Transcript Document

Epidemiology, genetics, and risk
evaluation of
postmenopausal women
at risk of breast cancer
Menopause: The Journal of The North
American Menopause Society
Vol. 15, No. 4, pp. 782/789
Jul-Aug, 2008
Classic Breast Cancer Risk Factors
All women are at risk of
breast cancer, and the
single most important
risk factor is age.
(in the child)
Sclerosing adenosis
increases the risk of
breast cancer by
approximately 70%.
5% to 10% of
proliferative lesions
show cellular atypia,
which increases the
risk of breast cancer
fivefold.
Nearly 40% of women
with a family history of
breast cancer and
atypical hyperplasia
subsequently develop
breast cancer.
LCIS (lobular carcinoma
in situ) has generally
been considered a risk
indicator, conferring
an increased rate of
development of
invasive carcinoma of
approximately 1% to 2%
per year, with a lifetime
risk of 30% to 40%.
FAMILY HISTORY OF BREAST CANCER
AND BRCA1 AND BRCA2 MUTATIONS
• Genetic factors contribute to approximately 5% of all
breast cancers, but to 25% of cases diagnosed before 30
years of age.
• Having more relatives with breast cancer before age 50
increases the cumulative lifetime risk of developing the
disease to almost 50%
• The risk of breast cancer associated with either a BRCA1
or BRCA2 mutation is more than 200 times greater in
individuals younger than age 40 but drops to 15-fold in the
seventh decade of life.
• High-grade DCIS is more common in BRCA1 mutation
carriers than in patients without a mutation
MAMMOGRAPHIC DENSITY
AND
CIRCULATING ENDOGENOUS HORMONE LEVELS
• Levels of both circulating sex steroids and
mammographic density are significantly and
independently associated with breast cancer risk.
• High mammographic density on a first examination is
associated with a high rate of breast cancer that remains
high even if breast density decreases in subsequent
mammographic examinations.
• Increased risk with elevated total estradiol, free estradiol,
non-SHBG-bound estradiol (which comprises free and
albumin-bound estradiol), estrone, estrone sulfate,
androstenedione, DHEA, DHEA-S, and testosterone.
IMPACT OF DIET, EXERCISE,
AND ENVIRONMENTAL FACTORS
• Excess weight and weight gain in adult life are related to
higher risk of postmenopausal breast cancer.
• Weight loss after menopause is associated with
substantially reduced risk.
• Physical activity and the prevention of weight gain can
improve survival after a breast cancer diagnosis.
• The only well-established individual diet-related risk factor
for breast cancer other than obesity is alcohol consumption.
• Populations with high fat intakes generally have higher
rates of breast cancer, but studies of individual women
have not confirmed an association of high-fat diets with
breast cancer risk.
• Folic acid: dual effect?
• Phytoestrogen: inconsistent.
QUANTITATIVE RISK ASSESSMENT
AND THE GAIL MODEL
• The average age at diagnosis of breast cancer among
women in North America is 60 years, and the risk of
developing breast cancer among these women is 1.67%
in the 5 years between ages 60 and 65.
• Women whose 5-year risk of developing invasive breast
cancer is greater than 1.67% are considered to be at
increased risk.
• FDA used this risk level to define high-risk subjects who
might consider the use of selective estrogen receptor
modulators (tamoxifene or raloxifene) for reduction of
breast cancer risk.