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Thanks!
Bonnie
Breast Cancer Epidemiology
Incidence and prevalence
- Approximately 30% of all cancer diagnosed in U.S. women and 16% of all cancer diagnosed in the U.S.
- Approximately 15% of all cancer deaths in American women and 7% of all cancer deaths
- Approximately one million new cases annually worldwide
Incidence
- 185,000 women develop breast cancer each year in the U.S. (2005 data)
- 41,000 women die of breast cancer each year in the U.S.
- Male breast cancer: The lifetime risk is around 1 in 1000
Demographics
Age
In the U.S., a woman’s lifetime risk of developing breast cancer is estimated at 1 in 8 if she lives to be 110 (SEER 2001-2003 data from the National Cancer Institute):
- More than half the risk is incurred after the age of 60 years
- One-third of the risk occurs after age 75 years
- While the average age of breast cancer diagnosis in the general population is 62 years, women with BRCA mutations have significant risk (45%-50%) to develop an initial primary before age 50 years
A more practical way to contemplate the risk is over periods of time: from birth, the chance of developing cancer by age 50 years is 1 in 50 and the overall lifetime risk is approximately 1 in 8. Risk decreases with age in the absence of a previous diagnosis of breast cancer. For example:
- A 40-year-old woman has a 1 in 14 chance of developing breast cancer by age 70
- A 60-year-old woman has a 1 in 28 chance of developing breast cancer by age 70
- A 70-year-old woman has a 1 in 14 chance of ever developing breast cancer
Male breast cancer has a peak incidence 5 to 10 years later than that in women.
Gender
- Breast cancer is 100 times more common in women than men
- <1% of breast cancers occur in men
Race
- Ashkenazi Jews have a higher incidence of mutations in the BRCA1 and BRCA2 genes
- The frequency of both mutations is approximately 2.0% to 2.5% in the Ashkenazi Jewish population vs 1 in 217 in the general U.S. population
- Mutations in either of these genes confer lifetime risks of 50% to 85% for developing breast cancer and 15% to 40% for developing ovarian cancer
- Mutations are most common in Ashkenazi Jewish families with both ovarian and breast cancer (50%-90%), and less common in families with breast cancer only (25%-45%)
Genetics
- In cross-sectional studies of adult populations, 5% to 10% of women have a first-degree relative (parent, sibling, child) with breast cancer, whereas about twice as many have a second-degree relative (aunt, uncle, grandparent, grandchild, niece, nephew, or half-sibling) with breast cancer. This susceptibility may be inherited through either the mother’s or father’s side of the family. The number of affected relatives and the closeness of their biologic relationship are also important factors. In general, the greater the number of affected relatives, the younger the age at diagnosis, and the closer the biologic relationship, the greater the risk
- Genetic involvement should be suspected if there are multiple cases of early-onset (premenopausal) breast cancer within the family; if there is ovarian or fallopian tube cancer alongside a family history of breast or ovarian cancer; if breast and ovarian cancer occur in the same woman; if there is male breast cancer; if there is bilateral breast cancer; or if there is Ashkenazi Jewish heritage
- 3% to 5% of all women who have breast cancer have mutations in two genes, BRCA1 and BRCA2. This accounts for 25% of all women with some familial history of breast cancer as well as 50% to 80% of inherited breast cancer. Thus, a significant proportion of higher-risk women remains genetically unexplained. The frequency of each of the mutations in the general population is approximately 0.5% (1 in 217) in the U.S.
- The lifetime risk of developing breast cancer in a patient with either mutation is 60% to 80%
- After the initial diagnosis of breast cancer in a BRCA carrier, the risk of contralateral or ipsilateral breast cancer is higher per year (3%) than in non-carriers (1%). Although the management of most women with hereditary breast cancer differs little from the management of nonhereditary cancer, because of the 30% estimated 10-year risk of a second primary, and increased ovarian cancer risk, some women with stage I or II breast cancer may choose to undergo prophylactic contralateral mastectomy as part of their initial treatment plan. The incidence of a second primary also appears to be reduced by oophorectomy and tamoxifen, each of which appears to reduce risk by approximately 50%
- Both of these genes are involved in the cellular response to DNA damage and interact with other proteins involved in double-stranded DNA repair
- In general, one allelic mutation is inherited and the other allele becomes somatically mutated in the patient, thereby rendering an aberrant protein product leading to increased susceptibility for development of cancer
- The pattern of inheritance is autosomal dominant in a family, with passage either through the maternal or paternal lineage, although at the molecular level, both alleles must be mutated for the syndrome to be expressed: new (de novo) mutations are rare so will usually find an associated family cancer history; ductal carcinoma in situ (DCIS) is rare in BRCA carriers compared with control patients without mutations
- Higher lifetime risk (20%-60%) and earlier age of onset of ovarian cancer than seen for women in the general population (1.5%) require referral to a gynecologic oncologist to discuss option of prophylactic salpingo-oophorectomy
BRCA1:
- Mutations are more common in families with both breast and ovarian cancer (approximately 81% of such families)
- Women with BRCA1 mutations appear to have a lifetime breast cancer risk similar to that of women with BRCA2 mutations, although the age of onset for both breast and ovarian cancer may be somewhat younger in BRCA1 families
- Cumulative risk for breast cancer by age: 30 years (3.2%); 40 years (19%); 50 years (51%); 60 years (54%); 70 years (85%)
- Histology: see excess of breast cancers with medullary features, basaloid phenotype, and more frequently negative for estrogen and progesterone receptors, ERBB2 (formerly HER2 or HER2/neu)/c-erb-2 and cyclin-D
- Higher lifetime risk (20%-60%) and earlier age of onset of ovarian cancer than for women in the general population (1.5%), requires referral to gynecologic oncologist to discuss option of prophylactic salpingo-oophorectomy
- Some BRCA1 families also have male breast cancer although this is more commonly seen in BRCA2 families
- Families also have a higher incidence of prostate cancer with male carriers having a 3-fold risk over the general population
BRCA2:
- Mutations seen less frequently in families with both breast and ovarian cancer (approximately 14% of such families)
- Women with BRCA2 mutations appear to have a lifetime breast cancer risk similar to that of women with BRCA1 mutations, although the age of onset for both breast and ovarian cancer may be somewhat older in BRCA2 families
- Cumulative risk for breast cancer by age: 30 years (4.6%); 40 years (12%); 50 years (46%); 60 years (61%); 70 years (85%)
- Breast tumors in BRCA2 carriers tend to be similar in histology to their nonhereditary counterparts
- Lower lifetime risk of ovarian cancer (10%-27%) than BRCA1 families but still significant over general population risk of 1.5%. Also earlier age of onset requires referral to gynecologic oncologist to discuss option of prophylactic salpingo-oophorectomy
- Male carriers have a 6% lifetime risk for developing breast cancer
- An increased risk of prostate (3-fold) and pancreatic cancer (1%-2% lifetime)
Klinefelter’s disease:
- Men with this syndrome with enlarged breasts have the same risk of breast cancer as do women – roughly 50 times the risk as men in the general population
Family history:
- After gender and age, a positive family history is the strongest known predictive risk factor for breast cancer: one first-degree relative gives a relative risk of 1.5 to 2.0 (even higher if the relative had bilateral or premenopausal breast cancer); two first-degree relatives give a relative risk of 5.0
- Risk varies according to age at which the affected relative was diagnosed: the younger that age, the greater the risk in relatives. This effect is strongest for women with breast cancer younger than 50 years who had a first-degree relative (parent, sibling, child) affected before age 50 years
- In most cases an extensive family history (two or more relatives in either the maternal or paternal lineage) is present, although if a patient is diagnosed with breast cancer at an early age (20-40s), or in families with few women, a possible genetic effect may be masked. Thus, when in doubt, refer to a genetic specialist for more comprehensive risk assessment (more than four relatives in the same biological line affected) is not present
Geography
- Incidence of breast cancer increases when populations migrate from areas of low incidence of breast cancer to those with high incidence, indicating that environmental factors are important
- Highest rates are in Western countries (>100 cases per 100,000 women) and lowest are in Asian countries (10-15 cases per 100,000 women)
- Within a country, rates can be greater in urban areas than rural
- Rates can be associated with religious and cultural differences (e.g. Mormons have a much lower breast cancer rate than the general population)
