Breast cancer risk factors

Prevention

Preventable cases of breast cancer, UK

Excess bodyweight

Breast cancer cases linked to excess bodyweight, UK

Alcohol

Breast cancer cases linked to alcohol consumption, UK

Physical inactivity

Breast cancer cases linked to too little physical activity, UK

27% of breast cancer cases each year in the UK are linked to major lifestyle and other risk factors.[1]

Breast cancer is associated with a number of risk factors.[2-4]

Breast Cancer Risk Factors

  Increases risk Decreases risk
'Sufficient' or 'convincing' evidence
  • Alcoholic drinks [a]
  • Diethylstilbestrol
  • Oestrogen-progestogen contraceptives
  • Hormone replacement therapy (HRT) (oestrogen-progestogen)
  • X radiation and gamma-radiation
  • Body fatness [b]
  • Adult attained height
  • Adult weight gain [b]
 
'Limited' or 'Probable' evidence
  • Digoxin
  • HRT (oestrogen-only)
  • Ethylene oxide
  • Polychlorinated biphenyls
  • Shiftwork that involves circadian disruption
  • Tobacco smoking
  • Body fatness[c]
  • Greater birth weight [c]
  • Body fatness [c]
  • Body fatness in young adulthood [b]
  • Breastfeeding
  • Physical activity [b,e]
  • Vigorous physical activity [c]

International Agency for Research on Cancer (IARC) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifications.

a IARC classification does not specify menopausal status, WCRF/AICR classifies evidence on alcoholic drinks as convincing for post-menopausal and probable for pre-menopausal breast cancer; b Post-menopausal breast cancer only; c Pre-menopausal breast cancer only; d IARC classifies evidence on body fatness in males as limited; e Includes vigorous, occupational, recreational, walking, and household activity.

References

  1. Parkin DM, Boyd L, Walker LC. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer 2011;105(S2):S77-S81. 
  2. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118*.  Accessed June 2017.
  3. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794-8.
  4. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed June 2017.
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Sex hormones

Many breast cancer risk factors are associated with higher levels of sex hormones, and it is thought to be by this mechanism that they are linked with breast cancer risk.[1] Sex hormones (also known as sex steroids) include oestrogen, progesterone and testosterone.

In post-menopausal women, breast cancer risk is around twice as high in those with the highest sex hormone levels (including oestradiol, oestriol, androstenedione and testosterone) compared with the lowest, a pooled analysis of cohort studies showed.[2]

In pre-menopausal women, breast cancer risk is not significantly associated with oestrogen levels, a meta-analysis and the EPIC cohort study have shown.[3,4] Pre-menopausal breast cancer risk is 56% higher in those with the highest serum testosterone levels compared with the lowest, whilst other sex hormones show no clear association, EPIC showed.[4]

Breast density

Breast cancer risk is up to 3-5 times higher in women with the most dense breasts (higher percentage non-fatty tissue) compared with the least dense, meta- and pooled analyses have shown.[5,6]

Dense breasts are also associated with an increased risk of in situ breast carcinoma.[7] Breast density is generally higher in younger, pre-menopausal women with lower body mass index (BMI) and lower parity, but there is also a genetic element.[8,9] Sex hormone levels do not appear to explain the association between breast density and breast cancer risk.[10-12]

References

  1. Endogenous Hormones Breast Cancer Collaborative Group. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 2011;105 (5):709-22. 
  2. Key T, Appleby P, Reeves G, et al. Predictors of early death in female patients with breast cancer in the UK: a cohort study. J Natl Cancer Inst 2002;94(8):606- 16. 
  3. Walker K, Bratton DJ, Frost C. Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis. Br J Cancer 2011;105(9):1451-57.
  4. Kaaks R, Tikk K, Sookthai D, et al. Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort. Int J Cancer 2013;doi: 10.1002/ijc.28528. 
  5. Pettersson A, Graff RE, Ursin G, et al. Mammographic density phenotypes and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 2014;106(5).
  6. McCormack VA, dos Santos Silva I. Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: A Meta- analysis. Cancer Epidem Biomar Prev 2006;15(6):1159-69. 
  7. Bertrand KA, Tamimi RM, Scott CG, et al. Mammographic density and risk of breast cancer by age and tumor characteristics. Breast Cancer Res 2013;15(6):R104. 
  8. Boyd NF, Dite GS, Stone J, et al. Heritability of Mammographic Density, a Risk Factor for Breast Cancer. New Engl J Med 2002;347(12):886-94.
  9. Ursin G, Lillie EO, Lee E, et al. The Relative Importance of Genetics and Environment on Mammographic Density. Cancer Epidem Biomar Prev 2009;18(1):102-12. 
  10. Tamimi RM, Byrne C, Colditz GA, et al. Endogenous Hormone Levels, Mammographic Density, and Subsequent Risk of Breast Cancer in Postmenopausal Women. J Natl Cancer Inst 2007;99(15):1178-87.
  11. Varghese JS, Smith PL, Folkerd E, et al. The Heritability of Mammographic Breast Density and Circulating Sex-Hormone Levels: Two Independent Breast Cancer Risk Factors. Cancer Epidem Biomar Prev 2012;21(12):2167-75. 
  12. Schoemaker MJ, Folkerd EJ, Jones ME, et al. Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study. Br J Cancer. 2014 Apr 1;110(7):1898-907. ​
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Some reproductive factors modify sex hormone levels; reduction in overall oestrogen exposure may partly explain the link between reproductive factors and breast cancer risk.

Older age at first giving birth

Breast cancer risk increases by 3% for each year older a woman is when she first gives birth, a meta-analysis showed.[1] The association may be limited to ER/PR-positive tumours.[2-4] ER/PR-positive breast cancer risk is 15% higher in women who first gave birth at an older age, compared with those who did so at a younger age, a meta-analysis showed.[4] HER2-positive and triple-negative breast cancers are not associated with age at first birth.[4]

Conversely among BRCA1 mutation carriers, breast cancer risk may be lower in those who are older at first birth, meta-analyses have shown;[5,6] among BRCA2 carriers, breast cancer risk is not associated with age at first birth.[5,6]

Younger age at menarche

Breast cancer risk increases by 5% for each year younger at menarche (first menstrual period), a meta-analysis has shown.[7] The association is stronger for oestrogen receptor (ER)-positive and progesterone receptor (PR)-positive tumours than for ER- and PR-negative tumours.[2] Breast cancer risk may be higher in women whose breast development started at a younger age, a cohort study indicates.[8]

Among BRCA1 mutation carriers too, breast cancer risk may be higher in those who are younger at menarche, a meta-analysis showed; among BRCA2 carriers, breast cancer risk is not associated with age at menarche.[5,6]

Older age at menopause

Breast cancer risk increases by around 3% for each year older at menopause, a meta-analysis has shown.[7] Post-menopausal women (natural menopause or induced by surgery) have a lower risk of breast cancer than pre-menopausal women of the same age and childbearing pattern, a meta-analysis showed.[7]
Reproductive organ surgery

Breast cancer risk is not associated with tubal sterilisation, a meta-analysis showed.[9] Breast cancer risk is 24-41% lower in women who have hysterectomy and oophorectomy before menopause, compared with women who do not have these surgeries, a pooled analysis and case-control study showed.[10,11] Hysterectomy and oophorectomy after menopause may be associated with increased breast cancer risk if oestrogen therapy is used after the surgery, a pooled analysis showed.[10]

Having children

Breast cancer risk decreases by 7% with each live birth, meta-analyses have shown.[1,2] Breast cancer risk may not be associated with twin pregnancy, a meta-analysis showed.[12] ER/PR-positive breast cancer risk is 25% lower in women who have had children compared with those who have not, a meta-analysis showed.[4] HER2-positive and triple-negative breast cancer is not associated with parity.[4]

The association between parity and breast cancer may vary by tumour types, with the largest risk reduction for mucinous tumours, and a risk increase for medullary tumours, a cohort study indicates.[13]

Conversely among BRCA1/2 mutation carriers, breast cancer risk is not associated with parity, one meta-analysis showed,[5] though another showed a decreased risk with higher parity.[6]

References

  1. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease. Lancet 2002;360(9328):187-95.  
  2. Ma H, Bernstein L, Pike MC, et al. Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res 2006;8:R43. 
  3. Ritte R, Tikk K, Lukanova A, et al. Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study. BMC Cancer. 2013 Dec 9;13:584. 
  4. Lambertini M, Santoro L, Del Mastro L, et al. Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies. Cancer Treat Rev. 2016 Sep;49:65-76.
  5. Pan H, He Z, Ling L, et al. Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: Results from ten studies. Cancer Epidemiol. 2014 Feb;38(1):1-8. 
  6. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 2014;106(6):dju091.
  7. Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012;13(11):1141-51.
  8. Bodicoat DH, Schoemaker MJ, Jones ME, et al. Timing of pubertal stages and breast cancer risk: the Breakthrough Generations Study. Breast Cancer Res. 2014 Feb 4;16(1):R18.
  9. Gaudet MM, Patel AV, Sun J, et al. Tubal sterilization and breast cancer incidence: results from the cancer prevention study II nutrition cohort and meta-analysis. Am J Epidemiol. 2013 Mar 15;177(6):492-9.
  10. Nichols HB, Trentham-Dietz A, Newcomb PA, et al. Postoophorectomy estrogen use and breast cancer risk. Obstet Gynecol. 2012 Jul;120(1):27-36.
  11. Press DJ, Sullivan-Halley J, Ursin G, et al. Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the women's contraceptive and reproductive experiences study. Am J Epidemiol. 2011 Jan 1;173(1):38-47.
  12. Kim H, Woo O, Park K, et al. The relationship between twin births and maternal risk of breast cancer: a meta-analysis. Breast Cancer Res Treat 2012;131(2):671-77. 
  13. Reeves GK, Pirie K, Green J, et al. Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis. Br J Cancer 2009;100(3):538-44.

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International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1]  An estimated 1% of female breast cancers in the UK are linked to oral contraceptives (OCs); because breast cancer risk is generally low in the OC-using population (typically younger women), OC-related risk contributes a relatively small number of additional cases.[2]

OCs contain synthetic sex hormones, which may explain the link between OC use and breast cancer risk.

Current users of OCs have around 24% higher breast cancer risk compared to never users, a meta-analysis showed.[3] However, breast cancers in OC users tend to be less advanced compared with those in OC never-users.[3] The relative risk of breast cancer declines after OC cessation, such that 10 years after cessation no excess risk remains.[3,4] Breast cancer risk does not appear to increase with longer duration of OC use,[3,4] however, younger age at first OC use is associated with a larger increase in breast cancer risk.[3]

The risk associated with OC use appears to be similar across OC formulations (which have changed considerably over time), family history, BRCA carrier status (though some evidence of no association with OC use in BRCA1/2 mutation carriers), and ethnicity.[3,5,6]

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International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1] Hormone replacement therapy (HRT) contains synthetic sex hormones, which may explain the link between HRT use and breast cancer risk. An estimated 3% of female breast cancers in the UK are linked to HRT use.[2]

HRT contains synthetic sex hormones, which may explain the link between HRT use and breast cancer risk.

Breast cancer risk is 55-100% higher in oestrogen-progestogen HRT (combined HRT) current users versus never users, cohort studies have shown.[3,4]

Breast cancer risk is also higher in oestrogen-only HRT users, though to a lesser extent than with combined HRT, cohort studies have shown.[3,5-9]

Breast cancer risk is not associated with past HRT use 5 years or longer ago, cohort studies have shown.[3,10] Breast cancer risk among current HRT users increases with duration of use, and with lower body mass index (BMI).[3,5,10] Breast cancer risk among HRT users may vary with previous use of OCs, but evidence remains unclear.[11-13]

Breast cancer risk does not appear to be increased by use of phytoestrogens (plant-derived chemicals used by some women as an alternative to HRT), a meta-analysis showed;[14] however the efficacy of phytoestrogens for relieving menopausal symptoms remains unclear.[15]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118.  Accessed June 2017.
  2. Parkin DM. Cancers attributable to exposure to hormones in the UK in 2010. Br J Cancer 2011;105(S2):S42-S48.
  3. Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362(9382):419-27.
  4. Chlebowski RT, Manson JE, Anderson GL, et al. Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. J Natl Cancer Inst 2013;105(8):526-35.
  5. Reeves GK, Beral V, Green J, et al. Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 2006;7(11):910-18.
  6. Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000;283(4):485-91.
  7. Flesch-Janys D, Slanger T, Mutschelknauss E, et al. Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy. Int J Cancer 2008;123(4):933- 41.
  8. Magnusson C, Baron JA, Correia N, et al. Breast- cancer risk following long-term oestrogen- and oestrogen-progestin- replacement therapy. Int J Cancer 1999;81(3):339-44.
  9. Ross RK, Paganini-Hill A, Wan PC, et al. Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin. J Natl Cancer Inst 2000;92(4):328-32.
  10. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 1997;350(9084):1047-59.
  11. Thorbjarnardottir T, Olafsdottir EJ, Valdimarsdottir UA, et al. Oral contraceptives, hormone replacement therapy and breast cancer risk: A cohort study of 16 928 women 48 years and older. Acta Oncol. 2014 Jan 24.
  12. Lund E, Bakken K, Dumeaux V, et al. Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study. Int J Cancer. 2007 Aug 1;121(3):645-8.
  13. Norman SA, Berlin JA, Weber AL, et al. Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women. Cancer Causes Control. 2003 Dec;14(10):933-43.
  14. Tempfer CB, Froese G, Heinze G, et al. Side effects of phytoestrogens: a meta-analysis of randomized trials. Am J Med. 2009 Oct;122(10):939-46.e9.
  15. Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013 Dec 10;12:CD001395. 
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Hereditary factors explain only around a quarter of breast cancer risk.[1] Breast cancer risk is not associated with breast cancer in an adoptive parent, and does not vary with time since the family member was diagnosed, indicating genetic/biological factors or increased diagnostic activity rather than environmental factors underpin familial clustering of breast cancer cases.[2,3]

Family history

Breast cancer risk is around twice higher in women with one first-degree relative with breast cancer, versus women with no first-degree relatives with the disease, meta- and pooled-analyses have shown.[4,5] The risk is higher still with a larger number of affected first-degree relatives, or relatives affected aged under 50.[4,5] ER-positive or ER-negative breast cancer risk are associated to a similar extent with family history.[6]

Over 85% of women with a first-degree relative with breast cancer will never develop breast cancer themselves.[4] 87% of women with breast cancer have no first-degree relatives with the disease.[4]

BRCA1 and BRCA2

BRCA1 and BRCA2 mutations confer a high risk of breast cancer in carriers (high-penetrance). Women with a BRCA1 or BRCA2 mutation have a 45-65% chance of developing breast cancer by age 70.[7] BRCA1/2 mutation-carriers have higher breast cancer risk compared with the general population in all age groups.[1] BRCA2-negative women with a BRCA2-carrying first-degree relative may also have increased breast cancer risk, a small UK cohort study showed.[8] Higher sex hormone levels in BRCA mutation carriers may explain some of the increased risk.[9]

Breast cancer risk in BRCA mutation carriers may be modified by other factors including family history (breast cancer risk among BRCA2 mutation carriers is 70% higher for each first-degree relative with breast cancer aged 50 or younger, versus BRCA2 mutation carriers with no such family history; breast cancer risk in BRCA1 mutation carriers is not associated with family history),[10] previous breast cancer,[11] and lifestyle factors (indicated by higher risk in BRCA mutation carriers born post-1950 versus pre-1950[12]).

BRCA1 and BRCA2 mutations are uncommon, though this varies by ethnicity/country of origin.[13] They affect an estimated 0.11% and 0.12% of the general population respectively,[14] equating to around 1 in 450 women carrying a mutation. Their relative rarity means BRCA1 and BRCA2 mutations probably account for around 2% of all breast cancers overall.[14-16] However, they explain around 15-20% of cases with first-degree family history.[13]

NHS screening for BRCA1 and BRCA2 mutation is available to people who meet eligibility criteria relating to their family history.

References

  1. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland. New Engl J Med 2000;343(2):78-85. 
  2. Zöller B, Li X, Sundquist J, Sundquist K. Familial transmission of prostate, breast and colorectal cancer in adoptees is related to cancer in biological but not in adoptive parents: a nationwide family study. Eur J Cancer 2014;50(13):2319-27. 
  3. Lee M, Czene K, Rebora P, et al. Patterns of changing cancer risks with time since diagnosis of a sibling. Int J Cancer 2015 April 15:136(8):1948-56
  4. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease. Lancet 2001;358 (9291):1389-99.
  5. Pharoah PD, Day NE, Duffy S, et al. Family history and the risk of breast cancer: A systematic review and meta- analysis. Int J Cancer 1997;71(5):800-09. 
  6. Mavaddat N, Pharoah P, Blows F, et al. Familial relative risks for breast cancer by pathological subtype: a population-based cohort study. Breast Cancer Res 2010;12(1):R10.
  7. Antoniou A, Pharoah PDP, Narod S, et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. Am J Hum Genet 2003;72(5):1117-30.
  8. Evans DGR, Ingham SL, Buchan I, et al. Increased Rate of Phenocopies in All Age Groups in BRCA1/BRCA2 Mutation Kindred, but Increased Prospective Breast Cancer Risk Is Confined to BRCA2 Mutation Carriers. Cancer Epidem Biomar Prev 2013;22(12):2269-76.  
  9. Widschwendter M, Rosenthal AN, Philpott S, et al. The sex hormone system in carriers of BRCA1/2 mutations: a case-control study. Lancet Oncol. 2013;14(12):1226-32.
  10. Metcalfe K, Lubinski J, Lynch HT, et al. Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations. J Natl Cancer Inst 2010;102(24):1874-8.
  11. Narod SA, Tung N, Lubinski J, et al. A prior diagnosis of breast cancer is a risk factor for breast cancer in BRCA1 and BRCA2 carriers. Curr Oncol 2014;21(2):64-8. 
  12. Tea MK, Kroiss R, Muhr D, et al. Central European BRCA2 mutation carriers: Birth cohort status correlates with onset of breast cancer. Maturitas 2013;77(1):68-72.
  13. Turnbull C, Rahman N. Genetic Predisposition to Breast Cancer: Past, Present, and Future. Ann Rev Genom Hum Genet 2008;9(1):321-45.
  14. Peto J, Collins N, Barfoot R, et al. Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer. J Natl Cancer Inst 1999;91(11):943- 49. 
  15. Easton DF. How many more breast cancer predisposition genes are there? Breast Cancer Res 1999;1(1):14 - 17.
  16. Ford D, Easton DF, Stratton M, et al. Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer Families. Am J Hum Genet 1998;62(3):676-89.
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International Agency for Research on Cancer (IARC) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classify the role of this risk factor in cancer development.[1,2]

Greater body fatness is associated with higher sex hormone levels (fatty tissue produces more oestrogen), which may partly explain the link between body fatness and breast cancer risk.[3] Abdominal fatness and weight gain during adulthood are thought to be more accurate measures of fatty tissue levels, compared with body mass index (BMI), because BMI includes lean tissue mass.[4] An estimated 9% of female breast cancers in the UK are linked to excess body weight.[5]

Post-menopausal

Breast cancer among post-menopausal women is 12-13% higher in those who are overweight (body mass index [BMI] 25-29.9) and 16-20% higher in those who are obese (BMI 30+), compared with those who are underweight and normal weight (BMI of less than 25), meta-analyses have shown.[6,7] The increased risk may be limited to ER- and PR-positive tumours,[6-8] and women who have never used oestrogen-progestogen hormone replacement therapy.

Breast cancer risk among post-menopausal women is 50% higher in those with the highest waist-to-hip ratio (WHR, a measure of abdominal obesity) versus the lowest WHR, a meta-analysis showed.[9] However the association with WHR or waist circumference probably reflects the effect of BMI, rather than a specific effect of abdominal obesity.[10,11]

Breast cancer risk among post-menopausal women not using HRT is 50% higher in those with the highest levels of adulthood weight gain, versus those with the lowest, a pooled analysis showed.[12] The risk increase is larger for ER- and PR- positive tumours (133% increase) than ER- and PR-negative tumours (34% increase), a meta-analysis showed.[4]

Pre-menopausal

Breast cancer risk among pre-menopausal women is slightly lower in those who are overweight or obese, compared with healthy weight, meta-analyses have shown.[7,8,13,14] However this may be limited to Caucasians and Africans (not Asians), and to ER- and PR-positive tumours.[6-7,13,14]

Breast cancer risk among pre-menopausal women is 79% higher in those with the highest waist-to-hip ratio (WHR) versus those with the lowest, a meta-analysis showed.[9] Breast cancer risk is 8% higher per 0.1 unit WHR increase.[14]

Breast cancer risk among pre-menopausal women is not associated with weight gain during adulthood (since age 20), a pooled-analysis showed.[12] This may vary by hormone receptor status and parity, a case control study indicated.[15] Breast cancer risk among pre-menopausal women may be higher in those who gain weight during middle adulthood (age 40-50) versus those who do not, a cohort study showed.[16]

Breast cancer risk is higher in women with a higher birth weight, with a stronger effect for pre-menopausal breast cancer, meta-analyses have shown.[17-19] Higher in utero oestrogen levels probably explain this association; birth size is not associated with breast cancer risk in women with a male twin, who are also exposed to male sex hormones in utero.[20]

Males

Male breast cancer is 30% higher in men with the highest body mass index (BMI) versus those with the lowest.[21]

References

  1. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794-8.
  2. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed June 2017.
  3. Endogenous Hormones Breast Cancer Collaborative Group. Body Mass Index, Serum Sex Hormones, and Breast Cancer Risk in Postmenopausal Women. J Natl Cancer Inst 2003;95(16):1218-26.
  4. Vrieling A, Buck K, Kaaks R, et al. Adult weight gain in relation to breast cancer risk by estrogen and progesterone receptor status: a meta-analysis. Breast Cancer Res Treat 2010;123 (3):641-49. 
  5. Parkin DM, Boyd L. Cancers attributable to overweight and obesity in the UK in 2010. Br J Cancer 2011;105(S2):S34-S37.
  6. Cheraghi Z, Poorolajal J, Hashem T, et al. Effect of Body Mass Index on Breast Cancer during Premenopausal and Postmenopausal Periods: A Meta-Analysis. PLoS ONE 2012;7(12):e51446.  
  7. Munsell MF, Sprague BL, Berry DA, et al. Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev. 2014;36(1):114-36.
  8. Suzuki R, Orsini N, Saji S, et al. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—A meta-analysis. Int J Cancer 2009;124(3):698-712. 
  9. Connolly BS, Barnett C, Vogt KN, et al. A Meta- Analysis of Published Literature on Waist-to-Hip Ratio and Risk of Breast Cancer. Nutr Cancer 2002;44(2):127-38. 
  10. Harvie M, Hooper L, Howell AH. Central obesity and breast cancer risk: a systematic review. Obes Rev 2003;4 (3):157-73.  
  11. Gaudet MM, Carter BD, Patel AV, et al. Waist circumference, body mass index, and postmenopausal breast cancer incidence in the Cancer Prevention Study-II Nutrition Cohort. Cancer Causes Control. 2014;25(6):737-45. 
  12. Lahmann PH, Schulz M, Hoffmann K, et al. Long- term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC). Br J Cancer 2005;93 (5):582-89. 
  13. Yang XR, Chang-Claude J, Goode EL, et al. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies. J Natl Cancer Inst 2011;103(3):250-63.
  14. Amadou A, Ferrari P, Muwonge R, et al. Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review and dose-response meta- analysis. Obes Rev 2013;14(8):665-78. 
  15. Kawai M, Malone KE, Tang MT, et al. Height, body mass index (BMI), BMI change, and the risk of estrogen receptor-positive, HER2-positive, and triple-negative breast cancer among women ages 20 to 44 years. Cancer. 2014 Feb 5. 
  16. Emaus MJ, van Gils CH, Bakker MF, et al. Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study. Int J Cancer 2014. 
  17. Xue F, Michels KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 2007;8(12):1088-100.
  18. Park S, Kang D, McGlynn K, et al. Intrauterine environments and breast cancer risk: meta- analysis and systematic review. Breast Cancer Res 2008;10(1):R8.
  19. Michels KB, Xue F. Role of birthweight in the etiology of breast cancer. Int J Cancer 2006;119 (9):2007-25. 
  20. Hajiebrahimi M, Bahmanyar S, Oberg S, et al. Breast cancer risk in opposite-sexed twins: influence of birth weight and co-twin birth weight. J Natl Cancer Inst. 2013;105(23):1833-6.
  21. Brinton LA, Cook MB, McCormack V, et al. Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst. 2014 Mar 1;106(3):djt465. 
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Women with in situ breast carcinoma have between double and triple the breast cancer risk of the general female population, cohort studies have found.[1,2] Among women with in situ breast carcinoma, cancer is similarly common in the breast with the in situ carcinoma as in the opposite breast.[2]

Ductal carcinoma in situ (DCIS) is considered a necessary precursor for breast cancer, meaning most breast cancer cases are thought to originate as DCIS, however not all DCIS develop into breast cancer.[3] LCIS is associated with increased breast cancer risk but is not thought to be necessary for breast cancer to develop.[3] DCIS overall is associated with 40-100% increased breast cancer risk, though risk does not appear to be elevated in all DCIS subtypes, US cohort studies indicate.[4,5]

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International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1] An estimated 1% of female breast cancers in the UK are linked to radiation exposure, with medical radiation and natural (background) radiation each accounting for around half the cases.[2]

Radiotherapy

Breast cancer risk is increased after several types previous cancer, with radiotherapy an important factor in this association. Breast cancer risk is non-significantly increased in survivors of childhood solid cancer who received radiotherapy, compared with those who did not receive radiotherapy.[3] Breast cancer risk is 9-11% higher in women who received radiotherapy for cancer in the opposite breast, compared with women who had surgery alone.[4,5]

An estimated 11% of the radiotherapy-associated second cancers in the UK each year are breast cancers.[6]

Diagnostic radiology

Diagnostic radiology involves much lower radiation doses than radiotherapy.

An estimated 0.1% of breast cancers in women under 75 are caused by diagnostic x-rays.[7] Breast cancer risk among women with BRCA1/2 mutation may be higher in those who have received diagnostic radiation, but evidence is mixed, a systematic review showed.[8]

An estimated 0.03-0.06% of breast cancers are caused by receiving a mammogram Open a glossary item[4] Breast cancer risk among women with BRCA1/2 mutation is not associated with receiving mammograms a meta-analysis showed.[8]

Breast cancer risk is not associated with receiving computed tomography (CT) scans in childhood or adolescence, a cohort study showed.[9]

References

  1.  International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118.  Accessed June 2017.
  2. Parkin DM, Darby SC. Cancers in 2010 attributable to ionising radiation exposure in the UK. Br J Cancer 2011;105(S2):S57-S65. 
  3. Reulen RC, Frobisher C, Winter DL, et al. Long- term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA 2011;305(22):2311-19.
  4. Berrington de Gonzalez A, Curtis RE, Gilbert E, et al. Second solid cancers after radiotherapy for breast cancer in SEER cancer registries. Br J Cancer 2009;102(1):220-26.
  5. Neta G, Anderson W, Gilbert E, et al. Variation in the risk of radiation-related contralateral breast cancer by histology and estrogen receptor expression in SEER. Breast Cancer Res Treat 2012;131(3):1021-27. 
  6. Maddams J, Parkin DM, Darby SC. The cancer burden in the United Kingdom in 2007 due to radiotherapy. Int J Cancer 2011;129 (12):2885-93. 
  7. de González AB, Darby S. Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. Lancet 2004;363(9406):345-51. 
  8. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 2014;106(6):dju091. 
  9. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680 000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 2013;346.  
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International Agency for Research on Cancer (IARC) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classify the role of this risk factor in cancer development.[1,2] An estimated 6% of female breast cancers in the UK are linked to alcohol consumption.[3]

Breast cancer risk is 7-12% higher per unit of alcohol per day, meta-analyses have shown.[4-6] Breast cancer risk is 4% higher in women who consume up to 12.5g (1.5 units) of alcohol per day, 23% higher in women who consume around 12.5-50g (1.5-6 units) of alcohol per day, and 60% higher in women who consume 50g+ (6+ units) of alcohol per day, compared with non-drinkers, a meta-analysis showed.[7]

Breast cancer risk among BRCA1/2 mutation carriers is not associated with alcohol intake, a meta-analysis showed.[8]

Alcohol consumption is associated with higher levels of sex hormones, which may partly explain the link between alcohol and breast cancer risk.[9]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118.  Accessed June 2017.
  2. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed June 2017.
  3. Parkin D.M. Cancers attributable to consumption of alcohol in the UK in 2010. Br J Cancer 2011;105(S2):S14-S18. 
  4. Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease. Br J Cancer 2002;87(11):1234-45.
  5. Allen NE, Beral V, Casabonne D, et al. Moderate Alcohol Intake and Cancer Incidence in Women. J Natl Cancer Inst 2009;101(5):296-305.
  6. Key J, Hodgson S, Omar R, et al. Meta- analysis of Studies of Alcohol and Breast Cancer with Consideration of the Methodological Issues. Cancer Cause Control 2006;17(6):759-70 
  7. Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer. 2015 Feb 3;112(3):580-93.
  8. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 2014;106(6):dju091. 
  9. Rinaldi S, Peeters PHM, Bezemer ID, et al. Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition. Cancer Cause Control 2006;17(8):1033-43. 
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International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1]

Tobacco smoking is associated with higher levels of sex hormones, which may partly explain the link between tobacco and breast cancer risk.[2]

Breast cancer risk is 7-13% higher in current smokers, and 6-9% higher in former smokers, compared with never-smokers, meta- and pooled analyses have shown;[3-5] however confounding by alcohol is possible.

Breast cancer risk increases with years since starting smoking prior to first giving birth in ever smokers, compared with never smokers.[4] The effect of smoking may be limited to non-obese women,[5] women who drink alcohol,[4] women without a family history of breast cancer,[6] and ER-positive (not triple negative) breast cancer.[3,4,8,9]

Breast cancer risk among BRCA1 mutation carriers is not associated with smoking, a meta-analysis showed; breast cancer risk among BRCA2 mutation carriers is higher in smokers.[10]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118 .  Accessed June 2017.
  2. Endogenous Hormones Breast Cancer Collaborative Group. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 2011;105 (5):709-22. 
  3. Gaudet MM, Gapstur SM, Sun J, et al. Active Smoking and Breast Cancer Risk: Original Cohort Data and Meta-Analysis. J Natl Cancer Inst 2013;105(8):515-25. 
  4. Gaudet MM, Carter BD, Brinton LA, et al. Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies. Int J Epidemiol. 2016 Dec 28. pii: dyw288.
  5. Macacu A, Autier P, Boniol M, et al. Active and passive smoking and risk of breast cancer: a meta-analysis. Breast Cancer Res Treat. 2015 Nov;154(2):213-24.
  6. Luo J, Horn K, Ockene JK, et al. Interaction Between Smoking and Obesity and the Risk of Developing Breast Cancer Among Postmenopausal Women: The Women's Health Initiative Observational Study. Am J Epidemiol 2011;174(8):919-28. 
  7. Nyante SJ, Gierach GL, Dallal CM, et al. Cigarette smoking and postmenopausal breast cancer risk in a prospective cohort. Br J Cancer. 2014;110(9):2339-47.
  8. Kawai M, Malone KE, Tang MT, et al. Active smoking and the risk of estrogen receptor-positive and triple-negative breast cancer among women ages 20 to 44 years. Cancer. 2014 Apr 1;120(7):1026-34.
  9. Kabat GC, Kim M, Phipps AI, et al. Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women. Cancer Causes Control. 2011 May;22(5):775-83. 
  10. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 2014;106(6):dju091.
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World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifies the role of this risk factor in cancer development.[1] An estimated 3% of female breast cancers in the UK are linked to women breastfeeding each of their children for fewer than six months.[2]

Breast cancer risk is 22% lower in women who have ever breastfed, versus those who have never done so, a meta-analysis showed; risk decreases further with longer breastfeeding duration.[3] ER/PR-positive breast cancer risk is 23% lower in women who have ever breastfed, versus those who have never done so, a meta-analysis showed.[4] Triple-negative breast cancer risk is 21% lower in women who have ever breastfed, versus those who have never done so.[4] HER2-positive breast cancer is not associated with breastfeeding.[4]

Among BRCA1 mutation carriers, breast cancer risk may be lower in those who breastfeed for at least 1-2 years, a meta-analysis showed; among BRCA2 carriers, breast cancer risk is not associated with breastfeeding.[5,6]

References

  1. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed June 2017.
  2. Parkin DM. Cancers attributable to reproductive factors in the UK in 2010. Br J Cancer 2011;105(S2):S73-S76.
  3. Chowdhury R, Sinha B, Sankar MJ, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr. 2015 Dec;104(467):96-113.
  4. Lambertini M, Santoro L, Del Mastro L, et al. Reproductive behaviors and risk of developing breast cancer according to tumor subtype: A systematic review and meta-analysis of epidemiological studies. Cancer Treat Rev. 2016 Sep;49:65-76.
  5. Pan H, He Z, Ling L, et al. Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: Results from ten studies. Cancer Epidemiol. 2014 Feb;38(1):1-8. 
  6. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst 2014;106(6):dju091. 
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World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifies the role of this risk factor in cancer development.[1]

Higher levels of physical activity are associated with lower levels of sex hormones, which may partly explain the link between physical activity and breast cancer risk. An estimated 3% of female breast cancers in the UK are linked to inadequate physical activity (less than 150 minutes moderate physical activity per week).[2]

Breast cancer risk is 13-25% lower in the most active (including recreational and household activity) women compared with the least, meta-analyses have shown.[3-5] Breast cancer risk decreases by 5% for every 2 hours per week increment in recreational activity (moderate and vigorous), a meta-analysis showed.[4]

Light-intensity activity may be insufficient to reduce breast cancer risk, a Canadian case-control study indicated.[6]

References

  1. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed June 2017.
  2. Parkin DM. Cancers attributable to inadequate physical exercise in the UK in 2010. Br J Cancer 2011;105(S2):S38-S41. 
  3. Friedenreich CM, Neilson HK, Lynch BM. State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer 2010;46(14):2593-604. 
  4. Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat 2013;137(3):869-82.
  5. Shi Y, Li T, Wang Y, et al. Household physical activity and cancer risk: a systematic review and dose-response meta-analysis of epidemiological studies. Sci Rep. 2015. doi: 10.1038/srep14901.
  6. Kobayashi LC, Janssen I, Richardson H, et al. A case- control study of lifetime light intensity physical activity and breast cancer risk. Cancer Cause Control 2013;25(1):133-40. 
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Acknowledgements

We are grateful to the many organisations across the UK which collect, analyse, and share the data which we use, and to the patients and public who consent for their data to be used. Find out more about the sources which are essential for our statistics.

Cancer stats explained

See information and explanations on terminology used for statistics and reporting of cancer, and the methods used to calculate some of our statistics.

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