Obesity and Diabetes Have Adverse Effects on Outcomes Across Breast Tumor Types, Should Be Taken Into Account When Planning Treatment
Both obesity and diabetes have adverse effects on outcomes in breast cancer patients who receive neoadjuvant chemotherapy, according to research presented at the 9th European Breast Cancer Conference. Although a high body mass index (BMI) is known to have a negative impact on cancer development and prognosis, until now there has been uncertainty as to whether having a high BMI had an equal effect on patients with different types of breast tumors.
Caterina Fontanella, MD, of the University of Udine, Italy, and a research fellow with the German Breast Group, presented an analysis based on nearly 11,000 patients with early-stage breast cancer treated with neoadjuvant chemotherapy. The findings showed that a high BMI adversely affects the chances of surviving without the cancer recurring or spreading to other parts of the body, although this detriment was not seen in women who had been diagnosed with HER2-positive disease.
“Although the overall survival of patients with metastatic breast cancer has increased over the past few decades, it remains an incurable disease,” Dr. Fontanella said. “So preventing disease relapse after primary treatment of early breast cancer is fundamentally important in oncology daily practice. Considering that about one-third of the worldwide population has a body mass index higher than 25 kg/m², investigating the possible higher risk of relapse that affects overweight and obese patients compared with normal weight patients should be a priority.”
Effect of Obesity
The researchers studied data from 8,872 patients with early-stage breast cancer patients from the German Breast Group, and 1,855 from a joint EORTC/BIG trial. All had received treatment consisting of an anthracycline/taxane-based neoadjuvant chemotherapy, anti-HER2 drugs, or hormone therapy according to tumor type and national guidelines.
The vast majority of the patients in this study received chemotherapy doses capped at a body surface area (BSA) of 2.0 m², which is often the limit when calculating doses. “Obese patients may have a BSA of more than 2.0 m², but the chemotherapy dose they receive will not reflect this. It is a very common practice in these patients for fear of overdosing, but of course it means that they will often receive a relatively lower quantity of chemotherapy,” Dr. Fontanella said. “In my opinion, a deeper understanding of chemotherapy metabolism and distribution in patients with high BMI and with increased adipose tissue is needed.”
“We already know that obese hormone receptor–positive tumor patients respond less well to aromatase inhibitors as adjuvant treatment, and this underlines a key role of higher aromatase activity in patients with increased adipose tissue,” she said.
Final analysis of outcomes from the two groups in the joint study showed a significant decrease in distant disease-free survival or distant relapse-free survival in patients with increased BMI in all tumor types, apart from those with HER2-positive tumors.
“The exception in this group can probably be explained by the impressive impact of anti-HER2 treatment,” Dr. Fontanella said. “Given the significant proportion of the world’s population with a BMI higher than recommended for good health, it is vitally important that we find a way to treat overweight and obese cancer patients that combines maximum efficacy with the avoidance of unnecessary side effects.”
Diabetes Study
In a second study, Dr. Fontanella and colleagues investigated the incidence of type 2 diabetes in patients with early breast cancer at the time of diagnosis, as well as its effect on the outcome after neoadjuvant chemotherapy. Diabetes has been reported in 15% to 20% of elderly breast cancer patients, although in the group of just over 4,000 patients studied it was considerably lower. “This was probably because these patients were enrolled in clinical trials and were therefore selected to be in good physical condition without other illnesses that could complicate procedures and outcomes,” Dr. Fontanella said.
“However, we did find that patients with diabetes were more likely to have their cancer diagnosed at a more advanced stage, and this suggests that diabetes may affect the size of the tumor. We also found that patients with diabetes had worse distant disease–free survival rates,” she said.
Diabetes is currently believed to be associated with a 49% increased risk of death from all causes in breast cancer patients, as well as being an independent prognostic factor for the risk of recurrence and metastasis. Increased insulin levels seem to be related to a high risk of recurrence after primary treatment, and an increase in C-peptide levels has been associated with an increased risk of cancer-related deaths, particularly in hormone receptor–positive tumors.
“We think that hyperinsulinemia … may encourage the growth of tumor cells by providing them with large amounts of glucose. We therefore believe that strict control of blood sugar levels is essential to the successful treatment of breast cancer,” she concluded.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
