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

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05642104
• Other study ID #: Z211100002921033
• Status: Recruiting
• Start date: October 1, 2021
• Est. completion date: October 1, 2024

Study information

• Verified date: November 2022
• Source: Beijing Shijitan Hospital, Capital Medical University
• Contact: Hongyan Huang, PHD
• Phone: 18911358631
• Email: hhongy1999[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 175
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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;

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Neoadjuvant therapy
all procedures is in accordance with international guidelines and domestic expert consensus on breast cancer.

Locations

Country	Name	City	State
China	Beijing Shijitan Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Shijitan Hospital, Capital Medical University

Country where clinical trial is conducted

China, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Disease-free survival (DFS)	It refers to the length of time from the start of medication after enrollment to the death of the patient because of the recurrence, distant metastasis of the disease, invasive contralateral breast cancer, or any other cause.	Within 5 years after surgery
Other	Overall survival (OS)	It refers to the length of time from the start of treatment to the death of the patient.	Within 10 years after surgery
Other	CEA(carcinoembryonic antigen)	Counts of international units per milliliter (IU/mL) of tumor marker CEA	Up to 24 weeks.
Other	CA125(Carbohydrate antigen125)	Counts of international units per milliliter (IU/mL) of tumor marker CA 125	Up to 24 weeks.
Other	CA199(Carbohydrate antigen199)	Counts of international units per milliliter (IU/mL) of tumor marker CA 199	Up to 24 weeks.
Primary	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.
Primary	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.
Primary	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.