A Prospective Evaluation of the Peri-operative Hypoxia in Breast Cancer (Hypoxia)

To understand the effects induced by acute hypoxia that sets in during surgery in breast cancer. To study this, clinical samples (Tumor biopsies) will be obtained during the surgery after partial devascularisation (sample B) and stored for future genomic and proteonomic evaluations.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Female
• Intervention / Treatment: Procedure: Intra-operative Tumor Tissue Biopsy

Detailed Description

Three tumor samples will be obtained after the patient is under anaesthesia,

1. Prior to starting surgery (Sample A)
2. The middle intra-operative sample, which will be collected when half the tumour has been devascularized (i.e., somewhere midway during the surgery). (Sample B)
3. A third post excision (anoxic sample C). These tumour tissue samples will be stored as snap frozen, in RNA later and as paraffin sections.

To understand the effects induced by acute hypoxia that sets in during surgery in breast cancer. To study this, clinical samples (Tumor biopsies) will be obtained during and stored for future genomic and proteonomic evaluations.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Shalaka Joshi, MS, MCh; Phone Number: 4265 9869089803; Email: drjoshishalaka@gmail.com
• Study Contact Backup: Name: Rohini A Hawaldar; Phone Number: 09820432613; Email: rwhawaldar@gmail.com

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Tata Memorial Center
      • Contact: Shalaka Joshi, MS, MCh; Phone Number: 4265 22241608601; Email: drjoshishalaka@gmail.com
      • Contact: Rohini A Hawaldar, BSc; Phone Number: 09820432613; Email: rwhawaldar@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women diagnosed with breast cancer at outpatient clinic

Description

Inclusion Criteria:

1. Clinically diagnosis of breast cancer (by FNAC or Biopsy)
2. Not received any chemotherapy or surgical intervention except core biopsy.
3. Planed for Breast cancer surgery
4. Willing to give consent for the study

Exclusion Criteria:

1. Clinically diagnosis of Metastatic breast cancer
2. Received any anticancer therapy

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Intra-operative tumour tissue biopsies; Intra-operative tumour tissue biopsies will be collected for all patients

Procedure: Intra-operative Tumor Tissue Biopsy; The changing pattern of gene expression during surgery has never been studied. This could be an effect of acute hypoxia that sets in the tumour during surgery or could be a surgical response. To study these changes happening in the tumour during surgery, we are taking serial biopsies during surgery, one at the beginning, one midway during surgery and one at the end of surgery. These samples will be snap frozen and stored at -80 deg celsius in biorepository for future analysis.; Other Names: Breast cancer surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression changes	The primary outcome measured will be gene expression changes during surgical resection. Messenger ribonucleic acid (mRNA) transcripts will be quantitated and their levels evaluated during different time-points of surgical resection, using high throughput omics technologies (Next generation sequencing, nanostring ncounter, qRT-PCR array).	The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunohistochemistry for other markers	The secondary outcome measured will be protein expression changes during surgical resection. Protein levels will be quantitated, and their levels evaluated, during different time-points of surgical resection. Transcripts found to be de-regulated or changed at different time-points of surgical resection will be evaluated using IHC at protein level. We will also use high throughput omics technologies (SILAC, ITRAQ) for characterising these changes at protein levels.	The study aims to evaluate gene expression changes during surgical resection, which lasts for 30-90 minutes on an average. Thus, we have not planned a clinical follow-up or collection of data for the patients post sampling during surgical resection.

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Rajendra Badwe, Director, Tata Memorial Centre

Publications and helpful links

General Publications

• Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene. 2013 Aug 29;32(35):4057-63. doi: 10.1038/onc.2012.578. Epub 2012 Dec 10.
• Hockel M, Vaupel P. Biological consequences of tumor hypoxia. Semin Oncol. 2001 Apr;28(2 Suppl 8):36-41.
• Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer. 2013 Aug 2;12:86. doi: 10.1186/1476-4598-12-86.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Anticipated): July 30, 2024
• Study Completion (Anticipated): November 30, 2025

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: January 4, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Signs and Symptoms, Respiratory; Breast Neoplasms; Hypoxia
• Other Study ID Numbers: Protocol 254

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