Risk factors for breast cancer by Dr.jfr

Risk factors for breast cancer •

Updated 2013 Feb 28 10:33:00 AM: job strain not associated with risk of breast cancer (BMJ 2013 Feb 7) view updateShow more updates

Related Summaries: • •

Breast cancer in women Breast cancer screening

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Breast cancer (list of topics)

Overview: • •

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Breast Cancer Risk Assessment Tool (Gail model) can predict risk for breast cancer in most women genetic risk factors include o

family history of breast cancer

BRCA mutation

rare genetic conditions

for postmenopausal hormone replacement therapy (HRT) o

combination estrogen plus progestin increases risk (level 1 [likely reliable] evidence)

estrogen alone may not increase risk for short-term use but may increase risk with use > 5 years (level 2 [mid-level] evidence)

for hormonal contraceptives o

combination oral contraceptive use associated with small increase in risk for breast cancer during use and for up to 10 years after cessation (level 2 [midlevel] evidence)

progestin-only contraceptive use not associated with increased risk for breast cancer (level 2 [mid-level] evidence)

breast-related risk factors include o

mammographic density

carcinoma in situ and other histologic lesions

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overweight and weight gain associated with increased risk in postmenopausal women

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radiation therapy to chest associated with increased risk

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lifestyle factors affecting breast cancer risk may include

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dietary factors (but evidence inconsistent)

alcohol use

tobacco use

possible risk factors with limited or inconsistent evidence include o

history of childhood cancer

gestational diabetes

infertility treatment

organochlorine compounds

Risk Prediction • to determine a woman's risk for breast cancer, see the National Cancer Institute Breast Cancer Risk Assessment Tool (Gail model) o risk assessment based on age, age at first menstrual period, age at first live birth, number of first-degree relatives with breast cancer, history of breast biopsy, and race/ethnicity o

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cannot be applied to women with history of breast cancer, ductal carcinoma in situ, lobular carcinoma in situ, or inherited gene mutations

addition of 10 common genetic variants appears to add little to predictive performance of Breast Cancer Risk Assessment Tool (Gail model) (level 2 [mid-level] evidence) o

based on pooled analysis of data from 4 cohort studies in United States and 1 case-control study in Poland

5,590 patients with invasive breast cancer and 5,998 controls aged 50-79 years evaluated for traditional risk factors and 10 common genetic variants (single-nucleotide polymorphisms [SNPs]) associated with breast cancer

analysis limited to women with European ancestry

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risk factors for breast cancer in women having screening mammography o

based on prospective data of 1 million women having 2,392,998 screening mammograms

11,638 women were diagnosed with breast cancer within 1 year of screening mammogram

statistically significant risk factors in both premenopausal and postmenopausal women

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Reference - N Engl J Med 2010 Mar 18;362(11):986 full-text, correction can be found in N Engl J Med 2010 Dec 2;363(23):2272, commentary can be found in N Engl J Med 2010 Mar 18;362(11):1043

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age

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breast density

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family history of breast cancer

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prior breast procedure

additional risk factors for postmenopausal women 

race

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ethnicity

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body mass index (BMI)

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natural menopause

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hormone therapy

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prior false-positive mammogram

prediction model developed but not validated

Reference - J Natl Cancer Inst 2006 Sep 6;98(17):1204

review of risk factors for breast cancer can be found in BMJ 2000 Sep 9;321(7261):624 full-text, correction can be found in BMJ 2000 Nov 11;321(7270):1198, commentary can be found in BMJ 2001 Feb 10;322(7282):365

Genetic Factors Family history of breast and other cancers: •

family history of breast cancer associated with increased risk o based on case-control study

first-degree relatives (mothers, sisters, and daughters) of 58,209 women with breast cancer and 101,986 controls evaluated

estimated cumulative incidence of breast cancer up to age 50 years

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1.7% with 0 affected first-degree relatives

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3.7% with 1 affected first-degree relative

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8% with 2 affected first-degree relatives

estimated cumulative incidence of breast cancer up to age 80 years 

7.8% with 0 affected first-degree relatives

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13.3% with 1 affected first-degree relative

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21.1% with 2 affected first-degree relatives

estimated breast cancer mortality up to age 80 years 

2.3% with 0 affected first-degree relatives

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4.2% with 1 affected first-degree relative

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7.6% with 2 affected first-degree relatives

Reference - Lancet 2001 Oct 27;358(9291):1389, commentary can be found in ACP J Club 2002 May-Jun;136(3):115

sister with breast cancer associated with increased risk o

based on cohort study

23,654 sisters of women with breast cancer and 1,732,775 sisters of unaffected women in national cancer registry evaluated for incident breast cancer

sisters of breast cancer patients had increased risk for breast cancer at all ages compared to sisters of unaffected patients

relative risk increase was highest at age 20-39 years (relative risk 6.64, 95% CI 4.66-9.48)

Reference - J Natl Cancer Inst 2008 May 21;100(10):721

family history of some malignancies may be associated with increased risk, especially for women < 55 years old o

based on cohort study

73,222 women aged 40-70 years followed for ≥ 5 years

570 women (0.78%) newly diagnosed with breast cancer during follow-up

risk of breast cancer increased for women with family history of

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breast cancer (relative risk [RR] 1.74, 95% CI 1.1-2.73)

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leukemia (RR 2.06, 95% CI 1.02-4.15)

among women < 55 years old, risk for breast cancer increased for women with family history of 

breast cancer (RR 2.07, 95% CI 1.17-3.64)

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any cancer (RR 1.41, 95% CI 1.1-1.82)

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lung cancer (RR 1.72, 95% CI 1.12-2.65)

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esophageal cancer (RR 2.99, 95% CI 1.62-5.51)

Reference - Cancer Causes Control 2008 Dec;19(10):1139

family history of concordant cancer associated with increased risk of cancer in offspring o

based on prospective cohort study

7,904,092 persons aged 0-76 years in Sweden and their biological parents were analyzed

183,200 persons had cancer and included in analyses

compared to having no affected parent, having parent affected with concordant cancer associated with increased risk of (in overall adjusted analyses) 

colorectal cancer (hazard ratio [HR] 1.9, 95% CI 1.8-2)

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lung cancer (HR 2.1, 95% CI 1.9-2.2)

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breast cancer (HR 2, 95% CI 1.9-2.1)

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prostate cancer (HR 2.3, 95% CI 2.2-2.4)

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bladder cancer (HR 2, 95% CI 1.8-2.2)

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melanoma (HR 2.9, 95% CI 2.7-3.2)

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skin squamous cell carcinoma (HR 2.2, 95% CI 2-2.5)

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non-Hodgkin lymphoma (HR 1.8, 95% CI 1.5-2)

having parent diagnosed with concordant cancer at early age associated with highest familial risk

Reference - BMJ 2012 Dec 20;345:e8076 full-text

BRCA mutations: •

estimated 0.2%-0.33% of population have BRCA1 or BRCA2 gene mutations o BRCA1 and BRCA2 mutations estimated to account for 5%-10% of breast cancers and 10%-15% of ovarian cancers in white women in United States o

mutations in women associated with lifetime risks of breast cancer up to 85% and ovarian cancer up to 40%

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United States Preventive Services Task Force (USPSTF) recommends against routine referral for genetic counseling or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with increased risk for deleterious mutations in BRCA1 or BRCA2 (USPSTF Grade D)

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USPSTF recommends women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing (USPSTF Grade B) o

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for Ashkenazi Jewish women 

any first-degree relative with breast or ovarian cancer

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2 second-degree relatives on same side of family with breast or ovarian cancer

for other women 

2 first-degree relatives with breast cancer (including 1 diagnosed ≤ 50 years old)

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3 or more first- or second-degree relatives with breast cancer

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both breast cancer and ovarian cancer among first- and seconddegree relatives

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first-degree relative with bilateral breast cancer

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2 or more first- or second-degree relatives with ovarian cancer

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first- or second-degree relative with both breast or ovarian cancer

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male relative with breast cancer

models for predicting risk of BRCA1 and BRCA2 mutation have high falsenegative and false-positive rates

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see BRCA mutation testing and management for details

Rare genetic conditions: • •

Li-Fraumeni syndrome - autosomal dominant p53 mutation; breast cancer, sarcoma, brain tumors, leukemia, adrenocortical carcinoma hamartomatous polyposis (Cowden's Disease) - autosomal dominant associated with PTEN mutation; multiple mucocutaneous lesions, vitiligo, angiomas, benign organ proliferative disease, breast cancer, thyroid cancer, colonic neoplasms

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Muir-Torre Syndrome - autosomal dominant MSH2 or MLH1 mutation; cancers of gastrointestinal (GI) tract, skin, and genitourinary systems, breast tumors (Cutis 2011 Mar;87(3):125)as referenced in

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Peutz-Jeghers syndrome - autosomal dominant, associated with STK11; abnormal melanin deposits, GI polyposis, cancers of GI tract, breast, uterus, ovary, testis

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hereditary diffuse gastric cancer syndrome - mutation in CDH1 can be associated with lobular cancer (N Engl J Med 2007 Jul 19;357(3):283)

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ataxia-telangiectasia (ATM) - autosomal recessive, linked to chromosome 11q21; associated with cerebellar ataxia, oculocutaneous telangiectasias, radiation hypersensitivity, leukemia, lymphoma, solid tumors including breast

Other genetic associations: •

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spectrum of mutations in 300 families with 4 or more cases of breast or ovarian cancer but with negative (wild-type) commercial genetic tests for BRCA1 and BRCA2 o 35 (12%) had genomic rearrangements of BRCA1 or BRCA2 o

14 (5%) had CHEK2 mutations

3 (1%) had TP53 mutations

Reference - JAMA 2006 Mar 22-29;295(12):1379, commentary can be found in JAMA 2006 Nov 1;296(17):2091

genetic variations in MBD2 (gene encoding methyl-CpG-binding domain [MBD]2) associated with breast cancer risk in premenopausal women o

based on case-control study with 393 Caucasian breast cancer patients and 496 matched controls

association between genetic variations seen in premenopausal women but not postmenopausal women or general population

Reference - Breast Cancer Res 2005;7(5):R745 full-text

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heterozygous hereditary hemochromatosis gene HFE H63D mutation associated with increased risk of breast cancer o

based on case-control study

H63D allele frequency found in 22.2% of 176 breast cancer patients and 14% of 200 healthy controls in Turkey

Reference - BMC Cancer 2006 Feb 19;6:37 full-text

leptin and leptin receptor polymorphisms associated with increased risk and poor prognosis of breast cancer o

based on case-control study

308 unrelated Tunisian patients with breast cancer and 222 healthy controls had genetic screening

Reference - BMC Cancer 2006 Feb 20;6:38 full-text

transforming growth factor (TGF)-beta-1 polymorphism associated with decreased risk for breast cancer o

based on prospective cohort study of 3,075 women > 65 years old

Reference - JAMA 2001 Jun 13;285(22):2859, correction can be found in JAMA 2001 Dec 26;286(24):3081, editorial can be found in JAMA 2001 Jun 13;285(22):2907

interleukin gene polymorphisms do not appear to affect breast cancer susceptibility or severity o

based on systematic review of 14 studies

Reference - BMC Cancer 2006 Jul 14;6:188 full-text

environmental risk factors not associated with greater risk of breast cancer in women already at risk with low-penetrance susceptibility polymorphisms o

based on case-control genetic study of 7,610 women with breast cancer and 10,196 controls

10 established environmental risk factors compared were age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body mass index, height, and alcohol consumption

Reference - Lancet 2010 Jun 19;375(9732):2143, correction can be found in Lancet 2010 Jun 19;375(9732):2142

Breast-related Factors

Mammographic density: •

higher mammogram breast density associated with higher 5-year breast cancer risk o based on prospective cohort study o

1,095,484 women who had mammogram and no previous diagnosis of breast cancer were followed for mean 5.3 years

14,766 women (1.3%) diagnosed with invasive breast cancer

breast cancer risk increased with age and breast density 

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very low density (almost entirely fat) 

0.2% risk for ages 40-44 years

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0.7% risk for ages 55-59 years

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1.4% risk for ages 70-74 years

extreme density 

1% risk for ages 40-44 years

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2.1% risk for ages 55-59 years

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3.3% risk for ages 70-74 years

groups with scattered fibroglandular densities and heterogeneous densities had intermediate risk

Reference - Ann Intern Med 2008 Mar 4;148(5):337

extensive mammographic density associated with risk of breast cancer o

based on 3 nested case-control studies in screened populations with 1,112 matched case-control pairs

Reference - N Engl J Med 2007 Jan 18;356(3):227, editorial can be found in N Engl J Med 2007 Jan 18;356(3):297, commentary can be found in N Engl J Med 2007 May 3;356(18):1885

mammographic density associated with risk for invasive breast cancer and breast ductal carcinoma in situ o

based on case-control study with 482 patients with invasive breast cancer, 119 patients with breast ductal carcinoma in situ, and 667 cancer-free controls

Reference - Breast Cancer Res 2006;8(3):R30 full-text

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physical activity not associated with mammographic breast density o

based on systematic review of 20 studies

Reference - Breast Cancer Res Treat 2012 Sep;135(2):367

Carcinoma in situ and other histologic lesions: •

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breast carcinoma in situ associated with increased risk for subsequent invasive breast cancer o based on record review o

12,836 women with breast carcinoma in situ evaluated for incidence of subsequent invasive breast cancer

carcinoma in situ associated with increased risk for invasive breast cancer (standardized incidence ratio 1.96, 95% CI 1.79-2.14)

Reference - Br J Cancer 2008 Aug 19;99(4):611

lobular carcinoma in situ increases risk of invasive breast cancer, especially in ipsilateral breast o

based on retrospective study of 252 women with breast biopsy showing atypical lobular hyperplasia

50 (20%) developed invasive breast cancer including 34 ipsilateral, 12 contralateral, and 4 bilateral or unknown breast cancers

Reference - Lancet 2003 Jan 11;361(9352):125, correction can be found in Lancet 2003 Jun 7;361(9373):1994, editorial can be found in Lancet 2003 Jan 11;361(9352):96

benign breast disease with proliferative changes (especially atypia) associated with increased risk for breast cancer o

based on cohort study

9,087 women with benign breast disease followed for median 15 years 

67% had nonproliferative lesions

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30% had proliferative lesions without atypia

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4% had atypical hyperplasia

707 developed breast cancer

relative risk for breast cancer compared with historical controls was 

1.27 (95% CI 1.15-1.41) with nonproliferative lesions

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1.88 (95% CI 1.66-2.12) with proliferative lesions without atypia

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4.24 (95% CI 3.26-5.41) with atypia

Reference - N Engl J Med 2005 Jul 21;353(3):229, editorial can be found in N Engl J Med 2005 Jul 21;353(3):297, commentary can be found in N Engl J Med 2005 Oct 27;353(17):1856

multifocal atypia associated with increased risk for breast cancer among women with atypia o

based on cohort of 331 women with atypical hyperplasia followed for mean 13.7 years

66 (19.9%) developed breast cancer with relative risk (RR) from atypia 3.88 (95% CI 3-4.94)

multifocal atypia (3 or more foci with calcifications) associated with highest RR 10.35 (95% CI 6.13-16.4)

Reference - J Clin Oncol 2007 Jul 1;25(19):2671

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abnormal cytology in nipple aspirates associated with increased risk for breast cancer in cohort study (J Natl Cancer Inst 2001 Dec 5;93(23):1791 full-text)

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radial scars in benign breast biopsy specimens an independent histologic risk factor for breast cancer in case-control study (N Engl J Med 1999 Feb 11;340(6):430 fulltext), commentary can be found in N Engl J Med 1999 Jul 15;341(3):210

Breast cysts: •

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breast cyst associated with 2.8 times risk of breast cancer o based on prospective study of 1,374 women with palpable breast cysts compared to historical controls, 65 patients developed cancer o

Reference - Lancet 1999 May 22;353(9166):1742, commentary can be found in Lancet 1999 Aug 21;354(9179):677

DynaMed commentary -- use of historical controls does not account for potentially increased incidence related to increased surveillance

breast cyst fluid with potassium/sodium ratio > 1.5 associated with greater risk than ratio < 1.5 (relative risk [RR] 4.62, 95% CI 1.26-29.7) o

based on cohort study in 802 women with aspirated breast cysts

Reference - BMJ 1997 Mar 29;314(7085):925 full-text

Lifestyle Factors

Dietary factors: •

inconsistent evidence for fat intake as risk factor o supporting data based on epidemiologic studies with many confounding factors o

meta-analyses have inconsistent results 

literature review concludes at least moderate association between dietary fat and breast cancer risk, although some associations are equivocal with specific types of dietary fat (World J Surg Oncol 2005 Jul 18;3:45 full-text)

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higher intakes of total and saturated fat associated with slight increased risk of breast cancer in meta-analysis of 14 cohort studies (summary relative risk [RR] 1.11 comparing highest and lowest levels of intake) and 31 case-control studies (summary RR 1.14) (Br J Cancer 2003 Nov 3;89(9):1672)

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pooled analysis of 7 prospective studies with 337,819 women and 4,980 breast cancers showed no correlation between risk of breast cancer and type or amount of fat intake (N Engl J Med 1996 Feb 8;334(6):356 full-text), commentary can be found in N Engl J Med 1996 Jun 13;334(24):1606

large cohort studies have inconsistent results 

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premenopausal intake of animal fat may be associated with increased risk of breast cancer 

based on prospective analysis of 90,655 premenopausal women aged 26-46 years enrolled in Nurses' Health Study II, followed for 8 years

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714 women developed invasive breast cancer

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total fat intake not associated with breast cancer risk, animal fat intake associated with breast cancer risk in dosedependent fashion but increased risk with highest animal fat intake still < 2 times

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Reference - J Natl Cancer Inst 2003 Jul 16;95(14):1079 fulltext

no evidence that intake of total fat or specific major types of fat associated with risk of breast cancer 

based on prospective Nurses' Health Study with 88,795 women followed for 14 years of whom 2,956 developed breast cancer

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Reference - JAMA 1999 Mar 10;281(10):914, commentary can be found in JAMA 1999 Oct 6;282(13):1223

monounsaturated fat might be protective for risk of breast cancer, while polyunsaturated fat associated with increased risk of breast cancer 

based on cohort study of 61,471 Swedish women aged 40-76 years followed about 4 years

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674 women developed invasive breast cancer

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Reference - Arch Intern Med 1998 Jan 12;158(1):41, commentary can be found in ACP J Club 1998 Jul-Aug;129(1):19

trans fats reported to be possible risk factor for breast cancer based on association between high serum trans-monounsaturated fatty acid levels and risk for breast cancer 

based on prospective cohort study of 19,934 women followed for mean 7 years

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diet history questionnaire and serum levels assessed at baseline

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363 cases of incident breast cancer occurred

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increased risk associated with highest quintiles of serum transmonounsaturated fatty acids compared to lowest quintiles (adjusted odds ratio [OR] 1.75, 95% CI 1.08-2.83)

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diet history associations not reported

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Reference - Am J Epidemiol 2008 Jun 1;167(11):1312 full-text

omega-3 fatty acid intake not associated with cancer incidence o

based on systematic review of 38 articles describing 20 prospective cohorts for 11 different types of cancer

65 estimates of association between omega-3 fatty acid consumption and cancer were reported, data not pooled due to heterogeneity

for breast cancer, 1 estimate was for increased risk, 3 estimates were for decreased risk, and 7 estimates did not find significant association

Reference - JAMA 2006 Jan 25;295(4):403, correction can be found in JAMA 2006 Apr 26;295(16):1900, commentary can be found in JAMA 2006 Jul 19;296(3):282

higher dietary fiber intake associated with reduced risk of breast cancer o

based on systematic review of prospective observational studies

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systematic review of 16 prospective cohort and case-control studies evaluating dietary fiber intake and breast cancer risk in 999,271 persons including 26,623 with breast cancer

highest dietary fiber intake levels ranged from 16.3 g/day to 35.2 g/day

reduced risk of breast cancer associated with higher intake of dietary fiber (relative risk per 10 g/day increment 0.95, 95% CI 0.910.98) in analysis of 15 studies

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soluble dietary fiber (relative risk per 10 g/day increment 0.74, 95% CI 0.63-0.88) in analysis of 4 studies

breast cancer risk not significantly associated with intake of fruit fiber, vegetable fiber, cereal fiber, or insoluble fiber

Reference - Ann Oncol 2012 Jun;23(6):1394 full-text

dietary calcium intake of 650 mg/day and vitamin D intake of 350 units/day associated with reduced risk of breast cancer o

based on systematic review of observational studies evaluating calcium intakes of 250-1,100 mg/day, vitamin D intakes of 50-600 units/day, and serum vitamin D levels

risk of breast cancer reduced with increasing (p < 0.001 for each)

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dietary calcium intake of 650 mg/day (relative risk [RR] 0.91, 95% CI 0.86-0.97) in analysis of 10 studies with 14,450 breast cancer cases

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dietary vitamin D intake of 350 units/day (RR 0.9, 95% CI 0.860.95) in analysis of 13 studies with 20,343 breast cancer cases

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serum vitamin D levels 35 ng/ml (RR 0.77, 95% CI 0.71-0.84) in analysis of 4 studies with 8,716 breast cancer cases

Reference - Breast Cancer Res Treat 2012 Nov;136(1):309

conflicting evidence regarding meat or dairy intake as risk factor o

no significant associations between intake of meat or dairy products and risk of breast cancer 

based on review of primary data from 8 prospective cohort studies with 351,041 women followed for up to 15 years

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7,379 were diagnosed with invasive breast cancer

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no significant association between intakes of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast cancer risk

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inconsistent relation between egg consumption and risk of breast cancer

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Reference - Int J Epidemiol 2002;31(1):78 full-text, editorial can be found in Int J Epidemiol 2002 Feb;31(1):86

heterocyclic amines (formed in meat and fish cooked at high temperatures) not associated with increased risk for invasive breast cancer 

based on prospective population-based study of 11,699 women ≥ 50 years old in Sweden followed for mean 10.4 years

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430 women diagnosed with incident invasive breast cancer

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intake of heterocyclic amines not associated with incident breast cancer

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among women with low heterocyclic amines intake, omega-6 polyunsaturated fatty acids were associated with increased risk for breast cancer

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Reference - Int J Cancer 2008 Oct 1;123(7):1637

some studies suggest association between higher red meat intake and breast cancer 

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consumption of well-done red meat associated with increased risk of breast cancer compared with rare- or medium-done red meat 

based on case-control study of 930 women aged 55-69 years

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Reference - J Natl Cancer Inst 1998 Nov 18;90(22):1724 fulltext

higher red meat intake associated with increased risk for estrogen receptor-positive/progesterone receptor-positive breast cancer but not estrogen receptor-negative/progesterone receptornegative breast cancer 

based on questionnaire study of 90,659 premenopausal women followed for 12 years

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Reference - Arch Intern Med 2006 Nov 13;166(20):2253, commentary can be found in Am Fam Physician 2007 Aug 1;76(3):430

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higher red meat consumption during adolescence may be associated with increased risk for invasive breast cancer in premenopausal women 

based on prospective cohort study

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39,268 premenopausal women in Nurses' Health Study II completed validated food frequency questionnaire and were followed 7 years

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455 cases of premenopausal invasive breast cancer occurred 

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compared to women in lowest quintile of intake during high school, women in highest quintile had increased risk (adjusted relative risk [RR] 1.34, 95% CI 0.94-1.89, p for trend = 0.05)

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significant linear association observed for every additional 100-g increase per day in red meat intake (RR 1.2, 95% CI 11.43, p = 0.05)

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association stronger for estrogen receptor-positive and progesterone receptor-positive tumors

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Reference - Cancer Epidemiol Biomarkers Prev 2008 Aug;17(8):2146 full-text

some evidence that higher intake of fruits and vegetables is associated with a small reduction breast cancer risk o

higher intake of fruits or fruits and vegetables associated with small reduction in risk of breast cancer 

based on systematic review of 1 nested case-control and 14 cohort studies

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systematic review comparing higher to lower intake of fruits and vegetables in up to 780,000 women with more than 16,000 cases of breast cancer

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reduced risk of breast cancer associated with higher intake of

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fruits relative risk 0.92 (95% CI 0.86-0.98) in analysis of 10 studies

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fruits and vegetables relative risk 0.89 (95% CI 0.8-0.99) in analysis of 6 studies

risk of breast cancer not significantly associated with higher intake of vegetables in analysis of 10 studies

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Reference - Breast Cancer Res Treat 2012 Jul;134(2):479

total or specific fruit and vegetable intake not associated with risk of breast cancer 

based on 10-year cohort of 285,526 women aged 25-70 years

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median duration of follow-up 5.4 years

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Reference - JAMA 2005 Jan 12;293(2):183, editorial can be found in JAMA 2005 Jan 12;293(2):233, commentary can be found in JAMA 2005 May 11;293(18):2209

no significant association between fruit and vegetable consumption during adulthood and breast cancer risk 

based on review of 8 prospective cohort studies with 7,377 incident breast cancer cases among 351,825 women

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Reference - JAMA 2001 Feb 14;285(6):769, editorial can be found in JAMA 2001 Feb 14;285(6):799, commentary can be found in JAMA 2001 Jun 20;285(23):2975

caffeine consumption may not be associated with increased risk for breast cancer o

based on prospective cohort with 38,432 women ≥ 45 years old followed for mean 10 years

1,188 incident cases of invasive breast cancer

≥ 4 cups of coffee/day associated with increased risk of benign breast disease

Reference - Arch Intern Med 2008 Oct 13;168(18):2022

no evidence of association between dietary acrylamide intake and breast cancer o

based on prospective cohort of 43,404 Swedish women (mean age 39 years) followed for 11 years

acrylamide found in coffee, fried potatoes, crisp and soft bread, cereal, biscuits, crackers, pancakes, meatballs

Reference - JAMA 2005 Mar 16;293(11):1326

review of diet and breast cancer can be found in Nutr Clin Pract 2012 Oct;27(5):636

Alcohol use:

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low levels of alcohol consumption (5-9.9 g of alcohol/day) associated with small increase in risk of invasive breast cancer o based on prospective cohort study o

105,986 women from Nurses' Health Study periodically evaluated for alcohol intake from 1980 to 2008

7,690 cases of invasive breast cancer diagnosed during 2.4 million personyears of follow-up

cumulative alcohol intake calculated using average alcohol intake since baseline

increased risk of invasive breast cancer associated with cumulative alcohol intake of (vs. no alcohol consumption) 

5-9.9 g of alcohol/day (relative risk [RR] 1.15, 95% CI 1.06-1.24)

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10-19.9 g of alcohol/day (RR 1.22, 95% CI 1.13-1.32)

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20-29.9 g of alcohol/day (RR 1.2, 95% CI 1.07-1.35)

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≥ 30 g of alcohol/day (RR 1.51, 95% CI 1.35-1.7)

alcohol consumption earlier (ages 18-40 years) or later (> 40 years old) in life independently associated with increased risk of breast cancer

Reference - JAMA 2011 Nov 2;306(17):1884, editorial can be found in JAMA 2011 Nov 2;306(17):1920

alcohol use increases risk of breast cancer in dose-dependent fashion o

based on analysis of 6 prospective studies of 322,647 women followed up to 11 years with 4,335 developing invasive breast cancer

women consuming 30-60 g/day of alcohol had 40% increase in risk of breast cancer

Reference - JAMA 1998 Feb 18;279(7):535, commentary can be found in JAMA 1998 Oct 7;280(13):1139

alcohol use but not smoking associated with increased risk of breast cancer o

based on analysis of 58,515 cases and 95,067 controls from 53 studies

for each 10 g of alcohol (average 1 drink) consumed per day, relative risk of breast cancer increased by 7%

Reference - Br J Cancer 2002 Nov 18;87(11):1234 full-text, commentary can be found in CMAJ 2003 Apr 29;168(9):1147 full-text, Bandolier 2003 Mar;109:4;

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alcohol use associated with increased risk of fatal breast cancer in postmenopausal women o

based on retrospective cohort study

242,010 women, followed for 14 years, 1,442 breast cancer deaths

< 1 drink/day associated with 30% increase in breast cancer mortality in postmenopausal women

no association in pre- or peri-menopausal women, no clear dose-response relationship

Reference - Cancer Causes Control 2001 Dec;12(10):895

excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake o

prospective study of 88,818 women who completed dietary questionnaire section of Nurses' Health Study in 1980 with 16 years of follow-up

3,483 cases of breast cancer were documented

total folate intake was not associated with overall risk of breast cancer

among women who consumed at least 15 g/day of alcohol, risk of breast cancer was highest among those with low folate intake

Reference - JAMA 1999 May 5;281(17):1632

similar findings reported in prospective study of 17,447 women aged 40-69 years followed 13-14 years (BMJ 2005 Oct 8;331(7520):807 full-text)

•

alcohol use > 20 g/day (1.5-2 drinks) and hormone replacement therapy (HRT) both associated with increased risk for invasive breast cancer among 44,187 postmenopausal women in Nurses' Health Study (Ann Intern Med 2002 Nov 19;137(10):798), commentary can be found in Ann Intern Med 2003 Oct 7;139(7):601

•

review of association of alcohol consumption with increased risk for breast cancer can be found in JAMA 2001 Nov 7;286(17):2143

Tobacco use: •

active smoking and passive smoke exposure associated with increased risk of invasive breast cancer in postmenopausal women o based on prospective cohort study of 79,990 women aged 50-79 years o

49% reported smoking or former smoking

3,520 incidents of invasive breast cancer were identified in 10-year followup

increased risk of invasive breast cancer (vs. nonsmokers) in

o •

•



former smokers (hazard ratio [HR] 1.09, 95% CI 1.02-1.17)



current smokers (HR 1.16, 95% CI 1-1.34)



women with ≥ 50 years of smoking (HR 1.35, 95% CI 1.03-1.77)



women with highest passive exposure (≥ 10 years in childhood, ≥ 20 years as adult at home, ≥ 10 years as adult at work) (HR 1.32, 95% CI 1.04-1.67)

Reference - BMJ 2011 Mar 1;342:d1016 full-text

smoking associated with small increase in risk for breast cancer o

based on retrospective study (Nurses' Health Study) following 78,206 women for 14 years

3,140 women had invasive breast cancer during follow-up, no association found with passive smoking

Reference - Epidemiology 2002 Mar;13(2):138

smoking before first pregnancy associated with increased risk of postmenopausal breast cancer o

based on prospective cohort of 37,015 women aged 55-69 years followed for 13 years

smoking prior to first pregnancy associated with increased risk of postmenopausal breast cancer (risk ratio 1.21, 95% CI 1.07-1.37)

no association with smoking after first pregnancy

Reference - Mayo Clin Proc 2005 Nov;80(11):1423

cigarette smoking associated with increased risk for breast cancer in premenopausal women o

based on case-control study of 318 premenopausal women who had breast cancer and 340 age-matched controls

Reference - Lancet 2002 Oct 5;360(9339):1044, commentary can be found in Lancet 2002 Oct 5;360(9339):1033

review of cigarette smoking and breast cancer risk can be found in Cancer Epidemiol Biomarkers Prev 2002 Oct;11(10):953

Medications and Toxins Hormonal exposure: Hormone replacement therapy (HRT): •

•

for combined estrogen and progestin (hormone replacement therapy [HRT]) o HRT increases risk for invasive breast cancer (NNH 204 over 5.6 years) (level 1 [likely reliable] evidence), based on largest randomized trial (16,608 women) o

conflicting evidence on ongoing risk of breast cancer after stopping HRT in this trial

largest prospective cohort study (1 million women) suggests current use of HRT associated with increased risk of incident breast cancer and breast cancer mortality (level 2 [mid-level] evidence)

for estrogen alone o

estrogen alone may not increase risk of breast cancer (level 2 [mid-level] evidence), based on largest randomized trial with 10,739 women with prior hysterectomy and follow-up < 7 years

large cohort study (111,000 women) suggests increased risk for breast cancer with use of estrogen alone for > 5 years (level 2 [mid-level] evidence)

among women with breast cancer o

prediagnostic use of hormone therapy may be associated with decreased breast cancer mortality (level 2 [mid-level] evidence), based on cohort study

HRT increases risk of recurrent breast cancer in breast cancer survivors (level 1 [likely reliable] evidence), based on 2 randomized trials

see Hormonal replacement therapy (HRT) and breast cancer for details

Hormonal contraceptives: •

small increased risk of having breast cancer diagnosed while taking combined oral contraceptives and for up to 10 years after stopping (level 2 [mid-level] evidence) o based on review of individual-level data from 54 epidemiologic studies with 53,297 women with breast cancer and 100,239 women without breast cancer from 25 countries

â&#x20AC;˘

current users had 1.24 times risk of breast cancer, risk decreased progressively after stopping with no increased risk of having breast cancer diagnosed 10 or more years after stopping use

higher dose oral contraceptives associated with greater risk of diagnosis of breast cancer

number of excess cancers diagnosed during and for up to 10 years after stopping oral contraceptives varied from 0.5 to 4.7 per 10,000 women as age varied from 16 to 29 years

Reference - Lancet 1996 Jun 22;347(9017):1713, editorial can be found in Lancet 1996 Sep 7;348(9028):682 , commentary can be found in ACP J Club 1996 Nov-Dec;125(3):77

oral contraceptive use associated with increased risk for premenopausal breast cancer (level 2 [mid-level] evidence) o

based on systematic review and meta-analysis of 34 case-control studies

oral contraceptive use associated with increased risk of premenopausal breast cancer (odds ratio [OR] 1.19, 95% CI 1.09-1.29)

increased risk found in both parous women (OR 1.29, 95% CI 1.2-1.4) and nulliparous women (OR 1.24, 95% CI 0.92-1.67)

Reference - Mayo Clin Proc 2006 Oct;81(10):1290, editorial can be found in Mayo Clin Proc 2006 Oct;81(10):1287, commentary can be found in Am Fam Physician 2007 Mar 15;75(6):899, Mayo Clin Proc 2007 Mar;82(3):385

current or former oral contraceptive use may not be associated with increased risk for breast cancer in women aged 35-64 years (level 2 [mid-level] evidence) o

based on case-control study

4,575 women with breast cancer compared to 4,682 controls

relative risk (RR) was 1 for current use (95% CI 0.8-1.3) and 0.9 for former use (95% CI 0.8-1)

Reference - N Engl J Med 2002 Jun 27;346(26):2025 full-text, editorial can be found in N Engl J Med 2002 Jun 27;346(26):2078, commentary can be found in N Engl J Med 2002 Oct 31;347(18):1448, Am Fam Physician 2002 Nov 1;66(9):1776

DynaMed commentary -- limitation of cases to women < 65 years old does not provide information regarding later development of breast cancer

•

review of oral contraceptive use and risk of breast cancer can be found in Mayo Clin Proc 2008 Jan;83(1):86, commentary can be found in Mayo Clin Proc 2008 Jul;83(7):849

•

progestin-only injectable and implantable contraceptives NOT associated with increased risk of breast cancer (level 2 [mid-level] evidence) o

case-control study supported by National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) compared 4,575 women aged 35-64 years with first primary invasive breast cancer and 4,682 matched controls

comparing cases vs. controls

•



58 (1.3%) vs. 69 (1.5%) had used depot medroxyprogesterone



36 (0.8%) vs. 41 (0.9%) had used injectable contraceptives of unknown type



5 (0.1%) vs. 7 (0.1%) had used implantable progestin (Norplant)

Reference - Contraception 2004 May;69(5):353 in J Watch Online 2004 Jun 11

levonorgestrel-releasing intrauterine device does not appear to be associated with increased risk of breast cancer (level 2 [mid-level] evidence) o

based on postmarketing study of 17,360 levonorgestrel-releasing intrauterine system (LNG-IUD) users aged 30-54 years in Finland

incidence comparison between LNG-IUD users and average Finnish female population as derived from Finnish Cancer Registry

no significant difference in breast cancer risk between the levonorgestrel system users and average female population in any of 5-year age groups

Reference - Obstet Gynecol 2005 Oct;106(4):813, commentary can be found in Obstet Gynecol 2006 Jan;107(1):207

Infertility treatment: •

in vitro fertilization (IVF) may not be associated with increased risk for breast cancer (level 2 [mid-level] evidence) o based on systematic review of observational studies o

systematic review of 11 cohort studies (with 60,050 women) and 4 casecontrol studies (with 11,303 women with breast cancer and 10,930 controls)

no clear association found between ovulation induction or IVF and increased risk of breast cancer

o •

•



pooled relative risk 1.06 in analysis of cohort studies (not significant)



pooled relative risk 0.88 in analysis of case-control studies (not significant)

Reference - Int J Fertil Womens Med 2005 Nov-Dec;50(6):259

in vitro fertilization (IVF) might be associated with modestly increased breast cancer risk o

based on retrospective cohort study of 3,375 women having IVF

35 breast carcinomas diagnosed (1%) (standardized incidence ratio 1.4, 95% CI 0.98-1.96)

Reference - Ann Surg Oncol 2008 Apr;15(4):1048

long-term use of human menopausal gonadotropin might increase risk for breast cancer o

based on case-control study

4,575 women aged 35-64 years with primary invasive breast cancer and 4,682 controls answered questionnaire

history of infertility drug use did not have overall effect on risk for breast cancer

human menopausal gonadotropin use ≥ 6 months or 6 cycles had odds ratios 2.7-3.8 for breast cancer

Reference - Fertil Steril 2003 Apr;79(4):844, editorial can be found in Fertil Steril 2003 Apr;79(4):852

Statins: •

no association between breast cancer and statin use o statins do not affect incidence of cancer or cancer death 

systematic review and meta-analysis of 26 randomized trials with 86,936 participants, trial durations ranged from 1.9 years to 10.4 years



no significant effect on incidence of breast cancer in meta-analysis of 5 trials with 33,776 patients (odds ratio [OR] 1.33, 95% CI 0.792.26)



Reference - JAMA 2006 Jan 4;295(1):74, commentary can be found in JAMA 2006 Jun 21;295(23):2720

no association between breast cancer and statin use 

based on systematic review and meta-analysis of 7 randomized trials, 4 cohort studies, and 5 case-control studies



Reference - J Clin Oncol 2005 Dec 1;23(34):8606

no association of breast cancer with cholesterol levels, statins, or general lipid-lowering drugs 

based on retrospective analysis of 79,994 women aged 42-69 years followed prospectively for up to 12 years



Reference - Arch Intern Med 2005 Oct 24;165(19):2264, commentary can be found in Arch Intern Med 2006 May 22;166(10):1143

Aldosterone antagonists: •

spironolactone not associated with increased risk of incident breast cancer in women > 55 years old o based on retrospective cohort study o

28,032 women > 55 years old without history of breast cancer who received ≥ 2 prescriptions for spironolactone were compared to 55,961 matched controls without history of breast cancer and no exposure to spironolactone

mean follow-up 4.1 years

unadjusted incident breast cancer rate 0.39% per year in spironolactone group vs. 0.38% per year in unexposed control group (not significant in adjusted analyses)

Reference - BMJ 2012 Jul 13;345:e4447 full-text

Dopamine antagonists: •

dopamine antagonists may be associated with small increased risk for breast cancer (level 2 [mid-level] evidence) o based on retrospective cohort study o

52,819 women exposed to prolactin-elevating dopamine antagonists (typical antipsychotics and antiemetics) and 55,289 unexposed women in New Jersey Medicaid and Medicare databases free of breast cancer in 1989 New Jersey Cancer Registry were evaluated for 6 years

use of antipsychotic dopamine antagonists associated with 16% increase in risk of breast cancer with dose-response relationship

similar increase with antiemetic dopamine antagonists

no increased risk for colon cancer with dopamine antagonists

Reference - Arch Gen Psychiatry 2002 Dec;59(12):1147

Nonsteroidal anti-inflammatory drugs and acetaminophen: •

nonsteroidal anti-inflammatory drugs and acetaminophen not associated with risk of breast cancer in postmenopausal women o based on prospective cohort of 84,602 postmenopausal women followed for 28 years o

4,734 cases of invasive breast cancer reported

no significant association between incidence of breast cancer and use of aspirin, other nonsteroidal anti-inflammatory drugs, or acetaminophen

Reference - J Clin Oncol 2012 Oct 1;30(28):3468

Organochlorine compounds: •

organochlorine compounds may be associated with increased risk, but controversial o organochlorine levels (and presumptively exposure to dichlorodiphenyltrichloroethane [DDT] or polychlorinated biphenyls [PCBs]) not associated with risk of breast cancer 

based on case-control study with 240 pairs



Reference - N Engl J Med 1997 Oct 30;337(18):1253 full-text, commentary can be found in N Engl J Med 1998 Apr 2;338(14):988

organochlorine insecticide residues commonly found in foods of animal origin and strongly associated with increased risk of breast cancer, presumably due to estrogenic effects (J Natl Cancer Inst 1993 Apr 21;85(8):648), editorial can be found in J Natl Cancer Inst 1993 Apr 21;85(8):598, commentary can be found in J Natl Cancer Inst 1993 Oct 20;85(20):1696, J Natl Cancer Inst 1993 Nov 17;85(22):1872, J Natl Cancer Inst 1994 Jan 5;86(1):65, J Natl Cancer Inst 1994 Nov 2;86(21):1642

no support for association with DDT and breast cancer



265 postmenopausal women with breast cancer had adipose dichlorodiphenyldichloroethylene (DDE) concentrations 9.2% lower than 341 controls



Reference - BMJ 1997 Jul 12;315(7100):81 full-text

dieldrin, an organochlorine compound, found to be associated with increased risk of breast cancer in prospective study (Lancet 1998 Dec

5;352(9143):1816), commentary can be found in Lancet 2000 Nov 25;356(9244):1852 o

higher serum dieldrin levels associated with increased risk for estrogen receptor-negative breast cancer in case-control study (BMC Cancer 2001;1:18 full-text)

female electronics workers exposed to trichloroethylene and/or mixture of solvents before 1974 had higher risk of breast cancer than general population in Taiwan (BMC Public Health 2007 Jun 8;7:102 full-text)

Weight-related Factors • in postmenopausal women, weight gain and higher body mass index (BMI) associated with increased risk for breast cancer o based on multiple cohort studies o

higher weight may be correlated with increasing risk for breast cancer in postmenopausal women 

based on pooled analysis of cohort studies



pooled data from 7 cohort studies with 337,819 women and 4,385 incident cases of invasive breast cancer were analyzed for weight and BMI



in pooled subgroup analyses for postmenopausal women

 o



each 10-kg (22-lb) increase in weight associated with 6% increase in risk for breast cancer (pooled relative risk 1.06, 95% CI 1.03-1.1)



each 4-kg/m2 increase in BMI associated with 7% increase in risk for breast cancer (pooled relative risk 1.07, 95% CI 1.021.11)

Reference - Am J Epidemiol 2000 Sep 15;152(6):514 full-text

weight gain since age 18 years, BMI at age 35 years, and BMI at age 50 years are associated with increased postmenopausal breast cancer risk 

based on prospective cohort of 99,039 women aged 50-71 years



associations significant in women not taking hormone replacement therapy



Reference - Arch Intern Med 2007 Oct 22;167(19):2091

weight gain since age 18 years and weight gain since menopause associated with increased risk of invasive breast cancer



based on prospective cohort of 87,143 postmenopausal women aged 30-44 years followed for up to 26 years



weight loss since menopause in women who never used postmenopausal hormones associated with decreased risk



Reference - JAMA 2006 Jul 12;296(2):193

excessive weight gain (> 60 lbs [27.2 kg]) associated with increased risk for breast cancer 

based on cohort of 44,161 postmenopausal women not taking hormone therapy



1,200 had incident invasive breast cancer



Reference - Cancer 2006 Jul 1;107(1):12

higher adiposity associated with increased risk for breast cancer in elderly women 

prospective cohort of 7,523 women (mean age 73.5 years) followed for mean 11.3 years



after adjusting for multiple risk factors, highest quartile had higher breast cancer rates than lowest quartile for

 •



weight



weight gain since age 25 years



BMI



waist circumference



percentage of body fat

Reference - J Am Geriatr Soc 2006 Jan;54(1):63

in premenopausal women, lower BMI associated with increased risk for breast cancer o

higher weight might be correlated with decreasing risk for breast cancer in premenopausal women 

based on pooled analysis of cohort studies



pooled data from 7 cohort studies with 337,819 women and 4,385 incident cases of invasive breast cancer were analyzed for BMI



4 studies provided data on premenopausal women



 o

•

in pooled subgroup analyses for premenopausal women 

each 10-kg (22-lb) increase in weight associated with 10% decrease in risk for breast cancer (pooled relative risk 0.9, 95% CI 0.83-0.97)



each 4-kg/m2 increase in BMI associated with 11% decrease in risk for breast cancer (pooled relative risk 0.89, 95% CI 0.81-0.97)

Reference - Am J Epidemiol 2000 Sep 15;152(6):514 full-text

lower BMI at age 18 years associated with increased breast cancer incidence in premenopausal women 

based on 113,130 premenopausal participants with 1,225,520 personyears of prospective follow-up



BMI 20-22.4 kg/m2 at age 18 years associated with higher breast cancer incidence than BMI ≥ 27.5 kg/m2



in multivariate analysis increasing BMI at age 18 years (by 5 kg/m2) associated with 17% relative decrease in breast cancer incidence (hazard ratio 0.83, 95% CI 0.74-0.94)



Reference - Arch Intern Med 2006 Nov 27;166(21):2395 full-text

rapid adolescent growth may increase risk of breast cancer o

based on study of 65,140 women in Nurses' Health Study, of whom 2,291 developed breast cancer over 16 years

risk factors for breast cancer included earlier menarche, extremely lean body mass at age 10 years, and taller adult height

Reference - Cancer 1999 Jun 1;85(11):2400

Medical Conditions Prior cancer: •

history of childhood cancer may be associated with increased risk for breast cancer, but increased risk may not persist after aged 50 years o based on population-based cohort study o

8,093 women survivors of childhood cancer evaluated

81 patients were diagnosed with breast cancer (standardized incidence ratio 2.2, 95% CI 1.7-2.7)

standardized incidence ratios increased with age until aged 40 years, then decreased with increasing age (no additional risk after aged 50 years)

Reference - Int J Cancer 2008 Nov 1;123(9):2156

Gestational diabetes: •

gestational diabetes might be associated with increased risk for breast cancer o based on retrospective cohort study of 37,926 women who had ≥ 1 live birth 

1,626 cases of breast cancer occurred overall



410 women had gestational diabetes (29 of whom developed breast cancer)

breast cancer occurred in 29 (7%) women who had gestational diabetes vs. 1,597 (4.3%) women without gestational diabetes (adjusted relative risk [RR] 1.5, 95% CI 1-2.1)

significant association seen only in women ≥ 50 years old (RR 1.7, 95% CI 1.2-2.5)

Reference - Breast Cancer Res Treat 2008 Mar;108(1):129

Other Risk Factors Age: •

risk for breast cancer increases with age o based on invasive female breast cancer incidence in United States 2005 to 2007 o

probability of developing breast cancer in next 10 years of life based on age 

0.06% (1 in 1,681) at age 20 years



0.43% (1 in 232) at age 30 years



1.45% (1 in 69) at age 40 years



2.38% (1 in 42) at age 50 years



3.45% (1 in 29) at age 60 years



3.74% (1 in 27) at age 70 years

lifetime risk 12.15% (1 in 8)

Reference - American Cancer Society Breast Cancer Facts & Figures 20112012 PDF

Reproductive history: •

National Cancer Institute Breast Cancer Risk Assessment Tool (Gail model) includes reproductive history factors in predicting breast cancer risk, including o age at first menstrual period o

•

age at first live birth

reproductive history may be associated with breast cancer risk o

systematic review and meta-analysis of 2 cohort studies and 8 case-control studies

increasing parity associated with increasing risk of estrogen receptorpositive, progesterone receptor-positive breast cancer, but not estrogen receptor-negative, progesterone receptor-negative breast cancer, based on 8 studies

older age at first birth associated with increasing risk of estrogen receptorpositive, progesterone receptor-positive breast cancer, but not estrogen receptor-negative, progesterone receptor-negative breast cancer, based on 9 studies

breastfeeding associated with decreased risk of estrogen receptor-positive, progesterone receptor-positive and estrogen receptor-negative, progesterone receptor-negative breast cancer, based on 7 studies

older age at menarche associated with decreased risk of estrogen receptorpositive, progesterone receptor-positive and estrogen receptor-negative, progesterone receptor-negative breast cancer, based on 9 studies

Reference - Breast Cancer Res 2006 Jul 19;8(4):R43 full-text

infertility due to ovulatory disorder associated with reduced risk for breast cancer o

based on prospective cohort study with 116,671 female nurses aged 25-42 years followed for mean 11 years

1,357 nurses developed breast cancer

Reference - Arch Intern Med 2006 Dec 11;166(22):2484

Abortion: •

abortion does not appear to increase risk for breast cancer o neither spontaneous abortion nor induced abortion associated with increased risk for breast cancer 

based on systematic review and prospective cohort study



systematic review 

53 studies in 16 countries with liberal abortion laws including 44,000 women with breast cancer in 13 studies with prospective abortion records and 39,000 with breast cancer in 40 retrospective studies



relative risk of breast cancer in prospective studies 0.98 for spontaneous abortion and 0.93 for induced abortion



relative risk of breast cancer in retrospective studies was 0.98 for spontaneous abortion and 1.11 for induced abortion



Reference - Lancet 2004 Mar 27;363(9414):1007, commentary can be found in Lancet 2004 Jun 5;363(9424):1910, Am Fam Physician 2004 Aug 1;70(3):573

prospective cohort study 

105,716 women aged 29-46 years in Nurses' Health Study II followed for mean 9.2 years



1,458 (1.38%) developed invasive breast cancer



16,118 (15%) had history of induced abortion, 21,753 (21%) had history of spontaneous abortion



after adjustment for established breast cancer risk factors 

history of spontaneous abortion not associated with significantly lower risk of breast cancer (hazard ratio [HR] 0.89, 95% CI 0.78-1.01)



history of induced abortion not associated with changed risk of breast cancer



no significant associations with number of abortions, age at abortion, or parity



Reference - Arch Intern Med 2007 Apr 23;167(8):814 fulltext

induced abortion not associated with risk of breast cancer 

based on retrospective cohort of 370,715 induced abortions among 280,965 women in population of 1.5 million women



10,246 women identified with breast cancer



Reference - N Engl J Med 1997 Jan 9;336(2):81 full-text, commentary can be found in N Engl J Med 1997 Jun 19;336(25):1834

prospective study found no association with interruption of pregnancy (spontaneous or induced) and breast cancer (J Epidemiol Community Health 2001 May;55(5):336 full-text)

American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 434 agrees with National Cancer Institute 2003 conclusion that there is NO evidence supporting causal link between induced abortion and subsequent breast cancer (Obstet Gynecol 2009 Jun;113(6):1417, ACOG News Release 2003 Jul 31 [reaffirmed 2011 Jun])

Radiation exposure: •

radiation therapy o radiation therapy for pediatric or young adult cancer associated with increased risk of breast cancer by age 40-45 years 

based on systematic review of 11 retrospective cohort studies with > 14,000 women and 3 case-control studies



about 7,000 women had chest radiation in cohort studies, 422 cases of breast cancer



radiation therapy associated with



cumulative incidence of breast cancer 13%-20%



standardized incidence ratios of breast cancer 13.5-55.5 per 10,000 person-years



excess breast cancer risk 18.6-79 per 10,000 person-years

Reference - Ann Intern Med 2010 Apr 6;152(7):444, editorial can be found in Ann Intern Med 2010 Apr 6;152(7):465

chest radiation therapy associated with 25 times increase in risk of breast cancer 

based on retrospective cohort study of 6,068 women who survived childhood cancer



95 (1.6%) developed breast cancer



Reference - Ann Intern Med 2004 Oct 19;141(8):590, commentary can be found in Ann Intern Med 2005 Mar 15;142(6):471

radiation therapy for Hodgkin lymphoma may increase risk of breast cancer



supradiaphragmatic radiation therapy for childhood Hodgkin lymphoma associated with increased risk of breast cancer 

based on cohort of 383 female 5-year survivors of childhood Hodgkin lymphoma



cumulative risk of breast cancer by 25 years of follow-up was 9.9% overall and 12.2% for those treated with supradiaphragmatic radiation therapy



Reference - Int J Cancer 2007 Jan 15;120(2):384

radiation therapy for Hodgkin lymphoma associated with dosedependent increased risk of breast cancer persisting at least 25 years 

based on case-control study with 371 women with Hodgkin lymphoma



Reference - JAMA 2003 Jul 23-30;290(4):465 full-text, correction can be found in JAMA 2003 Sep 10;290(10):1318, editorial can be found in JAMA 2003 Jul 23/30;290(4):529

risk of breast cancer increases with increasing radiation doses in patients with Hodgkin lymphoma 

based on case-control study comparing 48 women who developed breast cancer > 5 years after Hodgkin lymphoma and 175 matched controls with Hodgkin lymphoma



Reference - J Natl Cancer Inst 2003 Jul 2;95(13):971 full-text

increased risk of breast cancer among patients treated with supradiaphragmatic radiation for Hodgkin lymphoma if radiation therapy before age 30 years or if splenectomy 

based on medical record review of 653 women who received such treatment with median follow-up 8.7 years



Reference - Mayo Clin Proc 2003 Jun;78(6):708

total body irradiation after allogeneic hematopoietic cell transplant associated with increased risk of breast cancer 

3,337 female 5-year survivors who had allogeneic hematopoietic cell transplant were followed for 5.7-24.8 years (median 12.5 years)



52 (1.6%) developed breast cancer (standardized incidence ratio 2.2)



25-year cumulative incidence

 •

11% for total cohort



17% of patients who had total body irradiation



3% of patients without total body irradiation

Reference - Blood 2008 Jan 15;111(2):939

diagnostic radiation o

•



diagnostic radiation exposure before age 30 years associated with increased risk of breast cancer in women with BRCA1 and BRCA2 mutations 

based on retrospective cohort study



1,993 women with BRCA1 and BRCA2 mutations were assessed for lifetime exposure to all radiation types involving chest or shoulders and incidence of breast cancer



43% had breast cancer diagnosis



compared to no radiation exposure, any diagnostic radiation exposure before age 30 years associated with increased risk of breast cancer (hazard ratio 1.9, 95% CI 1.2-3)



increasing cumulative radiation dose associated with increasing risk of breast cancer risk



Reference - BMJ 2012 Sep 6;345:e5660 full-text

electromagnetic field exposure not associated with risk for breast cancer o

extremely low-frequency electromagnetic fields (ELF-EMF) exposure not associated with increased risk for breast cancer 

based on systematic review



systematic review of 15 studies evaluating association between exposure to ELF-EMF and breast cancer risk in 24,338 women with breast cancer and 60,628 controls



ELF-EMF exposure not associated with female breast cancer



in total analysis



in subgroup analysis by exposure mode, menopausal status, or estrogen receptor status

Reference - Breast Cancer Res Treat 2010 Sep;123(2):569

occupational exposure to magnetic fields not associated with increased risk of breast cancer 

based on cohort of 28,224 electric utility workers



Reference - Occup Environ Med 2007 Nov;64(11):782

electric blanket use not associated with breast cancer 

based on case-control study, with responses from 576 (87%) cases and 585 (83%) controls



Reference - Epidemiology 2003 Sep;14(5):514, commentary can be found in Epidemiology 2004 May;15(3):375

High bone mineral density: •

high bone mineral density (BMD) associated with increased risk for incident breast cancer in postmenopausal women o based on subgroup analysis of prospective cohort study o

9,941 women (mean age 63 years at baseline) from Women's Health Initiative with baseline BMD measurement and Gail score were evaluated

mean follow-up 8.43 years

327 incident cases of breast cancer occurred

increased risk for incident breast cancer was associated with

o •



increasing BMD (hazard ratio [HR] 1.25, 95% CI 1.11-1.4 for each unit of increase in T-score)



Gail score ≥ 1.67% (HR 1.35, 95% CI 1.05-1.73)



combination of highest Gail scores and highest BMD (p < 0.05)

Reference - Cancer 2008 Sep 1;113(5):907

high bone mass associated with increased risk of breast cancer o

based on study of 1,373 women aged 47-80 years with no history of breast cancer followed for > 20 years

Reference - N Engl J Med 1997 Feb 27;336(9);611 full-text, commentary can be found in N Engl J Med 1997 Jul 17;337(3):199 (correction can be found in N Engl J Med 1997 Sep 18;337(12):867)

Prenatal and perinatal factors:

•

diethylstilbestrol (DES) exposure in utero may be associated with increased lifetime risk of breast cancer in women ≥ 40 years old o based on retrospective cohort study of 4,653 women exposed to DES in utero and 1,927 women without DES exposure o

DES exposure associated with increased risk of breast cancer in women ≥ 40 years old compared to no exposure (3.9% vs. 2.2%, p < 0.05)

Reference - N Engl J Med 2011 Oct 6;365(14):1304 full-text, commentary can be found in Nat Rev Endocrinol 2011 Nov 1;7(12):692

some perinatal factors may be associated with subsequent risk for developing breast cancer o

based on systematic review and meta-analysis of 57 studies evaluating intrauterine exposures and risk for breast cancer

increased risk for breast cancer significantly associated with 

increased birth weight (relative risk [RR] 1.15)



birth length (RR 1.28)



higher maternal age (RR 1.13)



higher paternal age (RR 1.12)



Reference - Lancet Oncol 2007 Dec;8(12):1088, editorial can be found in Lancet Oncol 2007 Dec;8(12):1047

fetal growth (increased birth length, increased head circumference, lower gestational age for given birth size) associated with increased risk of premenopausal breast cancer o

based on retrospective cohort of 5,358 singleton females born

Reference - BMJ 2003 Feb 1;326(7383):248 full-text

placental weight positively associated with maternal risk of breast cancer o

based on population-based cohort study with 314,019 women in Swedish Birth Register

Reference - JAMA 2005 Nov 16;294(19):2474, commentary can be found in JAMA 2006 Mar 8;295(10):1124

Other risk factors: •

increased concentrations of estrogens and androgens associated with breast cancer

•

based on case-control study of 97 women with breast cancer and 244 controls from osteoporosis study involving white women ≥ 65 years old not taking estrogen replacement therapy

Reference - Ann Intern Med 1999 Feb 16;130(4 Pt 1):270

increased insulin-like growth factor (IGF)-I levels o

IGF-I and increased IGF binding protein 3 levels associated with increased risk of premenopausal breast cancer 

based on systematic review of 21 case-control studies



Reference - Lancet 2004 Apr 24;363(9418):1346, editorial can be found in Lancet 2004 Apr 24;363(9418):1336, commentary can be found in Lancet 2004 Jul 24-30;364(9431):325 (correction can be found in Lancet 2004 Oct 30;364(9445))

IGF-I levels associated with risk of breast cancer in premenopausal but not postmenopausal women 

based on case-control study of 397 women with breast cancer and 620 age-matched controls



Reference - Lancet 1998 May 9;357(9113):1393, commentary can be found in Lancet 1998 Aug 8;352(9126):488

personal use of hair dyes does not appear to increase cancer risk 

based on systematic review of 79 cohort and case-control studies evaluating personal use of hair dyes and relative risk of cancer, including 

14 studies of breast cancer



10 studies of bladder cancer



no significant increased risk of cancer found among personal hair dye users



Reference - JAMA 2005 May 25;293(20):2516, commentary can be found in JAMA 2005 Sep 14;294(10):1205, Am Fam Physician 2005 Oct 15;72(8):1590

increased risk of breast cancer associated with increased insulin-like growth factor (IGF)-1 may be limited to estrogen receptor-positive breast cancer 

based on pooled analysis of 17 case-control studies with 4,790 women with breast cancer and 9,428 matched women without breast cancer



•

odds ratio for developing breast cancer comparing highest vs. lowest quintile of IGF-1 concentration 

1.28 (95% CI 1.14-1.44) for all breast cancer



1.38 (95% CI 1.14-1.68) for estrogen receptor-positive breast cancer



0.8 (95% CI 0.57-1.13) for estrogen receptor-negative breast cancer

Reference - Lancet Oncol 2010 Jun;11(6):530, editorial can be found in Lancet Oncol 2010 Jun;11(6):501

stress does not appear to be risk factor for breast cancer o

job strain not associated with risk of breast cancer 

based on meta-analysis of individual patient data



meta-analysis of individual patient data from 12 prospective cohort studies with 116,056 persons without cancer at baseline who were followed for median 12 years



5,765 persons (5%) were diagnosed with incident cancer during follow-up including colorectal cancer in 0.5%, lung cancer in 0.3%, breast cancer in 0.9%, and prostate cancer in 0.7%



job strain (combination of high demands and low control at work) not associated with overall risk of cancer or breast cancer



Reference - BMJ 2013 Feb 7;346:f165 full-text

work-related stress not associated with risk for breast cancer 

based on longitudinal study



18,932 women in Danish Nurse Cohort followed for 10 years, 455 diagnosed with breast cancer



breast cancer risk not increased for women with high work pressure, low influence on work organization, or long working hours compared to women without these stressors



high work tempo associated with risk for breast cancer (hazard ratio [HR] 1.25, 95% CI 1.02-1.54)



Reference - Cancer Causes Control 2008 Apr;19(3):297

high levels of stress not associated with increased risk of incident breast cancer

•

based on prospective study of 6,689 women followed for 18 years



Reference - BMJ 2005 Sep 10;331(7516):548 full-text

vitamin D and sun exposure o

•



no association between vitamin D intake, sun-seeking holidays, or frequency of sunburn and breast cancer risk 

based on prospective cohort study of 41,811 Norwegian women aged 40-70 years followed for 8.5 years



Reference - Int J Cancer 2011 Mar 15;128(6):1425

higher serum vitamin D level might be associated with reduced risk of breast cancer 

based on systematic review of 10 case-control studies



serum vitamin D (25(OH)D) measured at breast cancer diagnosis in cases



20 ng/mL increase of vitamin D associated with decreased risk (risk ratio [RR] 0.73, 95% CI 0.6-0.88) of breast cancer in analysis of 9 retrospective case-control studies



Reference - Eur J Cancer 2010 Aug;46(12):2196

history of migraine may be associated with reduced risk for postmenopausal breast cancer o

based on case-control study

1,938 women with invasive breast cancer matched to 1,474 controls

women reporting clinical diagnosis of migraine had reduced risk for 

ductal carcinoma (odds ratio [OR] 0.67, 95% CI 0.54-0.82)



lobular carcinoma (OR 0.68, 95% CI 0.52-0.9)

associations primarily limited to hormone receptor-positive tumors

Reference - Cancer Epidemiol Biomarkers Prev 2008 Nov;17(11):3116

night shift work associated with modest increased risk for breast cancer o

based on cohort study

Reference - J Natl Cancer Inst 2001 Oct 17;93(20):1563 full-text, J Natl Cancer Inst 2001 Oct 17;93(20):1557 full-text

•

urinary melatonin levels reported to be associated with risk of invasive breast cancer in case-control study from Nurses' Health Study II cohort (J Natl Cancer Inst 2005 Jul 20;97(14):1084 full-text)

•

left handedness reported to be associated with risk of breast cancer in subset of women in breast cancer screening study, but not clearly significant in adjusted analysis and data in text and table inconsistent (BMJ 2005 Oct 15;331(7521):882 full-text), commentary can be found in BMJ 2005 Oct 29;331(7523):1023 1024

References Recommendation grading systems used: •

United States Preventive Services Task Force (USPSTF) grades of recommendation (prior to May 2007) o Grade A - USPSTF strongly recommends that clinicians provide the service to eligible patients, based on good evidence that the service improves important health outcomes and that benefits substantially outweigh harms o

Grade B - USPSTF recommends that clinicians provide the service to eligible patients, based on at least fair evidence that the service improves important health outcomes and that benefits outweigh harms

Grade C - USPSTF makes no recommendation for or against routinely providing the service, based on at least fair evidence that the service can improve health outcomes but the balance of benefits and harms is too close to justify a general recommendation

Grade D - USPSTF recommends against routinely providing the service to asymptomatic patients, based on at least fair evidence that the service is ineffective or that harms outweigh benefits

Grade I - USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing the service

Reference - USPSTF Grade Definitions

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