Does PREDICT Accurately Estimate Breast Cancer Survival?

Cristina Ferrario

August 15, 2022

The PREDICT score does not seem to be particularly accurate when it comes to estimating overall survival (OS) in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2–targeted therapies. This is the conclusion of an international study published in the journal npj Breast Cancer. The work was supervised by Matteo Lambertini, MD, PhD, an oncologist at the IRCCS San Martino Polyclinic Hospital in Genoa, Italy.

As the authors explain, "PREDICT is a publicly available online tool that helps to predict the individual prognosis of patients with early breast cancer and to show the impact of adjuvant treatments administered after breast cancer surgery." The tool uses traditional clinical-pathological factors. The authors also point out that the original version of this tool was validated in several datasets of patients with breast cancer. In 2011, it was updated to include HER2 status.

The investigators noted that although the use of PREDICT is recommended to aid decision-making in the adjuvant setting, its prognostic role in patients with HER2-positive early breast cancer who are treated with modern chemotherapy and anti-HER2 therapies — even trastuzumab-based ones — remains unclear.

Therefore, they decided to analyze PREDICT's prognostic performance using data extracted from the ALTTO trial, the largest adjuvant study ever conducted in the field of HER2-positive early breast cancer. That trial "represented a unique opportunity to investigate the reliability and prognostic performance of PREDICT in women with HER2-positive disease," according to the investigators. They went on to specify that ALTTO evaluated adjuvant lapatinib plus trastuzumab vs trastuzumab alone in 8381 patients — 2794 of whom were included in their own analysis.

What the analysis found was that, overall, PREDICT underestimated 5-year OS by 6.7%. The observed 5-year OS was 94.7%, and the predicted 5-year OS was 88.0%.

"The underestimation was consistent across all subgroups, including those according to the type of anti-HER2 therapy. The highest absolute differences were observed for patients with hormone receptor–negative disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively)," they wrote. Furthermore, they reported that "the suboptimal performance of this prognostic tool was observed irrespective of type of anti-HER2 treatment, type of chemotherapy regimen, age of the patients at the time of diagnosis, central hormone receptor status, pathological nodal status, and pathological tumor size."

To potentially explain the reasons for the underestimation of patients' OS, the authors questioned whether the population used to validate PREDICT accurately mirrored the real-world population of patients with HER2-positive disease treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies. "Moreover, the current standard of care for early breast cancer is even superior to the treatment received by many patients in the ALTTO study…As such, the discordance between OS estimated by PREDICT and the current real-world OS is expected to be even higher. Therefore," the researchers concluded, "our results suggest that the current version of PREDICT should be used with caution for prognostication in HER2-positive early breast cancer patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies."

This article was translated from Univadis Italy.

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