epidemiology

Epidemiology

In the United States in 1997, approximately 181,600 new cases of
breast cancer were diagnosed, and 43,900 women died of the disease.
[ref: 10] Breast and lung cancer are the foremost causes of cancer
death in women. Breast cancer mortality has been stable for the last
50 years; however, in recent years there has been a slight overall
decline in breast cancer age-adjusted mortality, in contrast to
pronounced peaks in incidence. Almost all of the increase (83%) is
accounted for by early diagnosis of in situ or invasive lesions less
than 2 cm in diameter with screening mammography. Reduced mortality is
a reflection of earlier diagnosis and more effective treatment,
including adjuvant chemotherapy, particularly in premenopausal
patients.

Although 1 of every 10 wo men in the United States is projected to
develop carcinoma of the breast, 80% to 92% of all breast masses are
benign. [ref: 452] Approximately 1% of breast cancers occur in men.

The risk factors for breast cancer in women are well documented: age
greater than 50 years, personal or family history of breast cancer
(e.g., mother, aunt), nulliparous, or first child after 30 years of
age. [ref: 850] Madigan and colleagues [ref: 462] identified 193 women
with breast cancer; the most important risk factors were age at first
birth and nulliparity, higher socioeconomic status, and family
history. Most of the increased incidence rates over the last two
decades have occurred among women aged 45 to 74 years, with a further
increase in black women.

Breast cancer is more common in Jewish than in non-Jewish women and in
black women compared with white women. Low incidence and mortality
rates for female breast cancer are found in most Asian and African
countries, intermediate rates in southern European and South American
countries, and high rates in North America and northern European
countries. [ref: 389] Among the possible explanations for this
variability are environmental factors, including diet.

Japanese women show lower rates of breast cancer than Caucasian women,
a difference accounted for by an increased incidence of this cancer in
postmenopausal Caucasian women. Postmenopausal breast cancer is also
less common among Japanese women who have migrated to a Western
country. After two or three generations, the incidence of female
breast cancer among descendants of Japanese immigrants to Hawaii or to
the mainland of the United States approached that of Caucasian
residents. [ref: 389]

Newcomb and associates [ref: 527] noted that relative breast cancer
risk among premenopausal women was reduced by a history of lactation
(relative risk [RR], 0.78) and by a cumulative lactation time
exceeding 24 months.

Several large-scale studies have failed to demonstrate a correlation
between the prolonged use of oral contraceptives and breast cancer.
[ref: 453,624,775,810] White and associates, [ref: 844] in an analysis
of 961 women born in 1944 or later who took oral contraceptives all of
their reproductive life, reported no increase in breast cancer
incidence. However, there was a small increased risk, particularly for
patients aged 35 years or younger, among those who used oral
contraceptives for a long time, used them in early reproductive life,
or used high-progestin oral contraceptives for at least 1 year.

Stanford and co-workers [ref: 729] found no increased breast cancer
risk among middle-aged women taking estrogen or combined estrogen and
progestin as hormone replacement therapy in a case-control study of
537 women with breast cancer and 492 control women without breast
cancer. Long-term use (>/= 8 years) of the combined therapy regimen
was associated with, if anything, a reduction in risk of breast
cancer. On the other hand, Colditz and colleagues [ref: 123] noted
that the addition of progestins to estrogen therapy in postmenopausal
patients did not reduce the risk of breast cancer (RR, 1.41), compared
with postmenopausal women who had never used hormones.

Exposure to ionizing radiation during or after puberty increases the
risk of developing carcinoma of the breast. Land and associates [ref:
426] reviewed reports on three populations of patients: a report by
Tokunaga and colleagues [ref: 772] on survivors of the atomic bombings
in Hiroshima and Nagasaki; a report by Boice and Monson [ref: 65] on
women in Massachusetts who had multiple fluoroscopic examinations of
the chest for pulmonary tuberculosis; and a study by Shore and
co-workers [ref: 683] of patients with postpartum mastitis who were
exposed to multiple x-ray examinations, in which nonexposed civilians
were used as a control group. They concluded that the risk of
radiation-induced cancer of the breast increased approximately
linearly with increasing doses and was heavily dependent on age at
exposure. In an update, Land [ref: 425] reported that most of the 54
cancers observed among women receiving doses higher than 100 rem (1
Sv) were probably caused by radiation. These observations were later
confirmed by other investigators. In a study of 31,710 women who had
tuberculosis and were examined with repeated fluoroscopic studies, a
substantial proportion (26.4%) received doses to the breast of 10 cGy
or more [ref: 503]; the breast cancer risk was greatest among women
who had radiation exposure between the ages of 10 and 14 (RR, 4.5 per
1 cGy and an additive risk of 6.1 per 104 person-years per 1 cGy);
there was substantially less excess risk with increasing age at first
exposure.

In another study of 1030 women with scoliosis who had multiple
radiographic examinations over a period of 8.7 years, 11 cases of
breast cancer were reported, compared with 6 expected (risk factor,
1.82) [ref: 353]; risk also increased with the number of x-ray
examinations and estimated irradiation dose to the breast (mean, 0.13
Gy). Furthermore, in a cohort of 1201 women who received x-ray
treatment in infancy for enlarged thymus gland (estimated mean
absorbed dose of irradiation to the breast, 6.9 Gy), after an average
of 36 years of follow-up, 22 breast cancers were diagnosed, compared
with 12 in 2469 nonirradiated sisters (adjusted risk factor, 3.6).
[ref: 350] The dose-response relation was linear, with an RR of 3.48
per 1 Gy and an additive excess risk of 5.7 per 104 person-years per 1
cGy.

A high risk of solid tumors, especially breast cancer, has been
described in women treated with radiation therapy at young age for
Hodgkin's disease. In a review of 1380 women treated at 15
institutions before the age of 16 years, 17 women developed breast
cancer -- 7 after radiation therapy alone and 10 after irradiation and
chemotherapy. Sixteen breast cancers appeared within or at the margin
of the irradiation fields. The cumulative probability of breast cancer
at 40 years of age was 35%. Women in this cohort of survivors had a
risk of breast cancer 70 times higher than that of the general
population. [ref: 56]

It should be stressed that the risk of breast cancer associated with
radiation exposure decreases sharply with increasing age at exposure,
and even a small benefit to women of screening mammography would
outweigh any possible risk of radiation-induced breast cancer. [ref:
204,206,503] For women between 50 and 75 years of age, the benefit of
annual screening mammography exceeds the radiation risk by a factor of
almost 100, and for women aged 35 to 75 years the benefit of reduced
mortality is projected to exceed the radiation risk by a factor of
more than 75. [ref: 497]

Loomis and associates [ref: 458] examined the relation between breast
cancer and exposure to low-frequency magnetic fields in 68 women with
breast cancer and 199 controls, all electrical workers, compared with
27,814 women with breast cancer and 110,750 controls, all with other
occupations; the electrical workers demonstrated excess mortality from
breast cancer (odds ratio, 1.38). There was no excess breast mortality
for seven other occupations with potential for increased electrical
exposure, including telephone operators and computer operators. Six
other studies have not shown an etiologic correlation between women
exposed to electromagnetic fields and the risk of breast cancer. [ref:
777]

Higher alcohol consumption has been correlated with increased risk of
breast cancer. [ref: 847] A study of 62,573 women from the Netherlands
reported an RR for breast cancer of 1.3 among women who consumed up to
30 g of alcohol daily and 1.72 among those who consumed greater
amounts. [ref: 789] Longnecker and associates [ref: 457] also noted an
RR of 1.39 with about one drink daily, 1.69 with two, and 2.3 with
three drinks daily.

A study of more than 100,000 women showed no association between
smoking and risk of breast cancer. [ref: 456]

Byrne and associates, [ref: 88] in a review of 280,000 women, noted
that women with 75% or greater breast density parenchymal patterns on
the mammogram, as measured by the proportion of breast area composed
of epithelial and stromal tissue, had a fivefold greater risk of
breast cancer. This parameter was independent of other prognostic
factors, such as family history, age at first birth, or alcohol
consumption.

Analysis of 2201 women between the ages of 30 to 62 years showed no
significant association between degree of adiposity and the incidence
of breast cancer but suggested that increased central-to-peripheral
body fat distribution may be a more specific marker than premalignant
hormonal pattern predisposing to this disease. [ref: 36]