Breast Cancer Risk Factors

Report
Edmund Tai, MD
Hematology/Oncology
PAMF
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American Cancer Society Cancer Prevention
Study-II
Harvard Nurses' Health Study (NHS)
Hawaii-Los Angeles Multiethnic Cohort
Prostate, Lung, Colorectal and Ovarian Cancer
Screening Trial
European Prospective Investigation into
Cancer and Nutrition (EPIC)
Factors that increase the risk of breast cancer include the following:
• Advanced age
• Family history of cancer in a first-degree relative – Family history of
ovarian cancer at < 50 years, 1 first-degree relative with breast
cancer, ≥2 first-degree-relatives with breast cancer
• Personal history – Positive BRCA1/BRCA2 mutation, breast biopsy
with atypical hyperplasia, breast biopsy with lobular or ductal
carcinoma in situ
• Reproductive history – Early menarche (< 12 years), late
menopause, late age of first term pregnancy (>30 years) or
nulliparity
• Use of estrogen-progesterone hormone replacement therapy (HRT)
• Current or recent oral contraceptive use
• Lifestyle factors – Adult weight gain, sedentary lifestyle, alcohol
consumption
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Essential update: Calcium-channel blockers associated
with increased breast cancer risk and ACEIs with reduced
risk
A population-based observational study of 880 women
with invasive ductal breast carcinoma (IDC), 1027 with
invasive lobular breast carcinoma (ILC), and 856 without
cancer determined that long-term (≥10 years) use of
calcium-channel blockers was associated with a more than
doubled risk of developing either type of cancer.[1, 2, 3]
In this study, the odds ratio (OR) was 2.4 for developing
IDC (95% confidence interval [CI], 1.2-4.9) and 2.6 for
developing ILC (95% CI, 1.3-5.3).[2] Long-term use of
angiotensin-converting enzyme (ACE) inhibitors was
associated with a reduced risk for both IDC (OR, 0.7) and
ILC (OR, 0.6)
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BRCA probability tools include the following:
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Breast cancer risk prediction tools include the
following:
BRCAPRO model
Myriad I and II
Manchester
Breast and Ovarian Analysis of Disease Incidence and
Carrier Estimation Algorithm (BOADICEA)
◦ Ontario Family History Assessment Tool (FHAT)
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◦ Gail model
◦ Gail model 2 (used as the basis for eligibility for a number
of the breast cancer prevention trials)
◦ Women’s Contraceptive and Reproductive Experiences
(CARE) model (developed to address concerns regarding
applicability of the Gail model to black women)
This model is much more accurate
in predicting outcome than stage.
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There is no clear evidence that when taken as
part of a normal diet in reasonable amounts
that soy would cause breast cancer.
In patients who has breast ca there is no
evidence that soy increases relapse risk
despite it weak estrogenic effect. The biology
of the cancer probably dictates relapse risk to
a much higher degree than the amount of soy
intake.
Avoid supplement of soy, prefer natural foods
like edamame, tofu, etc.
Table 1. Risk Factors for Breast Cancer
Risk Factors
Estimated Relative Risk
Advanced age
>4
Family history
•Family history of ovarian cancer in women < 50y
>5
•One first-degree relative
>2
•Two or more relatives (mother, sister)
>2
Personal history
•Personal history
3-4
•Positive BRCA1/BRCA2 mutation
>4 up to 10
•Breast biopsy with atypical hyperplasia
4-5
•Breast biopsy with LCIS or DCIS
8-10
Reproductive history
•Early age at menarche (< 12 y)
2
•Late age of menopause
1.5-2
•Late age of first term pregnancy (>30 y)/nulliparity
2
Use of combined estrogen/progesterone HRT
1.5-2
Current or recent use of oral contraceptives
1.25
Lifestyle factors
•Adult weight gain
1.5-2
•Sedentary lifestyle
1.3-1.5
•Alcohol consumption
1.5
DCIS = ductal carcinoma in situ; HRT = hormone replacement therapy; LCIS = lobular carcinoma in situ
Table 2. Genetic Breast Cancer Syndromes
Syndrome
Gene
Inheritance
Cancers
Breast/ovarian
BRCA1
AD
Breast, ovarian
Cancer syndrome
BRCA2
AD
Breast, ovarian, prostate,
pancreatic
Li-Fraumeni syndrome
TP53
AD
Breast, brain, soft-tissue
sarcomas, leukemia,
adrenocortical, others
Cowden disease
PTEN
AD
Breast, ovary, follicular
thyroid, colon
Adenomas of thyroid,
fibroids, GI polyps
Peutz-Jeghers syndrome
STKII/LKB1
AD
GI, breast
Hamartomas of bowel,
pigmentation of buccal
mucosa
Ataxia-telangiectasia
ATM
AD
Breast
Homozygotes: leukemia,
lymphoma, cerebella ataxia,
immune deficiency,
telangiectasias
Site-specific
CHEK2
AD
Breast
Low penetrance
Muir-Torre syndrome
MSH2/MLH1
AD
Colorectal, breast
AD = autosomal dominant; GI = gastrointestinal.
Other Features
Fanconi anemia in
homozygotes
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Birth to age 39 – 0.49 (1 in 203 women)
Age 40 to 59 – 3.76 (1 in 27 women)
Age 60 to 69 – 3.53 (1 in 28 women)
Age 70 and older – 6.58 (1 in 15 women)
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Birth to death – 12.29 (1 in 8 women)
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Data from SEER between 2006-2008
Average five-year and lifetime risk of developing breast cancer among white women, by age
Data from: Breast Cancer Risk Assessment Tool. National Institutes of
Health.
Age
Five-year risk, percent
Lifetime (until age 90) risk,
percent
35
0.3
12.6
40
0.6
12.4
50
1.3
11.2
60
1.8
9.1
70
2.2
6.3
80
2.0
3.1
85
1.4
1.4
Asian women has
Earlier age of onset but
Screening is not universal
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Weight — Obesity (defined body mass index ≥30 kg/m2) is
associated with an overall increase in morbidity and mortality.
However, the risk of breast cancer associated with BMI appears
to depend on the menopausal status of women.
Postmenopausal women — A higher body mass index
(BMI) and/or perimenopausal weight gain have been consistently
associated with a higher risk of breast cancer among
postmenopausal women [10-16]. As examples:
●In a 2000 analysis of seven cohort studies, women with a BMI
>33 kg/m2 had a higher breast cancer risk compared with those
with a BMI <21 kg/m2 (relative risk [RR] 1.27, 95% CI 1.031.55) [10].
●In the Nurses' Health Study, women who gained 10 kg or more
since menopause had a higher risk of breast cancer compared
with women who maintained their weight (400 versus 339 per
100,000 person-years; RR 1.18, 95% VI 1.03-1.35) [12].
These are considered a low impact risk factor.
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Premenopausal women — Unlike
postmenopausal women, an increased BMI is
associated with a lower risk of breast cancer
in premenopausal women [10,19]. In the
2000 pooled analysis discussed above,
premenopausal women with a BMI
≥31 kg/m2 were 46 percent less likely to
develop breast cancer than those with a BMI
<21 kg/m2 [10]
There is no plausible explanation for this.
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Higher native estrogen levels is associated
with increased risk in pre- and postmenopausal women
The level of estradiol and estrone correlates
with increased risk of BC
Premenopausal women-The limited data
suggest that estrogen levels also play a role
in the development of breast cancer among
premenopausal women with the highest
quartile has a RR 2.4 compare with the lowest
quartile.
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The density of breast tissue reflects the relative
amount of glandular and connective tissue
(parenchyma) to adipose tissue(dense tissue
comprising ≥75 percent of the breast).
Age and frequency of dense breast
◦ age 30-70%
◦ age 50-50%
◦ age 70-30%
Breast density does not lead to increased
mortality from BC
Dense breast is 4-5x higher risk compare with
normal breast.
No correlation between estrogen level and dense
breast.
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This is considered a surrogate marker for
exposure to estrogens.
A high bone density correlates with incidence
of breast cancer
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Androgens — Elevated androgen (ie, testosterone) levels
have been associated with an increased risk of
postmenopausal and premenopausal breast
Insulin pathway and related hormones — Although
diabetes is not considered a breast cancer risk a large
pooled analysis drawing from 17 prospective studies
suggested that insulin growth factor-1 was associated
with breast cancer risk in both premenopausal and
postmenopausal women
In addition, the Women’s Health Initiative reported that
higher endogenous insulin levels were associated with an
increased risk of breast cancer among nondiabetic,
postmenopausal women who did not take menopausal
hormone therapy (HR for highest versus lowest quartile of
insulin level 2.40, 95% CI 1.30-4.41)
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In utero exposure to diethylstilbestrol — Before 1971,
several million women were exposed in utero to
diethylstilbestrol (DES) that was given to their mothers to
prevent pregnancy complications. Whether these women
are also at an increased risk for breast cancer is unclear:
●A long-term follow-up study of 4653 DES-exposed
women and 1927 unexposed controls reported a nearly
twofold increase in the cumulative risk of breast cancer in
exposed women aged 40 or older (3.9 versus 2.2 percent,
HR 1.82, 95% CI 1.04-3.08) [61].
●However, in a long-term follow-up study of 12,091 DES
exposed women in the Netherlands, there was no excess
risk for breast cancer when compared with Dutch
population-based controls, even when the analysis was
restricted to women over the age of 40 (standardized
incidence ratio [SIR] 1.09, 95% CI 0.91-1.31) [62].

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