Chapter 15: Breast Cancer and Related Diseases

INTRODUCTION

Breast cancer is the most common malignancy in women throughout the world, and particularly in Westernized, developed countries. The relative roles of genetic, environmental, and lifestyle factors in explaining the high incidence of breast cancer in the modern world is a subject of much debate. However, it is clear that the complex biology of the human breast and its involvement in the reproductive cycle is also the basis for the increased susceptibility of this organ to malignant transformation.¹

EPIDEMIOLOGY

Key Points

1. The most significant risk factors for breast cancer include increasing age and deleterious mutations in the BRCA1 and BRCA2 genes.

2. Reproductive factors that contribute to breast cancer risk are related to the length of estrogen and progesterone exposure.

3. The total number of ovulatory cycles promotes an increased estrogenic exposure that can modulate breast cancer risk.

Breast cancer remains the most common cancer diagnosed in women worldwide. In the United States, more than 209,060 new cases of breast cancer are expected in 2011.² Despite the preponderance of epidemiologic studies examining risk factors and causes of breast cancer, only very few highly significant risk factors, such as increasing age and deleterious mutations in the BRCA genes, have been identified.³ Epidemiologic factors reproducibly associated with increased risk of breast cancer are shown in Table 15-1.^{4,5, and 6} Although increasing age is recognized as a universal risk factor for many cancers, including that of the breast, reproductive factors play a significant role in modulating breast cancer risk. The common thread appears to be the timing and length of exposure to estrogen and progesterone, and the age at which a pregnancy is first carried to term, leading to differentiation of the breast epithelium, lactation, and eventual involution. Furthermore, breast density, as measured on mammography, appears to be an anatomical surrogate for the glandular and potentially proliferative cellular content of the breast and is increasingly recognized as an additional marker of risk.⁷ In addition, a growing body of evidence supports the cancer-promoting effect of increasing length of exposure of the breast tissue to estrogen and progestin as a result of the use of postmenopausal hormone replacement therapy (HRT).⁸ The use of as little as 2 years of postmenopausal HRT yields an increased risk.⁹