Editing Breast cancer (section)

== Risk factors ==
{{Main|Risk factors of breast cancer}}

=== Hormonal ===
Up to 80% of the variation in breast cancer frequency across countries is due to differences in reproductive history
that impact a woman's levels of female sex hormones ([[estrogen]]s).{{sfn|Hayes|Lippman|2022|loc="Clinical, Hormonal, and other Nongenetic Risk Factors"}} Women who [[menarche|begin menstruating]] earlier (before age 12) or who undergo [[menopause]] later (after 51) are at increased risk of developing breast cancer.{{sfn|Britt|Cuzick|Phillips|2020|loc="Non-Genetic Risk Factors"}} Women who give birth early in life are protected from breast cancer – someone who gives birth as a teenager has around a 70% lower risk of developing breast cancer than someone who does not have children.{{sfn|Britt|Cuzick|Phillips|2020|loc="Non-Genetic Risk Factors"}} That protection wanes with higher maternal age at first birth, and disappears completely by age 35.{{sfn|Britt|Cuzick|Phillips|2020|loc="Non-Genetic Risk Factors"}} [[Breastfeed]]ing also reduces one's chance of developing breast cancer, with an approximately 4% reduction in breast cancer risk for every 12 months of breastfeeding experience.{{sfn|Britt|Cuzick|Phillips|2020|loc="Non-Genetic Risk Factors"}} Those who lack functioning [[ovaries]] have reduced levels of estrogens, and therefore greatly reduced breast cancer risk.{{sfn|Hayes|Lippman|2022|loc="Clinical, Hormonal, and other Nongenetic Risk Factors"}}

[[Hormone replacement therapy]] for treatment of [[menopause]] symptoms can also increase a woman's risk of developing breast cancer, though the effect depends on the type and duration of therapy.<ref>{{cite news |title=Research shows some types of HRT are linked to lower risks of breast cancer |date=20 December 2021 |doi=10.3310/alert_48575 }}</ref><ref>{{cite journal | vauthors = Vinogradova Y, Coupland C, Hippisley-Cox J | title = Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases | journal = BMJ | volume = 371 | pages = m3873 | date = October 2020 | pmid = 33115755 | pmc = 7592147 | doi = 10.1136/bmj.m3873 }}</ref> Combined [[progesterone]]/estrogen therapy increases breast cancer risk – approximately doubling one's risk after 6–7 years of treatment (though the same therapy decreases the risk of [[colorectal cancer]]).{{sfn|Hayes|Lippman|2022|loc="Clinical, Hormonal, and other Nongenetic Risk Factors"}} Hormone treatment with estrogen alone has no effect on breast cancer risk, but increases one's risk of developing [[endometrial cancer]], and therefore is only given to women who have undergone [[hysterectomies]].{{sfn|Hayes|Lippman|2022|loc="Clinical, Hormonal, and other Nongenetic Risk Factors"}}

In the 1980s, the [[abortion–breast cancer hypothesis]] posited that [[induced abortion]] increased the risk of developing breast cancer.<ref name="RUSSO_505">{{cite journal | vauthors = Russo J, Russo IH | title = Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence | journal = The American Journal of Pathology | volume = 100 | issue = 2 | pages = 497–512 | date = August 1980 | pmid = 6773421 | pmc = 1903536 | quote = In contrast, abortion is associated with increased risk of carcinomas of the breast. The explanation for these epidemiologic findings is not known, but the parallelism between the DMBA-induced rat mammary carcinoma model and the human situation is striking. ... Abortion would interrupt this process, leaving in the gland undifferentiated structures like those observed in the rat mammary gland, which could render the gland again susceptible to carcinogenesis. }}</ref> This hypothesis was the subject of extensive scientific inquiry, which concluded that neither [[miscarriage]]s nor abortions are associated with a heightened risk for breast cancer.<ref>{{cite journal | vauthors = Beral V, Bull D, Doll R, Peto R, Reeves G | title = Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83 000 women with breast cancer from 16 countries | journal = Lancet | volume = 363 | issue = 9414 | pages = 1007–16 | date = March 2004 | pmid = 15051280 | doi = 10.1016/S0140-6736(04)15835-2 }}</ref>

The use of [[hormonal birth control]] does not cause breast cancer for most women;<ref>{{cite journal |vauthors=Kanadys W, Barańska A, Malm M, Błaszczuk A, Polz-Dacewicz M, Janiszewska M, Jędrych M |date=April 2021 |title=Use of Oral Contraceptives as a Potential Risk Factor for Breast Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies Up to 2010 |journal=International Journal of Environmental Research and Public Health |volume=18 |issue=9 |pages=4638 |doi=10.3390/ijerph18094638 |pmc=8123798 |pmid=33925599 |doi-access=free}}</ref> if it has an effect, it is small (on the order of 0.01% per user–year), temporary, and offset by the users' significantly reduced risk of ovarian and endometrial cancers.<ref name="Chelmow_2020">{{cite journal |vauthors=Chelmow D, Pearlman MD, Young A, Bozzuto L, Dayaratna S, Jeudy M, Kremer ME, Scott DM, O'Hara JS |date=June 2020 |title=Executive Summary of the Early-Onset Breast Cancer Evidence Review Conference |journal=Obstetrics and Gynecology |volume=135 |issue=6 |pages=1457–1478 |doi=10.1097/AOG.0000000000003889 |pmc=7253192 |pmid=32459439}}</ref> Among those with a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.<ref>{{cite journal |vauthors=Gaffield ME, Culwell KR, Ravi A |date=October 2009 |title=Oral contraceptives and family history of breast cancer |journal=Contraception |volume=80 |issue=4 |pages=372–380 |doi=10.1016/j.contraception.2009.04.010 |pmid=19751860}}</ref>

=== Lifestyle ===
{{See also|Alcohol and breast cancer|Risk factors for breast cancer}}

[[File:NIH standard drink comparison.jpg|upright=1.2|alt=Diagram of different sizes, showing how big a single serving of alcohol is for different types of alcoholic beverages|thumb|All types of [[alcoholic beverage]]s, including beer, wine, or liquor, cause breast cancer.]]

Drinking [[alcoholic beverage]]s increases the risk of breast cancer, even among very light drinkers (women drinking less than half of one alcoholic drink per day).<ref name="Choi">{{cite journal | vauthors = Choi YJ, Myung SK, Lee JH | title = Light Alcohol Drinking and Risk of Cancer: A Meta-Analysis of Cohort Studies | journal = Cancer Research and Treatment | volume = 50 | issue = 2 | pages = 474–487 | date = April 2018 | pmid = 28546524 | pmc = 5912140 | doi = 10.4143/crt.2017.094 }}</ref> The risk is highest among heavy drinkers.<ref name="Shield">{{cite journal | vauthors = Shield KD, Soerjomataram I, Rehm J | title = Alcohol Use and Breast Cancer: A Critical Review | journal = Alcoholism: Clinical and Experimental Research | volume = 40 | issue = 6 | pages = 1166–1181 | date = June 2016 | pmid = 27130687 | doi = 10.1111/acer.13071 | quote = All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption. }}</ref> Globally, about one in ten cases of breast cancer is caused by women drinking alcoholic beverages.<ref name="Shield" /> Alcohol use is among the most common modifiable risk factors.<ref>{{cite journal | vauthors = McDonald JA, Goyal A, Terry MB | title = Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence | journal = Current Breast Cancer Reports | volume = 5 | issue = 3 | pages = 208–221 | date = September 2013 | pmid = 24265860 | pmc = 3832299 | doi = 10.1007/s12609-013-0114-z }}</ref>

[[Obesity]] and [[diabetes]] increase the risk of breast cancer. A high [[body mass index]] (BMI) causes 7% of breast cancers while diabetes is responsible for 2%.<ref name="NIHR Evidence_2023">{{cite news |title=Why we need to understand breast cancer risk |date=5 October 2023 |doi=10.3310/nihrevidence_60242 }}</ref><ref>{{cite journal | vauthors = Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M | title = Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment | journal = The Lancet. Diabetes & Endocrinology | volume = 6 | issue = 6 | pages = e6–e15 | date = June 2018 | pmid = 29803268 | pmc = 5982644 | doi = 10.1016/S2213-8587(18)30150-5 }}</ref> At the same time the correlation between obesity and breast cancer is not at all linear. Studies show that those who rapidly gain weight in adulthood are at higher risk than those who have been overweight since childhood. Likewise, excess fat in the [[midriff]] seems to induce a higher risk than excess weight carried in the lower body.<ref>{{cite web|title=Lifestyle-related Breast Cancer Risk Factors|url=https://www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html|website=[[American Cancer Society]]|access-date=18 April 2018|archive-date=27 July 2020|archive-url=https://web.archive.org/web/20200727075717/https://www.cancer.org/cancer/breast-cancer/risk-and-prevention/lifestyle-related-breast-cancer-risk-factors.html|url-status=live}}</ref> Dietary factors that may increase risk include a high-fat diet<ref>{{cite journal | vauthors = Blackburn GL, Wang KA | title = Dietary fat reduction and breast cancer outcome: results from the Women's Intervention Nutrition Study (WINS) | journal = The American Journal of Clinical Nutrition | volume = 86 | issue = 3 | pages = s878-81 | date = September 2007 | pmid = 18265482 | doi = 10.1093/ajcn/86.3.878S | doi-access = free }}</ref> and obesity-related [[high cholesterol]] levels.<ref>{{cite web|work=BBC News|url=http://news.bbc.co.uk/1/hi/health/5171838.stm |title=Weight link to breast cancer risk |date=12 July 2006 |archive-url=https://web.archive.org/web/20070313141518/http://news.bbc.co.uk/1/hi/health/5171838.stm |archive-date=13 March 2007 }}</ref><ref>{{cite journal | vauthors = Kaiser J | title = Cancer. Cholesterol forges link between obesity and breast cancer | journal = Science | volume = 342 | issue = 6162 | pages = 1028 | date = November 2013 | pmid = 24288308 | doi = 10.1126/science.342.6162.1028 }}</ref>

Dietary iodine deficiency may also play a role in the development of breast cancer.<ref>{{cite journal | vauthors = Aceves C, Anguiano B, Delgado G | title = Is iodine a gatekeeper of the integrity of the mammary gland? | journal = Journal of Mammary Gland Biology and Neoplasia | volume = 10 | issue = 2 | pages = 189–96 | date = April 2005 | pmid = 16025225 | doi = 10.1007/s10911-005-5401-5 }}</ref>

[[Smoking tobacco]] appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk.<ref name="Smoking2011">{{cite journal | vauthors = Johnson KC, Miller AB, Collishaw NE, Palmer JR, Hammond SK, Salmon AG, Cantor KP, Miller MD, Boyd NF, Millar J, Turcotte F | title = Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009) | journal = Tobacco Control | volume = 20 | issue = 1 | pages = e2 | date = January 2011 | pmid = 21148114 | doi = 10.1136/tc.2010.035931 }}</ref> In those who are long-term smokers, the relative risk is increased by 35% to 50%.<ref name="Smoking2011" />

A lack of physical activity has been linked to about 10% of cases.<ref>{{cite journal | vauthors = Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT | title = Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy | journal = Lancet | volume = 380 | issue = 9838 | pages = 219–29 | date = July 2012 | pmid = 22818936 | pmc = 3645500 | doi = 10.1016/S0140-6736(12)61031-9 }}</ref> [[Sitting]] regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.<ref name="Biswas">{{cite journal | vauthors = Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA | title = Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 162 | issue = 2 | pages = 123–32 | date = January 2015 | pmid = 25599350 | doi = 10.7326/M14-1651 }}</ref>

Actions to prevent breast cancer include not drinking [[alcoholic beverages]], maintaining a healthy [[body composition]], avoiding [[smoking]] and eating [[Healthy diet|healthy food]]. Combining all of these (leading the healthiest possible lifestyle) would make almost a quarter of breast cancer cases worldwide preventable.<ref name="Zhang_2020">{{cite journal | vauthors = Zhang YB, Pan XF, Chen J, Cao A, Zhang YG, Xia L, Wang J, Li H, Liu G, Pan A | title = Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies | journal = British Journal of Cancer | volume = 122 | issue = 7 | pages = 1085–1093 | date = March 2020 | pmid = 32037402 | pmc = 7109112 | doi = 10.1038/s41416-020-0741-x }}</ref> The remaining three-quarters of breast cancer cases cannot be prevented through lifestyle changes.<ref name="Zhang_2020" />

Other risk factors include [[circadian]] disruptions related to [[shift-work]]<ref>{{cite journal | vauthors = Wang XS, Armstrong ME, Cairns BJ, Key TJ, Travis RC | title = Shift work and chronic disease: the epidemiological evidence | journal = Occupational Medicine | volume = 61 | issue = 2 | pages = 78–89 | date = March 2011 | pmid = 21355031 | pmc = 3045028 | doi = 10.1093/occmed/kqr001 }}</ref> and routine late-night eating.<ref>{{cite journal | vauthors = Marinac CR, Nelson SH, Breen CI, Hartman SJ, Natarajan L, Pierce JP, Flatt SW, Sears DD, Patterson RE | title = Prolonged Nightly Fasting and Breast Cancer Prognosis | journal = JAMA Oncology | volume = 2 | issue = 8 | pages = 1049–55 | date = August 2016 | pmid = 27032109 | pmc = 4982776 | doi = 10.1001/jamaoncol.2016.0164 }}</ref> A number of chemicals have also been linked, including [[polychlorinated biphenyl]]s, [[polycyclic aromatic hydrocarbon]]s, and [[organic solvents]].<ref>{{cite journal | vauthors = Brody JG, Rudel RA, Michels KB, Moysich KB, Bernstein L, Attfield KR, Gray S | title = Environmental pollutants, diet, physical activity, body size, and breast cancer: where do we stand in research to identify opportunities for prevention? | journal = Cancer | volume = 109 | issue = 12 Suppl | pages = 2627–34 | date = June 2007 | pmid = 17503444 | doi = 10.1002/cncr.22656 }}</ref> Although the radiation from [[mammography]] is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.<ref>{{cite journal | vauthors = Hendrick RE | title = Radiation doses and cancer risks from breast imaging studies | journal = Radiology | volume = 257 | issue = 1 | pages = 246–53 | date = October 2010 | pmid = 20736332 | doi = 10.1148/radiol.10100570 | doi-access = free }}</ref>

=== Genetics ===

Around 10% of those with breast cancer have a family history of the disease or genetic factors that put them at higher risk.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc="Epidemiology and risk factors"}} Women who have had a first-degree relative (mother or sister) diagnosed with breast cancer are at a 30–50% increased risk of being diagnosed with breast cancer themselves.{{sfn|Hayes|Lippman|2022|loc="Inherited germline susceptibility factors"}} In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively.<ref>{{cite journal | title = 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 | journal = Lancet | volume = 358 | issue = 9291 | pages = 1389–99 | date = October 2001 | pmid = 11705483 | doi = 10.1016/S0140-6736(01)06524-2 | author1 = Collaborative Group on Hormonal Factors in Breast Cancer }}</ref>

Women with certain genetic variants are at higher risk of developing breast cancer. The most well known are variants of the [[BRCA mutation|BRCA genes]] ''BRCA1'' and ''BRCA2''.{{sfn|Hayes|Lippman|2022|loc="Inherited germline susceptibility factors"}} Women with pathogenic variants in either gene have around a 70% chance of developing breast cancer in their lifetime, as well as an approximately 33% chance of developing [[ovarian cancer]].{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc="Epidemiology and risk factors"}}{{sfn|Hayes|Lippman|2022|loc="Inherited germline susceptibility factors"}} Pathogenic variants in ''[[PALB2]]'' – a gene whose product directly interacts with that of ''BRCA2'' – also increase breast cancer risk; a woman with such a variant has around a 50% increased risk of developing breast cancer.{{sfn|Loibl|Poortmans|Morrow|Denkert|2021|loc="Epidemiology and risk factors"}} Variants in other [[tumor suppressor]] genes can also increase one's risk of developing breast cancer, namely ''[[p53]]'' (causes [[Li–Fraumeni syndrome]]), ''[[PTEN (gene)|PTEN]]'' (causes [[Cowden syndrome]]), and ''[[PALB1]]''.{{sfn|Hayes|Lippman|2022|loc="Inherited germline susceptibility factors"}}

=== Medical conditions ===

Breast changes like [[atypical ductal hyperplasia]]<ref name="urlUnderstanding Breast Changes – National Cancer Institute">{{cite web |url = http://www.cancer.gov/cancertopics/understanding-breast-changes/page6#F8 |title = Understanding Breast Changes – National Cancer Institute |archive-url = https://web.archive.org/web/20100527185336/http://www.cancer.gov/cancertopics/understanding-breast-changes/page6 |archive-date = 27 May 2010 }}</ref> found in benign breast conditions such as [[fibrocystic breast changes]], are correlated with an increased breast cancer risk.

[[Diabetes mellitus]] might also increase the risk of breast cancer.<ref name="pmid23709491">{{cite journal | vauthors = Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, Thakkinstian A | title = Risk factors of breast cancer: a systematic review and meta-analysis | journal = Asia-Pacific Journal of Public Health | volume = 25 | issue = 5 | pages = 368–87 | date = September 2013 | pmid = 23709491 | doi = 10.1177/1010539513488795 }}</ref> Autoimmune diseases such as [[lupus erythematosus]] seem also to increase the risk for the acquisition of breast cancer.<ref name="pmid21237645">{{cite journal | vauthors = Böhm I | title = Breast cancer in lupus | journal = Breast | volume = 20 | issue = 3 | pages = 288–90 | date = June 2011 | pmid = 21237645 | doi = 10.1016/j.breast.2010.12.005 | doi-access = free }}</ref>

Women whose breasts have been exposed to substantial radiation doses before the age of 30 – typically due to repeated chest [[fluoroscopies]] or treatment for [[Hodgkin lymphoma]] – are at increased risk for developing breast cancer. Radioactive iodine therapy (used to treat thyroid disease) and radiation exposures after age 30 are not associated with breast cancer risk.{{sfn|Hayes|Lippman|2022|loc="Clinical, Hormonal, and other Nongenetic Risk Factors"}}