Obesity and Cancer Treatment: Weighing the Evidence

Obesity rates in the United States have increased tremendously over the past few decades. 1 Obesity is associated with an increased risk of several cancers, including breast cancer, colorectal cancer, and endometrial cancer, and is associated with higher cancer mortality rates. 2,3 Multiple factors contribute to the unfavorable survival rates in obese patients with cancer, including a higher likelihood of comorbid conditions and a higher likelihood of unfavorable tumor characteristics. In addition, systematic underdosing of chemotherapy in overweight and obese patients with breast cancer, 4-7 which occurs in up to 40% of patients, may contribute to the poorer survival rates, particularly among those with estrogen receptor (ER)–negative cancers. 8 This issue of theJournalofClinicalOncology features three studies that broadly address the complicated relationship between weight, factors associated with obesity, and cancer, spanning the bench to the bedside. Creighton and colleagues 9 examined the effect of insulinlike growth factor-2 (IGF-1) exposure on gene expression profiles in MCF-7 breast cancer cells. After developing an IGF-1 gene signature, the investigators assessed the IGF activation score in tumor samples contained within publicly available expression profile databases. The IGF gene signature was associated in this study with other known poor prognostic factors, such as ER-negative status, higher tumor grade, and higher stage. The authors conclude “Transcriptional targets of IGF-1 represent pathways of increased aggressiveness and possibly hormone independence i n... breast cancer.” The findings of this study contribute to our understanding of cancer biology in obese patients, who have higher levels of IGF-1 activity 10 and, in some studies (including the paper by Litton and colleagues in this issue of the Journal 11 ), a higher likelihood of ER-negative breast cancer.