# Oncologic Outcomes and Safety of Neoadjuvant Treatment with Anthracyclines Versus Anthracycline-Free Regimens in HER2-Positive Early Breast Cancer in a Colombian Cancer Center: An Observational, Analytical, Retrospective Study

## TL;DR

A study in Colombia compared two breast cancer treatment regimens and found similar effectiveness but different side effects.

## Contribution

The study provides real-world evidence comparing anthracycline-based and anthracycline-free regimens in HER2-positive breast cancer in a Latin American setting.

## Key findings

- No significant difference in pathologic complete response between anthracycline and non-anthracycline regimens.
- Anthracycline-based regimens showed a trend toward better response in patients with T3-T4, nodal involvement, and hormone receptor positivity.
- Peripheral neuropathy was lower with anthracycline-based treatment, while cardiac events were similar.

## Abstract

There are no clinical trials that compare the two most used neoadjuvant treatment schemes in HER2-positive early breast cancer; the BERENICE protocol with anthracyclines and TRAIN-2 protocol without anthracyclines. Our retrospective observational study at the National Cancer Institute in Colombia shows there is no statistically significant difference in pathologic complete response between both regimens. In our descriptive subgroup analysis, patients with positive hormone receptors, T3-T4, and nodal involvement, tended to have a greater pathologic complete response when receiving the anthracycline-containing regimen. Cardiac adverse events reported in our patients were similar to those reported in the BERENICE trial; however, peripheral neuropathy was lower than in the TRAIN-2 trial. This information can help in the selection of the scheme and number of cycles for patients with positive hormone receptors T3-T4 and nodal involvement.

Background: There are no comparative trials between the two most common schemes in HER2-positive early breast cancer treatment; BERENICE (with anthracyclines) and TRAIN-2 (without anthracyclines). In this study, we investigated the pathological complete response (pCR) and safety events achieved with each. Methods: This analytical retrospective observational study included 111 patients with early and locally advanced HER-2-positive breast cancer who initiated neoadjuvant treatment with an anthracycline-based scheme (four cycles of doxorubicin and cyclophosphamide, followed by four cycles of taxane, trastuzumab, and pertuzumab = AC-THP) and a non-anthracycline scheme (carboplatin, weekly paclitaxel, trastuzumab, and pertuzumab for six–nine cycles = TCbHP) at the National Cancer Institute in Colombia, between April 2020 and December 2024. The primary endpoint was the pCR. Safety was analyzed in patients who received at least one treatment cycle. Results: A total of 51 patients received AC-THP and 60 TCbHP (89.6% of which received six cycles). The pCR was 58.3% in ACHTP and 60.4% in TCbHP (p = 0.84). As a descriptive analysis, with the anthracycline-based scheme, there was a trend toward a higher pCR in patients with T3-T4, positive nodal involvement (N+), and positive hormone receptor (HR+). Cardiac toxicity events during the neoadjuvant phase were 9.8% in ACTHP and 3.3% in TCbHP. Grade 2 neuropathy events were higher in patients with the TCbHP scheme, at 23.3%, versus 9.8% in ACTHP. Conclusions: We found similar pCR rates between the schemes with anthracyclines and without anthracyclines. It is still pertinent to discuss the risk–benefit of using anthracycline-based regimens in patients with HR+, T3-T4, and N+. The cardiac adverse events reported in our patients were similar to those reported in the BERENICE trial.