Trastuzumab Related Cardiotoxicity in Taiwanese Breast Cancer Women

  • 錢 叙芝

Student thesis: Doctoral Thesis

Abstract

Scope and Objective: Asian women accounted for 40% of newly diagnosed breast cancer cases worldwide but real-world evidence regarding the cardiac safety of trastuzumab in the Asian population is limited This thesis is thus aimed to describe the prescribing pattern of trastuzumab to evaluate the rate and the risk factors related to heart failure and/or cardiomyopathy (HF/CM) among Taiwanese breast cancer women and trastuzumab users and to estimate the risk of HF/CM Taiwanese trastuzumab users Methods: Using National Health Insurance Research Database (NHIRD) we described the prescribing pattern of trastuzumab and estimated the incidence and risk factors for HF/CM among breast cancer women within 2 years after chemotherapy initiation and trastuzumab related HF/CM within the first year of treatment course in all trastuzumab users during 2006 to 2012 We also evaluated the risk of trastuzumab related HF/CM among all incident breast cancer women that were diagnosed during 2006 to 2009 The median follow-up duration was 5 29 years We applied a land mark design and matched trastuzumab user with nonusers using the year of breast cancer diagnosis and propensity score (PS) with caliper widths of 0 25 standard deviation of PS and allowing up to 4 nonusers per trastuzumab user We applied cause-specific hazard model using trastuzumab as a time dependent variable and cumulative courses of chemotherapy agents with known cardiotoxicity (including anthracyclines taxanes and cyclophosphamide) as time dependent covariates in the analysis model to evaluate the risk of HF/CM in the matched cohort We also examined the robustness of our finding by performing 8 sensitivity analyses Results: Among 65 135 incident breast cancer patients from January 1 2006 to December 31 2012 there were 7 333 trastuzumab users in our cohort The crude HF/CM incident rate of trastuzumab users was 2 58% Risk factors of HF/CM in Taiwanese breast cancer women that received chemotherapy were age receiving cardiotoxic chemotherapy agents (including trastuzumab anthracyclines and taxanes) hypertensive agents (including beta-blockers diuretics and angiotensin converting enzyme inhibitors) alpha-glucosidase inhibitors and statins Women with a breast cancer screening within 2 years prior to the diagnosis were at a lower risk of HF/CM while those who received computed tomography (CT) prior chemotherapy initiation had higher risks to have HF/CM In 6 337 women that survived at least one year after trastuzumab initiation 89 (1 40%) women had HF/CM within a year after trastuzumab initiation Receiving a baseline cardiac monitoring diagnosed as hypertension and arrhythmia prior trastuzumab were risk factors for trastuzumab related HF/CM Compared with non-users the 1-year cumulative HR for HF/CM in trastuzumab users was 1 71 (95% CI 1 02-2 86) Our sensitivity analyses yielded similar results Conclusion: Compared to the published results our cohort was approximately 10 years younger; the trastuzumab-related HF/CM rate was 5-fold lower Nonetheless our cohort had a similar trastuzumab-related HF/CM risk Our results provide the critical cardiac safety information of trastuzumab for the Asian patient population
Date of Award2016 Aug 17
Original languageEnglish
SupervisorYea-Huei Kao (Supervisor)

Cite this

'