Excerpt
Over the past several decades, the global incidence rate of breast cancer has increased continuously [
1‐
4] with the most rapid increase occurring in economically developing countries [
4]. In 2008, approximately 1.3 million new cases of breast cancer were diagnosed, accounting for 23 % of all cancers [
3] and making breast cancer the most commonly diagnosed cancer in women [
3,
5]. Approximately, 55 % of breast cancer cases were diagnosed in developed countries and the remaining 45 % of the cases were diagnosed in developing countries [
3]. Although breast cancer is the most common cancer in women worldwide, developed countries have a higher overall incidence rate and a three-fold higher age-standardized rate [
4]. In Western Europe, the incidence rate is 89.7 per 100,000 women while in Eastern Africa, the incidence rate is 19.3 per 100,000 women [
3]. Although the global incidence rate of breast cancer is increasing, the underlying causes of the disease are still largely unknown. During the 1980s, screening practices, access to mammography, and the use of exogenous estrogens and progestins contributed to the high incidence rates in developed countries, but these factors do not explain the increase in these countries before the 1980s or the increase in countries with low rates of screening and use of hormones [
6]. It has been suggested that the increasing incidence is due to a combination of an increase in the prevalence of known risk factors and to new unidentified risk factors [
2,
7]. Family history is a risk factor for developing breast cancer (8), but only 5–10 % of breast cancers are associated with the highly penetrant BRCA1 and BRCA2 genes [
8]. In contrast to family history, endocrine status is a prominent risk factor for developing breast cancer. Early age at menarche [
9,
10], late age at menopause [
11,
12], and later age at first full-term pregnancy [
13] increase the risk of developing the disease. Exposure to exogenous estrogens and progestins after menopause [
14‐
16] and a history of benign breast disease also increase the risk of developing breast cancer. These well established risk factors, i.e., family history, reproductive and menstrual history, and history of benign breast disease, are estimated to account for only about 40 % of breast cancer cases [
17]. Childhood exposure to ionizing radiation [
18‐
20], adult alcohol consumption [
21], and obesity [
7,
22,
23] also increase the risk of developing breast cancer. However, these risk factors are unlikely to account for the remaining cases of the disease [
2,
7,
24] suggesting that there are still unidentified causes of breast cancer. …
