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Cite this page: Risk factors for breast cancer. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantriskfactors.html. Accessed July 14th, 2017.
Definition / general
- Primarily genetic, hormonal or environmental
- After menopause, about 40% of risk is modifiable (Am J Epidemiol 2008;168:404)
Genetic risk factors
- First degree relatives with breast cancer; having one first degree relative (mother, sister, daughter) creates a relative risk of 2 - 3x, higher if relative is affected before age 50 or had bilateral disease (Int J Cancer 1997;71:800); relative risk with two first degree relatives is 4 - 6x
- Li-Fraumeni syndrome (germline p53 mutations) - 25% of patients develop breast cancer
- Mutations of BRCA1 and BRCA2 genes are associated with familial breast cancer at an early age, account for 20 - 60% of familial breast cancer, but only 5% of all cases
- Cowden's disease (multiple hamartoma syndrome) - autosomal dominant, due to 10q mutation: 30 - 50% risk of breast cancer (DCIS or invasive ductal carcinoma) by age 50; also benign skin tumors (Hum Pathol 1998;29:47)
- Heterozygous carriers for ataxia-telangiectasia have an 11% risk of breast cancer by age 50
- Blacks (compared to whites) have more frequent breast cancers in women < age 40; present with higher stage tumors with higher nuclear grade that are more likely ER / PR negative, have higher mortality rate
- Women have 100x risk of breast cancer compared to men
Hormone related risk factors
- Early menarche
- Late menopause
- Nulliparity
- Having first child after age 30
- Postmenopausal women with obesity (BJOG 2006;113:1160) or estrogen producing ovarian tumors
- Women using combined hormone replacement therapy with progestins, or estrogens alone (Int J Cancer 2007;121:645)
- Risk with oral contraceptives is controversial, but see Mayo Clin Proc 2006;81:1290
- Proposed mechanism of hormonal related risk factors is strong or prolonged estrogen stimulation, which may allow secretion of growth promoters
Factors associated with reduced risk of breast cancer:
- Oophorectomy before age 35 or first child before age 18
- Obesity prior to age 40 - due to anovulatory cycles and lower progesterone levels in late cycle
Environmental risk factors
- Rates in US > Japan / Taiwan (5:1), also high in Northern Europe, low in Asia / Africa; may be due to known risks of obesity / high fat diet (Nutr Cancer 2008;60:492) and heavy alcohol use (Am J Epidemiol 2000;152:950)
- Differences diminish with immigration
- Breast cancer is not associated with smoking
- In Nigeria, breast cancers are high-grade, high-stage and high-proliferating, and occur at a younger age than in Western countries (Mod Pathol 2002;15:783)
- Physical activity has a protective effect (J Natl Cancer Inst 2008;100:728, Breast Cancer Res Treat 2010;120:235)
- Adult dietary soy foods (Am J Clin Nutr 2009;89:1920) and carotenoids (Int J Cancer 2009;124:2929) have protective effect
Other risk factors
- Older age
- Proliferative breast disease (see individual topics in Breast-nonmalignant chapter), particularly in situ carcinoma, and possibly concurrent multiple nonproliferative or proliferative benign breast lesions at biopsy (Clin Cancer Res 2007;13:5474)
- Carcinoma of opposite breast or endometrium
- Radiation exposure in young women, including women < age 30 with supradiaphragmatic radiation for Hodgkin's lymphoma (Int J Radiat Oncol Biol Phys 2009;73:69); reduced risk if also have irradiation of ovaries > 5 Gy (J Clin Oncol 2009;27:3901)
- Mammographic density (J Br Menopause Soc 2006;12:186) is a highly heritable risk (Breast Cancer Res 2011;13:R132)
- Birth weight > 3000 g (for cancers arising at age 50 years or less, Cancer Epidemiol Biomarkers Prev 2009;18:2447)
- Previous breast biopsy (Rev Med Inst Mex Seguro Soc 2011;49:655)
Additional references
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