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Epidemiology of Breast Cancer
Descriptive Epidemiology
Breast cancer is the most common cancer in American women other than skin cancers. The average woman in the United States has a lifetime risk of developing breast cancer of about 13%. The American Cancer Society estimates about 281,550 new cases of invasive breast cancer will have been diagnosed in women during 2021, and there will have been approximately 49,290 new cases of ductal carcinoma in situ (DCIS). About 43,600 women will have died from breast cancer in the United States in 2021.
In recent years, incidence rates have increased by 0.5% per year. Breast cancer is the second leading cause of cancer death in women. (Lung cancer kills more women each year.) The chance that a woman will ever die from breast cancer is about 1 in 39 (about 2.6%). Since 2007, breast cancer death rates have been steady in women younger than 50 but have continued to decrease in older women, down by 1% per year. These decreases are believed to be the result of finding breast cancer earlier through screening and increased awareness, as well as better early adjuvant treatments.
Incidence Rates for Breast Cancer Subtypes
There are racial and ethnic variations in both incidence rates and mortality by breast cancer subtype and age ( Fig. 7.1 ). Among women 20 years and older, incidence rates of hormone receptor (HR)–positive/HER2-negative breast cancer are highest in White women (138 cases per 100,000), with rates 23% higher than in Black women (112 per 100,000) and about 45% higher than in Hispanic and American Indian/Alaskan Native (AIAN) women, who have the lowest incidence rates (94–97 per 100,000). Furthermore, lower overall breast cancer incidence rates in Hispanic, Asian Pacific Islander (API), and AIAN women primarily result from their lower rates of the HR-positive/HER2-negative subtype.
In contrast, incidence rates for triple-negative breast cancers are about twice as high in Black (38 per 100,000) compared with White (19 per 100,000) women. There is less racial/ethnic variation in the HER2-positive subtypes. These patterns are remarkably like those in younger (ages 20–49 years) and older (ages ≥50 years) women, except for HR-positive/HER2-negative breast cancer. For example, API women have the second highest rate of HR-positive/HER2-negative breast cancer among younger women (46 per 100,000, only slightly lower than in young White women, 51 per 100,000), but they have the lowest rate among older women (177 vs. 275 per 100,000 in White women). This may reflect age-related differences in the make-up of the Asian population in the United States that includes women from more than 30 countries who differ in their immigration patterns and risk factor profiles.
Temporal Trends in Incidence and Mortality
Incidence
Much of the historic increase in breast cancer incidence rates reflects changes in reproductive patterns, such as delayed childbearing and fewer births, associated with increased breast cancer risk. During the 1980s and 1990s, incidence rates of DCIS and invasive breast cancer rose rapidly, particularly among women aged ≥50 years ( Fig. 7.1 ), largely because of increased use of mammography screening that increased from 29% in 1987 to 70% in 2000. Among women aged ≥50 years, DCIS rates increased more than 11-fold, from 7 cases per 100,000 in 1980 to 83 cases per 100,000 in 2008, but during 2012 to 2016, the DCIS incidence rate decreased by 2.1% per year.
In contrast, there was a 13% drop in the incidence rate of invasive breast cancer between 1999 and 2004, largely attributed to the decreased use of menopausal hormones after publication of the Women’s Health Initiative randomized trial linking use of estrogen plus progesterone menopausal hormone therapy (HT) to breast cancer and heart disease. The decrease in breast cancer incidence was limited to White women, primarily for estrogen receptor (ER)-positive disease.
Since 2004, the overall invasive breast cancer incidence rate has risen by about 0.3% per year. Increases in body mass index (BMI) and continued declines in the fertility rate likely contributed to the increase in incidence. The overall increase in breast cancer incidence largely reflects a rise in local-stage disease.
Trends in breast cancer incidence rates and mortality by race/ethnicity are shown in Fig. 7.2 . During 2012 through 2016, incidence rates increased among API (1.5% per year), AIAN (0.8% per year), and Black and White (both 0.5% per year) women but were relatively stable among Hispanic women.
Parity is associated with a lower risk of HR-positive breast cancer and a higher risk of triple-negative breast cancer. In the United States, the fertility rate, that was once as high as 118 births per 1000 women aged 15 to 44 years, declined from 69.4 births per 1000 women aged 15 to 44 years in 2007 to an all-time low of 60.3 in 2017.
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 of this decline, 375,900 breast cancer deaths were averted in US women through 2017, attributed both to improvements in treatment and to early detection by mammography.
Higher breast cancer death rates in Black women reflect a combination of factors including later stage at diagnosis and other unfavorable tumor characteristics, higher prevalence of obesity and comorbidities, and less access to timely and high-quality prevention, early detection, and treatment services.
Survival
Breast cancer survival rates vary substantially by stage at diagnosis. The overall 5-year breast cancer survival rate for patients diagnosed during 2009 through 2015 was 98% for stage I, 92% for stage II, 75% for stage III, and 27% for stage IV. For every stage at diagnosis, breast cancer survival is highest for API women and lowest for Black women, with racial disparities most striking for patients diagnosed with stage III breast cancer.
Traditional Risk Factors for Breast Cancer
Well-accepted risk factors for breast cancer have been identified during the past several decades and are shown in Table 7.1 . Age is the most important risk factor for breast cancer, and breast cancer incidence rises sharply with age as noted earlier. The Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute allows calculation of the probability of a woman developing breast cancer in the United States through specific attained ages ( Table 7.2 ). The overall incidence rate of breast cancer is low at younger ages (e.g., 1.4 per 100,000 in women 20–24 years of age).
Table 7.1
Traditional Risk Factors for Breast Cancer, Relative Risks, and Associated Population Attributable Risks
Adapted from Harris JR, Lippman ME, Veronesi U, Willet W. Breast cancer (1). N Engl J Med . 1992;327:319-328. Copyright © 1992 Massachusetts Medical Society. All rights reserved.
| Risk Factor | Comparison Category | Risk Category | Relative Risk | Prevalence (%) | Population Attributable Risk a |
|---|---|---|---|---|---|
| Age at menarche | 16 years | Younger than 12 years | 1.3 | 16 | 0.05 |
| Age at menopause | 45 to 54 years | After 55 years | 1.5 | 6 | 0.03 |
| Age when first child born alive | Before 20 years | Nulliparous or older than 30 years | 1.9 | 21 | 0.16 |
| Benign breast disease | No biopsy or fine-needle aspiration | Any benign disease | 1.5 | 15 | 0.07 |
| Proliferative disease | 2 | 4 | 0.04 | ||
| Atypical hyperplasia | 4 | 1 | 0.03 | ||
| Family history of breast cancer | No first-degree relative affected | Mother affected | 1.7 | 8 | 0.05 |
| Two first-degree relatives affected | 5 | 4 | 0.14 |
a Population attributable risk = [prevalence × (relative risk − 1)]/{[prevalence × (relative risk − 1)] + 1}.
Table 7.2
Probability of a Woman Developing Breast Cancer in the United States Through Specific Attained Ages
| Current Age | Diagnosed With Invasive Breast Cancer | Dying From Breast Cancer |
|---|---|---|
| 20 | 0.1% (1 in 1479) | <0.1% (1 in 18,503) |
| 30 | 0.5% (1 in 209) | <0.1% (1 in 2016) |
| 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) |
Benign Breast Disease
Benign breast lesions can be classified according to their histologic appearance ( Table 7.3 ). Benign breast lesions thought to impart no increased risk of breast cancer include adenosis, duct ectasia, simple fibroadenoma, fibrosis, mastitis, mild hyperplasia, cysts, and metaplasia of the apocrine or squamous types. Lesions associated with a slight increase in the subsequent risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia with or without atypia, sclerosing adenosis, and papilloma. Atypical hyperplasia of the ductal or lobular type is associated with a four- to fivefold increased risk of developing subsequent breast cancer, and this risk increases to approximately 10-fold if it is also associated with a family history of invasive breast cancer in a first-degree relative.
Table 7.3
Classification of Benign Breast Disease and the Risk of Subsequent Breast Cancer
Modified from Vogel VG. Breast cancer risk factors and preventive approaches to breast cancer. In: Kavanagh JS, Einhorn N, DePetrillo AD, eds. Cancer in Women . Cambridge, MA: Blackwell Scientific Publications; 1998: 58-91; Fitzgibbons PL, Henson DE, Hutter RV. Benign breast changes and the risk for subsequent breast cancer: an update of the 1985 consensus statement. Cancer Committee of the College of American Pathologists. Arch Pathol Lab Med . 1998;122:1053-1055.
| Associated Relative Risk of Breast Cancer a | |||
|---|---|---|---|
| Benign Lesion | Description | With Family History of Breast Cancer | Without Family History of Breast Cancer |
| Proliferative Disease Without Atypia | 2.4–2.7 | 1.7–1.9 | |
| Moderate and florid ductal hyperplasia of the usual type | Most common type of hyperplasia; cells do not have the cytologic appearance of lobular or apocrine-like lesions; florid lesions have a proliferation of cells that fill more than 70% of the involved space | ||
| Additional lesions | Intraductal papilloma, radial scar, sclerosing adenosis, apocrine metaplasia | ||
| Atypical Hyperplasia | 11 | 4.2–4.3 | |
| Atypical ductal hyperplasia | Has features similar to ductal carcinoma in situ but lacks the complete criteria for that diagnosis | ||
| Atypical lobular hyperplasia | Defined by changes that are similar to lobular carcinoma in situ but lack the complete criteria for that diagnosis | ||
| Nonproliferative | Normal, cysts, duct, ectasia, mild hyperplasia, fibroadenoma | 1.2–2.6 | 0.9–1 |
a Relative risks represent the range of values reported in the published literature.
Lobular Carcinoma in Situ and Atypical Hyperplasia
Women with a history of lobular carcinoma in situ (LCIS) experience an annual risk of invasive breast cancer of approximately 1.5% per year. Women with atypical ductal or lobular hyperplasia also experience an increased risk of subsequent invasive breast cancer. There are two types of atypical hyperplasia, as classified based on microscopic appearance: atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH); atypical hyperplasia confers a relative risk (RR) of 4.0 and an absolute risk of approximately 1% per year for developing future invasive breast cancer. These risk statistics have been recognized for decades, and the absolute risk among women with atypical hyperplasia has been shown to approach 30% at 25 years of follow-up. The risk of developing invasive disease after a diagnosis of atypia is inversely related to the age at diagnosis, directly related to the number of atypical foci seen on the biopsy, and appears to be slightly higher with ADH compared with ALH. Atypical hyperplasia is found in approximately 10% of biopsies with benign findings.
In studies with long-term follow-up, atypical hyperplasia has been shown to confer high RRs for future breast cancer with an absolute risk of approximately 1% to 2% per year of developing invasive breast cancer.
Family History
Women who have a first-degree relative with a history of breast cancer are at increased risk of the disease themselves. The risk conferred by family history is further increased if the affected family member was diagnosed with the disease at a younger age. For example, a woman with a first-degree relative diagnosed with breast cancer before 40 years of age has a 5.7 times increased risk (99% confidence interval [CI] 2.7–11.8) of being diagnosed with breast cancer before she is 40 compared with a woman of the same age but without a family history of breast cancer. Two genes, BRCA1 and BRCA2 , have been implicated in familial breast cancer but account for less than 10% of all breast cancer cases. BRCA mutations are most strongly related to breast cancer occurring in younger, premenopausal women. In women diagnosed with breast cancer before age 40, 9% have a BRCA mutation, compared with only 2% of women of any age diagnosed with breast cancer.
Reproductive Factors
Early age at menarche and late age at menopause have been found to increase the risk of breast cancer, whereas premenopausal oophorectomy reduces risk. Late age at first and possibly last full-term pregnancy have been associated with an elevated risk; risk decreases with increasing parity. Breastfeeding has also been shown to decrease the risk of breast cancer. The timing of the initiation of the carcinogenic process is an important consideration when studying the effect of reproductive factors on the risk of breast cancer. Risk of premenopausal breast cancer decreases about 9% (95% CI 7%–11%) for each 1-year increase in age at menarche, whereas risk of postmenopausal breast cancer decreases only about 4% (95% CI 2%–5%) for each 1-year increase in age at menarche. Risk of breast cancer increases with increasing age at first full-term pregnancy by 5% (95% CI 5%–6%) per year for breast cancer diagnosed before menopause, and by 3% (95% CI 2%–4%) for cancers diagnosed after menopause. Each full-term pregnancy is associated with a 3% (95% CI 1%–6%) reduction in risk of breast cancer diagnosed before menopause, whereas the reduction was 12% (95% CI 10%–14%) for breast cancer diagnosed later.
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