American Cancer Society. Breast Cancer Overview [Interne Breast Cancer Burden 3 CHAPTER 3-2 Breast Cancer and the Environment: Prioritizing Prevention 3 marker tests are expressed as either positive “+” (having expression) or negative “−” (lacking expression). Some major molecular markers are based on whether a tumor has receptors (binding sites) for the hormones estrogen (estrogen receptor is abbreviated as ER) and progesterone (progesterone receptor is abbreviated as PR) or the protein HER2. Triple-negative breast cancers (TNBCs) are cancers in which the tumor does not express any of the three major molecular markers (ER, PR, or HER2). Other molecular markers have been identified that are based on the expression of other proteins (e.g., Ki-67, cytokeratin 5/6 [CK5/6]).10 Five molecular subtypes of breast cancer have been identified that involve specific combinations of these markers that reflect distinct gene-expression patterns, including: (1) Luminal A; (2) Luminal B; (3) HER2+/ ER−; (4) basal-like; and (5) unclassified.10 Because these gene-expression patterns include, among other markers, ER, PR, and HER2, there is some overlap between the five molecular subtypes and classifications based on ER, PR, and HER2 only. Recent research suggests that additional breast cancer subtypes may exist.11 TNBC and basal-like breast cancer (TNBC with additional molecular characteristics) are particularly aggressive.12 Women with basal-like, TNBC, and HER2+ tumors have a worse overall prognosis with shorter time to progression and lower overall survival compared to women with Luminal A or B tumors, which are ER+ and/or PR+.13, 14 Another type of breast cancer that is not defined by molecular markers is inflammatory breast cancer (IBC). This type of breast cancer has a unique clinical and pathological presentation and has been hypothesized to have a different etiology from other forms of the disease.15 IBC is considered a very aggressive form of breast cancer with rapid progression and poor survival.16 Racial/ethnic differences in incidence and mortality have been found for these breast cancer types. These differences are discussed in Section 3.4. 1999 and 2005 is thought to result from a decrease in the use of postmenopausal combined hormone therapy (HT) after the 2002 publication of the Women’s Health Initiative findings linking combined estrogen plus progestin HT with increased breast cancer risk.8 Breast cancer accounts for approximately 14 percent of all cancer deaths in the United States.6 Approximately 40,000 breast cancer deaths are expected to occur in 2012. Breast cancer mortality trends reveal a drop in death rates, currently by 1.9 percent from 1990 to 2009, with a larger decline among women under the age of 50 compared with women of ages 50 and older.7 These decreases in mortality are thought to result from treatment advances and earlier detection through screening.9 Death rates for male breast cancer have decreased at an average rate of 2.3 percent per year since 2000.6 In 2012, approximately 410 men will die from breast cancer.6 Statistics cited in the rest of this chapter refer to women only because of the disproportionate impact of breast cancer on women. 3.3 How Breast Cancer Is Classified Breast cancers can be classified in many different ways and for different purposes. Considerations include understanding how the disease develops, the tissues involved (e.g., whether it originated in the breast ducts that carry milk or the lobules), the prognosis, and treatment options. Classification systems have changed over time as more is learned about the biology and behavior of breast cancer. Major classification systems include: (1) an assessment by a pathologist examining tumor tissue that yields information about features, such as histologic cell type, extent of invasion into surrounding tissues, and indicators of aggressiveness; (2) staging, which classifies patients according to the size of the tumor and the extent of spread to nearby lymph nodes or other parts of the body; and (3) certain molecular markers found on or in tumor cells that influence prognosis (i.e., the likely outcome or course of a disease, including the chance of recovery or recurrence). The results of molecular There are at least five different breast cancer subtypes—each with distinct biologic features, clinical outcomes, and responses to therapy. 3-3 Breast Cancer and the Environment: Prioritizing Prevention 3 3.4 Breast Cancer Risk and Mortality Varies Significantly by Race and Ethnicity As shown in Figure 3.1, breast cancer incidence rates (the number of new cases of breast cancer per 100,000 women per year) are highest for White women, next highest for Black women, followed by Hispanic, Asian and Pacific Islander, and American Indian and Alaska Native women. Trends in breast cancer rates over time also vary by race and ethnicity.7 Most recently, from 2000 to 2009, breast cancer incidence rates declined among White women but have been statistically stable for the other racial/ ethnic groups (Figure 3.1). Breast cancer death rates are declining in all racial and ethnic groups over time (Figure 3.2). Black women experience A recent pooled analysis of epidemiologic studies of breast cancer subtypes17 showed that higher body mass index (BMI) was associated with Luminal A tumors in postmenopausal women and suggested a higher TNBC risk in