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Estimated average five-year and lifetime breast-cancer risks for women with moderate-penetrance mutations in selected genes

Estimated average five-year and lifetime breast-cancer risks for women with moderate-penetrance mutations in selected genes
Age
(years)		 Population ATM/NBN
(RR 2.7 to 2.8)*		 CHEK2(1100delC)
(RR 3.0)		 CHEK2(I157T)
(RR 1.58)		 PALB2[1]
5-year (%) Cumulative (%) 5-year (%) Cumulative (%) 5-year (%) Cumulative (%) 5-year (%) Cumulative (%) 5-year (%) Cumulative (%)
25 to 29 0.04 0.1 0.12 0.1 0.13 0.2 0.07 0.1 0.35 0.4
30 to 34 0.14 0.2 0.38 0.5 0.41 0.6 0.21 0.3 1.05Δ 2.0
35 to 39 0.30 0.5 0.84 1.4 0.90 1.5 0.48 0.8 2.50◊ 4.0
40 to 44 0.61 1.1 1.70Δ 3.0 1.83Δ 3.2 0.96Δ 1.7 4.25◊ 8.0
45 to 49 0.94Δ 2.0 2.64◊ 5.6 2.83◊ 5.9 1.49Δ 3.2 6.35◊ 14.0
50 to 54 1.12Δ 3.1 3.14◊ 8.5 3.36◊ 9.1 1.77Δ 4.9 8.00◊ 20.0
55 to 59 1.33Δ 4.4 3.71◊ 11.8 3.98◊ 12.6 2.09Δ 6.8 7.25◊ 26.0
60 to 64 1.72Δ 6.0 4.81◊ 16.0 5.15◊ 17.0 2.71◊ 9.3 7.35◊ 31.0
65 to 69 2.11Δ 8.0 5.92◊ 20.8 6.34◊ 22.1 3.34◊ 12.3 5.95◊ 35.0
70 to 75 2.20◊ 10.0 6.17◊ 25.5 6.61◊ 27.1 3.48◊ 15.3 6.70◊ 40.0
CLTR (80) NA 12.0 NA 30.0 NA 31.8 NA 18.3 NA 44.0
These data represent the estimated cumulative five-year incidence of breast cancer associated with moderate-penetrance mutations with established clinical validity (based on the method of Song et al[2]).
RR: relative risk; CLTR: cumulative lifetime risk; NA: not applicable.
* ATM CLTR (80 years) estimated to be 27.1% with an RR of 5.0 up to age 50 years and then 2.0 thereafter (based on data from Thompson et al[3]). Data for NBN derived from study of a single truncating mutation.
CHEK2 truncating mutation CLTR (80 years) estimated to be 23.4% if RR declines with age (according to the CHEK2 Breast Cancer Case-Control Consortium[4]).
Δ Indicates the age ranges at which five-year risk approaches or exceeds 1% (the approximate population risk of breast cancer among United States women aged 45 years).
◊ Indicates the age ranges at which the five-year risk of breast cancer exceeds 2.2% (the highest risk estimated for United States women in the general population, specifically, those aged between 70 to 79 years).
References:
  1. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371:497.
  2. Song H, Dicks E, Ramus SJ, et al. Contribution of germline mutations in the RAD51B, RAD51C, and RAD51D genes to ovarian cancer in the population. J Clin Oncol 2015; 33:2901.
  3. Thompson D, Duedal S, Kirner J, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 2005; 97:813.
  4. CHEK2 Breast Cancer Case-Control Consortium. CHEK2*1100delC and susceptibility to breast cancer: A collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 2004; 74:1175.
Reprinted by permission from Nature: Nature Reviews Clinical Oncology. Tung N, Domchek SM, Stadler Z, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol 2016; 13:581. Copyright © 2016. http://www.nature.com/nrclinonc/.
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