Neil M. Iyengar, MD
Fellow, Medical Oncology and Hematology
Breast Medicine Service
Memorial Sloan-Kettering Cancer Center, New York, New York
2013-2014 BCRF Project:
(Conquer Cancer Foundation of ASCO 2013 Young Investigator Award in Honor of Susan Hirschhorn and in Memory of Her Mother, Ellen B. Hirschhorn)
A key strategy for the development of ways to effectively prevent and treat cancer is to identify shared features within high-risk groups of people that can be modified. Obese and overweight women are one such high risk group. The rising rates of obesity in the US and worldwide have brought increasing attention to this public health problem and its associated medical complications including heart disease, diabetes, high blood pressure, and cancer. Obese and overweight women are at an increased risk of developing estrogen receptor-positive (ER+) breast cancer after menopause. Additionally, obese and overweight women who have been diagnosed with breast cancer do not respond as well as lean women to cancer treatments. However, the reasons why obese and overweight women are at a higher risk of developing breast cancer are not well known. In order to reduce their risk and improve the effectiveness of cancer treatments in these women, a better scientific understanding of the links between obesity and breast cancer is urgently needed.
Dr. Iyengar, as a member of a multidisciplinary group including surgeons, oncologists, pathologists, and laboratory scientists, has been studying this question in collaboration with BCRF grantees Clifford Hudis, MD, and Andrew Dannenberg, MD. He and colleagues have identified inflammation as an important link between obesity and breast cancer. Obesity is associated with low-grade inflammation throughout the body that can go unnoticed by the patient and her doctors. Furthermore, blood levels of inflammation are known to be elevated in women with breast cancer. They have identified inflammation within the fatty tissue of the mammary gland in obese models. Guided by this finding, this team then discovered inflamed fat in the breasts of women. Breast inflammation was increasingly severe in the more overweight and obese women. However, these investigators did find breast inflammation in some lean women as well. Importantly, the presence of breast inflammation was associated with increased levels of aromatase – the enzyme responsible for the production of estrogen, which can stimulate estrogen receptor-positive (ER+) breast cancers. Therefore, they discovered a new pathway through which obesity and inflammation can lead to breast cancer and worse outcomes after breast cancer diagnosis.
Building upon these preliminary findings, Dr. Iyengar now hopes to determine whether the presence of breast inflammation is associated with worse prognosis after breast cancer diagnosis and if there are certain factors, such as medications, that may protect against breast inflammation. This group also aims to validate their initial findings in a larger population. To do this, they plan to study the breast tissue from several hundred women.
Dr. Iyengar reports that his research team has obtained breast tissue from 150 women who underwent mastectomy and remained free of breast cancer, as well as 150 women who underwent mastectomy and developed recurrent metastatic disease (total300 patients). All tissue has been retrieved, prepared, and analyzed for the presence or absence of crown-like structures (CLS-B) and further measurement of inflammation. Data assembly and inter-pretation is currently ongoing and will be completed by the expected date of April 2014.
Towards the second aim of examining the effect of age, menopausal status, and use of specific medications on breast inflammation (CLS-B) in a prospective study of women undergoing mastectomy, the researchers have met their accrual goal of 100 patients. Tissue preparation, analysis for CLS-B, and measurement of WAT area have been completed. Review of the electronic medical record to obtain clinic-pathologic data has also been completed. Preliminary data was presented at the 2013 San Antonio Breast Cancer Symposium. Overall, Dr, Iyengar and his team are on target to complete data analyses, present findings at ASCO 2014 and other relevant national meetings, and prepare a manuscript by June 30, 2014.
Dr. Neil Iyengar is a Fellow in Medical Oncology and Hematology in the Breast Medicine Service at Memorial Sloan-Kettering Cancer Center (MSKCC). He attended the University of Illinois College of Medicine and completed his internal medicine residency training at the University of Chicago Medical Center where he became interested in oncology while caring for patients with cancer. Dr. Iyengar has a broad research interest in translating preclinical laboratory findings into initiatives that can improve the care of patients with cancer. After joining MSKCC, Dr. Iyengar became specifically interested in breast cancer while working in the clinic of his now mentor, Dr. Clifford Hudis. Under the mentorship of Dr. Hudis and Dr. Andrew Dannenberg at NewYork-Presbyterian/Weill Cornell Medical Center, Dr. Iyengar is studying the links between obesity, inflammation, and breast cancer. This group has identified evidence of inflammation within the breasts of many obese, and some lean, women. Dr. Iyengar is now studying the prognostic implications of breast inflammation and ways to protect patients from its potentially deleterious effects. In doing so, he aims to develop preventive and treatment strategies that could be tested in the near future and could impact the health of millions of women. This would have a broad public health impact given the rising obesity rates worldwide.