Obese Patients With HER2-Positive Breast Cancer Have Worse Outcomes but Trastuzumab Equalizes Weight Differences

A large study of HER2+ breast cancer patients shows that obese patients had worse outcomes than normal weight or overweight patients.

Jennifer A. Crozier, MD

A large study of HER2-positive (HER2+) breast cancer patients shows that obese patients with this type of breast cancer had worse outcomes than normal weight or overweight patients. These included: larger tumors, greater lymph-node involvement, and worse long-term outcomes compared with normal weight counterparts. However, when obese patients were treated with trastuzumab, the negative prognostics of obesity appeared to be abrogated.

“We knew that obesity was a risk factor for breast cancer. However, we had not explored the relationship between body mass and how patients respond to treatment and disease-free survival (DFS),” said Jennifer A. Crozier, MD, medical resident at The Mayo Clinic in Jacksonville, FL, who presented this study at CTRC-AACR San Antonio Breast Cancer Symposium. This is the first study to examine the relationship between obesity and HER2+ breast cancer, she noted.

The North Central Cancer Treatment Group N9831 study included 3017 patients with early-stage, HER2+ breast cancer classified according to World Health Organization body mass index (BMI) guidelines as: obese (BMI >30) or normal weight (BMI <30). BMI was measured at the start of chemotherapy in this 3-arm, randomized, Phase III clinical trial. Patients were randomized to chemotherapy alone (Arm A); chemotherapy followed by trastuzumab for 1 year (sequential trastuzumab, Arm B); chemotherapy plus trastuzumab followed by trastuzumab for 1 year (concurrent trastuzumab, Arm C). Obese patients were more likely to be older and postmenopausal compared with normal-weight patients (P<.0001 for both). No significant association was present between BMI and estrogen or progesterone receptor status or histological tumor grade.

Across all 3 treatment arms, obese patients had worse outcomes compared with normal-weight patients, but these trends were not statistically significant. Obese and overweight patients who were treated with chemotherapy alone had lower rates of 7-year disease-free survival (DFS); 70.6% for obese patients and 65.9% for overweight patients, versus 74.7% among normal-weight patients. When trastuzumab was added to chemotherapy, either sequentially or concurrently, these differences were attenuated; in the two trastuzumab-containing arms, 5-year DFS were 85% for normal-weight and overweight patients and 82.6% for obese patients.

Edith A. Perez, MD

Disease-free survival rates were similar among all patients who received concurrent trastuzumab as part of therapy, regardless of BMI, Crozier said. In the sequential trastuzumab arm, normal-weight patients appeared to have more benefit than obese patients. Those patients who were treated with chemotherapy alone had the worst DFS of all 3 treatment arms. According to Crozier, these results underscore the importance of using trastuzumab as part of the treatment regimen for HER2+ breast cancer. She and her colleagues believe that this research alleviates the concern that hormonal differences associated with obesity could interfere with trastuzumab’s effect.

“This study supports weight loss intervention for obese women with early-stage HER2+ breast cancer. Overall, we can see that weight management should be an important strategy in management of HER2+ breast cancer. The next step [In our research] will be to examine how weight management during different stages of treatment affects outcomes,” Crozier said.

Senior investigator of this trial, Edith Perez, MD, Mayo Clinic, Jacksonville, FL, said: “We are continually searching for approaches that will help our patients have the best outcome possible after their diagnosis of breast cancer, and this study suggests that excess body weight may make a difference.”

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