The Detection of Cell-in-cell Structure (CICs) in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy

NCT05642104 | Unknown DMC

• 1 other identifier: Z211100002921033
• Study Type: observational
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is the most common malignant tumor in women worldwide and neoadjuvant therapy has been the standard care for local advanced breast cancer. Moreover, neoadjuvant therapy undoubtedly provides an ideal model to evaluate the response to therapy. Cell-in-cell structures (CICs) refer to the presence of one or more cells inside host cell, which generally leads to the death of inner cells. Notably, established evidences indicated that CICs were present in breast cancer and tend to impact patient survival. However, whether CICs profile could predict efficacy of therapy remains unclear. In this prospective cohort study, the CICs number and profile will be detected in tumor tissue before and after the neoadjuvant therapy. Then the association between CICs number including dynamic changing and response rate will be explored.

Conditions

Breast Neoplasms

Keywords

Breast Neoplasms; cell-in-cell structures; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (3)

• pCR(complete pathological response)

  no invasive malignant cells identifiable in sections from the site of the tumor（Miller-Payne grades 5） the Miller-Payne grades 4 and 5 patients are grouped as responders.

  Up to 24 weeks.

• Objective response rate (ORR)

  Response Evaluation Criteria in Solid Tumors (RECIST)：Progressive Disease (PD); Partial Response (PR); Complete Response (CR); Stable Disease (SD) Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) partial response (PR) to treatment.

  Up to 24 weeks.

• Quantification of CIC structure in tumor tissue

  CICs number and subtypes in tumor tissue (Core needle biopsy specimens before and after neoadjuvant therapy and surgical specimens based on neoadjuvant therapy.)

  Up to 24 weeks.

Other Outcomes (5)

• Disease-free survival (DFS)

  Within 5 years after surgery

• Overall survival (OS)

  Within 10 years after surgery

• CEA(carcinoembryonic antigen)

  Up to 24 weeks.

Study Arms (1)

Single group assignment

Patients with invasive breast cancer who need neoadjuvant therapy.

Drug: Neoadjuvant therapy

Interventions

Neoadjuvant therapy DRUG

all procedures is in accordance with international guidelines and domestic expert consensus on breast cancer.

Single group assignment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with breast cancer treated with neoadjuvant therapy attending Beijing Shijitan Hospital from 2021-2023.

You may qualify if:

• Age 18-65, female;
• Pathological biopsy confirmed invasive ductal carcinoma;
• Karnofsky Performance Status (KPS)≥ 60, expected survival ≥4 months;
• Locally advanced breast cancer (HER2-positive disease and TNBC, ≥cT1c or ≥cN0； HER2-negative，HR positive disease，≥cT2 or ≥cN1；Large primary tumor relative to breast size in a patient who desires breast conservation) ;
• According to the RECIST1.1 standard, at least one measurable lesion exists;

You may not qualify if:

• Pregnant or lactating women;
• Left ventricular ejection fraction less than 50%;
• History of malignant tumor and concurrent occurrence of other tumors;
• Serious medical pathology, such as congestive heart failure; unstable angina; uncontrolled high risk arrhythmias, and other serious illness or medical condition that may interfere with the study;
• Refuse to participate in the study.

Sponsors & Collaborators

• Beijing Shijitan Hospital, Capital Medical University: lead

Study Sites (1)

Beijing Shijitan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100038, China

RECRUITING

Related Publications (8)

• Fais S, Overholtzer M. Cell-in-cell phenomena in cancer. Nat Rev Cancer. 2018 Dec;18(12):758-766. doi: 10.1038/s41568-018-0073-9.

  PMID: 30420767 BACKGROUND

• Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, Cibas ES, Brugge JS. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007 Nov 30;131(5):966-79. doi: 10.1016/j.cell.2007.10.040.

  PMID: 18045538 BACKGROUND

• Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nunez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012 Jan;19(1):107-20. doi: 10.1038/cdd.2011.96. Epub 2011 Jul 15.

  PMID: 21760595 BACKGROUND

• Schwegler M, Wirsing AM, Schenker HM, Ott L, Ries JM, Buttner-Herold M, Fietkau R, Putz F, Distel LV. Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells. Biomed Res Int. 2015;2015:359392. doi: 10.1155/2015/359392. Epub 2015 Oct 4.

  PMID: 26504802 BACKGROUND

• Schenker H, Buttner-Herold M, Fietkau R, Distel LV. Cell-in-cell structures are more potent predictors of outcome than senescence or apoptosis in head and neck squamous cell carcinomas. Radiat Oncol. 2017 Jan 18;12(1):21. doi: 10.1186/s13014-016-0746-z.

  PMID: 28100275 BACKGROUND

• Huang H, Chen A, Wang T, Wang M, Ning X, He M, Hu Y, Yuan L, Li S, Wang Q, Liu H, Chen Z, Ren J, Sun Q. Detecting cell-in-cell structures in human tumor samples by E-cadherin/CD68/CD45 triple staining. Oncotarget. 2015 Aug 21;6(24):20278-87. doi: 10.18632/oncotarget.4275.

  PMID: 26109430 BACKGROUND

• Ruan B, Niu Z, Jiang X, Li Z, Tai Y, Huang H, Sun Q. High Frequency of Cell-in-Cell Formation in Heterogeneous Human Breast Cancer Tissue in a Patient With Poor Prognosis: A Case Report and Literature Review. Front Oncol. 2019 Dec 19;9:1444. doi: 10.3389/fonc.2019.01444. eCollection 2019.

  PMID: 31921689 BACKGROUND

• Zhang X, Niu Z, Qin H, Fan J, Wang M, Zhang B, Zheng Y, Gao L, Chen Z, Tai Y, Yang M, Huang H, Sun Q. Subtype-Based Prognostic Analysis of Cell-in-Cell Structures in Early Breast Cancer. Front Oncol. 2019 Sep 20;9:895. doi: 10.3389/fonc.2019.00895. eCollection 2019.

  PMID: 31681557 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Histopathological section

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Hongyan Huang, PHD

  Beijing Shijitan Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hongyan Huang, PHD

CONTACT

18911358631; hhongy1999@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: December 8, 2022
• Study Start: October 1, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2024
• Last Updated: December 8, 2022

Record last verified: 2022-11

Locations

CN (1)