Anthracycline-Free Neoadjuvant Regimen Induces Response for HER2-Positive Breast Cancer Patients

Neoadjuvant chemotherapy is sometimes paired with anthracyclines, such as daunorubicin, doxorubicin, and epirubicin, to treat some types of breast cancer. Because of the success of this regimen for patients with breast cancer--with up to 65% of pathological complete responses (pCR)--this has become a standard of care.¹

However, the side effects of these powerful antibiotics can cause permanent heart damage when paired with a targeted therapy drug such as trastuzumab. Because of this cardiotoxicity, researchers at the National Cancer Institute (NCI) in Italy created a study to determine whether other ways to treat patients--without causing cardiac damage--could be just as effective.

Researchers enrolled 109 patients with stage II-III HER2-positive breast cancer, seeking to assess pathological complete responses (pCR) as a primary endpoint. Patients received 24 weeks of paclitaxel and trastuzumab neoadjuvant chemotherapy, followed by 1 year of adjuvant trastuzumab ± hormonal and/or radiotherapy. Also, the researchers performed immunomonitoring to assess the contribution of patients' immunological background to the induction of clinical responses.²

This study confirms that an anthracycline-free neoadjuvant chemotherapy regimen for patients with locally advanced HER2-positive breast cancer can be safely used without compromising clinical outcome, provided that trastuzumab is given concurrently with a weekly taxane.

The 50% pCR rate observed in this study is very encouraging. No patients developed symptomatic congestive heart failure, and only four patients experienced a left ventricular ejection fraction (LVEF) reduction (grade1).

Going forward, follow-up of the cohort of patients will hopefully show a correlation between the high pCR rate obtained and also a longer disease-free interval with low-risk of cardiotioxicity. Furthermore, immunomonitoring of follow-up patients will reveal whether the immunological parameters identified in this study may be regarded as biomarkers. This may help predict the clinical outcome of patients with locally advanced HER2-overexpressing breast cancer who were treated with chemotherapeutic regimens minus anthracyclines. Perhaps a future study with a larger cohort of patients will show similar results.

References:

• Buzdar AU, Ibrahim NK, Francis D, et al. (2005). Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol., Jun 1;23(16): 3676-85.
• Miolo G, Muraro E, Martorelli D, et al. (2014). Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients. BMC Cancer, 14: 954.