Insulin Resistance and Breast Cancer
Condition: Breast Cancer; Insulin Resistance
MeSH terms: Breast Neoplasms; Insulin Resistance
Study type: Observational

Summary: 
      This study will characterize risk factors associated with breast cancer development in some
      patients. In particular, it will examine the role of insulin in breast cancer in patients
      with and without a family history of the disease.

      Women 30 to 70 years old who have been diagnosed with breast cancer and matched control
      healthy subjects with and without a family history of breast cancer may be eligible for this
      study.

      Participants undergo the following procedures:

        -  Cancer-genetic counseling session, including family history, risk assessment, genetic
           testing for BRCA1 and BRCA2 (if criteria is met), interpretation of results and
           management options

        -  Medical history, including questions about symptoms or diseases, reproductive history,
           use of oral contraceptives, body weight, exercise, lifestyle, and demographic issues

        -  Drawing of family tree

        -  Examination of medical records

        -  Blood drawing for genetic and other tests

        -  CT scan of the abdomen (approximate time < 1 minute)

        -  Filling out questionnaires
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Breast Cancer; Family History; Pre/Post Menopausal; Prevention; Risk-Factor; Body-Mass-Index; BRCA1; Insulin; Genetic Counseling; Penetrance; Risk Assessment; Healthy Volunteer; HV