Anthracycline- and taxane-containing chemotherapy for early-stage breast cancer

We read with great interest the publication titled “Anthracycline- and taxane-containing chemotherapy for early-stage operable breast cancer: A patient-level meta-analysis of 100,000 women from 86 randomized trials.”[1] The long-term adverse effect profiles were of particular interest to us. The authors analyzed the individual patient data of trials comparing taxane with versus without anthracyclines and reported a 14% reduction in recurrence rates, although the data were insufficient for human epidermal growth factor receptor 2 (HER2)-positive tumors. Treating 700 women with anthracycline-based adjuvant therapy led to one additional case of acute myeloid leukemia.[1,2] Similarly, there was no difference in the rates of non-breast-cancer mortality despite anthracycline-related cardiotoxicity. Prior studies have reported a much higher risk of acute myeloid leukemia (AML) with anthracycline-based therapy (8-year cumulative risk of MDS/AML of 0.37%). However, given the concomitant increase in cyclophosphamide dose as well, extrapolation to patients receiving anthracycline-free, but cyclophosphamide-containing regimes remains doubtful.[3] Similarly, Greenlee et al.[4] reported a near doubling of rates of dilated cardiomyopathy with heart failure (leading to clinical symptoms severe enough for outpatient or inpatient assessment) in anthracycline recipients (4.1% versus 2.3%). However, the study compared patients with breast cancer with healthy women (of similar age), leading to a possible overestimation of risk stemming from the additive risk of radiotherapy and other baseline differences (in rates of hypertension, educational level, and socioeconomic status as measured by the median neighborhood household income) in these populations. These contrasting estimates are a reminder of the value of prospective randomized studies. Furthermore, anthracycline-based therapy is now delivered as a dose-dense regimen with obligatory growth factor support, leading to significantly lower rates of febrile neutropenia.[5] On the other hand, a randomized study demonstrating the non-inferiority of the TC (docetaxel-cyclophosphamide) regime versus anthracycline-based regimes reported higher rates of neutropenic sepsis and deaths in the anthracycline-free arm.[6] We believe that the estimates of long-term risks with anthracyclines provided in this meta-analysis and the likely higher rates of acute toxicity with TC chemotherapy challenge the implied advantages of an anthracycline-free approach needed to justify testing non-inferiority. An anthracycline-free approach seems to switch from a marginal risk of remote toxicity to a higher risk of acute toxicity. For elderly patients (where these approaches are more likely to be preferred), this seems imprudent. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.