Single-cell RNAseq Breast Cancer (SCRBC)

Study of the Impact of Neoadjuvant Therapy on the Heterogeneity of Triple Negative Breast Cancer Through Single-cell RNA Sequencing (scRNAseq) and Whole-exome Sequencing (WES)

Molecular characterization of persistent tumor cells remaining after NAC and infiltrating immune cells, for example, M2 macrophages, could strongly contribute to identifying targeted therapeutic approaches for this disease.

Study Overview

• Status: Recruiting
• Conditions: Breast Neoplasms
• Intervention / Treatment: Other: Single-cell RNA sequencing (scRNAseq), whole-exome sequencing (WES)

Detailed Description

Triple negative breast cancer (TNBC) represents approximately 15-20% of all breast cancers. Its features are lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). TNBC exhibits a biologically aggressive behavior and a high inter- and intra-tumor molecular heterogeneity which has recently been highlighted also in single cell RNAseq (scRNAseq) studies. Patients with TNBC often have less positive outcomes then other breast cancer subtypes, due to the absence of specific therapeutic targets.

Results of single cell RNA sequencing (scRNAseq) in TNBC before and after treatment with chemotherapy (NAC) were recently reported for a small group of patients. Genetic alterations are also investigated by Whole Exome Sequencing (WES).

In addition scRNAseq analysis confirmed the presence of a high percentage of M2 macrophages in TNBC and tumor-adjacent tissue. These macrophages are clinically relevant and able to predict outcome in TNBC.

Based on the above evidence, we hypothesize that molecular characterization of persistent tumor cells remaining after NAC and infiltrating immune cells, for example, M2 macrophages, could strongly contribute to identifying targeted therapeutic approaches for this disease.

We will conduct a pilot study with a combined retrospective and prospective observational design.

Cancer patients diagnosed with histologically proven primary invasive breast cancer with a stage IIA to IIIB and assessed at the molecular level and defined as TNBC, will be eligible to participate to the study. Furthermore, only patients with a tumor >1.5cm in size will be considered, which is the selection criterion for the administration of neoadjuvant therapy.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Giovanni Blandino; Phone Number: +39 06 52662911; Email: giovanni.blandino@ifo.gov.it

Study Locations

• Italy
  • Roma, Italy, 00161
    • Recruiting
    • Policlinico Umberto I
    • Contact: Paolo Marchetti
  • Rome, Italy, 00144
    • Recruiting
    • "Regina Elena" National Cancer Institute

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The retrospective study will be performed using only formalin-fixed paraffin-embedded (FFPE) tissue samples for protein expression profiling (proteomics) from patients withthe above inclusion/exclusion criteria from the archives of the Pathological anatomy of the IRE.

The prospective study foresees the collection of biological samples by the centers involved in the study and the freezing of all the samples at the IRE Biological Bank.

Description

Inclusion Criteria:

• Patients with histologically proven primary invasive breast cancer >1.5cm in size, with molecular assessed stage IIA to IIIB defined as TNBC, and who will undergo neoadjuvant chemotherapy and subsequent surgery (and/or have undergone - retrospective part).
• informed consent (prospective part)

Exclusion Criteria:

• pregnancy, metastatic breast cancer, previous chemotherapy, hormone therapy, radiation therapy, previous other cancers or contralateral breast cancer

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate chemoterapy effect	Decipher, through the execution of scRNAseq profiles, the transcriptional reprogramming that occurs during chemotherapy (NAC) in triple negative breast cancers (TNBC) and provide information of prognostic and/or predictive relevance of response to NAC	26 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): December 12, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: March 29, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: RS1637/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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