Trial Information

Breast Cancer and Insulin Resistance: Implications for Preventive Counseling in Familial and Sporadic Cases

The etiology of breast cancer is still poorly understood with known risk factors explaining
only a small proportion of cases. Risk factors that modulate the development of breast
cancer include: age, geographic location, socioeconomic status, reproductive events,
exogenous hormones, lifestyle, familial history of breast cancer, mammographic density,
history of benign breast disease, ionizing radiation, and bone density.

Several lines of evidence have demonstrated that insulin and the insulin receptor play a key
role in the formation and progression of breast cancer. Insulin has direct and indirect
effects on breast cancer; direct effects as a growth promoting factor and indirect effects
through actions on other hormones involved in breast cancer. In addition, certain
conditions associated with insulin resistance, such as obesity and abdominal fat, are known
risk factors for breast cancer.

Family history of breast cancer is also a well established major risk factor. To date, both
genetic and non-genetic factors have been suggested to influence breast cancer risk in women
with a positive family history of breast cancer including those with recognized mutations in
the BRCA1 and BRCA2 genes. Women with a family history of breast cancer inherit a
susceptibility to the condition; the development of the disease requires a series of
promoting steps including lifestyle, diet, and environmental factors. Several hormones
involved in breast cancer such as IGF-1, testosterone, and SHBG are affected by a positive
family history of breast cancer. Also, women with a high Waist-to-Hip ratio (WHR) and a
positive family history of breast cancer are at higher risk of developing breast cancer than
those women with a high WHR without a positive family history. The role of insulin and
insulin-related factors in women with a family history of breast cancer has not been
examined.

There is growing recognition that insulin may be a potential mediator of breast cancer. The
above evidence suggests that actions of insulin may be involved in the promoting steps that
predispose some women to breast cancer. These findings provide the biological basis for
insulin related factors to serve as potential targets for breast cancer prevention and risk
assessment.

The main goal of this proposal is to unravel the contributions of insulin and
insulin-related actions (e.g. insulin resistance, abdominal fat) on breast cancer risk. The
purpose of the present study is to characterize the role of insulin in newly diagnosed
premenopausal and postmenopausal women with and without a family history of breast cancer.
The objective is to assess the relative strength of each risk factor associated with insulin
actions and their individual impact on breast cancer. This study will provide data that may
serve as the basis for future studies on preventive strategies targeted at lowering insulin
levels and increasing insulin sensitivity (e.g. decrease glucose, decrease abdominal fat,
decrease omega-6 fatty acids/increase omega-3 fatty acids, increase fiber intake, increase
exercise) in a subset of patients.

This protocol will recruit only female patients, and will concentrate only on breast cancer
risk. Subjects will be asked to complete several questionnaires in the course of genetic
counseling to provide information on medical and reproductive history, demographics, risk
factors, physical activity as well as other information needed to establish an appropriate
sample for the study. Genetic testing will be offered as part of the initial evaluation and
to check for BRCA1/2 mutation status.