Dr Tarantino on the Evolving Role of Anthracycline- and Taxane-Based Regimens in HER2+ Breast Cancer

"In HER2-positive breast cancer, anthracyclines and taxanes have never been directly compared in head-to-head studies, primarily because anthracyclines were introduced first and taxanes were later added to anthracycline-based regimens. However, there has been a recent shift toward minimizing the use of anthracyclines as much as possible."

Paolo Tarantino, MD, a breast medical oncologist at Dana-Farber Cancer Institute and researcher at the University of Milan, discussed the evolving role of anthracycline- and taxane-based regimens in the treatment of HER2-positive breast cancer, noting a growing preference for anthracycline-sparing approaches in clinical practice.

Direct head-to-head comparisons between anthracycline- and taxane-based regimens have not been conducted, Tarantino noted, largely because anthracyclines were historically introduced first, with taxanes subsequently added to improve efficacy. However, concerns over the long-term toxicities associated with anthracyclines—including cardiotoxicity and rare but potentially life-threatening secondary leukemias—have led to a deliberate shift away from their routine use.

This shift is reflected in current National Comprehensive Cancer Network (NCCN) Guidelines, which recommend a neoadjuvant regimen of docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta; TCHP) for most patients with stage II and III HER2-positive breast cancer. In early-stage disease, particularly stage I, weekly paclitaxel plus trastuzumab, or ado-trastuzumab emtansine (Kadcyla; T-DM1), are commonly employed. According to Tarantino, these taxane-based regimens, when combined with HER2-targeted therapies, provide high pathologic complete response (pCR) rates and minimize long-term treatment-related risks.

Tarantino also highlighted the ongoing phase 2 COMPASSHER2-pCR trial (NCT04266249), which is investigating whether a 12-week course of paclitaxel plus trastuzumab is sufficient for patients who achieve pCR. This trial could support a de-escalation strategy, enabling further reduction in exposure to cytotoxic agents among low-risk patients.

Despite the increasing reliance on taxane-based regimens, Tarantino acknowledged that anthracyclines may still be appropriate in select clinical scenarios. These include cases with equivocal HER2 expression, hormone receptor–positive, or luminal-like tumors with borderline HER2 status, and inflammatory breast cancer. He also emphasized their utility in pregnant patients, where treatment options may be limited.