What are the risk factors for breast cancer?

Breast Cancer Risk Factors

The most important risk factors for breast cancer include genetic predisposition, hormonal exposure (endogenous and exogenous estrogens including long-term HRT), ionizing radiation, low parity, high breast density, history of atypical hyperplasia, Western-style diet, obesity, and alcohol consumption. 1

Major Non-Modifiable Risk Factors

Genetic and Family History

• Genetic predisposition is the single most important risk factor, with women having first-degree relatives affected at young ages considered at substantially higher risk 2
• Family history confers a 4-fold increased risk even in women who test negative for BRCA1/BRCA2 mutations when there are two or more breast cancers before age 50 or three or more at any age 3
• Sisters of women diagnosed before age 40 have a 6-fold increased cumulative risk to age 50, while mothers have 3-fold and aunts 2-fold increased risk 4
• BRCA1 and BRCA2 mutations account for fewer than one-third of excess breast cancers in relatives of young-onset cases, indicating other genetic factors are involved 4

Breast Tissue Characteristics

• Dense breast tissue is an independent risk factor requiring consideration in screening strategies 2
• History of atypical hyperplasia (ductal and lobular atypia) significantly increases risk 1, 2
• Carcinoma in situ, particularly lobular carcinoma in situ (LCIS), substantially increases breast cancer risk 2

Age and Reproductive Factors

• Advanced age is a critical risk factor, with a steep age gradient showing about 25% of cases occurring before age 50 and less than 5% before age 35 1
• Early menarche (before age 12) increases risk by approximately 4-5% for each year younger at menarche 5
• Late menopause (after age 55) confers approximately 12% higher risk compared to menopause before age 50 5
• The mechanism involves longer lifetime exposure to estrogen and progesterone, which stimulate breast tissue cell division and increase DNA replication errors 5

Parity and Pregnancy Timing

• Low parity and nulliparity increase breast cancer risk 1
• First childbirth after age 30 or being nulliparous elevates risk 2
• Conversely, pregnancy at early age and high parity are protective 6

Radiation Exposure

• Ionizing radiation exposure is an established risk factor, particularly therapeutic radiation 1, 6

Modifiable Risk Factors

Hormonal Exposures

• Long-term hormone replacement therapy (HRT) significantly increases risk through exogenous estrogen exposure 1
• The duration and timing of hormonal exposures matter more than single exposures 5

Lifestyle Factors

• Western-style diet contributes to increased incidence 1, 2
• Obesity, particularly in postmenopausal women, increases risk due to elevated circulating estrogens 2
• Alcohol consumption shows a dose-response relationship with breast cancer risk 2, 5
• Limiting alcohol to no more than one drink per day for women is recommended 5

Protective Factors and Risk Reduction

Physical Activity

• Regular physical activity (45-60 minutes, 5+ days per week) reduces breast cancer risk 2, 5
• This can help mitigate risk associated with reproductive factors 5

Weight Management

• Maintaining healthy body weight through caloric restriction and regular physical activity reduces risk 5

Screening and Prevention

• Women with multiple risk factors should consider more intensive early detection strategies and possible preventive interventions 2
• Appropriate breast cancer screening based on individual risk assessment is crucial 5
• Women with significant family history (two or more breast cancers under age 50, or three or more at any age) who test negative for BRCA mutations may be candidates for tamoxifen chemoprevention and/or intensified breast screening with MRI 3

Critical Clinical Pitfalls

Avoid focusing solely on BRCA mutations when assessing familial risk - the majority of familial breast cancer is not explained by BRCA1/BRCA2 mutations 4, 3

Do not overlook the cumulative effect of multiple moderate risk factors - women with several risk factors may have substantially elevated risk even without a strong family history 2

Remember that absolute risk varies by age - while relative risk is highest in younger women with family history, absolute risk peaks between ages 50-70 (1% per year versus 0.4% per year for ages 30-50) 3