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Francesco Schettini: Molecular changes induced by neoadjuvant CT and ET in breast cancer

Photo taken from Francesco Schettini/X

Jul 2, 2024, 15:04

Francesco Schettini: Molecular changes induced by neoadjuvant CT and ET in breast cancer

Francesco Schettini, Medical Oncologist at the Breast Unit of the Hospital Clinic of Barcelona and Postdoc Researcher at the IDIBAPS, shared a post on their X:

“Super proud to share our new study unraveling the clinicopathological and molecular changes induced by neoadjuvant CT and ET in HR+/HER2-low and HER2-0 breast cancer, just published in ESMO Open.

We hereby present an analysis focused on dissecting molecular, pathologic, gene expression changes and HER2 status dynamics under NACT and NET in HR+/HER2-low versus HR+/HER2-0 tumors and their potential prognostic implications..

We included 186 patients with stage I-IIIB HR+/HER2-negative BC treated as per SOC NACT or NET at the hospital clinic:

1) 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT, not NET, with consistent ERBB2 mRNA dynamics.

Francesco Schettini

2) Similar gene expression, PAM50 intrinsic subtype and ROR-P changes were induced in HER2-0 and HER2-low BC by NACT and NET, with shift to Normal-like and Luminal A disease, ROR-P-low risk category and consistent genomic up/down regulations

Francesco Schettini

Specifically, we observed a significant down-regulation of PAM50 proliferation- and luminal-related genes/signatures and an up-regulation of selected immune genes. At IHC reduction of ER, PgR and Ki67 % were induced in both HER2-0 and HER2-low, no TILs changes observed

Gene expression changes were similar regardless of neoadjuvant treatment

Francesco Schettini

The % of patients achieving pCR, RCB-1 or RCB-2/3 was not dissimilar according to HER2 status, nor EFS and OS

Francesco Schettini

To note, at univariate analysis, a stability in HER2 IHC status from baseline to surgery was associated with worse EFS (P = 0.003) and OS (P = 0.030) than HER2 shifts (from 0 to low or positive and from low to 0 or positive), but lost significance at the multivariable analyses

These result can help tailoring new targeted adjuvant strategies and support not relying on HER2 IHC levels in HR+/HER2-negative BC for molecular downstaging-based approaches. HER2-low-targeting should be explored to pursue more effective and/or less toxic dimensional downstaging.”

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Source: Francesco Schettini/X