325P - The clinical validity of histological grade in neoadjuvant treated breast cancer

Background

The Nottingham histological grading (NHG) system has shown robust prognostic implication in breast cancer. However, the independent prognostic value of the NHG system in neoadjuvant setting has not been demonstrated yet.

Methods

505 neoadjuvant treated (NT) patients with available grades for core needle biopsy (CNB) and subsequent resection specimen (RS) were evaluated. To adjust for pre-analytical/analytical bias between CNB and RS, the grades were compared with a control cohort (CC) of 297 primary operated patients. The change of grade between CNB and RS was compared, by Wilcoxon signed rank test and quadratic weighted kappa. As expected, the group of NHG1-cases was small with low event rate so the groups of NHG1 and NHG2 were merged. Survival curves for overall survival were estimated using the Kaplan-Meier method and a 2-sided log-rank test. Univariate Cox proportional hazards models were used to report hazard ratios (HR) with 95% CIs for NHG for CNB, RS and computed delta-values between the two. Multivariate Cox proportional hazards regression was performed calculating adjusted hazard ratios for established prognostic markers.

Results

We found a significant decrease in grade from CNB to subsequent specimen (p-value < 0,001 and kappa = 0,40). Patient group with NHG high tumors (NHG3) had significantly worse overall survival compared to that of NHG low (NHG1+2) assessed on either CNB or RS (p-value < 0.001). Univariate analysis showed higher risk for death for NHG high tumors in both CNB (HR:2.05, CI:1.39-3.03, p<0.001) and RS (HR:3.20, CI:2.17-4.71, p<0.001). In multivariate analysis adjusted for age, clinical T-stage, clinical N-stage, ER-status and Her2-status the NHG for RS remained an independent prognostic marker (HR:2.07, CI:1.25-3.43, p = 0.005).

Conclusions

Neoadjuvant treatment affects NHG with a significant decrease in grade from core biopsy sample to resection specimen. In the neoadjuvant setting, grades in core biopsy sample is not associated with independent prognostic implications. The grade for the resection specimen after neoadjuvant treatment shows independent prognostic implication adjusted for established prognostic markers. Therefore, we recommend continuing to perform NHG in resection specimen after neoadjuvant therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Karolinska Institutet.

Funding

Has not received any funding.

Disclosure

B. Acs: Financial Interests, Institutional, Funding: The Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning). J. Hartman: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Novartis, Pfizer, EliLilly, MSD, Gilead, Sakura; Financial Interests, Personal, Other, Co-counder and shareholder: Stratipath; Financial Interests, Institutional, Research Funding: AstraZeneca, Roche, MSD, Novartis. All other authors have declared no conflicts of interest.