Breast Cancer Research and Treatment

, Volume 144, Issue 2, pp 405–416 | Cite as

Comparative safety of cardiovascular medication use and breast cancer outcomes among women with early stage breast cancer

  • Denise M. BoudreauEmail author
  • Onchee Yu
  • Jessica Chubak
  • Heidi S. Wirtz
  • Erin J. Aiello Bowles
  • Monica Fujii
  • Diana S. M. Buist


Breast cancer tends to occur in an older age group of women also burdened with comorbidities such as cardiovascular disease (CVD). Numerous medications used to manage CVD (e.g., statins and antihypertensives) are hypothesized to alter breast cancer risk, but there are few studies on breast cancer outcomes. The COmmonly used Medications and Breast Cancer Outcomes (COMBO) cohort was developed to study how medications and co-morbidities influence breast cancer prognosis. Cohort study among adult women, diagnosed with incident early stage breast cancer, and enrolled in an integrated health plan. Data sources included health plan administrative databases, Surveillance, Epidemiology, and End Results tumor registry, and medical records. Statins, angiotensin-converting enzyme inhibitors (ACEI), beta blockers (BB), calcium blockers, and diuretics were the exposures of interest. The outcome was second breast cancer events (SBCE) defined as recurrence or second primary breast cancer. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for SBCE, and components of SBCE. 4,216 women were followed for a median of 6.3 years, and 13.2 % experienced a SBCE (first of: n = 415 recurrences and n = 143 s primary breast cancers). Compared to non-users, we observed an increased risk of second primary breast cancer with ACEI use (HR = 1.66; 95 % CI, 1.06–2.58) and an increased risk of recurrence with BB use (HR = 1.29; 95 % CI, 1.01–1.64). There was suggestion of a reduced risk of SBCE with statin use (HR = 0.82; 95 % CI, 0.62–1.08) and second primary breast cancer with BB use (HR = 0.77; 95 % CI, 0.50–1.19). No differences in outcomes were observed by duration of medication use. A majority of CVD medications evaluated in this study appear safe with respect to SBCE, but ACEI and BB use warrant further evaluation. The study presented is one example of the questions that can be addressed using the COMBO cohort.


Breast cancer Statins Antihypertensive medication Recurrence Cardiovascular disease 



This manuscript was supported by grant numbers CA120562 (Boudreau), CRTG-03-024-01 (Buist), and CA093772 (Silliman). The collection of cancer incidence data used in this study was supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center (Contract No. N01-CN-67009 and N01-PC-35142) from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10549_2014_2870_MOESM1_ESM.doc (28 kb)
Supplementary material 1 (DOC 28 kb)
10549_2014_2870_MOESM2_ESM.doc (76 kb)
Supplementary material 2 (DOC 76 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Denise M. Boudreau
    • 1
    • 2
    Email author
  • Onchee Yu
    • 1
  • Jessica Chubak
    • 1
  • Heidi S. Wirtz
    • 2
  • Erin J. Aiello Bowles
    • 1
  • Monica Fujii
    • 1
  • Diana S. M. Buist
    • 1
  1. 1.Group Health Research InstituteSeattleUSA
  2. 2.University of Washington School of PharmacySeattleUSA

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