Breast cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2] Mirdula Sharma, MBBS [3]

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Overview

Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol.

Common Risk Factor

Family history

  • Although less than 15 percent of women with breast cancer have a positive family history, a woman’s risk of breast cancer nearly doubles if she has a first-degree relative (mother, sister, daughter) with the history of breast cancer.
  • Around 5-10 percent of breast cancers are due to inherited gene mutations either from one’s mother or father.
  • BRCA1 and BRCA2 mutations are the most common genetic abnormality in breast cancer.[1]
  • Women with a BRCA1 and BRCA2 mutation have up to a 72% and 69% lifetime risk of developing breast cancer respectively.
  • Patients with BRCA1 or BRCA2 are often younger compared to their counterparts without these mutations.
  • There is also an increased risk of developing ovarian cancer risk in subjects with mutated BRCA1 andBRCA2.
  • Although BRCA1mutations are barely correlated to breast cancer in men, a 6.8% increased risk of developing breast cancer has been observed in men with BRCA2 mutations.
  • We should keep in mind that around 85% of women with breast cancers have no family history.
  • Sensitivity of commercial BRCA mutation tests like 23andMe is debated. For example 23andMe’s testing formula is based on solely three genetic variants, most prevalent among Ashkenazi Jews, while most people carry other mutations of the gene. This will result in false negative results. As accurately stated by Prof. Mary-Claire King, who discovered the BRCA1, “The F.D.A. should not have permitted this out-of-date approach to be used for medical purposes. Misleading, falsely reassuring results from their incomplete testing can cost women’s lives.”

A personal history of breast cancer or benign (noncancer) breast disease[2]

  • Women with any of the following have an increased risk of breast cancer:
  • A personal history of invasive breast cancer, ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS).
  • A personal history of benign (noncancer) breast disease.

A family history of breast cancer

  • Women with a family history of breast cancer in a first-degree relative (mother, sister, or daughter) have an increased risk of breast cancer.[3]

Inherited gene changes

  • Women who have inherited changes in the BRCA1 and BRCA2 genes or in certain other genes have a higher risk of breast cancer, ovarian cancer, and maybe colon cancer.
  • The risk of breast cancer caused by inherited gene changes depends on the type of gene mutation, family history of cancer, and other factors.

Dense breasts

  • Having breast tissue that is dense on a mammogram is a factor in breast cancer risk.[4]
  • The level of risk depends on how dense the breast tissue is.
  • Women with very dense breasts have a higher risk of breast cancer than women with low breast density.
  • Increased breast density is often an inherited trait, but it may also occur in women who:
  • Have not had children
  • Have the first pregnancy late in life
  • Take postmenopausal hormones (HRT)
  • Drink alcohol

Exposure of breast tissue to estrogen made in the body

  • Estrogen is a hormone made by the body. It helps the body develop and maintain female sex characteristics. Being exposed to estrogen over a long time may increase the risk of breast cancer. Estrogen levels are highest during the years a woman is menstruating.[5]
  • A woman's exposure to estrogen is increased in the following ways:
  • Early menstruation: Beginning to have menstrual periods at age 11 or younger increases the number of years the breast tissue is exposed to estrogen.
  • Starting menopause at a later age: The more years a woman menstruates, the longer her breast tissue is exposed to estrogen.
  • Older age at first birth or never having given birth: Because estrogen levels are lower during pregnancy, breast tissue is exposed to more estrogen in women who become pregnant for the first time after age 35 or who never become pregnant.

Taking hormone therapy for symptoms of menopause

  • Hormones, such as estrogen and progesterone, can be made into a pill form in a laboratory. Estrogen, progestin, or both may be given to replace the estrogen no longer made by the ovaries in postmenopausal women or women who have had their ovaries removed. This is called hormone replacement therapy (HRT) or hormone therapy (HT). Combination HRT/HT is estrogen combined with progestin. This type of HRT/HT increases the risk of breast cancer. Studies show that when women stop taking estrogen combined with progestin, the risk of breast cancer decreases.[6]

Radiation therapy to the breast or chest

  • Radiation therapy to the chest for the treatment of cancer increases the risk of breast cancer, starting 10 years after treatment. The risk of breast cancer depends on the dose of radiation and the age at which it is given.[7] The risk is highest if radiation treatment was used during puberty when breasts are forming.
  • Radiation therapy to treat cancer in one breast does not appear to increase the risk of cancer in the other breast.
  • For women who have inherited changes in theBRCA1 and BRCA2 genes, exposure to radiation, such as that from chest x-rays, may further increase the risk of breast cancer, especially in women who were x-rayed before 20 years of age.

Obesity

  • Obesity increases the risk of breast cancer, especially in postmenopausal women who have not used hormone replacement therapy.[8]

Drinking alcohol

  • Drinking alcohol increases the risk of breast cancer. The level of risk rises as the amount of alcohol consumed rises.[9]

Less Common Risk Factors

Tobacco

  • Most studies have not found an increased risk of breast cancer from active tobacco smoking, although a number of studies suggest an increased risk of breast cancer in both active smokers and those exposed to secondhand smoke compared to women who reported no exposure to secondhand smoke.[10]

Radiation

  • Women who have received high-dose ionizing radiation to the chest (for example, as treatments for other cancers) have a relative risk of breast cancer between 2.1 to 4.0.[10]
  • Serial mammography might slightly increase the risk of developing breast cancer in high-risk patients such as patients with a family history of breast cancer and patients with known genetic carcinogenic mutations.
  • According to a recently published study by Jansen-van der Weide et.al. average increased the risk of breast cancer because of low-dose radiation exposure was (OR between 1.3 and 2 with respect to the patients' risk and exposure) observed compared to that of high-risk women not exposed to low-dose radiation.[11]
  • Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8).
  • Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1)
  • A mean of ≥5 exposures (OR = 1.8, 95% CI: 1.1-3.0)
  • When using low-dose radiation among high-risk women, a careful approach is needed, by means of
  • They recommended careful approach in these subgroup of patients as follows:
  • Reducing repeated exposure,
  • Avoidance of exposure at a younger age
  • Using non-ionising screening techniques.
  • According to another study by Diana L. Miglioretti et.al. radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by:[12]
  • Dose variability from screening and resultant diagnostic work-up,
  • Initiation age
  • Screening frequency.
  • Women with large breasts may be at higher risk of radiation-induced breast cancer;
  • However, we should keep in mind that "the benefits of screening outweigh these risks".

Impact of environmental estrogenic mimics

  • Although environmental exposures are not generally cited as risk factors for the disease (except for diet, pharmaceuticals, and radiation), a substantial and growing body of evidence indicates that exposures to certain toxic chemicals and hormone-mimicking compounds, including chemicals used in pesticides, cosmetics, and cleaning products, contribute to the development of breast cancer.
  • A recent Canadian study concluded that female farm workers are three times more likely to have breast cancer.[13]

The increasing prevalence of these substances in the environment may explain the rising incidence of breast cancer, though direct evidence is sparse.

Dioxins

  • Although not well-quantified, there has long been a concern about the risk associated with environmental estrogenic compounds, such as dioxins. [14][15]

Light levels

References

  1. Yoshida K, Miki Y (2004) Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci 95 (11):866-71. PMID: 15546503
  2. Breast Cancer. National Cancer Institute (2016) http://www.cancer.gov/types/breast/patient/breast-prevention-pdq#section/_12 Accessed on January 15, 2016
  3. Brewer HR, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ (2017) Family history and risk of breast cancer: an analysis accounting for family structure. Breast Cancer Res Treat 165 (1):193-200. DOI:10.1007/s10549-017-4325-2 PMID: 28578505
  4. Freer PE (2015) Mammographic breast density: impact on breast cancer risk and implications for screening. Radiographics 35 (2):302-15. DOI:10.1148/rg.352140106 PMID: 25763718
  5. Yue W, Wang JP, Li Y, Fan P, Liu G, Zhang N et al. (2010) Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms. Int J Cancer 127 (8):1748-57. DOI:10.1002/ijc.25207 PMID: 20104523
  6. Howell A, Evans GD (2011) Hormone replacement therapy and breast cancer. Recent Results Cancer Res 188 ():115-24. DOI:10.1007/978-3-642-10858-7_10 PMID: 21253794
  7. Ng AK, Travis LB (2009) Radiation therapy and breast cancer risk. J Natl Compr Canc Netw 7 (10):1121-8. PMID: 19930978
  8. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, Friedman ER, Slingerland JM (2017) Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin 67 (5):378-397. DOI:10.3322/caac.21405 PMID: 28763097
  9. McDonald JA, Goyal A, Terry MB (2013) Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence. Curr Breast Cancer Rep 5 (3):. DOI:10.1007/s12609-013-0114-z PMID: 24265860
  10. 10.0 10.1 ACS (2005). "Breast Cancer Facts & Figures 2005-2006" (PDF). Retrieved 2007-04-26.
  11. Jansen-van der Weide MC, Greuter MJ, Jansen L, Oosterwijk JC, Pijnappel RM, de Bock GH (2010) Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis. Eur Radiol 20 (11):2547-56. DOI:10.1007/s00330-010-1839-y PMID: 20582702
  12. Miglioretti DL, Lange J, van den Broek JJ, Lee CI, van Ravesteyn NT, Ritley D et al. (2016) Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study. Ann Intern Med 164 (4):205-14. DOI:10.7326/M15-1241 PMID: 26756460
  13. Ctv.Ca News Staff (2006-10-12). "Breast cancer more likely in farm workers: study". Ctv.Ca. Retrieved 2007-03-11.
  14. Danjou AM, Fervers B, Boutron-Ruault MC, Philip T, Clavel-Chapelon F, Dossus L (2015) Estimated dietary dioxin exposure and breast cancer risk among women from the French E3N prospective cohort. Breast Cancer Res 17 ():39. DOI:10.1186/s13058-015-0536-9 PMID: 25849111
  15. Warner M, Eskenazi B, Mocarelli P, Gerthoux PM, Samuels S, Needham L et al. (2002) Serum dioxin concentrations and breast cancer risk in the Seveso Women's Health Study. Environ Health Perspect 110 (7):625-8. DOI:10.1289/ehp.02110625 PMID: 12117637
  16. The Independent Avoid breast cancer. Sleep in the dark...

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