Assessment of the accuracy of the Gail model in women with atypical hyperplasia

Abstract

Purpose: An accurate estimate of a woman's breast cancer risk is essential for optimal patient counseling and management. Women with biopsy-confirmed atypical hyperplasia of the breast (atypia) are at high risk for breast cancer. The Gail model is widely used in these women, but has not been validated in them.

Patients and methods: Women with atypia were identified from the Mayo Benign Breast Disease (BBD) cohort (1967 to 1991). Their risk factors for breast cancer were obtained, and the Gail model was used to predict 5-year-and follow-up-specific risks for each woman. The predicted and observed numbers of breast cancers were compared, and the concordance between individual risk levels and outcomes was computed.

Results: Of the 9,376 women in the BBD cohort, 331 women had atypia (3.5%). At a mean follow-up of 13.7 years, 58 of 331 (17.5%) patients had developed invasive breast cancer, 1.66 times more than the 34.9 predicted by the Gail model (95% CI, 1.29 to 2.15; P < .001). For individual women, the concordance between predicted and observed outcomes was low, with a concordance statistic of 0.50 (95% CI, 0.44 to 0.55).

Conclusion: The Gail model significantly underestimates the risk of breast cancer in women with atypia. Its ability to discriminate women with atypia into those who did and did not develop breast cancer is limited. Health care professionals should be cautious when using the Gail model to counsel individual patients with atypia.

Fig 1.

Cumulative incidence of invasive breast cancer among women with atypical hyperplasia (atypia) as a function of age. The red line represents the cumulative incidence, corrected for the competing risk of death, in the atypia cohort. For comparison, two lines representing the Gail-predicted and the baseline population risks are included. The blue line reflects the cumulative incidence predicted by the Gail model in this cohort, and the gray line represents the cumulative incidence that serves as the baseline risk for white women in the Gail model calculations.

Fig 2.

Distributions of Gail model risk probabilities in women with atypia who developed breast cancer (cases) and those who did not (noncases). The plot contains estimates for individualized risk at the end of the available follow-up. Given that risk predictions depend on age at benign breast disease (BBD) and length of follow-up, the risk predictions were corrected for these factors before comparison. The graph represents the percent of women whose Gail model risk predictions fell within categories ranging from 0.0 to 0.5 in 0.05 increments. Points connected with lines to facilitate comparison between case and noncase percentages. Though the cases received more predictions in the 10% to 15% interval than the noncases, their average risk prediction was slightly, although not significantly, lower.