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Heart-Specific Mortality Among Breast Cancer Patients
Study Questions:
What are the competing causes of death and prognostic factors in breast cancer patients, and what is the heart-specific mortality in relation to the general population?
Methods:
This was a registry-based retrospective cohort study that covered data from 18 regional cancer centers throughout the United States, and included female breast cancer patients treated with radiotherapy or chemotherapy. Cumulative mortality functions were computed. Heart-specific causes of death were defined according to the SEER recode 50060 (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] codes). Sensitivity analyses were also conducted including patients dying from primary hypertension and hypertensive renal disease (ICD-10 codes I10 and I12, respectively). As potential predictors of mortality, age (categorized as age <35, 35–49, 50–54, 55–64, 65–74, and ≥75 years), ethnicity (white, black, American Indian/Alaska native, Asian/Pacific islander, and other), year of diagnosis, stage (coded according to the breast cancer adjusted staging of the American Joint Committee on Cancer, 6th edition), grade (I–IV), and tumor site were considered. To investigate heart-specific mortality relative to the general population, long-term (≥10 years) standardized mortality ratios (SMRs) were calculated. Prognostic factors for heart-specific mortality were assessed by calculating cause-specific hazard ratios (HRcs) with corresponding 95% confidence intervals using the Cox proportional hazards regression. Subgroup analysis on intermediate-term mortality according to molecular subtypes, for which information was available since 2010, was performed.
Results:
Out of 572,341 identified breast cancer cases between 2000 and 2011, 501,547 (87.6%) female breast cancer patients were eligible to be included in the study, of whom 347,476 (69.3%) received either radiotherapy or chemotherapy or both. The median follow-up time for patients treated with radiotherapy or chemotherapy comprised 8.4 years [interquartile range (IQR) 5.5–11.6], and was slightly higher for untreated patients [8.6 (IQR 5.6–11.2)]. Among all possible competing causes of death, breast cancer accounted for the highest cumulative mortality, followed by other noncancer causes of death, which were not related to heart diseases. Heart-specific cumulative mortality was marginally lower than cumulative mortality due to cancers other than breast cancer. These patterns also did not substantially change when primary hypertension and hypertensive renal disease were included among the heart-specific causes of death or when using the imputed data sets. Compared with the general population, heart-specific mortality of breast cancer patients treated with radiotherapy or chemotherapy was lower [SMRoverall 0.84 (0.79–0.90)]. Heart-specific mortality also increased with stage, even though the association was less pronounced than for breast cancer mortality [HRcs 2.90 (2.43–3.46)] for Stage IV relative to Stage I). Compared with white ethnicities, black breast cancer patients were at higher risk for heart-specific death [HRcs 1.85 (1.72–1.99)], whereas patients with an Asian/Pacific island ethnicity were at lower risk [HRcs 0.74 (0.65–0.84)]. In subgroup analysis, human epidermal growth factor receptor 2 (HER2)-positive subtype was not associated with increased heart-specific mortality relative to HER2-negative patients [HRcs 0.96 (0.70–1.32)].
Conclusions:
The study authors concluded that heart-specific mortality among breast cancer survivors is not increased compared with the general population. Also, HER2-positive patients do not have increased heart-specific mortality compared to HER2-negative patients.
Perspective:
Although this is a retrospective analysis, the findings of this study are important. It suggests that the efforts done by oncologists to minimize cardiotoxic effects including surveillance for cardiovascular complications is bearing fruit. In addition, the efforts of survivorship clinics and the motivated patient may be important reasons that the burden of cardiovascular disease in these patients is commensurate with the general population. Well-designed prospective studies are now needed to confirm these important findings.
Keywords: Breast Neoplasms, Cardiotoxicity, Cardiotoxins, Chemotherapy, Adjuvant, Heart Failure, Hypertension, Renal, Nephritis, Radiation, Radiotherapy, Secondary Prevention
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