A Composite Assay for HER2-positive Early-stage Breast Cancer Management (HERCard)

The goal of this observational study is to assess the prognostic value of a genomic classifier (S18) and its refined version (S*) in women with early-stage HER2-positive breast cancer. The study aims to determine whether these tools can predict event-free (EFS) and disease-free survival (DFS) in patients treated with neoadjuvant and/or adjuvant trastuzumab-based therapies.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3); HER2

Detailed Description

The population includes women aged 18 or older with stage I-III HER2-positive breast cancer who received trastuzumab ± pertuzumab. Data and tumor tissue samples from this population have been collected prospectively from Istituto Nazionale dei Tumori IRCCS Fondazione Pascale, Naples (cohort A), and from Ospedale "Di Summa-Perrino", Brindisi (cohort B). The study integrates clinical-pathological and genomic data to refine and validate the prognostic capabilities of the S18 classifier.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Serena Di Cosimo, MD, PhD; Phone Number: +39 02 2390 2700; Email: serena.dicosimo@istitutotumori.mi.it
• Study Contact Backup: Name: Paolo Verderio, PhD; Phone Number: +39 02 2390 3201; Email: paolo.verderio@istitutotumori.mi.it

Study Locations

• Italy
  • Brindisi, Italy, 72100
    • Recruiting
    • Ospedale Di Summa-Perrino
    • Contact: Saverio Cinieri, MD; Phone Number: +39 0831537217; Email: saverio.cinieri@gmail.com
    • Principal Investigator: Laura Orlando, MD
  • Naples, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
    • Contact: Michelino De Laurentiis, MD; Phone Number: +39 081590369 +39 081 7461111; Email: m.delaurentiis@istitutotumori.na.it
    • Principal Investigator: Roberta Caputo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Clinical information and paraffin-embedded tumor tissue samples from HER2-positive operable breast cancer patients included in the study were prospectively and consecutively collected at the participating centers and are now being analyzed for the purpose of the protocol.

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Operable breast cancer (stage I-III)
3. Any status of hormone receptor in the primary tumor, according to institutional guidelines
4. HER2-positive primary tumor, according to ASCO guidelines, i.e., HER2-positive phenotype by immunohistochemistry (IHC) 3+ or 2+ with a positive result for ERBB2 gene amplification analysis using ISH techniques (CISH, SISH, FISH)
5. Neoadjuvant and/or adjuvant therapy based on trastuzumab ± pertuzumab
6. Written informed consent from patients

Exclusion Criteria:

1. Patient in follow-up for less than 3 years after surgery
2. A prior diagnosis of invasive cancer before the diagnosis of breast cancer

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS) and Disease-free survival (DFS) according to the value of S18 and S*	To assess the prognostic value of the gene expression based classifier, with or without the integration of clinical-pathological variables, in patients receiving neoadjuvant and/or adjuvant chemotherapy with trastuzumab ± pertuzumab, with respect to event-free survival (EFS) and disease-free survival (DFS).	From the initiation of systemic therapy through to at least 3 years post-treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explorative evaluation of overall survival (OS) according to the value of S18 and S*	To assess the prognostic value of the gene expression based classifier, with or without the integration of clinical-pathological variables, in patients receiving neoadjuvant and/or adjuvant chemotherapy with trastuzumab ± pertuzumab, with respect to overall survival (OS).	From the initiation of therapy through to at least 3 years post-treatment.
Evaluation of pathological complete response (pCR) according to the value of S18 and S*	To evaluate the predictive value of the gene expression based classifier in relation to pathological complete response (i.e., absence of breast cancer cells in surgical specimens) following neoadjuvant therapy with chemotherapy plus trastuzumab ± pertuzumab.	Assessed in the surgical specimen obtained from definitive surgery performed within up to 10 months of initiating neoadjuvant treatment.

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale; Ospedale Di Summa-Perrino
• Investigators: Principal Investigator: Serena Di Cosimo, MD, PhD, Fondazione IRCCS Istituto Nazionale dei tumori di Milano; Study Chair: Paolo Verderio, PhD, Fondazione IRCCS Istituto Nazionale dei tumori di Milano

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: prognosis; HER2-positive; operable breast cancer; gene-expression based classifier
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: INT 138/24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Our best efforts will be made to make IPD available in accordance with privacy, data security, and compliance with legal and ethical standards in place at the time of the study's conclusion. As of now, while the sharing of IPD remains a goal, these factors may occasionally present challenges that will need to be carefully addressed to ensure all necessary protections are in place at the appropriate time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No