Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study

Abstract

BackgroundClinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.MethodsWe conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. ResultsAmong 12 500 women (mean age = 60 years, range = 22–99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35).ConclusionsAnthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Similarly, in a retrospective analysis of women treated for metastatic breast cancer at the MD Anderson where 5% had a history of cardiovascular disease (CVD), 26.5% of those who received HER2 targeted therapies had symptomatic HF, which was reversible in the majority of cases 52. Data from the health maintenance organization Cancer Research Network reported the cumulative incidence of HF at 1 and 5 years was 6.2% and 20.1% for women who received a combination of anthracycline and trastuzumab and 3.6% and 12.1% for women who received trastuzumab alone 50. Such cumulative incidence increased significantly, with increasing age at cancer diagnosis being as high as 40.7% among women who were aged ≥75 years and received a combination of anthracycline and trastuzumab 49.…”

“…In a late follow‐up of the NSABP B‐31 trial, older age and lower baseline LVEF (50–54%) were associated with trastuzumab‐induced cardiotoxicity 11. Risk of cardiotoxicity appears to increase progressively with increasing age in several studies 11, 48, 50, 57. Higher body mass index has also been shown to significantly increase the odds of cardiac dysfunction associated with anthracycline or sequential treatment with anthracycline and trastuzumab.…”

Assessing HER2 testing quality in breast cancer: variables that influence HER2 positivity rate from a large, multicenter, observational study in Germany

“…1,[14][15][16][17][18] False-negative HER2 assessments could result in denial of an effective treatment, while false-positive assessments may lead to inappropriate administration of a potentially harmful, costly, and ineffective HER2-targeted therapy, or exclusion from treatment with other targeted therapies in the HER2-negative setting. 1,8,11,19,20 Despite 410 years of routine HER2 testing, studies have demonstrated variability in HER2 positivity assessments between local pathology laboratories and central testing centers, posing a challenge for clinicians. 15,[21][22][23][24][25] In some of these studies it was assumed that variations in HER2 positivity at individual centers equated to problems with testing quality.…”

Liposomal doxorubicin in patients with breast cancer and concomitant cardiovascular diseases — interdisciplinary expert opinion

“…Najnowsze dane wskazują na wzrastający odsetek powikłań sercowo-naczyniowych po przebytym leczeniu uzupełnia-jącym u chorych na raka piersi (największe ryzyko dotyczy pacjentów, którzy otrzymywali antracykliny i trastuzumab) [4][5][6]. Polskie obserwacje potwierdzają, że przebyte chemioterapie neoadiuwantowa i adiuwantowa z wykorzystaniem antracyklin oraz wywiad zdarzeń wieńcowych są najistotniejszymi czynnikami ryzyka wystąpienia skurczowej niewydolności lewokomorowej u kobiet z przerzutowym rakiem piersi [7].…”