Diabetes Mellitus and Breast Cancer

Breast cancer is the most common malignant neoplasm in women, affecting 1 of every
8 women. The estimated new breast cancer cases and deaths among women in the
USA in 2007 are 178,000 and 40,000 respectively [1]. Type 2 diabetes is another major
health problem in developed countries, and affects about 7% of adults and about 15%
of people older than 60 years [2]. The main risk factors for type 2 diabetes are old age obesity, and genetic predisposition. Similarly to type 2 diabetes, the incidence of breast cancer rises with age, and the cumulative incidence in Western Europe and the USA is about 2.7% by age 55, about 5.0% by age 65, and about 7.7% by age 75. Breast cancer is associated with multiple risk factors, which are commonly divided into modifiable and non-modifiable. Non-modifiable risk factors include family history of breast cancer, germline mutations in breast cancer susceptibility genes including BRCA1, BRCA2,

P53, PTEN, and ATM, hormonal factors such as younger age at menarche and older
age menopause, and the presence of benign breast disease [3]. Modifiable risk factors
include low parity, use of oral contraceptives and hormone replacement therapy, alcohol
consumption, obesity, and lack of physical activity [3].
Breast cancer and diabetes commonly occur together, and up to 16% of older
breast cancer patients may suffer from diabetes [4]. An association between diabetes
and various types of cancer was first reported more than 100 years ago and diabetes is now recognized as a risk factor for several types of cancer, including endometrial and pancreatic carcinoma [5]. In recent years, a growing number of data, both laboratory and clinical, suggest complex associations between type 2 diabetes mellitus and breast cancer (fig. 1). Diabetes may have direct biologic effects on breast cancer risk, clinical and pathological characteristics, and outcome. Moreover, certain antidiabetic therapies may have direct activity against breast cancer. Diabetes may also affect breast cancer outcome indirectly, and have been shown to influence medical decision-making regarding screening and management of breast cancer. Obesity, which affects more than 20% of the population in developed countries, is a major risk factor for the development of type 2 diabetes. It is also a well-established risk factor for breast cancer and is associated with increased risk for the development

of postmenopausal breast cancer, but with reduced breast cancer risk among premenopausal women [6]. Obesity is also a poor prognostic factor and is associated
with adverse outcomes in both pre- and postmenopausal women with breast cancer.
Mechanisms connecting obesity to postmenopausal breast cancer include altered regulation of estrogen and adipocytokines levels, and increased insulin synthesis. Thus, obesity is a major confounding factor in many studies regarding the association
between diabetes and breast cancer.


Ido Wolf Tamar Rubinek