Trastuzumab improves long-term outcomes in obese patients with HER2-positive breast cancer

A large, multicenter, randomized study has shown that obese patients with HER2-positive breast cancer have larger tumors, increased lymph node involvement and, when not treated with trastuzumab, poorer long-term outcomes than normal-weight patients.

This is the first time the relationship between obesity and HER2-positive breast cancer has been studied, according to Jennifer A. Crozier, M.D., a medical resident at Mayo Clinic, Jacksonville, who presented the results at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

"We knew that obesity was a risk factor for breast cancer," said Crozier. "However, we had not explored the relationship between body mass and how patients respond to treatment and disease-free survival (DFS)."

The study, known as N9831, included 3,017 patients who were initially classified into two categories based on World Health Organization body mass index (BMI) guidelines: normal-weight patients (BMI less than 30) and obese patients (BMI greater than 30). BMI was measured when patients began chemotherapy.

Researchers randomly assigned patients to treatment with only chemotherapy, with chemotherapy and sequential trastuzumab or with chemotherapy and concurrent trastuzumab.

When data were first examined, there were no significant differences in DFS between obese and normal-weight patients in any arm at three, five and seven years of follow-up. The team then subdivided normal-weight patients to determine if those patients considered overweight, with BMI between 25 and 29, might be affecting the analysis.

They found that obese patients and overweight patients had lower DFS rates of 70.6 percent and 65.9 percent, respectively, after seven years when not treated with trastuzumab compared with a rate of 74.7 percent among normal-weight patients also treated with chemotherapy alone. Results suggested that adding trastuzumab to treatment, particularly when received concurrently with chemotherapy, may potentially equalize DFS rates, with five-year rates of about 85 percent for normal-weight and overweight patients and 82.6 percent for obese patients.

Researchers observed these DFS rates among patients who received concurrent trastuzumab, regardless of BMI. Among patients treated with sequential trastuzumab, normal-weight patients appeared to have benefited more from the treatment than obese patients. Patients treated with chemotherapy alone had the worst observed DFS rate of the three groups, highlighting the potential importance of trastuzumab in treating HER2-positive breast cancer.

The researchers also alleviated the concern that hormonal differences in obese patients might undercut trastuzumab's effectiveness.

"Overall, we can see in the trends that weight management is going to be important in treating HER2-positive breast cancer," said Crozier. "The next step is to examine how weight management during different stages of treatment affects outcomes."