. , Quinn V. , Yood M.U. .
Source: The American Journal Of Managed Care, 2014; 20(1), p. 86-92.
PMID: 24512167
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Sleep disturbance, inflammation and depression risk in cancer survivors.
Authors: Irwin M.R. , Olmstead R.E. , Ganz P.A. , Haque R. .
Source: Brain, Behavior, And Immunity, 2013 Mar; 30 Suppl, p. S58-67.
PMID: 22634367
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Identifying primary and recurrent cancers using a SAS-based natural language processing algorithm.
Authors: Strauss J.A. , Chao C.R. , Kwan M.L. , Ahmed S.A. , Schottinger J.E. , Quinn V.P. .
Source: Journal Of The American Medical Informatics Association : Jamia, 2013 Mar-Apr; 20(2), p. 349-55.
PMID: 22822041
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Effectiveness of aromatase inhibitors and tamoxifen in reducing subsequent breast cancer.
Authors: Haque R. , Ahmed S.A. , Fisher A. , Avila C.C. , Shi J. , Guo A. , Craig Cheetham T. , Schottinger J.E. .
Source: Cancer Medicine, 2012 Dec; 1(3), p. 318-27.
PMID: 23342281
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Impact of breast cancer subtypes and treatment on survival: an analysis spanning two decades.
Authors: Haque R. , Ahmed S.A. , Inzhakova G. , Shi J. , Avila C. , Polikoff J. , Bernstein L. , Enger S.M. , Press M.F. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2012 Oct; 21(10), p. 1848-55.
PMID: 22989461
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Validation of AJCC TNM staging for breast tumors diagnosed before 2004 in cancer registries.
Authors: Kwan M.L. , Haque R. , Lee V.S. , Joanie Chung W.L. , Avila C.C. , Clancy H.A. , Quinn V.P. , Kushi L.H. .
Source: Cancer Causes & Control : Ccc, 2012 Sep; 23(9), p. 1587-91.
PMID: 22798182
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