Fine tuning of the Van Nuys prognostic index (VNPI) 2003 by integrating the genomic grade index (GGI): new tools for ductal carcinoma in situ (DCIS).

ABSTRACT

Ductal carcinoma in situ (DCIS) is considered a heterogeneous premalignant condition of the breast with a certain probability for progressing to malignancy. There is no standard of care. The updated Van Nuys Prognostic Index (VNPI) 2003 is a clinical tool in treatment decision making. This study assessed the prognostic value of the VNPI after integration of proliferative biomarkers (GGI and Ki-67). DCIS samples were divided into three VNPI subgroups (low risk [score 4-6], intermediate risk [score 7-9], high risk [score 10-12]) based on nuclear grade ± necrosis, tumor size, margin width, and age. Nuclear grade was substituted by the genomic grade index (GGI) to generate the VNPI-GGI and combined with the Ki-67 to generate the VNPI-Ki67. Disease-free survival was calculated by Kaplan-Meier survival plots with log-rank significance. Multiple regression analysis was carried out using Cox proportional hazard regression analysis. A total of 88 cases (median age 54 years) with representative tissue were identified out of 168 DCIS patients. Median follow-up was more than 5 years. Ten patients developed an ipsilateral recurrence of whom nine were invasive six patients were classified in the VNPI subgroup 2 and three patients in the VNPI subgroup 3. One non-invasive recurrence (DCIS) was classified in the VNPI subgroup III. A statistical association was observed between a high VNPI score and a higher risk of recurrence (HR = 7.72 [95% CI 1.01-58.91], p = 0.049). Ki-67 did not improve the prognostic value of VNPI (HR = 6.5, [95% CI 0.80-53.33], p = 0.08). In contrast, the VNPI-GGI could identify more accurately high-risk DCIS patients with early relapses within 5 years (HR = 18.14 [95% CI 1.75-188], p = 0.015). GGI incorporated into the VNPI improved its prognostic value for DCIS, especially for identifying early relapses. This method should be validated and incorporated in future prospective clinical DCIS trials.