Table 1.
Identification of women age 50 years in a UK population at moderate and high-risk of invasive breast cancer*
| Parameter | Model 1: Qx risk factors† | Model 2: Qx risk factors + density | Model 3: 76-SNP PRS |
Model 4: Qx risk factors
+ 76-SNP PRS |
Model 5: Qx risk factors
+ density + 76-SNP PRS |
Model 6: Improved PRS |
Model 7: Qx risk factors
+ improved PRS |
Model 8: Qx risk factors
+ density + improved PRS |
|---|---|---|---|---|---|---|---|---|
| AUC | 0.618 | 0.635 | 0.624 | 0.670 | 0.680 | 0.672 | 0.703 | 0.708 |
| % Population (% cases) at different risk thresholds‡ | ||||||||
| Moderate risk (RR > 2.0 - 3.0) | 3.8 (8.8) | 4.3 (10.0) | 3.6 (8.2) | 5.5 (13.0) | 5.8 (13.7) | 6.0 (14.1) | 6.0 (14.4) | 6.1 (14.7) |
| High risk (RR > 3.0) | 1.0 (3.7) | 1.3 (4.8) | 0.4 (1.4) | 2.4 (9.3) | 2.7 (10.8) | 2.1 (8.1) | 3.8 (16.0) | 4.1 (17.5) |
* Defined as relative risk (RR) > 2.0–3.0 and RR > 3.0, respectively, compared with the population average and for different combinations of risk factors and two polygenic risk scores (PRS). The following parameters are shown for eight risk prediction models: AUC, the % of the population found at moderate and high levels of risk according to the different models, and the % of cases in the population expected to occur among women at these levels of risk. AUC = area under the receiver operating characteristic curve; PRS = polygenic risk score; Qx = questionnaire; RR = relative risk; SNP = single nucleotide polymorphism.
† Questionnaire-based risk factors include age at menarche, parity, age at first birth, combined MHT, body mass index, benign breast disease, alcohol intake, smoking, and family history of breast cancer in first-degree relatives.
‡ Lifetime risk (from age 20 to 80 years), 10-year and five-year risk thresholds corresponding to RRs of 2.0 and 3.0 for a woman age 50 years: RR = 2.0: 19.4% lifetime risk, 5.2% 10-year risk and 2.6% five-year risk; RR = 3.0: 27.5% lifetime risk, 7.8% 10-year risk and 3.9% five-year risk.