Breast Cancer Risk Factors

Aka: Breast Cancer Risk Factors, Breast Cancer Risk Reduction

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II. Resources: Breast Cancer Risk

  1. Gail Model Breast Cancer Risk Calculator (BCRAT)
    1. https://bcrisktool.cancer.gov//
    2. Does not assess risk in BRCA 1/2 patients
    3. Risk >3% in 5 years is considered increased Breast Cancer risk
  2. Breast Cancer Surveillance Consortium Model
    1. https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm

III. Risk Factors: Major

  1. Female Gender: 75% have no other known risk factors
  2. Age related Breast CancerIncidence in women
    1. Age 25 years = 1:19608 risk
    2. Age 30 years = 1:2525 risk
    3. Age 35 years = 1:622 risk
    4. Age 40 years = 1:217 risk
    5. Age 45 years = 1:93 risk
    6. Age 50 years = 1:50 risk
    7. Age 55 years = 1:33 risk
    8. Age 60 years = 1:24 risk
    9. Age 65 years = 1:17 risk
    10. Age 70 years = 1:14 risk
    11. Age 75 years = 1:11 risk
    12. Age 80 years = 1:10 risk
    13. Age 85 years = 1:9 risk
    14. Lifetime = 1:8 risk
  3. Reference
    1. Feuer (1993) J Natl Cancer Inst 85:892-7 [PubMed]

IV. Risk Factors: Other

  1. History of Breast Cancer
    1. Personal History
      1. Inversely related to Age
      2. Risk: 0.5% - 1% per year for at least 15 years
      3. Overall Relative Risk: 1.42
    2. Family HistoryRelative Risk
      1. First Degree relative: 2.3 Relative Risk
        1. Unilateral/Postmenopausal: 1.2 Relative Risk
        2. Unilateral/Premenopausal: 1.8 Relative Risk
        3. Bilateral/Postmenopausal: 4.0 Relative Risk
        4. Bilateral/Premenopausal: 8.8 Relative Risk
      2. Second Degree relative: 1.5 Relative Risk
      3. Mother and Sister affected: 14.0 Relative Risk
    3. References
      1. Anderson (1985) Cancer 56:383 [PubMed]
      2. Sattin (1985) JAMA 253 [PubMed]
  2. Gene Mutations
    1. Most common types (>20 mutations have been identified)
      1. BRCA (BRCA1, BRCA2): 60% of Breast Cancer gene mutations
        1. See BRCA1 and BRCA2 for specific Relative Risk based on type and age
      2. AT (Ataxia Telangiectasia) on Chromosome 11
      3. PTEN gene (Cowden syndrome)
      4. CDH1 gene (hereditary diffuse Gastric Cancer)
      5. TP53 gene (Li-Fraumeni syndrome)
      6. STK11 gene (Peutz-Jeghers Syndrome)
    2. Associated risk
      1. Overall, these mutations account for only 3-5% of all Breast Cancers
      2. Cummulative lifetime risk of Breast Cancer in those with mutation: 25-85%
  3. Chest Radiation Therapy (childhood exposure)
    1. Standardized Incidence Ratio (SIR) 21.9 (overall) to 43.6 (whole lung)
    2. Risk of Breast Cancer by age 50 years old: 30%
  4. Parity
    1. Age at first birth
      1. Age at first birth <20 years: 1.0 Relative Risk
      2. Age at first birth 20-24 years: 1.2 Relative Risk
      3. Age at first birth 25-29 years: 1.6 Relative Risk
      4. Age at first birth 30-35 years: 1.9 Relative Risk
      5. Age at first birth >35 years: 1.9 Relative Risk
      6. Nulliparous: 1.6 Relative Risk
    2. References
      1. Modified from McMahon based on Gail Model
      2. McMahon (1970) Bull World Health Organ 43:209-12 [PubMed]
  5. Ethnicity
    1. Latinas may have higher Breast CancerIncidence
      1. Many of these latina patients were under age 35
      2. Also more aggressive Breast Cancer in this group
    2. References
      1. Biffl (2001) Am J Surg 182:596-600 [PubMed]
  6. Hyperplasia on Breast Biopsy
    1. Fibrocystic Breast changes: No increased risk
    2. Hyperplasia
      1. No atypia: 2.0 Relative Risk
      2. Atypia (4% Incidence): 5.0 Relative Risk
  7. Increased Breast density
    1. Breast density is the ratio of glandular and stromal tissue to adipose tissue
    2. Breast density >75% confers 4.7 Odds Ratio over those with Breast density <10%
      1. Boyd (2007) N Engl J Med 356(3): 227-36 [PubMed]

V. Risk Factors: Other Risks

  1. Estrogen Replacement Therapy (ERT or HRT)
    1. Controversial (study results vary widely)
    2. Some studies show significant risk with >5 years use
      1. Risk increased by 40% (1.4 Relative Risk)
      2. Colditz (1995) New Engl J Med 332:1589-93 [PubMed]
    3. Meta analysis shows no increased Breast Cancer risk
      1. Bush (2001) Obstet Gynecol 98:498-508 [PubMed]
    4. HRT associated with reduced Breast Cancer mortality
      1. May be a result of earlier detection
      2. Bush (2001) Obstet Gynecol 98:498-508 [PubMed]
  2. Tobacco Abuse
    1. Does not appear to increase the risk of the primary Breast Cancer
    2. Does appear to increase pulmonary metastasis risk (Odds Ratio 1.96)
      1. Murin (2001) Chest 119:1635-40 [PubMed]
  3. Alcohol
    1. Relative Risk increases 7% per drink consumed over 1 per day
    2. Hamajima (2002) Br J Cancer 87(11): 1234-45 [PubMed]
  4. Red meat consumption
    1. Increased risk of Estrogen receptor positive cancer
    2. Relative Risk: 1.97 for >1.5 red meat servings/day
    3. Cho (2006) Arch Intern Med 166:2253-9 [PubMed]
  5. Overweight
    1. Postmenopausal weight gain >20 kg doubles Breast Cancer risk
    2. BMI >31 confers 1.6 fold increased Breast Cancer risk

VI. Risk Factors: No effect (or minimal or inconclusive effect) on Breast Cancer risk

  1. Oral Contraceptives
    1. No (or minimal) increased Breast Cancer risk
    2. Reference
      1. Swanson (1992) J Am Med Womens Assoc 47:140-8 [PubMed]
  2. Elective or Spontaneous Abortion
    1. No increased risk of Breast Cancer
    2. Reference
      1. Melbye (1997) JAMA 336:81-5 [PubMed]
      2. Beral (2004) Lancet 363:1007-16 [PubMed]
  3. Cummulative Antibiotic use
    1. Was thought to be associated with Breast Cancer risk
      1. Velicer (2004) JAMA 291:827-35 [PubMed]
    2. Other studies suggest no increased risk
      1. Kaye (2005) Epidemiology 16(5): 688-90 [PubMed]
  4. Calcium Channel Blockers
    1. May be associated with increased Breast Cancer risk with more than 10 years of Calcium Channel Blocker use
    2. Additional studies are needed for confirmation
    3. Li (2013) JAMA Intern Med, Published online August 05, 2013
      1. http://archinte.jamanetwork.com/article.aspx?articleid=1723871

VII. Prevention: Protective against Breast Cancer

  1. Lactation
    1. Risk decreases with 2 years of cumulative Lactation
    2. Affects premenopausal risk (not postmenopausal risk)
    3. Reference
      1. Newcomb (1994) N Engl J Med 338: 81-7 [PubMed]
  2. Bilateral oophorectomy before age 50 years
    1. Cuts Breast CancerRelative Risk by half
  3. Bilateral risk reducing Mastectomy
    1. Indicated in high risk patients (BRCA1/2)
  4. Later onset Menarche
    1. Risk decreases 10% per every 2 years of Menarche delayed beyond age 12 years
  5. Exercise (greater risk reduction with increased duration and intensity)
    1. Premenopause: Breast CancerRelative Risk drops up to 30%
    2. Postmenopause: Breast CancerRelative Risk drops by up to 22%

VIII. Prevention: Primary prevention medication regimens

  1. Indications: High risk for Breast Cancer (5 year Breast Cancer risk >1.66%)
    1. See Risk Calculators under Resources above
    2. High risk indications typically include strong factors (e.g. atypical hyperplasia)
  2. Breast Cancer Prevention in pre-Menopause or post-Menopause
    1. Indicated if Breast Cancer risk >1.66% in 5 years and age over 35 years old
    2. Tamoxifen has higher efficacy than Raloxifene for breast Cancer Prevention
      1. But also higher Venous Thromboembolism and Endometrial Cancer Risks
    3. Unlike Tamoxifen, Raloxifene is not approved for pre-menopausal breast Cancer Prevention
  3. Preparations
    1. Tamoxifen 20 mg daily for 5 years
      1. Selective Estrogen Receptor Modulators (SERM)
      2. Indicated in pre-Menopause (age over 35 years) or post-Menopause patients
      3. Higher efficacy than Raloxifene for breast Cancer Prevention
        1. Prevents 7 Breast Cancers/1000 women over 5 years
      4. Higher Venous Thromboembolism (4/1000) risk than Raloxifene
      5. Higher Endometrial Cancer (4/1000) risk than Raloxifene
      6. Contraindicated in Venous Thromboembolism history or increased risks or with history of CVA or TIA
      7. Avoid with agents that decreased Tamoxifen efficacy
        1. Avoid with Bupropion (Wellbutrin), Fluoxetine (Prozac) or Paroxetine (Paxil)
    2. Raloxifene (Evista) 60 mg daily for 5 years
      1. Selective Estrogen Receptor Modulators (SERM) indicated in post-Menopause patients
      2. Lower efficacy than Tamoxifen for breast Cancer Prevention, but also lower VTE and Endometrial Cancer risk
      3. Also effective in Osteoporosis Prevention and management
      4. Contraindicated in Venous Thromboembolism history or increased risks or with history of CVA or TIA
    3. Exemestane (Aromasin) 25 mg daily for 5 years
      1. Aromatase Inhibitor indicated in post-menopausal women
        1. In whom Tamoxifen or Raloxifene are contraindicated
      2. May be more effective than SERMs, but has not been compared in study
        1. Prevents 9 Breast Cancers/1000 women over 3 years
      3. Contraindicated in Osteoporosis (decreases Bone Mineral Density)
        1. Calcium Supplementation (1200 mg daily) are recommended
        2. Vitamin D Supplemention (1000-2000 IU) are recommended
  4. References
    1. Visvanathan (2013) J Clin Oncol 31:2942-62 [PubMed]
      1. http://jco.ascopubs.org/content/31/23/2942.full.pdf

IX. References

  1. Steiner (2008) Am Fam Physician 78(12): 1361-6 [PubMed]

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