Evaluation of Recurrence Risk Factors in Locally Advanced Breast Cancer Patients Underwent Neoadjuvant Chemotherapy. (NEORISK)

Evaluation of Recurrence Risk Factors in Locally Advanced Breast Cancer Patients Underwent Neoadjuvant Chemotherapy. The NEORISK Study.

INTRODUCTION Breast cancer (BC) is the leading cause of cancer-related death in women. Since the early 1980s, the implementation of screening programs has reduced the number of patients diagnosed with locally advanced breast cancer. Currently, the treatment for these patients involves initial neoadjuvant chemotherapy (NACT) followed by surgical treatment. In recent years, NACT has also been used for highly chemoresponsive tumors such as triple-negative (TN) and HER2-positive (HER2+) breast cancer.

The widespread use of NACT has led to additional benefits, including downstaging of breast and axillary neoplasms, resulting in reduced morbidity; improved cosmetic outcomes due to increased use of conservative interventions; and personalized adjuvant chemotherapy treatment. Several studies have shown that response to chemotherapy predicts better systemic outcomes. Complete pathological response (pCR), defined as the absence of invasive neoplastic residue in the surgical specimen, has been predictive of better distant outcomes. Limited evidence exists regarding other predictive factors for distant outcomes.

Given the significant impact of disease recurrence on patient prognosis, efforts have been made to understand the factors contributing to recurrence and to predict which patients are more prone to relapse. In this context, the term "Early Disease Recurrence" (EDR) has been coined to define the occurrence of disease recurrence, both locally and distantly, within 3 years after completing treatment.

In recent years, the potential of radiomic analysis in aiding diagnostic and therapeutic decision-making processes in BC has been demonstrated. Specifically, radiomic features obtained from Magnetic Resonance Imaging (MRI) images appear capable of predicting tumor receptor status, differentiating tumor subtypes, and predicting response to NACT.

Although the role of radiomics in predicting recurrence has been investigated, research is still in its early stages, and there are variations in technology and methodology for extracting radiomic features. Additionally, to date, no studies have evaluated the feasibility and reliability of using radiomic models combined with clinical and radiological variables to predict disease recurrence in BC patients undergoing NACT.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Triple Negative Breast Cancer; Chemotherapy Effect; Risk Factors; Recurrence, Local Neoplasm
• Intervention / Treatment: Diagnostic test: MRI

• Study Type: Observational
• Enrollment (Estimated): 933

Contacts and Locations

• Study Contact: Name: Alessandra Fabi; Phone Number: 0630157337; Email: alessandra.fabi@policlinicogemelli.it
• Study Contact Backup: Name: Antonio Franco; Phone Number: 0630157337; Email: antonio.franco@guest.policlinicogemelli.it

Study Locations

• Italy
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli - IRCCS
    • Contact: Alessandra Fabi; Phone Number: +390630153773; Email: alessandra.fabi@policlinicogemelli.it
    • Contact: Alessandra Fabi; Phone Number: +390630155701; Email: alessandra.fabi@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All patients with breast cancer (Stage I, II, and III) undergoing NACT at our center between January 2014 and June 2021 will be included, for an estimated total of 933 patients.

Description

Inclusion Criteria:

• Histological diagnosis of locally advanced Luminal or HER2+ or Triple-negative breast cancer (cT2, T3, T4 N0 or any T N1, N2, N3, M0), clinical stage of disease from I to III.
• Patient undergoing neoadjuvant chemotherapy treatment from January 1, 2014, to June 30, 2021.
• Age > 18 years
• Availability of clinical data, staging MRI diagnostic images (for the radiomic sub-study), and biomolecular data.

Exclusion Criteria:

• Previous or synchronous history of systemic malignancies.
• History of ipsilateral or contralateral breast neoplasia.
• Evidence of metastatic disease (Stage IV).
• Neoadjuvant treatment with hormone therapy.
• Patients with unavailable or low-quality MRI images that did not allow lesion identification (for the radiomic study only).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast cancer patients underwent neoadjuvant chemotherapy; Patients undergoing neoadjuvant chemotherapy and subsequent surgical treatment. Patients must have undergone radiological evaluation by MRI at the beginning and end of chemotherapy treatment	Diagnostic test: MRI; Breast MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of molecular subtypes	Frequency of molecular subtypes (Her2 positive, hormone receptor-positive/Her2 negative, Triple Negative) in the considered cases	7 years
Association between radiomic features and risk of recurrence	Association between radiomic features extracted from pre-operative MRI and the onset of disease recurrence within 3 years from the end of neoadjuvant treatment	7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between chemotherapy and neoplastic characteristics	Evaluate whether clinical features (divided into: age assessed in years, menopausal status divided into menopausal or fertile age), radiological features such as initial extent of disease and lymph node involvement at diagnosis) and biomolecular features (such as histotype: divided into ductal, lobular or nonspecial type, grading, hormone receptor status) influence response to neoadjuvant chemotherapy Translated with DeepL.com (free version)	7 years
Evaluation of radiological response	Frequency of radiological response according to molecular subtype, treatment, type of imaging examination used, and initial staging.	7 years
Frequency of complete pathological response	Frequency of complete pathological response according to molecular subtype, treatment, and initial staging.	7 years
Description of surgical treatment according to the cancer characteristics	Frequency of surgical procedures based on radiological response, molecular subtypes, and initial staging.	7 years
Description of adjuvant treatments	Frequency of adjuvant therapies based on neoadjuvant treatment, molecular subtypes, and initial staging.	7 years
Evaluation of oncological outcomes	Disease-free survival (DFS) measured from the start of neoadjuvant therapy to the first evidence of disease recurrence or death, whichever occurs first.	7 years
Assessment of risk of recurrence using models	Accuracy of pure models (radiomic/clinical/radiological) and combined models in predicting disease recurrence within 3 years from the end of neoadjuvant treatment	7 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Alessandra Fabi, Policlinico Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Estimated): June 4, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Recurrence; Triple Negative Breast Neoplasms; Neoplasm Recurrence, Local
• Other Study ID Numbers: 6081

Drug and device information, study documents

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