Risk score predicts recurrence risk in women with DCIS

SAN ANTONIO — A novel biological risk score improved the ability to predict recurrence risk among women with ductal carcinoma in situ who received radiotherapy after undergoing breast-conserving surgery, according to results from a multivariate interaction analysis of the SweDCIS trial presented at the San Antonio Breast Cancer Symposium.

Better risk and treatment benefit prediction tools are needed for women with DCIS and their physicians. Moreover, the effect of radiotherapy on recurrence risk among women with DCIS who have undergone breast-conserving surgery is unclear.

Researchers at Kaiser Permanente NW validated a DCIS biologic signature — DCISionRT (PreludeDx) — in an observational study.

Fredrik Wärnberg , MD, PhD, associate professor of surgery at Uppsala University in Sweden, and colleagues assessed the predictive utility of DCISionRT by assessing the 10-year benefit of adjuvant radiotherapy on ipsilateral breast events and invasive breast cancer risks among 1,046 women in the SweDCIS trial. All women underwent breast-conserving surgery between 1987 and 1999 and were randomly assigned to receive or not receive radiation.

DCISionRT consists of four clinical factors (age, size, margin and palpability) and seven biomarkers measured by immunohistochemistry — HER-2, PR, Ki67, COX2, p16/INK4A, FOXA1 and SIAH2 — to calculate a continuous decision score of 0 to 10. Researchers used these findings to categorize women into a low-risk group (score 3) or elevated-risk group (score > 3).

Researchers randomly assigned 584 women with complete biomarker and clinical information to breast-conserving surgery alone (n = 291) or breast-conserving surgery plus radiotherapy (n = 293).

Among 506 women with clear margins, researchers observed 78 ipsilateral breast events — including 31 inflammatory breast cancers — within 10 years of diagnosis.

A multivariate analysis of the decision score and radiotherapy interaction appeared significant for risk for an ipsilateral breast event (P = .048) and invasive breast cancer (P < .001) at 10 years.

Researchers observed a nonsignificant 16% reduction (HR = 0.84; 95% CI, 0.32-2.22) in risk for invasive breast cancer among women at low risk in the radiotherapy arm, equating to a 1% absolute benefit with radiotherapy for these women. Conversely, those at elevated risk had a 76% risk reduction (HR = 0.24; 95% CI, 0.08-0.76), equating to 9% absolute benefit.

Radiotherapy also benefited the low-risk group (HR = 0.48; 95% Ci, 0.24-0.97) and elevated-risk group (HR = 0.31; 95% CI, 0.17-0.59) in terms of any ipsilateral breast event.

The decision score variable correlated with ipsilateral breast event, where each five-unit increase was associated with an HR of 1.49 (95% CI, 1.02-2.18).

“The effect that was calculated in the current cross-validation set turns out to be the same effect observed in the original SweDCIS randomized study — the data were highly consistent between these two sets,” Wärnberg said during his presentation. “The biological risk score correlated to a prognostic risk, which is not new knowledge. What is new knowledge is that the risk score predicted for radiotherapy benefit. Not all patient groups achieved the same benefit with radiotherapy.” – by Jennifer Southall

References:

Wärnberg F, et al. Abstract GS5-08. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.

Wärnberg F, et al. J Clin Oncol. 2014;doi:10.1200/JCO.2014.56.2595.

Disclosures: The study was funded in part by PreludeDx. Wärnberg reports research funding from PreludeDx. Please see the abstract for all other authors’ relevant financial disclosures.