Breast Cancer Risk Factors

Inherited Risk Factors

Familial Breast Cancer: BRCA-1 and BRCA-2 mutations
Probability of BRAC1 Mutation in Various Scenarios [1]

Age of Women in Years History of Breast Cancer first-degree relative with breast cancer Non-ashkenazi Ashkenazi
30 Unilateral + 20% 50%
40 Unilateral + 5% 20%
60 Bilateral + 5% 20%
  • 5% of all breast cancer is familial.
  • Women with a mother or father who is a proven carrier had 50% probability of BRAC1 mutation
  • Majority of ipsilateral breast cancer “recurrences” are in fact second primary.
  • Higher rate of ER/PR positivity compared to "normal" breast cancer.
  • Heterozygots for ATM, BRCA1, and BRCA2 do not have higher risk of developing irradiation related toxicity compared to normal individuals. However, having two ATM mutations may be more sensitive than normal individuals.
  • Some studies found tha BRCA1 or BRCA2 gene had no effect on local failure rates after breast-conservation therapy, but other series show substantially higher rates of failure.

Comparison of BRCA1 and BRAC2

BRCA1 BRCA-2 General Population
ER/PR Status ER Negative Almost Always Positive
HER-2/neu Status
Contralateral Breast Risk 40-60% life-time (1.8%/yr) 40-60% life-time (1.8%/yr) 0.7% per year
Other sites (Ovarian) 40% or higher Ovarian risk is less, but more pancreatic and male breast
Age of onset Early onset Later onset
familial breast cancer 50% of familial breast CA 35% of familial breast CA 5% of all breast cancer is familial

Patient Risk Factors

  • Age is the single most important risk factor
  • Obesity is associated with increased breast cancer risk, especially among postmenopausal women who do not use HRT/HT. Weight was the strongest predictor, with a RR of 2.85 (95% CI, 1.81–4.49) for women weighing more than 82.2 kg, compared with those weighing less than 58.7 kg.
  • Many epidemiologic studies have shown an increased risk of breast cancer associated with alcohol consumption.The RR of breast cancer increases by about 7% (95% CI, 5.5–8.7%; P < .001) for each 10 g per day (i.e., one drink).

Iatrogenic Risk Factors

  • Oral contraceptives have been associated with a small increased risk of breast cancer in current users that diminishes over time. A well-conducted case-control study did not observe an association between breast cancer risk and oral contraceptive use for every use, duration of use, or recency of use.
  • A well-established relationship exists between exposure to ionizing radiation and the risk of developing breast cancer.
  • Women treated for Hodgkin’s lymphoma by the age of 16 may have a subsequent risk, which is as high as 35%, of developing breast cancer by the age of 40.
Bibliography
1. Shattuck-Eidens D, Oliphant A, McClure M, McBride C, Gupte J, Rubano T, Pruss D, Tavtigian SV, Teng DH, Adey N, Staebell M, Gumpper K, Lundstrom R, Hulick M, Kelly M, Holmen J, Lingenfelter B, Manley S, Fujimura F, Luce M, Ward B, Cannon-Albright L, Steele L, Offit K, Thomas A, et al. BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA. 1997 Oct 15;278(15):1242-50. PMID: 9333265
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