Breast Cancer Risk Factors - PowerPoint Presentation

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Breast Cancer Risk Factors

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 CohortProstate, Lung, Colorectal and Ovarian Cancer Screening TrialEuropean Prospective Investigation into Cancer and Nutrition (EPIC)

Cohorts used to model

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Factors that increase the risk of breast cancer include the following

:

Advanced ageFamily 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)

Effect of calcium channel blockers and ACE inhibitors

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BRCA probability tools include the following:

BRCAPRO model

Myriad I and IIManchesterBreast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA)Ontario Family History Assessment Tool (FHAT)Breast cancer risk prediction tools include the following:Gail modelGail 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)

Models used to predict BC

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This model is much more accurate

in predicting outcome than stage.

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Soy and breast cancer

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.

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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

3-4Positive BRCA1/BRCA2 mutation>4 up to 10Breast biopsy with atypical hyperplasia4-5Breast biopsy with LCIS or DCIS8-10Reproductive historyEarly age at menarche (< 12 y)2Late age of menopause1.5-2Late age of first term pregnancy (>30 y)/nulliparity2Use of combined estrogen/progesterone HRT1.5-2Current or recent use of oral contraceptives1.25Lifestyle factorsAdult weight gain1.5-2Sedentary lifestyle1.3-1.5Alcohol consumption1.5DCIS = ductal carcinoma in situ; HRT = hormone replacement therapy; LCIS = lobular carcinoma in situ

Table 1. Risk Factors for Breast Cancer

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Syndrome

Gene

Inheritance

Cancers

Other Features

Breast/ovarian

BRCA1

AD

Breast, ovarian

Cancer syndrome

BRCA2

AD

Breast, ovarian, prostate, pancreatic

Fanconi anemia in homozygotesLi-Fraumeni syndromeTP53ADBreast, brain, soft-tissue sarcomas, leukemia, adrenocortical, othersCowden diseasePTENADBreast, ovary, follicular thyroid, colonAdenomas of thyroid, fibroids, GI polypsPeutz-Jeghers syndromeSTKII/LKB1ADGI, breastHamartomas of bowel, pigmentation of buccal mucosaAtaxia-telangiectasiaATMADBreastHomozygotes: leukemia, lymphoma, cerebella ataxia, immune deficiency, telangiectasiasSite-specificCHEK2ADBreastLow penetranceMuir-Torre syndromeMSH2/MLH1ADColorectal, breast

AD = autosomal dominant; GI = gastrointestinal.

Table 2. Genetic Breast Cancer Syndromes

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Age-risk increases with age

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)Birth to death – 12.29 (1 in 8 women)

Data from SEER between 2006-2008

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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

1.89.1702.26.3802.03.1851.41.4Average five-year and lifetime risk of developing breast cancer among white women, by ageData from: Breast Cancer Risk Assessment Tool. National Institutes of Health.Age

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Asian women has

Earlier age of onset but

Screening is not universal

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Weight

 — Obesity (defined body mass index ≥30 kg/m

2) 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/m

2

 had a higher breast cancer risk compared with those with a BMI <21 kg/m

2

 (

relative risk [RR] 1.27

, 95% CI 1.03-1.55)

 

[

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.Weight and obesity

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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.

Weight and Obesity

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Higher native estrogen levels is associated with increased risk in pre- and post-menopausal women

The level of estradiol and

estrone correlates with increased risk of BCPremenopausal 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.

Estrogen exposure

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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 breastage 30-70% age 50-50%age 70-30%Breast density does not lead to increased mortality from BCDense breast is 4-5x higher risk compare with normal breast.

No correlation between estrogen level and dense breast.

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

Bone mineral density

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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)

Other hormone exposure

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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

].

Other hormone exposure

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