Factors Associated with Increased Risk of Breast Cancer
        Hormone replacement therapy/hormone therapy
        Ionizing radiation
        Obesity
        Alcohol
        Major inheritance susceptibility
Factors Associated with Decreased Risk of Breast Cancer
        Exercise
        Early pregnancy
        Breast-feeding
Interventions Associated with Decreased Risk of Breast Cancer
         Selective estrogen receptor modulators (SERMs): Benefits
        Selective estrogen receptor modulators (SERMs): Harms
        Aromatase inhibitors or inactivators: Benefits
        Aromatase inhibitors or inactivators: Harms
        Prophylactic mastectomy: Benefits
        Prophylactic mastectomy: Harms
        Prophylactic oophorectomy or ovarian ablation: Benefits
        Prophylactic oophorectomy or ovarian ablation: Harms

Note: Separate PDQ summaries on Breast Cancer Screening; Breast Cancer Treatment; Male Breast Cancer Treatment; Breast Cancer Treatment and Pregnancy; and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Based on solid 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.

Magnitude of Effect for Combination Therapy: Approximately a 24% increase in incidence of invasive breast cancer.

Study Design: Randomized controlled trials.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Magnitude of Effect for Estrogen Only: Cannot determine because of mixed evidence.

Study Design: Randomized controlled trials.

Internal Validity: Good.

Consistency: Poor.

External Validity: Not applicable.

Based on solid evidence, exposure of the breast to ionizing radiation is associated with an increased risk of developing breast cancer, starting 10 years after exposure and persisting lifelong. Risk depends on dose and age at exposure, with the highest risk occurring during puberty.

Magnitude of Effect: Variable, but approximately a sixfold increase in incidence overall.

Study Design: Cohort or case-control studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, obesity is associated with an increased breast cancer risk in postmenopausal women who have not used HRT/HT. It is uncertain whether reducing weight would decrease the risk of breast cancer.

Magnitude of Effect: The Women’s Health Initiative observational study of 85,917 postmenopausal women found body weight to be associated with breast cancer. Comparing women weighing more than 82.2 kg with those weighing less than 58.7 kg, the relative risk (RR) was 2.85 (95% confidence interval [CI], 1.81–4.49).

Study Design: Observational study.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, exposure to alcohol is associated with an increased breast cancer risk in a dose-dependent fashion. It is uncertain whether decreasing alcohol exposure would decrease the risk of breast cancer.

Magnitude of Effect: The RR for women consuming approximately four alcoholic drinks per day compared with nondrinkers is 1.32 (95% CI, 1.19–1.45). The RR increases by 7% (95% CI, 5.5%–8.7%) for each drink per day.

Study Design: Case-control and cohort studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, women who inherit gene mutations associated with breast cancer have an increased risk.

Magnitude of Effect: Variable, depending on gene mutation, family history, and other risk factors affecting gene expression.

Study Design: Cohort or case-control studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, exercising strenuously for more than 4 hours per week is associated with reduced breast cancer risk.

Magnitude of Effect: Average RR reduction is 30% to 40%. The effect may be greatest for premenopausal women of normal or low body weight.

Study Design: Prospective observational and case-control studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, women who have a full-term pregnancy before age 20 years have decreased breast cancer risk.

Magnitude of Effect: 50% decrease in breast cancer compared to nulliparous women or those who give birth after age 35 years.

Study Design: Cohort and case-control studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, women who breast-feed have a decreased risk of breast cancer.

Magnitude of Effect: The relative risk of breast cancer is decreased 4.3% for every 12 months of breast-feeding, in addition to 7% for each birth.[1]

Study Design: Cohort and case-control studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid 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. The effects observed for tamoxifen show persistence several years after discontinuing active treatment.

Magnitude of Effect: Treatment with tamoxifen reduced breast cancer by about 50%. Treatment with raloxifene has a similar effect on reduction of invasive breast cancer but appears to be less effective for prevention of noninvasive tumors.

Study Design: Randomized controlled trials.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, tamoxifen treatment increases the risk of endometrial cancer, thrombotic vascular events (pulmonary embolism, stroke, deep venous thrombosis), and cataracts. Many of these risks, notably pulmonary embolism and deep venous thrombosis, are reduced after discontinuing active treatment with tamoxifen. Based on fair evidence, raloxifene also increases venous pulmonary embolism and deep venous thrombosis but not endometrial cancer.

Magnitude of Effect: Meta-analysis shows RR = 2.4 (95% CI, 1.5–4.0) for endometrial cancer and 1.9 (95% CI, 1.4–2.6) for venous thromboembolic events.

Study Design: Randomized controlled trials.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on fair evidence, aromatase inhibitors or inactivators (AIs) reduce the incidence of new breast cancers in postmenopausal women who have a history of breast cancer.

Magnitude of Effect: Compared with tamoxifen treatment, treatment with anastrozole reduces the incidence of new primary breast cancers by 50%. Similar results have been reported with letrozole and exemestane treatment.

Study Design: Randomized controlled trials performed in postmenopausal women with a previous history of breast cancer.

Internal Validity: Good.

Consistency: Good.

External Validity: Fair.

Based on fair evidence, AIs are associated with decreased bone mineral density, increased falls, and decreased cognitive function.

Magnitude of Effect: Fracture rate for women being treated with anastrozole was 5.9% compared with 3.7% for those being treated with tamoxifen.[2]

Study Design: Multiple randomized controlled trials demonstrate decreased bone mineral density with each AI. One randomized controlled trial shows an increase in fractures (in those using anastrozole).

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, bilateral prophylactic mastectomy reduces the risk of breast cancer in women with a strong family history.

Magnitude of Effect: Risk is reduced as much as 90%, but published study designs may have produced an overestimate.

Study Design: Evidence obtained from case-control and cohort studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on fair evidence, physical and psychological effects include anxiety, depression, and impaired body image.

Magnitude of Effect: 6% of women were dissatisfied with their decision to have a prophylactic mastectomy, usually for cosmesis. Regrets about mastectomy were less in 185 women who opted not to have reconstruction than in 111 women who chose it.[3]

Study Design: Convenience sample.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, prophylactic oophorectomies in women with BRCA gene mutations document lower breast cancer incidence. Similarly, oophorectomy or ovarian ablation is associated with decreased breast cancer incidence in normal women or in those who received thoracic irradiation.

Magnitude of Effect: Breast cancer incidence is decreased by 50%, but published study designs may have produced an overestimate.

Study Design: Observational, case-control, and cohort studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

Based on solid evidence, castration may cause the abrupt onset of menopausal symptoms such as hot flashes, insomnia, anxiety, and depression. Long-term effects include decreased libido, vaginal dryness, and decreased bone mineral density.

Magnitude of Effect: Nearly all women experience some sleep disturbances, mood changes, hot flashes, and bone demineralization, but the severity of these symptoms varies greatly.

Study Design: Case-control, cohort, and observational studies.

Internal Validity: Good.

Consistency: Good.

External Validity: Good.

References

1. Collaborative Group on Hormonal Factors in Breast Cancer.: Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 360 (9328): 187-95, 2002.  [PUBMED Abstract]
   
   
2. Smith IE, Dowsett M: Aromatase inhibitors in breast cancer. N Engl J Med 348 (24): 2431-42, 2003.  [PUBMED Abstract]
   
   
3. Montgomery LL, Tran KN, Heelan MC, et al.: Issues of regret in women with contralateral prophylactic mastectomies. Ann Surg Oncol 6 (6): 546-52, 1999.  [PUBMED Abstract]
   
   

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