and arrangement of breast cancer cells. More than 75% of invasive breast cancers are now histologically categorized as “no special type,” historically called “ductal” carcinomas.8 The most common special histologic subtype is invasive lobular carcinoma, representing about 15% of invasive breast cancers.8 Tubular, mucinous, cribriform, and papillary carcinoma are rare breast cancer subtypes that are generally associated with favorable prognoses.9 Inflammatory breast cancer is an uncommon but aggressive type of breast cancer that is characterized by swelling and redness of the skin of the breast. Molecular subtypes Breast cancer molecular subtypes are determined through gene expression analysis, a costly and complicated process that is not currently standard clinical practice. However, these subtypes can be approximated using routine methods for clinical evaluation of biological markers (ER, PR, HER2, and sometimes others). Hormone receptor positive (HR+) cancers are those that test positive for ER or PR, or both. Information about grade and proliferation (rate of cell division) is also sometimes used to assign subtype. The four main molecular subtypes are described below. It is worth noting that there are overlaps between categories and the clinical approximations do not perfectly correspond to the molecular breast cancer subtypes as described on the next page.10 HR = hormone receptor, HER2 = human epidermal growth factor receptor 2. Source: North American Association of Central Cancer Registries (NAACCR), 2019. ©2019, American Cancer Society, Inc., Surveillance Research Figure 1. Distribution of Female Breast Cancer Subtypes, US, 2012-2016 HR+/HER2- 73% HR+/HER2+ 11% HR-/HER2- 12% HR-/HER2+ 4% Breast Cancer Facts & Figures 2019-2020 3 Luminal A (HR+/HER2-): This is the most common type of breast cancer (Figure 1) and tends to be slower-growing and less aggressive than other subtypes. Luminal A tumors are associated with the most favorable prognosis in part because they are usually responsive to hormonal therapy (see page 26).11, 12 Luminal B (HR+/HER2+): In addition to being HR+, this subtype was originally characterized clinically as always being positive for HER2, but more recently has been defined by being highly positive for the protein Ki67 (an indicator of a large number of actively dividing cells) and/or HER2. Luminal B breast cancers tend to be higher grade than luminal A and thus are associated with poorer outcomes.11, 12 Basal-like (HR-/HER2-): These cancers are also called triple negative because they are ER-, PR- and HER2-. The majority (about 75%) of triple negative breast cancers fall in to the basal-like subtype defined by gene expression profiling.13 Triple negative breast cancers have a poorer prognosis than other subtypes, in part because treatment advances have lagged behind other molecular subtypes. 14, 15 These cancers occur at twice the rate in black women compared to white women in the US, and are also more common in premenopausal women and those with a BRCA1 gene mutation.16 HER2-enriched (HR-/HER2+): In the past, this subtype had the worst prognosis; however, the widespread use of targeted therapies for HER2+ cancers has substantially improved outcomes for these patients.14, 17 For more information about the treatment of HER2+ breast cancers, see the section on targeted therapy on page 26. Breast Cancer Occurrence How many cases and deaths are expected to occur in 2019? In 2019, an estimated 268,600 new cases of invasive breast cancer will be diagnosed among women (Table 1) and approximately 2,670 cases will be diagnosed in men. In addition, an estimated 48,100 cases of DCIS will be diagnosed among women. Approximately 41,760 women and 500 men are expected to die from breast cancer in 2019. How many women alive today have ever had breast cancer? More than 3.8 million US women with a history of breast cancer were alive on January 1, 2019.18 Some of these women were cancer-free, while others still had evidence of cancer and may have been undergoing treatment. More than 150,000 breast cancer survivors are living with metastatic disease, three-fourths of whom were originally diagnosed with stage I-III.19 What is the risk of being diagnosed with breast cancer? Approximately 1 in 8 women (13%) will be diagnosed with invasive breast cancer in their lifetime and 1 in 39 women (3%) will die from breast cancer (Table 2).20 Lifetime risk is an average of risk for all women and accounts for deaths from other causes that may preempt a breast cancer diagnosis. Breast cancer risk varies by age and race/ethnicity: Table 1. Estimated New DCIS and Invasive Breast Cancer Cases and Deaths among Women by Age, US, 2019 DCIS cases Invasive cases Deaths Age Number % Number % Number % <40 1,180 2% 11,870 4% 1,070 3% 40-49 8,130 17% 37,150 14% 3,250 8% 50-59 12,730 26% 61,560 23% 7,460 18% 60-69 14,460 30% 74,820 28% 9,920 24% 70-79 8,770 18% 52,810 20% 8,910 21% 80+ 2,830 6% 30,390 11% 11,150 27% All ages 48,100 268,600 41,760 Estimates are rounded to the nearest 10. Percentages may not sum to 100 due to rounding. ©2019, American Cancer Society, Inc., Surveillance Research 4 Breast Cancer Facts & Figures 2019-2020 Age • Breast cancer incidence and death rates increase with age until the seventh decade (Figure 2). The decrease in incidence rates that occurs in women 80 years of age and older may reflect lower rates of screening, the detection of cancers by mammography before 80 years of age, and/or incomplete detection. • During 2012-2016, the median age at the time of breast cancer diagnosis was 62.20 This means that half of women who developed breast cancer were 62 years of age or younger at the time of diagnosis. The median age of diagnosis was slightly younger for black women (60) than white women (63).20 • Table 2 provides 10-year probabilities of invasive breast cancer diagnosis or death for women of different ages. By 10-year age groups, the probability of a breast cancer diagnosis is highest for women in their 70s (4.1%), while breast cancer death is most likely among women in their 80s (1.0%). Race/Ethnicity • Breast cancer incidence and death rates by race and ethnicity during the most recent time period are shown in Figure 3. Incidence rates are highest among non-Hispanic (NH) whites (130.8 per 100,000), followed closely by NH blacks (126.7). However, NH black women have the highest breast cancer death rate (28.4 deaths per 100,000), more than double that in Asian/Pacific Islander (API) women (11.5), who have the lowest incidence and death rates. • NH black women have higher incidence rates than NH whites before age 40 (Figure 2) and are more likely to die from breast cancer at every age. • The distributions of breast cancer subtypes for the major racial/ethnic groups are shown in Figure 4. HR+/HER2- breast cancers are by far the most common subtype among women of all races/ ethnicities. About 21% of breast cancers in NH black women are triple negative, which is about double the proportion of this subtype in other racial/ethnic groups. The higher breast cancer death rate in black women in part reflects the disproportionate burden of triple negative breast cancers in this group. Stage • At the time of diagnosis, approximately 64% of breast cancer patients have local-stage breast cancer, 27% have regional stage, and 6% have distant (metastatic) disease. Figure 2. Age-specific Female Breast Cancer Incidence Rates by Race/Ethnicity, US, 2012-2016 Rate per 100,000 Age Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Source: NAACCR, 2019. Data for American Indians/Alaska Natives are based on Purchased/Referred Care Delivery Area (PRCDA) counties. ©2019, American Cancer Society, Inc., Surveillance Research Non-Hispanic White Non-Hispanic Black American Indian/Alaska Native Hispanic Asian/Pacific Islander 0 100 200 300 400 500 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Table 2. Age-specific Ten-year Probability of Breast Cancer Diagnosis or Death for US Women Current age Diagnosed with invasive breast cancer Dying from breast cancer 20 0.1% (1 in 1,479) ><0.1% (1 in 18,503) 30 0.5% (1 in 209) ><0.1% (1 in 2,016) 40 1.5% (1 in 65) 0.2% (1 in 645) 50 2.4% (1 in 42) 0.3% (1 in 310) 60 3.5% (1 in 28) 0.5% (1 in 193) 70 4.1% (1 in 25) 0.8% (1 in 132) 80 3.0% (1 in 33) 1.0% (1 in 101) Lifetime risk 12.8% (1 in 8) 2.6% (1 in 39) Note: Probability is among those who have not been previously diagnosed with cancer. Percentages and “1 in” numbers may not be numerically equivalent due to rounding. ©2019, American Cancer Society, Inc., Surveillance Research Breast Cancer Facts & Figures 2019-2020 5 • Stage at diagnosis also varies by race/ethnicity (Figure 5). NH black, Hispanic, and American Indian/Alaska Native (AIAN) patients are less likely to be diagnosed with local-stage disease (56%-60%) compared to NH white and API patients (64%-66%). How has the occurrence of breast cancer changed over time? Incidence Incidence rates of DCIS and invasive breast cancer rose rapidly during the 1980s and 1990s (Figure 6), particularly among women 50 years of age and older, largely due to increases in the prevalence of mammography screening, which increased from 29% in 1987 to 70% in 2000.21 For example, DCIS rates among women 50 and older, increased more than 11-fold from 1980 (7 cases per 100,000) to 2008 (83 cases per 100,000). In contrast, there was a sharp drop (nearly 13%) in the invasive breast cancer rate between 1999 and 2004, believed to be largely due to the decreased use of menopausal hormones following the 2002 publication of clinical trial results that found higher risk of breast cancer and heart disease among menopausal hormone users, and may also reflect small declines in mammography screening since 2000.22, 23 The decline in breast cancer incidence occurred primarily in white women, in those 50 years of age and older, and for ER+ disease.22, 24 In the most recent time period (2012-2016), the DCIS rate declined by 2.1% per year8 and the invasive breast cancer incidence rate rose by about 0.3% per year.20 In fact, the incidence rate for invasive breast cancer has been slowly increasing since 2004.20 A recent study concluded that increases in body mass index (BMI) and declines in the average number of births per woman (both breast cancer risk factors) have likely contributed to the recent increase in incidence.25 *Statistics based on data from PRCDA counties. Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Sources: Incidence – NAACCR, 2019. Mortality – National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention, 2019. ©2019, American Cancer Society, Inc., Surveillance Research Rate per 100,000 Incidence Mortality 0 30 60 90 120 150 Asian/ Pacific Islander Hispanic/ Latina American Indian/ Alaska Native* Non-Hispanic Black Non-Hispanic White 20.3 28.4 14.6 14.0 11.5 130.8 126.7 94.7 93.7 93.2 Figure 3. Female Breast Cancer Incidence (2012-2016) and Death (2013-2017) Rates by Race/Ethnicity, US HR = hormone receptor, HER2 = human epidermal growth factor receptor 2. Statsitics based on data from PRCDA counties. Source: NAACCR, 2019. ©2019, American Cancer Society, Inc., Surveillance Research Percent Figure 4. Distribution of Breast Cancer Subtypes by Race/Ethnicity, Ages 20 and Older, US, 2012-2016 0 20 40 60 80 100 Asian/ Pacific Islander American Indian/ Hispanic Alaska Native* Non-Hispanic Black Non-Hispanic White 76% 10% 4% 10% 61% 12% 6% 21% 69% 13% 6% 12% 71% 13% 6% 10% 70% 12% 6% 12% HR+/HER2- HR+/HER2+ HR-/HER2+ HR-/HER2- 6 Breast Cancer Facts & Figures 2019-2020 Race/Ethnicity Figure 7 presents trends in invasive female breast cancer incidence rates by race and ethnicity since 2001 based on data from 45 states, representing 92% of the US population. During the most recent 5 years of available data (2012 to 2016), overall breast cancer incidence rates increased most rapidly among APIs (1.5% per year), followed by AIANs (0.8% per year), and NH blacks and NH whites (both 0.5% per year), but were relatively stable in Hispanics. Stage The overall increase in breast cancer incidence is largely because of an increase in local-stage disease. From 2012 to 2016, the incidence rate increased by 1.1% per year for local-stage breast cancer, but declined by 0.8% per year for regional-stage disease, which may reflect a shift toward earlier stage at diagnosis. The incidence rate for distant-stage disease increased 2.5% annually during 2001-2011, but has since stabilized. The increase in distant-stage disease may be partly explained by the decrease in unknown stage, because of more complete staging of advanced tumors.26 This trend may also reflect increased detection of asymptomatic metastases due to the rise in the use of advanced imaging. Mortality The overall breast cancer death rate increased by 0.4% per year from 1975 to 1989, but since has decreased rapidly, for a total decline of 40% through 2017. As a result, 375,900 breast cancer deaths were averted in US women from 1989 to 2017. However, the decline in breast cancer mortality has slowed slightly in the most recent time period, from an annual decrease of 1.9% during 1988-2011 to 1.3% during 2011-2017. By race/ethnicity, the breast cancer death rate during 2013-2017 declined annually by 2.1% in Hispanics, 1.5% in NH blacks, 1.0% in NH whites, and 0.8% in APIs, but was stable in AIANs (Figure 8). The decline in breast cancer mortality has been attributed to both improvements in treatment and earlier detection.27 However, not all women have benefited equally from these advances, as indicated by the striking divergence in mortality trends between black and white women beginning in the early 1980s (Figure 8). This disparity likely reflects a combination of factors that are difficult to parse, including later stage at diagnosis and other unfavorable tumor characteristics, higher prevelance of obesity and other health conditions, less access to high-quality prevention, early detection, and treatment.28, 29 For example, black women are more likely to be screened at lower resourced and nonaccredited facilities and also experience longer intervals between mammograms, and between abnormal results and follow-up.30-33 Although self-reported screening rates based on national surveys are similar between black and white women, studies indicate that black (and Hispanic) women are more likely than white women to overestimate their screening history.34-36 The black-white disparity has grown as treatment for breast cancers has improved (particularly for HR+ breast cancers), but appears to have peaked in 2011, when rates in NH black *Statistics based on data from PRCDA counties. Source: NAACCR, 2019. ©2019, American Cancer Society, Inc., Surveillance Research Percent Localized Regional Distant Unknown 0 10 20 30 40 50 60 70 80 90 100 Asian/Pacific Islander American Indian/ Hispanic Alaska Native* Non-Hispanic Black Non-Hispanic White 26 33 56 66 3 5 3 8 30 60 4 6 32 58 4 6 28 64 2 5 Figure 5. Female Breast Cancer Stage Distribution, by Race/Ethnicity, Ages 20 and Older, US, 2012-2016 Breast Cancer Facts & Figures 2019-2020 7 women were 44% higher than those in whites. In the most recent period (2013-2017), the breast cancer death rate was 40% higher in black women versus white women (Figure 3). Are there geographic differences in breast cancer patterns? Table 3 shows variation in state-level breast cancer incidence and death rates per 100,000 women by race/ ethnicity. Although the overall incidence rate for breast cancer in the US remains slightly higher in NH white women compared to NH black women, rates are higher in NH black women in 4 of the 43 states with reliable data for both groups (Louisiana, Mississippi, Oklahoma, and Wisconsin), and are not statistically different in 26 other states and the District of Columbia.37 Data for AIAN women are too sparse to provide by state; however, during 2012-2016, incidence rates were more than twofold higher among women in Alaska (139.7 per 100,000) and the Southern Plains (150.8 per 100,000) compared to those living in the Southwest US (60.4 per 100,000).8 In contrast to incidence, breast cancer death rates are higher among NH black women than NH white women in every state, with rates in some states (e.g., Louisiana and Mississippi) as much as 60% higher (Table 3). Death rates reflect both cancer incidence and survival. Breast cancer mortality rates among NH white women tend to be highest in the North Central, Mid-Atlantic, and Western regions of the US (Figure 9). Among NH black women, the highest death rates are found in some of the South Central and Mid-Atlantic states, as well as California. Factors that contribute to geographic disparities include variations in risk factors and access to screening and treatment, which are influenced by socioeconomic factors, legislative policies, and proximity to medical services. During 2013-2017, breast cancer death rates decreased in all states except Nebraska.37 In addition, the decline in breast cancer mortality has leveled off for black women in Colorado and Wisconsin and for white women in Nebraska, Texas, and Virginia. Notably, during 2016-2017, breast cancer was the leading cause of cancer deaths (surpassing lung cancer) in 6 states (Arizona, Colorado, Florida, Georgia, Mississippi, and South Carolina) among black women and in Utah among white women.37 Figure 6. Trends in Incidence Rates of Ductal Carcinoma In Situ and Invasive Female Breast Cancer by Age, US, 1975-2016 a. DCIS Year Rate per 100,000 b. Invasive Year Rate per 100,000 Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Source: Surveillance, Epidemiology, and End Results (SEER) Program, SEER 9 Registries, National Cancer Institute, 2019. ©2019, American Cancer Society, Inc., Surveillance Research 0 50 100 150 200 250 300 350 400 1975 1980 1985 1990 1995 2000 2005 2010 2015 0 10 20 30 40 50 60 70 80 90 1975 1980 1985 1990 1995 2000 2005 2010 2015 Ages 20+ Ages 20-49 Ages 50+ 8 Breast Cancer Facts & Figures 2019-2020 Breast cancer survival Relative survival rates are an estimate of the percentage of patients who will survive their cancer for a given period of time after diagnosis, accounting for normal life expectancy. Survival among cancer patients is compared to survival among people of the same age and race who have not been diagnosed with cancer. Relative survival rates should be interpreted with caution because they are based on the average experience of all women and do not predict individual prognosis because many patient and tumor characteristics that influence breast cancer survival are not taken into account. In addition, long-term survival rates are based on data from patients diagnosed and treated many years ago and thus, do not reflect more recent improvements in early detection and treatment. Based on the most recent data, relative survival rates for women diagnosed with breast cancer are: • 91% at 5 years after diagnosis • 84% after 10 years • 80% after 15 years Stage at diagnosis Stage at diagnosis is one of the most important factors affecting prognosis. Five-year relative survival rates for breast cancer are: • 99% for localized disease • 86% for regional disease • 27% for patients diagnosed with metastatic disease20 Breast cancer subtype (HR/HER2) Breast cancer survival also varies by tumor subtype. Five-year relative survival rates are: • 92% for HR+/HER2- • 89% for HR+/HER2+ • 83% for HR-/HER2+ • 77% for HR-/HER2- Importantly, a recent study found that 4-year relative survival was 95% or greater for patients diagnosed with stage I breast cancers across all breast cancer subtypes.11 Figure 7. Trends in Female Breast Cancer Incidence Rates by Race/Ethnicity, US, 2001-2016 Rate per 100,000 Year NH indicates non-Hispanic. *Statistics based on data from PRCDA counties. Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Rates were adjusted for reporting delays. Source: NAACCR, 2019. © 2019, American Cancer Society, Inc., Surveillance Research NH white NH black American Indian/Alaska Native* Hispanic Asian/Pacific Islander 0 20 40 60 80 100 120 140 2001 2003 2005 2007 2009 2011 2013 2015 Figure 8. Trends in Female Breast Cancer Death Rates by Race/Ethnicity, US, 1975-2017 Rate per 100,000 Year Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Source: NCHS 2019. Rates for American Indian/Alaska Native are based on the PRCDA counties and are 3-year moving averages. © 2019, American Cancer Society, Inc., Surveillance Research 0 5 10 15 20 25 30 35 40 45 1975 1980 1985 1990 1995 2000 2005 2010 2015 American Indian/Alaska Native Hispanic Asian/Pacific Islander NH white NH black Breast Cancer Facts & Figures 2019-2020 9 Table 3. Female Breast Cancer Incidence and Death Rates by Race/Ethnicity and State Incidence Rates (2012-2016) Death Rates (2013-2017) State NonHispanic White NonHispanic Black Hispanic Asian/ Pacific Islander NonHispanic White NonHispanic Black Hispanic Asian/ Pacific Islander Alabama d population. *Statistic not displayed due to fewer than 25 cases or deaths. †This registry did not achieve high-quality data standards for one or more years during 2012-2016 and are not included in the overall US incidence rate. Sources: Incidence: Non-Hispanic Blacks Non-Hispanic Whites Figure 9. Geographic Variation in Female Breast Cancer Death Rates by Race/Ethnicity, 2013-2017 OH WV IL OK CA NV Breast Cancer Facts & Figures 2019-2020 11 Race/ethnicity Five-year relative survival has improved from 76% in 1975-1977 to 92% in 2009-2015 in white women and from 62% to 83% over the same time period in black women (Figure 10). While the racial disparity has narrowed, there remains a substantial gap, especially for late-stage diagnoses (Figure 11). Cause-specific survival instead of relative survival is used to describe the cancer experience of racial and ethnic minorities because reliable life expectancy is not historically available for some groups. Cause-specific survival is the probability of not dying of breast cancer within five years of diagnosis. For every stage at diagnosis, API women have the highest breast cancer survival and NH black women have the lowest (Figure 11). Poverty, less education, and a lack of health insurance are associated with lower breast cancer survival.38, 39 Of note, high survival rates for API and Hispanic patients are probably overestimated because of incomplete or inaccurate follow-up information in cancer registry data.40 Figure 10. Trends in Female Breast Cancer 5-year Relative Survival Rates by Race, US, 1975-2015 Percent 0 10 20 30 40 50 60 70 80 90 100 2009- 2015 2005- 2008 2002- 2004 1999- 2001 1996- 1998 1993- 1995 1990- 1992 1987- 1989 1984- 1986 1981- 1983 1978- 1980 1975- 1977 Year Source: SEER Program, 18 SEER registries, National Cancer Institute, 2019. ©2019, American Cancer Society, Inc., Surveillance Research White Black Survival rates are based on patients diagnosed during 2009-2015 and followed through 2016. Source: SEER Program, 18 SEER registries, National Cancer Institute, 2019. ©2019, American Cancer Society, Inc., Surveillance Research Percent 97 93 98. Five-year Breast Cancer-specific Survival Rates (%) by Stage at Diagnosis and Race/Ethnicity, US, 2009-2015 0 10 20 30 40 50 60 70 80 90 100 Localized Regional Distant Unstaged NH white NH black American Indian/Alaska Native Hispanic Asian/Pacific Islander 12 Breast Cancer Facts & Figures 2019-2020 Male breast cancer Breast cancer in men is rare, accounting for less than 1% of breast cancer cases in the US. However, since 1975, the incidence rate has increased slightly, from 1.0 case per 100,000 men during 1975-1979 to 1.2 cases per 100,000 men during 2012-2016.41 Men are more likely than women (51% versus 36%) to be diagnosed with advanced (regional- or distant-stage) breast cancer,8 which likely reflects delayed detection because of decreased awareness.42 The death rate for male breast cancer has decreased slightly from 0.4 deaths per 100,000 men during 1975-1979 to 0.3 per 100,000 men during 2013- 2017,43 reflecting improvements in treatment. Due to the infrequency of male breast cancer, much less is known about the disease. Similar to women, male breast cancer risk increases with age. Other risk factors include radiation exposure, BRCA1/2 gene mutations, family history of breast or ovarian cancer, Klinefelter syndrome, testicular disorders, diabetes, gynecomastia (enlarged breasts), and obesity.44, 45 In contrast to female breast cancer, studies have found that smoking, alcohol consumption, and physical inactivity are not linked to male breast cancer.46, 47 Breast Cancer Risk Factors The most well-established risk factors for breast cancer are summarized in Table 4. It is estimated that about one-third of postmenopausal breast cancers are linked to potentially modifiable factors, including postmenopausal obesity, physical inactivity, use of combined estrogen and progestin menopausal hormones, alcohol consumption, and not breastfeeding.48 Many risk factors (early menarche, late menopause, obesity, and hormone use) affect lifetime exposure of breast tissue to hormones. Hormones are thought to influence breast cancer risk by increasing cell division, thereby increasing the likelihood of DNA damage, as well as promoting cancer growth. Although exposures that influence risk accumulate throughout a woman’s life, research suggests that earlylife exposures during breast development may be particularly critical.49 Many established risk factors for breast cancer are specifically associated with HR+/ luminal breast cancer; less is known about risk factors for HR-, HER2+ or basal-like breast cancers.50 The following sections present current knowledge about factors associated with breast cancer risk. Family history and personal characteristics Family history Women (and men) with a family history of breast cancer, especially in a first-degree relative (parent, child, or sibling), are at increased risk for the disease. Compared to women without a family history, risk of breast cancer is about 1.5 times higher for women with one affected first-degree female relative and 2-4 times higher for women with more than one first-degree relative.51-53 Risk is further increased when the affected female relative was diagnosed at a young age or was diagnosed with cancer in both breasts, or if the affected relative is male. It is important to note that the majority of women with one or more affected first-degree relatives will never develop breast cancer and that most women who develop breast cancer do not have a family history of the disease.51 A family history of ovarian and perhaps pancreatic or prostate cancer is also associated with increased breast cancer risk.54, 55 Women should discuss their family history with their health care provider because it may signal the presence of a genetic predisposition to cancer and the need for a different plan for screening and risk reduction. Breast Cancer Facts & Figures 2019-2020 13 Genetic predisposition Inherited pathogenic (disease-causing) genetic variations in BRCA1 and BRCA2, the most well-studied breast cancer susceptibility genes, account for 5%-10% of all female breast cancers and 15%-20% of all familial breast cancers.56, 57 These variations are rare (about 1 in 400) in the general population, but occur slightly more often in certain ethnic or geographically isolated groups, such as those of Ashkenazi (Eastern European) Jewish descent (about 1 in 40). Recent studies also document increased frequency of BRCA mutations among black and Hispanic breast cancer patients.58-60 Compared to women in the general population who have a 10% risk of developing breast cancer by 80 years of age, risk is estimated to be about 70% in women with pathogenic variants in BRCA1 and BRCA2. 61 The risk of breast cancer by age 70 in women with pathogenic variations in PALB2, a different gene that works with BRCA2, is estimated to be 35%.62 Mutations in other genes are also associated with increased breast cancer risk, including TP53 (associated with Li-Fraumeni syndrome), PTEN (Cowden syndrome), STK11 (Peutz-Jeghers syndrome), and CDH1 (associated with diffuse gastric and lobular breast cancer syndrome). In addition, research studies have identified more than 300 more common genetic variants that are associated with slightly elevated risk.63 The US Preventive Services Task Force recommends that primary care providers routinely collect and update family medical history, as well as ancestry. Women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or those with ancestry associated with BRCA1/2 gene mutations should be screened with one of several brief questionnaires to determine if there is a need for in-depth genetic counseling to consider genetic testing.64 Those who consider testing are strongly encouraged to talk with a genetic counselor before making a decision so that the benefits and potential consequences can be understood and carefully considered. Personal history of breast cancer Women diagnosed with breast cancer have a small increased risk of developing a new cancer, with estimated 10-year risks ranging from 3%-7%.65 However, rates of subsequent new breast cancers (also referred to as a new primary breast cancer) have declined steadily since 1985.66 The decrease has predominantly been among ER+ breast cancer patients and may reflect the effect of hormonal therapy (e.g., tamoxifen and aromatase inhibitors) and other adjuvant treatments, as well as the rapid increase in breast cancer patients electing bilateral mastectomy for breast cancer treatment (see page 23).65, 67 DCIS and LCIS DCIS is considered a potential precursor to invasive cancer and risk of subsequent breast cancer is greatest at or near the site of DCIS.68 Similar to women with a prior Table 4. Factors That Increase the Relative Risk for Invasive Breast Cancer in Women Relative risk Factor >4.0 Age (65+ versus <65 years, although risk increases across all ages until age 80) Atypical hyperplasia Lobular carcinoma in situ Pathogenic genetic variations (e.g. BRCA1, BRCA2, PALB2, TP53) 2.1-4.0 Ductal carcinoma in situ High endogenous hormone levels (postmenopausal) High-dose radiation to chest (e.g. Hodgkin lymphoma treatment) Mammographically dense breasts Two or more first-degree relatives with breast cancer 1.1-2.0 Alcohol consumption Early menarche (><11 years) Excess body weight High endogenous estrogen or testosterone levels (premenopausal) Late age at first full-term pregnancy (>30 years) Late menopause (≥55 years) Never breastfed a child No full-term pregnancies One first-degree relative with breast cancer Obesity (postmenopausal) Personal history of ovarian or endometrial cancer Physical inactivity Proliferative breast disease without atypia (usual ductal hyperplasia, fibroadenoma) Recent and long-term use of menopausal hormone therapy containing estrogen and progestin Recent hormonal contraceptive use Weight gain in adulthood Tall height Note: Relative risks for some factors vary by breast