Herceptin and Chemotherapy Delivered Sequentially May Be Kinder to Heart in Breast Cancer

Specific treatment agents delivered sequentially versus concurrently may prove to be kinder to the heart while maintaining effectiveness against breast cancer. These results were recently published in the Lancet Oncology.

Approximately 20-25% of all breast cancers are referred to as human epidermal growth factor receptor (HER)-2 positive. This means that the cancerous cells are stimulated to grow and replicate through an aberrant biologic HER2 pathway. Targeted therapies reduce or mitigate the abnormal cellular growth through these HER2 pathways, producing anti-cancer effects without the severe side effects of chemotherapy .

Typically, agents targeted against the HER2 pathway, such as Herceptin (trastuzumab), are delivered in addition to chemotherapy. Results from trials have suggested that the combination of Herceptin and the chemotherapy class of agents referred to as anthracyclines is a highly effective treatment regimen; however, this specific combination may increase the risk of side effects affecting the heart. These effects can be both short-term and long-term. Researchers continue to evaluate ways in which to reduce the risk of damage to the heart caused by the effective combination of these agents.

Researchers from several cancer centers in the United States and Puerto Rica recently conducted a phase III clinical trial exploring the effectiveness of concurrent (same time) versus sequential (in succession) administration of Herceptin with the chemotherapy agents in the anthracycline and taxane classes. The way in which the heart was affected was closely evaluated in both groups of patients. Patients were given treatment prior to surgery (neoadjuvant therapy) in an attempt to shrink the cancer as much as possible prior to surgical removal.

Complete regression of cancer occurred in 56.5% of patients treated with sequential delivery of therapy and 54.2% of patients treated with concurrent delivery of therapy.
No treatment-related deaths occurred in either group of patients.
A significantly drop in left ventricular ejection fraction (LVEF), a potentially serious and chronic heart condition, was not significantly different between the two groups of patients at 12 and 24 weeks of treatment.
The researchers concluded that because breast cancer outcomes were not significantly different between the patients treated with sequential or concurrent therapy, the use of concurrent Herceptin in addition to an anthracycline/taxane combination is not warranted, as the potential for long-term severe heart damage might be increased compared to sequential therapy. Longer follow-up is necessary to confirm these findings.

Reference: Buzdar A, Suman V, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncology. Early online publication: 13 November 2013.doi:10.1016/S1470-2045(13)70502-3.