Adherence to endocrine therapy in breast cancer adjuvant ...€¦ · claims and pharmacy databases, medical record review, hospital databases, pill counts, patient self-reports, prospective
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Adherence to endocrine therapy in breast cancer adjuvant and prevention settings
December 8, 2013
Rowan T Chlebowski, M.D., PhD 1, 2
Jisang Kim, M.D 2
Reina Haque, Ph.D 3
Running title: Breast cancer endocrine therapy adherence
1 Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center, Torrance, CA 2 Harbor-UCLA Medical Center, Torrance, CA, email [email protected] 3 Kaiser Permanente Southern California, Pasadena, CA, email [email protected] Correspondence to: Rowan T Chlebowski, M.D., PhD, Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center, 1124 W. Carson St., Torrance, CA, 90502; phone: 310-222-2219; fax 310-320-2564; e-mail [email protected] Abstract Count: 200 Word Count: 3789
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
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Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Table 1. Systematic Reviews of Adherence to Adjuvant Endocrine Therapy Tamoxifen Aromatase inhibitor Adherence (range) 1, 2 41% to 88% 52% to 91% Therapy discontinuation (range) 1
15% to 20% within year 1 5% to 25% within 2 years
5 year therapy discontinuation from meta-regression analysis 2
47.2% (95% CI, 41.1% to 53.5%)
31.0% (95% CI, 25.9 % to 37.5%)
1 Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Research Treat 2012; 134 (2 ): 459-78. 2 Huiart L, Ferdynus C, Giorgi R. A meta-regression analysis of the available data on adherence to adjuvant hormonal therapy in breast cancer: a summarizing the data for clinicians. Breast Cancer Res Treat 2013 Feb3 [Epub ahead of print].
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Yood 2008 Cohort of 1,837 US early stage breast cancer patients ≥ 65 years old
Adjuvant tamoxifen < 1 year vs. ≥ 5 years with higher breast cancer mortality (HR 6.26, 95% CI: 3.10-12.64)
McCowan 2008 Resospective cohort of 2080 Scotish early stage breast cancer patients
Adherence to tamoxifen < 80% associated with poorer survival (HR 1.10, 95% CI: 1.001-1.21)
Hershman 2010 Northern California Kaiser Permanente cohort of 8769 women with early stage, hormone-sensitive breast cancer and endocrine therapy adherence (drug availability)
31% discontinued therapy, 10 years survival was 73.6% 69% continued therapy, 10 year survival was 80.7%; P<0.001
Xu 2012 Cohort of 116 men with early stage, hormone sensitive breast cancer and hormone therapy adherence
For those adherent, 10 year survival was 79.6%; For those non-adherent, 10 year survival was 50.5%, P=0.008
Markula 2012 Prospective cohort of 417 patients with early stage breast cancer Sweden and adherence (self-report) to adjuvant endocrine therapy
Non-adherence at the 1-year visit associated with increased early breast cancer events HR 2.97, 95% CI 1.08-8.15
Haque 2012 Southern California Kaiser Permanente cohort of 22,850 women with early stage breast cancer and endocrine therapy adherence (drug availability)
Women with high adherence had greater recurrence risk reduction (e.g., HR=0.42, 95% CI: 0.36-0.47 for tamoxifen) compared to those with less adherence (HR=0.46, 95% CI: 0.41-0.52 for tamoxifen) but the difference was not statistically significant.
Pagani 2013 International Breast Cancer Study Group trials 13-93 and 14-93 with 690 women with early stage breast cancer or SERM’s
Women with ≥ 4 years of SERM had longer 10-year disease-free survival (71%) compared to < 4 years use (64%), p value = 0.20
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Table 3. Adjuvant Hormone Therapy Use for Hormone Receptor Positive Postmenopausal Women with Early Stage Breast Cancer In Women’s Health Initiative Cohort1
Kaiser Permanente Southern California2
In SEER Population by Survey3
Kaiser Permanente Northern California4
3,588 surveyed 2009-2010
22,850 in years 1996-2006
743 surveyed in years 2005-2007
13,753 studied in year 1996-2007
Use AI 33%, SERM 31%, mix 36%
Use: SERM 38%, 19% AI, mix 16%
Use: Endocrine 75%
Not examined
17% none 24% none 10.8% none 30% none 33% of users became non-adherent
21% users became non-adherent
15.1% uses became non-adherent by year 4
Not examined
1 Livaudais J, LaCroix A, Chlebowski RT, et al. Use of and adherence to adjuvant hormonal therapy for breast cancer in the Women's Health Initiative. Cancer Epidemiol Biomark Prev 2013;22(3):365-73. 2 Haque R, Ahmed SA, Fisher A, Avila CC, Shi J, Guo A, Craig Cheetham T,Schottinger JE. Effectiveness of aromatase inhibitors and tamoxifen in reducing subsequent breast cancer. Cancer Med. 2012 Dec;1(3):318-27. 3 Frease CR, Pini TM, Li y, et al. Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer. Breast Cancer Res Treat 2013;138:931-939. 4Livaudais JC, Hershman DL, Habel L, et al. Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer. Breast Cancer Res Treat 2012; 131(2):607-617.
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
2011 Financial considerations or low SES Kimmeck 2001, Neugut 2011, Liu
2013, Riley 2011 Very young or older age Hershman 2010, Owusu 2008, Land
2011 Lack of physician recommendation Davidson 2007 Perception of low risk of recurrence Fink 2004 Lack of social support Cluze 2013, Land 2011 Follow-up care with general practitioner vs. oncologist
Murphy 2012
African American race/ethnicity Hershman 2010 Cigarette smoking Land 2011 Presence of anxiety/depression linked to better adherence
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on January 17, 2014; DOI: 10.1158/1940-6207.CAPR-13-0389
Published OnlineFirst January 17, 2014.Cancer Prev Res Rowan T. Chlebowski, Ji Sang Kim and Reina Haque prevention settingsAdherence to endocrine therapy in breast cancer adjuvant and
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