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The "Epidemic" of Breast Cancer in the U.S.--Determining the Factors

The "Epidemic" of Breast Cancer in the U.S.--Determining the Factors

ABSTRACT: Breast cancer incidence rates in the United States rose by 24% between 1973 and 1991. Mortality during this period, however, remained stable. Both the 5-year relative survival rate and the rates of in situ and stage I breast cancers have been increasing, while the incidence of later-stage cancers has been decreasing. Increased mammography screening may explain the documented jump in breast cancer incidence rates during the mid-1980s. Differences in the distribution of breast cancer risk factors may account, in part, for the temporal trends in breast cancer incidence. In particular, breast cancer risk factors may vary by birth cohort, including age at menarche, age at first birth, physical activity, obesity, diet, alcohol intake, estrogen therapy, and exposure to environmental organochlorines. After decades of epidemiologic research, a preventive approach to breast cancer that focuses on the physiologic effects of the sex steroid hormones, and their potential interactions with family history, is being carefully formulated. [ONCOLOGY 10(4):453-472, 1996]

Introduction

Between 1973 and 1991, breast cancer incidence rates in the United
States increased by 24%. In contrast, mortality from breast cancer
during the same period remained constant. Changes in the 5-year
relative survival rate and the incidence rates of different stages
of breast cancer have also been documented. In this article, we
will outline these recent trends in breast cancer incidence and
mortality and offer possible explanations for them. In particular,
we will explore the impact of increased mammography screening
on breast cancer incidence. We will also discuss breast cancer
risk factors that may vary by birth cohort, including age at menarche,
age at first birth, physical activity, obesity, diet, alcohol
intake, estrogen therapy, and exposure to organochlorines.

Recent Trends

Incidence

Breast cancer incidence in the United States has risen continually
during the past several decades. According to statistics from
the National Cancer Institute's Surveillance, Epidemiology and
End Results (SEER) Program, age-adjusted, invasive breast cancer
incidence rates rose by 24% between 1973 and 1991, with an estimated
average annual increase of 1.7% [1]. Data from the Connecticut
Tumor Registry, extending back to 1940, indicate that breast cancer
incidence rates have been increasing annually by at least 1.0%
since 1940 [2]. Evidence from the Connecticut Tumor Registry also
indicates that breast cancer incidence has been increasing with
successive birth cohorts [3]. Campbell et al [4] have modeled
the probability of breast cancer by birth cohort and have determined
that the risk of getting breast cancer by age 85 increased from
1 in 29 for women born between 1888 and 1892 to 1 in 10 for women
born between 1948 and 1952.

Breast cancer incidence has increased in both US white and black
populations. Although black women have experienced a higher percentage
increase in breast cancer incidence than white women during the
last 2 decades, particularly among women under 50 years of age
(26% vs 8.5%), white women have continually demonstrated the highest
rates [1]. In 1991, the breast cancer incidence rate for white
females, age-adjusted to the 1970 US population, was 113.6 per
100,000 women. The comparable rate for black women was 95.1 per
100,000 women (Figures 1 and 2).

Breast cancer incidence rates increase dramatically with age.
The 1987 to 1991 age-specific breast cancer incidence rates for
30- to 34-year-old women of all races was 26 per 100,000. This
rate increased to 229 per 100,000 for women 50 to 54 years old
and increased further to 450 per 100,00 for those 70 to 74 years
old [1]. A graph of the age-specific breast cancer incidence rates
plotted on a semilogarithmic scale illustrates that the rate of
change in breast cancer incidence among premenopausal women is
greater than the rate of change among postmenopausal women (Figure
3
). The difference in breast cancer rates between 30 and 50 year
olds is almost 10-fold, while the difference between 50 and 70
year olds is only 2-fold.

According to cross-sectional SEER data, most of the increase in
breast cancer incidence rates during the past 2 decades has been
experienced by postmenopausal women. Between 1973 and 1991, women
under 50 years of age experienced only a 9% increase in breast
cancer incidence rates [1]. During this same period, the increase
in breast cancer incidence for women over age 50 was 29%. However,
Holford et al [3], using data from the Connecticut Tumor Registry
beginning in 1950, reported that breast cancer incidence models
that account for the effect of birth cohort, in addition to age
at diagnosis and calendar period, showed similar patterns of increase
in breast cancer incidence in premenopausal and postmenopausal
women.

Mortality

Cross-sectional breast cancer mortality has remained fairly stable
during the last 2 decades (Figure 1). Data from the Connecticut
Tumor Registry indicate that mortality for breast cancer has been
declining in more recent birth cohorts [3]. Although white women
have higher breast cancer incidence rates, black women have disproportionately
higher breast cancer mortality. Mortality for black women of all
ages increased from 26.3 per 100,000 in 1973 to 31.9 per 100,000
in 1991-an increase of 20% [1]. Breast cancer mortality for white
women rose by only 0.6% during this same period. Among white women
under 65 years of age, breast cancer mortality declined by 8.6%
during the past 2 decades, whereas in black women under age 65,
breast cancer mortality increased by 12.2%.

Racial differences are also evident in the estimated lifetime
risks of developing and dying from breast cancer. Based on data
from SEER population-based cancer registries in nine US geographic
areas from 1989 to 1991, white women have a 12.9% lifetime risk
of being diagnosed with breast cancer and a 3.7% lifetime risk
of dying from breast cancer [1]. Black women, on the other hand,
have a 8.8% lifetime risk of developing breast cancer, while their
lifetime risk of dying from breast cancer is 3.3%. The ratio of
the age-adjusted death rate to the age-adjusted incidence rate
during a specific time interval suggests the likelihood of a case
fatality for each incident or newly diagnosed case of breast cancer.
In 1973, this ratio was 0.32 in white women and 0.38 in black
women; in 1991, the ratio decreased in white women (0.24) and,
to a lesser extent, in black women (0.34).

Survival

Survival rates for breast cancer have been increasing during the
past 2 decades. In 1973, the 5-year relative survival rate for
women of all races with breast cancer, adjusted for other causes
of mortality, was 72%.1 This rose significantly to 80.4% by 1986.
Survival rates are substantially higher among whites than blacks.
Between 1983 and 1990, the average 5-year relative survival rate
for breast cancer of all stages was 81.6% in white women, as compared
with 65.8% in black women.

There are also considerable differences in age-specific survival
rates. Younger women have worse breast cancer survival rates than
older women. The 5-year relative survival rate for women under
45 years old diagnosed in 1983 to 1990 was 76.3%, while women
65 to 74 years old had a survival rate of 82.7% [1]. Between 1973
and 1986, the 5-year relative survival rate for women diagnosed
with cancer when under 50 years of age rose from 74% to 78.1%;
however, for women over age 50, the survival rate increased from
71.3% to 81.3%.

Breast Cancer Incidence by Stage

Between 1983 and 1991, there have also been striking trends in
breast cancer incidence by stage. Among US white women, in situ
breast cancer incidence increased by 105% in those under age 50,
and by 180% in those age 50 and over; localized (stage I) breast
cancer incidence increased by 62% in women under age 50 and by
88% in older women [1]. During the same period, US black women
under age 50 experienced a 175% increase in the incidence of in
situ breast cancer and women age 50 and over experienced a 138%
increase.

Stages II, III, and IV breast cancer incidence remained fairly
constant during this period and even fell among certain age groups.
Miller et al [2] reported that the incidence of tumors < 2
cm in diameter increased steeply from 1982 to 1988 and has since
leveled off. In 1991, there were significant inequalities in localized
stage distribution between blacks and whites; 40% of incident
breast cancers in white women were stage I, as compared with only
26% in blacks. These differences in staging help explain some
of the discrepancy in breast cancer mortality between black and
white women.

International Trends in Incidence

The United States has the highest cross-sectional breast cancer
incidence rates in the world, but other countries are experiencing
similar increases in breast cancer incidence (Figures 4 and 5)
[5,6]. Japanese women have manifested significant increases in
incidence between the periods of 1973 to 1977 and 1983 to 1987.
While breast cancer incidence in US white women rose by 28% between
these two time periods, incidence in Japanese women increased
by 59%. However, the age-adjusted breast cancer incidence rates
in Japan are currently less than one-third those in the United
States. Other populations, such as the Chinese in Singapore and
Eastern Europeans in several countries, have also experienced
increases in breast cancer incidence, although none has been as
dramatic as the rise in incidence observed in Japan.

Kelsey et al have noted international differences in the shape
of the cross-sectional age-specific breast cancer incidence curves
[7]. Countries with the highest incidence rates of breast cancer
have a steeper rise in age-specific incidence during the premenopausal
years and a continuing but lesser rate of increase in incidence
during the postmenopausal years. Countries with intermediate breast
cancer incidence rates demonstrate a similar pattern of increase
during the premenopausal years and a relatively constant rate
during the postmenopausal years. Areas of lowest breast cancer
incidence also have a steep rise in premenopausal rates, but postmenopausal
rates appear to decline with increasing age (Figure 3) [5,6].
Moolgavkar argues, however, that these differences in age-specific
breast cancer incidence curves are due to birth cohort effects.
Once such cohort effects are adjusted for in the analysis, the
curves appear to be similar, and only the magnitude of the rates
differs among countries [8].

Within the United States, several minorities, especially Asian
immigrants, have also experienced large increases in breast cancer
incidence. Breast cancer incidence rates in Filipino-Americans
doubled during the 1970s and '80s, while rates in Japanese-Americans
rose by almost 50% [8]. Shimizu et al [9] demonstrated that breast
cancer incidence rates are further determined by the time since
immigration. Japanese immigrants who migrated late in life have
breast cancer incidence rates 3.6 times that of Japanese living
in Japan, and Japanese-Americans who were born in the United States
have incidence rates 4.1 times those of indigenous Japanese.

Mammography Screening and Breast Cancer Incidence

The long-term secular trend in age-adjusted breast cancer incidence
in the United States during 1940 to 1982 has reflected an annual
rate of increase of about 1%. This pattern changed dramatically
from 1982 to 1987, during which time the rate of increase was
about 4% per year. Studies by White et al, Feuer and Wun, Lantz
et al, and Liff et al noted that the increase was due primarily
to a higher frequency of in situ (intraductal) carcinomas and
early-stage invasive cancers, ie, those < 2 cm in diameter
[10-13]. The increase in the incidence of breast cancer during
1982 to 1987 was more pronounced in women age 60 years and over
(about 5% per year) than in women under age 60 (about 2.5% per
year). Since 1987, overall incidence rates of breast cancer have
declined slightly (eg, 293 per 100,000 population in 1987, 287
per 100,000 in 1988, and 284 per 100,000 in 1990). During this
period, annual cross-sectional breast cancer mortality in the
United States was relatively stable.

In the population-based studies of Reeves et al in Wisconsin and
Farwell et al in Vermont, 35% to 36% of breast cancers diagnosed
in the late 1980s were first detected by screening mammography
[14,15]. The percentage of women having mammograms and the reported
incidence rates for breast cancer in the United States both began
to rise dramatically after 1982. Thus, the studies of Miller et
al, Lantz et al, and Feuer and Wun concluded that the incidence
trends between 1982 and 1987 were generally consistent with population-based
increases in mammographic screening and were not due to the emergence
of a new risk factor [2,11,12]. The assumption of a direct correlation
between increasing screening-detected breast cancer cases and
the rising incidence of breast cancer is probably valid during
the initial years of dynamically changing screening practices
in a geographic area, and would persist in relation to the estimated
lead times for various age groups, which increase on average with
increasing age.

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