Summary of Evidence
Factors Associated with Increased Risk of Breast Cancer
Hormone Replacement Therapy/Hormone Therapy
Ionizing Radiation
Obesity
Alcohol
Factors Associated with Decreased Risk of Breast Cancer
Selective Estrogen Receptor Modulators (SERMs)
Prophylactic Mastectomy
Exercise
Note: Separate PDQ summaries on Screening for Breast Cancer; Breast Cancer
Treatment; Male Breast Cancer Treatment; Breast Cancer and Pregnancy Treatment; and Levels of Evidence for Cancer Screening and Prevention Studies are
also available.
Factors Associated with Increased Risk of Breast Cancer
Hormone Replacement Therapy/Hormone Therapy
Based on good evidence, combination hormone replacement therapy, (HRT; estrogen-progestin), also called hormone therapy (HT), is associated with an increased risk of developing breast cancer. The evidence concerning the association between estrogen-only therapy and breast cancer incidence is mixed; observational data suggest a small increased risk but the only completed randomized controlled trial found a suggestion of decreased risk of breast cancer. Description of the Evidence for Combination Therapy A. Study Design (Level of Evidence 1) - 1: Evidence obtained from randomized controlled trials.
B. Internal Validity: Good. C. Consistency: Good. D. Direction and Magnitude of Effect: Approximately 24% increase in incidence of invasive breast cancer. E. External Validity: Fair, due to lack of minority women. Description of the Evidence for Estrogen only A. Study Design (Levels of Evidence 1, 3) - 1: Evidence obtained from randomized controlled trials.
- 3: Evidence obtained from cohort or case-control studies.
B. Internal Validity: Good. C. Consistency: Poor. D. Direction and Magnitude of Effect: Cannot determine because of mixed evidence. E. External Validity: Not applicable.
Ionizing Radiation
Exposure of the breast to ionizing radiation is associated with an increased
risk of developing breast cancer, especially when the exposure occurs at a
young age. This finding supports the avoidance of unnecessary breast
irradiation.
Levels of Evidence - 3aii: Evidence obtained from well-designed and conducted cohort or case-control
studies, preferably from more than one center or research group, that have
a cancer incidence endpoint.
- 4aii: Ecologic and descriptive studies (e.g., international patterns studies,
migration studies, time series) that have a cancer incidence endpoint.
Obesity
Obesity is associated with increased breast cancer risk in postmenopausal women who have not used hormone replacement therapy/hormone therapy.
Level of Evidence - 3aii: Evidence obtained from well-designed and conducted cohort or case-control studies, preferably from more than one center or research group, that have a cancer incidence endpoint.
Alcohol
Exposure to alcohol may be associated with increased breast cancer risk.
Level of Evidence - 3aii: Evidence obtained from well-designed and conducted cohort or case-control
studies, preferably from more than one center or research group, that
have a cancer incidence endpoint.
Factors Associated with Decreased Risk of Breast Cancer
Selective Estrogen Receptor Modulators (SERMs)
Benefits
Based on good evidence for tamoxifen and fair evidence for raloxifene, treatment reduces the incidence of breast cancer in postmenopausal women. Tamoxifen also reduced the risk of breast cancer in high-risk premenopausal women. Description of the Evidence A. Study Design (Level of Evidence 1) - 1: Evidence obtained from randomized controlled trials.
B. Internal Validity: Good. C. Consistency: Good. D. Direction and Magnitude of Effect: Meta-analysis shows a 48% relative-risk reduction in the incidence of breast cancer. External Validity: Good.
Harms
Based on good evidence, tamoxifen
treatment increases the risk of endometrial cancer, thrombotic
vascular events (pulmonary embolism, stroke, deep venous thrombosis), and cataracts. Based on fair evidence, raloxifene also appears to increase venous pulmonary embolism and deep venous thrombosis, but not endometrial cancer. Description of the Evidence A. Study Design (Level of Evidence 1) - 1: Evidence obtained from randomized controlled trials.
B. Internal Validity: Good. C. Consistency: Good. D. Direction and Magnitude of Effect: Meta-analysis shows a relative risk of 2.4 (95% confidence interval (CI) 1.5-4.0) for endometrial cancer and 1.9 (95% CI 1.4-2.6) for venous thromboembolic events.
Prophylactic Mastectomy
Bilateral prophylactic mastectomy is associated with a reduction in the risk of
breast cancer by as much as 90% among women with an increased risk of breast
cancer due to a strong family history of breast cancer. Because of the
physical and psychological effects of bilateral mastectomy and the
irreversibility of the procedure, decisions regarding this option must be
carefully considered on an individual basis in association with risk assessment
and counseling.
Levels of Evidence - 3ai,3aii: Evidence obtained from well-designed and conducted cohort or
case-control studies, preferably from more than one center or research group, that have
a cancer incidence endpoint.
Exercise
Studies suggest that exercise may be associated with reduced breast
cancer risk.
Level of Evidence - 3aii: Evidence obtained from well-designed and conducted cohort or case-control
studies, preferably from more than one center or research group, that have
a cancer incidence endpoint.
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