Breast Cance
Lorraine Tafra
Scope of the
Problem: Incidence
Breast cancer is
the most frequently diagnosed malignancy of woman in the
United States. In 1998 the incidence was found to be
approximately 180,000 with 44,000 deaths attributed to
breast cancer. For women, the lifetime risk for developing
breast cancer is 1 in 8. Until 1998, mortality from breast
cancer had remained unchanged but now appears to be slowly
decreasing. More universal application of screening
mammography has resulted in gradual decrease in the size of
the primary tumor at time of diagnosis. Mortality reduction
appears to be at least in part due to the impact of
screening mammography in finding tumors at an earlier stage.
Worldwide
In general, less industrialized nations tend
to have lower rates of breast cancer, with Japan being an
exception to this rule. The highest rates are seen in Europe
and North America.
Race
The overall incidence of breast cancer is
higher among white women than African- American woman, but
the mortality is higher for the latter. Research has shown
that most African-American woman will present with
later-stage disease, a fact that may be secondary to
cultural factors.
Risk Factors
Gender
Breast cancer is predominantly a disease
occurring in women. Only about 0.5% of all breast cancer
cases occur in men.
Age
For most women, this is the single most
important risk factor. The majority of breast cancers are
diagnosed after the age of 50.
Family History
A major breakthrough providing insights into breast cancer
risk occurred in 1990 with the identification of the BRCA1
gene. This large gene is located on hromosome 17q. Breast
cancer in BRCA1 families is transmitted as a classic
endelian autosomal dominant trait with high but incomplete
penetrance. BRCA1 mutations are associated with an extremely
high risk of breast cancer development (50% chance by age
45, and 85% lifetime risk). This inherited form of breast
cancer, though, occurs in only 5-10% of patients with breast
cancer. The percentage of patients with breast cancer due to
known hereditary factors varies with age and is higher in
the younger age group. In patients less than 30 years of age
the risk of an identifiable abnormal gene is 33% and in
patients between ages of 40 and 49, 13% will have the
abnormal gene.
Genetically transmitted breast cancer should
be suspected in women with multiple relatives with the
disease, particularly when the family history includes
premenopausal or bilateral breast cancer. The risk of
developing breast cancer is increased 1.5 -3.0 times if a
mother or sister has the disease, and risk may be greater if
a sibling is affected. For most women with a family history,
the lifetime risk of developing the disease does not exceed
30%. Genetic conditions associated with an increased risk of
developing breast cancer include Li-Fraumeni, Cowden
disease, Muir Torre, Peutz-Jeghers, and
ataxia-telangiectasia.
Menstrual
and Reproductive Factors
Factors that have been linked to breast
cancer include early age of menarche (age< 12), late age of
menopause (> 55), and late age at first pregnancy (> 30). It
appears that increased duration of exposure to endogenous
estrogens is a common factor. Another interesting risk
factor may be related to the lifetime number of menstrual
cycles. In less industrialized countries women may have only
about 100 menstrual cycles in their lifetime due primarily
to childbearing and nursing. Women living in industrialized
countries may have an average lifetime number of menstrual
cycles exceeding 400. During each menstrual cycle the breast
undergoes cell growth stimulation. Increased cell growth
stimulation may contribute to an increased rate of cancer.
Weight
and Diet
These two variables have been suggested as a cultural
explanation for the differences in incidence rates between
countries. National per capita fat consumption correlates
with incidence and mortality from breast cancer. Although
Japanese women have a lower incidence of breast cancer,
after moving to the United States, their incidence
approaches that of Caucasian women. However, numerous
epidemiological studies have found no correlation of fat
consumption to an increased incidence of breast cancer.
Weight and diet remain inconclusive risk factors for
developing breast cancer.
Radiation Exposure
Exposure to radioactivity from therapeutic irradiation,
medical diagnostics, or nuclear explosions has been shown to
increase the risk of breast cancer. The risk is greatest
when the radiation was received before the age of 40.
Lactation
Prolonged lactation in recent studies has
been shown to reduce the incidence of breast cancer in
premenopausal women. This may also be related to a lower
frequency of menstrual cycles.
LCIS
and Atypical Hyperplasia
These pathological findings found at the time of biopsy
place the patient at higher risk for subsequent development
of breast cancer. This risk is increased further if
associated with a positive family history.
Exogenous Estrogen
The effect on risk of developing breast cancer by
exogenous hormones for oral contraception and hormone
replacement therapy is controversial. It appears that there
is some increased risk of developing cancer in the overall
population but this is relatively small. An important area
of investigation is to define which groups of women may be
at exceptionally higher risk due to exogenous estrogens.
Prevention
Medical Prevention
During the 1990s, Tamoxifen was evaluated by the National
Surgical Adjuvant Breast and Bowel Project (NSABP) for
prevention of breast cancer. Women were randomized to
receive Tamoxifen versus a placebo.1 This antiestrogen agent
was chosen since a prior study showed that when Tamoxifen
was used as adjuvant therapy in patients with breast cancer,
it reduced the rate of contralateral breast cancers by
approximately 40%. The results of the breast cancer
prevention trial were released in 1999 and showed a 49%
reduction in the incidence of breast cancer in women taking
tamoxifen. Tamoxifen has both short and long term side
effects. Although it has been demonstrated to reduce the
incidence of breast cancer in a defined patient population
over a defined period of time, the indications for use in
the general population remain to be determined.
Surgical Prevention
In high risk patients, bilateral prophylactic mastectomy
can decrease the incidence of breast cancer by at least 90%.
The physical and psychological price for this method of
prevention is very high and should be undertaken only after
considerable evaluation.
Screening
The elements of screening for breast cancer are self
breast examination (SBE), clinical breast examination (CBE),
and mammography. Ultrasound is not currently part of
standard screening methods but may have a role in women with
dense breasts and multiple cysts. Prospective randomized
trials have established that breast cancer mortality is
reduced in woman ages 50-74 by approximately 26% if patients
are screened annually with mammography. It has been less
well established for women ages 40-50. The American Cancer
Society and other groups continue to recommend mammography
and breast exams every 1-2 years for these women. |
