Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

BACKGROUND: Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS: We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS: Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS: Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.

The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer.

BACKGROUND: Identifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer. Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation, sympathetic activity and oxidative stress. This study tested the relationship between heart rate variability (HRV), a vagal nerve index, and the colon cancer (CC) marker carcinoembryonic antigen (CEA), in an 'historical prospective' design. METHODS: We examined data of 72 CC patients, without inflammatory or cardiac diseases, of whom 38 had baseline electrocardiograms (ECG) and 12 month CEA levels. We measured HRV (SDNN, RMSSD) from brief archived ECG. Multiple confounders were considered. RESULTS: Controlling for effects of tumor stage and treatment-orientation, baseline HRV predicted CEA levels at 12 months (r=-.43, p=.006). Patients with SDNN<20 ms had significantly higher CEA at 12months than those with SDNN>20 ms. CONCLUSION: These preliminary results showed that higher HRV predicts lower levels of a tumor marker, one year later, independent of confounders. This supports the hypothesized role of vagal activity in tumor modulation. Replication in larger samples is needed.

Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial.

BACKGROUND: The potential cardiotoxicity of the doxorubicin-paclitaxel regimen, when paclitaxel is given shortly after the end of the anthracycline infusion, is an issue of concern, as suggested by small single institution Phase II studies. METHODS: In a large multicenter Phase III trial, 275 anthracycline naive metastatic breast carcinoma patients were randomized to receive either doxorubicin (60 mg/m(2)) followed 30 minutes later by paclitaxel (175 mg/m(2) 3-hour infusion; AT) or a standard doxorubicin-cyclophosphamide regimen (AC; 60/600 mg/m(2)). Both treatments were given once every 3 weeks for a maximum of six cycles. Close cardiac monitoring was implemented in the study design. RESULTS: Congestive heart failure (CHF) occurred in three patients in the AT arm and in one patient in the AC arm (P = 0.62). Decreases in left ventricular ejection fraction to below the limit of normal were documented in 33% AT and 19% AC patients and were not predictive of CHF development. CONCLUSIONS: AT is devoid of excessive cardiac risk among metastatic breast carcinoma patients, when the maximum planned cumulative dose of doxorubicin does not exceed 360 mg/m(2).