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.

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.

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

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.

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.