What causes breast cancer?

Causes of Breast Cancer

Breast cancer is primarily caused by a combination of genetic predisposition, exposure to estrogens (both endogenous and exogenous), ionizing radiation, reproductive factors, and lifestyle elements including Western-style diet, obesity, and alcohol consumption. 1, 2

Genetic and Hereditary Risk Factors

• Genetic mutations:

  • BRCA1/2 mutations increase lifetime breast cancer risk to 56-84% 1
  • Other significant genetic mutations: TP53, PTEN, CDH1, and STK11 1
  • Family history of breast or ovarian cancer significantly increases risk 1

• Familial patterns:

  • Hereditary cancers often show early age of onset and specific inheritance patterns 1
  • Women with first or second-degree relatives with breast cancer have increased risk 1
  • Male breast cancer (1% of cases) is strongly associated with genetic predisposition 1

Hormonal and Reproductive Factors

• Estrogen exposure is a major risk factor:

  • Higher endogenous estrogen levels in postmenopausal women increase risk 2
  • Long-term use (≥20 years) of estrogen alone carries relative risk of 1.42 2
  • Current use of estrogen-only HRT increases risk (relative risk 1.30) 2

• Reproductive history:

  • Early menarche or late age of first live birth 1
  • Nulliparity (having no children) 1
  • Low parity (having few children) 1

Environmental and Lifestyle Factors

• Body composition:

  • High BMI in postmenopausal women increases risk through elevated estrogen levels from fat tissue 1, 2
  • Adult weight gain is associated with increased postmenopausal breast cancer risk 1

• Lifestyle factors:

  • Alcohol consumption - even moderate levels increase risk 1
  • Western-style diet contributes to rising incidence 1
  • Physical inactivity 2

• Other environmental exposures:

  • Ionizing radiation, particularly before age 30 1
  • Prior thoracic radiation therapy (e.g., for Hodgkin lymphoma) increases risk 56.7-fold 1

Breast Tissue Abnormalities

• Previous breast conditions:
  • Atypical hyperplasia (both ductal and lobular) substantially increases risk 1
  • Lobular carcinoma in situ (LCIS) significantly increases risk 1
  • Multiple breast biopsies increase risk 1

Age and Demographics

• Age gradient:

  • Steep increase with age - about 25% of breast cancers occur before age 50 1
  • Less than 5% occur before age 35 1

• Ethnicity/race:

  • Ashkenazi Jewish descent associated with increased BRCA1/2 mutation incidence 1

Risk Assessment and Prevention

• Risk assessment should use appropriate models based on individual factors:

  • Modified Gail model for general population 1
  • BRCAPRO, BOADICEA, or Tyrer-Cuzick models for those with family history 1
  • Claus tables for white women with 1-2 first/second-degree relatives with breast cancer 1

• Preventive strategies:

  • Lifestyle modifications (maintaining healthy weight, limiting alcohol, increasing physical activity) 2
  • Risk reduction medications for eligible high-risk women 1
  • Risk-reducing surgery for carriers of high-risk genetic mutations 1

Common Pitfalls in Breast Cancer Risk Assessment

• Failing to consider duration of estrogen exposure when assessing risk 2
• Not accounting for BMI when evaluating postmenopausal women 2
• Overlooking interaction between estrogen and other hormones 2
• Using inappropriate risk assessment models (e.g., Gail model for women with thoracic radiation history or LCIS) 1

Understanding these multiple risk factors is essential for identifying high-risk individuals and implementing appropriate risk reduction strategies to decrease breast cancer morbidity and mortality.