254P - IHC and GEX biomarkers and their prognostic and treatment predictive role in the neoadjuvant treatment of breast cancer

Background

A preoperative core-needle biopsy (CNB) guides decisions on neoadjuvant chemotherapy (NACT). Biomarkers (ER, PgR, HER2, Ki67 and NHG) assesed by conventional pathology and immuhistochemistry (IHC) inform tumor characterization. Gene expression (GEX) can be used to quantify biomarkers, complementing IHC. This exploratoy study aims to assess the impact of NACT on biomarker status in residual disease, and asses the effect on patient outcome.

Methods

Early breast cancer patients from Skåne and Halmstad (subset of SCAN-B cohort) planned for NACT (2010-2019) were included. Patients were treated per Swedish guidelines. Tumors were analyzed by whole-genome mRNA sequencing, and RNAseq classifiers developed by the SCAN-B group for predicting standard biomarkers were utilized.

Results

Of 443 patients, 23% achieved pCR (29% HR+/HER2+, 6% HR+/HER2-, 59% HR-/HER2+, 30% HR-/HER2-). In residual disease, ER, PgR, HER2, and Ki67 status by IHC between the preNACT biopsy and surgical resection were concordant in 96.3%, 83.7%, 89.9%, and 53.7% of cases, with kappa values of 0.913, 0.678, 0.668, and 0.174, respectively. Similar concordance rates were seen on GEX classifiers. Significant switches were observed from PgR and HER2 positive to negative (p < 0.001 and p=0.02) and from high to low Ki67 (p < 0.001) by IHC. Among HER2-amplified disease, 3+ score on IHC on a preNACT biopsy was associated with a higher pCR rate than 2+ score (48% vs 11%, p<0.001). In ER+ tumors with high Ki67 status as per GEX at baseline, switching to low Ki67 after NACT was prognostic of a superior invasive breast cancer free survival (HR=0.17 [0.06-0.52], p<0.001].

Conclusions

While ER is a stable biomarker, NACT affects PgR, HER2, and Ki67 expression. A reduction in tumor proliferation detected by GEX in luminal tumors is prognostic of a favorable outcome. Strong membrane staining for HER2 (3+ vs 2+) in HER2+ tumors is predictive of pCR. The biological significance of the PgR and HER2 switch should be further explored.

Clinical trial identification

NCT02306096.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fru Berta Kamprads stiftelse, Mats Paulssons Stiftelse, Swiss Cancer Center Biltema Foundation.

Disclosure

All authors have declared no conflicts of interest.