Keio Research Highlights

Women suffering from breast cancer fueled by the overexpression of human epidermal growth factor receptor-2 (HER2) have the best chance of eliminating the disease when receiving two presurgical treatments in conjunction with chemotherapy, a Keio University School of Medicine research team has discovered¹.

Breast cancer ― the most common cancer in women ― kills about half a million women each year worldwide. Of the more than 1.5 million new cases diagnosed annually, about 20 per cent are HER2 positive ― an aggressive form of the disease characterized by elevated levels of the HER2 protein, which promotes cancer cell growth and division.

Historically, HER2-positive breast cancer has had a poor prognosis. This has made it the focus of an expanding range of neoadjuvant therapies ― treatments administered prior to primary treatments such as the surgical removal of cancerous tissue. As a result, HER2-positive breast cancer has become highly treatable, with four US Food and Drug Administration-approved anti-HER2 therapies now available. Of these, the monoclonal antibody trastuzumab has become the preferred therapy option for the metastatic form of the disease.

To identify the most effective treatment, Tetsu Hayashida and his colleagues at Keio University conducted a 'network meta-analysis' of the available relevant research on neoadjuvant therapies. Unlike conventional meta-analysis, which compares two subjects and determines which is better, the network meta-analysis approach compares and ranks all available subjects, resulting in improved decision making. "Network meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness of the treatments," explains Hayashida.

By using an electronic database, the Keio research team assessed 1,047 studies from which they identified 10 studies that met the eligibility criteria for their analysis, covering a total 2,247 patients in 7 different treatment arms.

To measure the efficacy of the different neoadjuvant therapies, the researchers compared for each treatment the number of patients with no residual histological evidence of a tumor at the time of surgery, a measure known as the pathological complete response. Patients who achieve this response are at a reduced risk of disease recurrence, which is associated with long-term survival ― "one of the most important values in cancer treatment," says Hayashida.

The researchers' analysis identified that the most effective neoadjuvant treatment for HER2-positive breast cancer is to combine chemotherapy with two anti-HER2 agents ― trastuzumab plus lapatinib and trastuzumab plus pertuzumab. This finding will directly impact the clinical treatment of HER2-postive breast cancer, says Hayashida.

1. Nagayama, A. et al. Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer: A network meta-analysis. Journal of the National Cancer Institute 106, dju203 (2014). | article