David Cohen, M.D.·Published 6 June 2008·11 min read
Key points
High-Risk and Low-Risk Populations The incidence of female breast cancer varies markedly between countries.
Age-Incidence Curve of Breast Cancer Risk Breast cancer is extremely rare among women younger than age 20 years and is uncommon among women younger than age 30 years.
In 1995, the overall age-adjusted incidence of breast cancer among white women in the United States was 115 per 100,000 women, whereas the corresponding rate among African-American women was 101 per 100,000 women.
Unlike most other illnesses, the lifetime risk of breast cancer is positively associated with higher socioeconomic status.
High-Risk and Low-Risk Populations The incidence of female breast cancer varies markedly between countries. It is highest in the United States and Northern Europe, intermediate in Southern and Eastern Europe and South America, and lowest in Asia. During 1983 to 1987, the age-adjusted incidence of breast cancer varied by approximately a factor of five among countries. However, rates have been rising in traditionally low-incidence Asian countries, particularly in Japan, Singapore, and urban areas of China, as these regions make the transition toward a Western-style economy and pattern of reproductive behavior. As a result of unfavorable trends in these countries, the international gap in breast cancer incidence has narrowed since 1970.
Age-Incidence Curve of Breast Cancer Risk Breast cancer is extremely rare among women younger than age 20 years and is uncommon among women younger than age 30 years. Incidence increases sharply with age, however, and becomes substantial before age 50. During 1991 to 1995, the incidence of breast cancer among American women aged 30 to 34 years was 25 per 100,000 and increased to 200 per 100,000 among women aged 45 to 49 years. The rate of increase in breast cancer incidence continues throughout life but slows somewhat between ages 45 and 50 years. This finding strongly suggests the involvement of reproductive hormones in breast cancer etiology, because non-hormone-dependent cancers do not exhibit this change in slope of the incidence curve around the time of menopause. The incidence of breast cancer among American women aged 70 to 74 years rises to 463 per 100,000. The shape of the age-incidence curve in low-risk and intermediate-risk populationsis similar to that in the United States, although the absolute rates are lower at each age.
Racial and Ethnic Groups within the United States and Studies of Migrants According to data from the Surveillance, Epidemiology, and End Results (SEER) Program registries, the lifetime risk of breast cancer for white women in the United States is 13.1%, slightly higher than 1 in 8, whereas that for African-American women is 9.6%, slightly less than 1 in 10. In 1995, the overall age-adjusted incidence of breast cancer among white women in the United States was 115 per 100,000 women, whereas the corresponding rate among African-American women was 101 per 100,000 women. These age-adjusted figures conceal a crossover pattern, however, in which the risk of breast cancer at a young age is modestly higher among African-American women than among white women. At older ages, breast cancer rates for white women are substantially higher than for African-American women.
Unlike most other illnesses, the lifetime risk of breast cancer is positively associated with higher socioeconomic status. This association is largely explained by the known reproductive risk factors; women in lower socioeconomic strata are more likely to have more children and to have them at a younger age than women in higher socioeconomic strata. Much, if not all, of the differences in breast cancer rates between African-Americans and whites in older age groups are likely to reflect racial differences in social class distribution, and thus in the distribution of established reproductive risk factors.
Written and revised by
David Cohen, M.D.
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The modestly higher incidences of breast cancer among young African-American women relative to young white women is consistent with the hypothesis of a short-term increase in breast cancer risk immediately after pregnancy, whereas the overall lower lifetime risk of breast cancer among African-American women is consistent with the hypothesis of a long-term benefit of early and repeated pregnancy. The effect of these reproductive factors on breast cancer risk is described in greater detail in the section Models of Reproductive Factors and Breast Cancer Incidence. Although African-American women have a lower probability of developing breast cancer over their lifetimes, their risk of dying from breast cancer is the same as, or perhaps even slightly higher than, that of white women (3.6% for African-American women, compared with 3.5% for white women). African-American women have poorer 5-year survival rates from breast cancer at all ages of diagnosis compared with white women. This poorer survival can be attributed, in part, to the tendency for African-American women to be diagnosed at later stages of disease.
Breast cancer rates are considerably lower among Asian, Hispanic, and American Indian women in the United States than among (non-Hispanic) white women. The magnitude of the difference in incidence among various ethnic groups often depends on migrant status. For instance, breast cancer incidence for Chinese-American and Japanese-American women during 1973 to 1986 was approximately 50% lower for those born in Asia and approximately 25% lower for those born in the United States compared with U.S.-born white women. Among Filipino residents of the United States, the incidence of breast cancer was nearly identical for foreign-born and U.S.-born women, and rates for both were less than one-half the rates for U.S.-born white women. Compared with Chinese women living in the mainland, Singapore, and Hong Kong, Asian-born Chinese women living in the United States had an almost twofold higher annual rate of breast cancer, and U.S.-born Chinese women had a rate that was higher still. The pattern for Japanese women was similar.
These findings are consistent with a large body of literature showing increases in breast cancer incidence after migration from a low-risk country to the United States. Ziegler et al. noted a sixfold gradient in risk of breast cancer among Asian women, depending on recency of migration. Asian-American women with three or four grandparents born in the West were at highest risk, whereas women who were born in rural areas of Asia and whose length of residence in the United States was a decade or less were at lowest risk. Whereas the studies of breast cancer risk among migrants have focused almost exclusively on migrants from low-risk to high-risk countries and have shown convergence of rates, some data also suggest that a convergence of rates similarly occurs when migrants move from high-risk to low-risk countries. For instance, Kliewer and Smith, reporting on immigrants to Australia and Canada, noted that immigrant groups coming from countries in which breast cancer mortality rates were higher than those of native-born women often showed a decrease in mortality. Such findings strongly suggest that factors associated with the lifestyle or environment of the destination country influence breast cancer risk and are consistent with a positive relationship between length of time in the destination country and adoption of that country's lifestyle. For example, among immigrants, the fertility rate as well as average number of children born tend to converge to the rates of the destination country.{pagebreak}
Geographic Variation within the United States Breast cancer incidence and mortality rates vary within the United States, although to a much smaller degree than among countries. During the 1980s, the incidence of breast cancer in the San Francisco Bay area was somewhat higher than that in the rest of the United States, and international comparisons based on data from this time period led to an often-quoted statement that white women in the San Francisco Bay area had the highest incidence of breast cancer in the world. Based on the SEER data, the age-adjusted annual incidence among white women in the San Francisco area (127 per 100,000) is now surpassed by that of white women in Hawaii, where the age-adjusted incidence is 128 per 100,000. The incidence of breast cancer is also higher than the national average among white women in the northeastern United States (age-adjusted incidence for Connecticut, 119 per 100,000). Reports have concluded that the high incidence of breast cancer in the San Francisco area and in the Northeast can probably be accounted for by regional differences in the prevalence of known risk factors, including parity, age at first full-term pregnancy, age at menarche, and age at menopause.
Among the 11 SEER registry sites, the lowest age-adjusted incidences among white women are found in Utah (98 per 100,000) and New Mexico (99 per 100,000). Again, regional differences in reproductive risk factors probably largely explain these lower rates. Seven of the 11 SEER registry sites have data on incidence among African-American women. The variation in age-adjusted rates for African-American women across the geographic sites is relatively small, ranging from 94 per 100,000 in Connecticut to 106 per 100,000 in metropolitan Atlanta.
Geographic differences in breast cancer mortality parallel those in incidence. Mortality is highest in the urban Northeast and West, and lowest in the South and Midwest. These differences have remained remarkably constant over the past 50 years. In 1940, before the introduction of DDT, polychlorinated biphenyls (PCBs), and other environmental causes postulated to be linked to geographic differences in breast cancer risk, the Northeast and western areas of the United States tended to have the highest age-adjusted mortality rates, whereas the South had the lowest. Again, geographic differences in the prevalence of established risk factors explain much of the geographic differences in mortality. In 1987, age-adjusted mortality ratios among women aged 50 years and older were 1.15, 1.18, and 1.30 in the West, Midwest, and Northeast, respectively, compared with the South. After adjustment for established breast cancer risk factors, these mortality ratios fell to 1.13, 1.08, and 1.13, respectively.
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Trends in Incidence and Mortality in the United States Rates of breast cancer have been steadily increasing in the United States since formal record-keeping began in Connecticut in the 1930s. Between 1940 and 1982, the age-adjusted incidence rose by an average of 1.2% per year in this state, which has the oldest cancer registry in continuous operation. This represents a cumulative increase of approximately 65% over the 42 years. During the 1980s, incidences rose more sharply. Data from the SEER program, which began collecting data from different registries across the country in 1973, confirm the trends in incidence portrayed in the Connecticut registry since that time. Increases have occurred in all age groups since 1935, although the magnitude of increase has been greater for older women. In recent decades, rates have increased more sharply among African-American women than among white women. According to SEER data, between 1973 and 1995, incidence amongAfrican-American women younger than 50 years of age increased by 34% compared with a cumulative increase of 10% for white women under age 50 years. Among women 50 years of age and older, the cumulative increase was 51% for African-American women and 45% for white women.
Several studies have examined whether the increase in breast cancer incidence in the United States has been due to the increasing use of screening mammography. Because screening causes at most a transient increase in incidence, and because its use was limited before the 1980s, it can explain little of the long-term increase between the 1930s and the 1980s. During the 1980s, however, the increased incidence was due almost entirely to an increase in localized disease and in tumors measuring less than 2 cm in diameter; the incidence of tumors 2 cm or larger remained stable. These findings, as well as the observed decrease in mortality for white women (discussed in the following paragraph), suggest that the increase in use of screening mammography accounts for part of the increase in breast cancer incidence in the 1980s and 1990s.
Trends in breast cancer mortality are of major public health interest, but their interpretation is complex, because they reflect the combined effects of trends in underlying risk of breast cancer, changes in screening practices, and effectiveness of treatment. Furthermore, mortality rates lag behind changes in breast cancer risk, screening, and treatment by at least 5 to 10 years. Age-adjusted mortality rates in the United States were relatively stable between the 1950s and the late 1980s, when an overall decline was first noted. These overall trends obscure important variation by age and race, however. Since the 1970s, mortality rates have fallen for younger white women, and this decline has accelerated since the late 1980s. From 1973 to 1995, the cumulative decline in mortality rates for white women younger than age 60 was more than 20%, with much of this decline occurring since 1988. In contrast to these trends among younger white women, mortality rates for white women aged 60 years and older increased slowly during the 1970s and 1980s, although since the late 1980s mortality has also begun to decline in this group. The trends in breast cancer mortality among African-American women have been unfavorable; since the 1970s, mortality rates have increased for African-American women in all age groups, and no evidence is seen of a recent decline in mortality, as has been noted for white women.
Trends in Incidence and Mortality around the World Since the 1950s, breast cancer incidence has been increasing in many of the lower-risk countries and in high-risk Western countries. Some of the recent increases in incidence in high-risk populations may be due to greater use of mammography, as in the United States. This appears to be the case in Sweden, as well as in England and Wales. In Norway, however, a substantial increase in breast cancer incidence occurred between 1983 and 1993 despite low use of mammographic screening. Breast cancer rates have nearly doubled since the 1950s in traditionally low-risk countries such as Japan and Singapore, and in the urban areas of China. Dramatic changes in lifestyle in such regions brought about by growing economies, increasing affluence, and increases in the proportion of women in the industrial workforce have had an impact on the population distribution of established breast cancer risk factors, including age at menarche and fertility, and nutritional status. These changes have resulted in a convergence toward the risk factor profile of Western countries.
Trends in breast cancer mortality around the world have largely paralleled the trends in incidence. Since the 1960s, mortality has been increasing in both high-risk and lower-risk populations, although a slight decline in mortality has been observed since 1990 in the United Kingdom, The Netherlands, and Sweden, similar to the decline over the same time period in the United States. As in the United States, some of the downturn in mortality in these countries may be due to more widespread use of screening mammography and adjuvant chemotherapy during the 1980s. Countries with a recent downturn in mortality are generally those with the highest incidence and mortality rates, whereas those countries with mortality rates that are still increasing tend to be those with the lowest mortality. For instance, among European countries, Poland and Spain have had the lowest mortality rates, and these rates are continuing to rise. Thus, a convergence of breast cancer mortality rates may be occurring internationally, in part reflecting an international convergence of reproductive factors.
Walter C. Willett, Beverly Rockhill, Susan E. Hankinson, David J. Hunter and Graham A. Colditz
W. C. Willett: Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts B. Rockhill: Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts S. E. Hankinson: Departments of Medicine and Epidemiology, Harvard Medical School and Harvard School of Public Health, Boston Massachusetts D. J. Hunter: Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachussetts G. A. Colditz: Department of Medicine, Harvard Medical School, Boston, Massachussetts
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