GENe EXpression After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery (GENEXAN)

GENe EXpression in Tissues From Operating Field After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery. The GENEXAN Randomized Controlled Genomic Trial

Breast cancer is the most commonly diagnosed cancer in females and the second leading cause of death from cancer in women. It was estimated that 2 million new cases have occurred in 2018 worldwide 1.

Standard anesthetic procedures for the surgery of breast cancer include general and regional anesthesia 2. Growing preclinical and clinical data support the hypothesis that anesthetic choice may affect cancer-related outcomes.

Recurrence in breast cancer was reduced to four-fold in a retrospective study with a 2.5 to 4 year follow up 3. Recurrence and metastasis-free survival, with multivariate analysis, was 94% (95% CI 87,100) versus 82% (74, 91) at 24 months, and 94 (87, 100) versus 77 (68, 87) at 36 months in the paravertebral and general anesthesia patients, respectively, (p=0.013). Currently large confirmatory randomized trials evaluating breast cancer recurrence in patients operated with general or regional anesthesia are yet undergoing 4.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer Female
• Intervention / Treatment: Procedure: General anesthesia; Procedure: Regional anesthesia

Detailed Description

Background: Exposure to general or regional anesthesia, can modulate differently breast cancer biology through a direct activity on cancer cells or indirectly through modifications in host response (immune system, angiogenesis, nervous system). Alterations occur both systemically and locally on the surgical site and is supposed that can affect cancer-related outcomes after months or years.

It is not known whether the action of this short exposure to anesthetics on the host and cancer biology is driven by epigenetic alterations in gene and protein expression during the immediate to early post-anesthesia period.

An altered gene and protein expression profile may affect the response of the immune system, angiogenesis and the nervous system and induce more or less propitious conditions to tumor progression. Data from studies in animals and humans show that gene expression may change in the brain and heart after only a short exposure to general anesthesia and that changes may persist for several weeks.

Methods: The GENEXAN is a randomized, controlled, monocentric, genomic trial aiming to test the hypothesis that regional (paravertebral) anesthesia, compared to general anesthesia, would elicit a differential gene and protein expression pattern in cancer tissue and normal surgical microenvironment after breast cancer surgery in women.

Discussion: This research will serve to map gene and protein expression profile after surgery with different anesthetics and elucidate which genes specific to biological systems may affect tumor biology in the immediate operative period.

The findings may also address further research depending on the tissue specificity of the up or down-regulated genes.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women 18-85 years old
• No undergoing pregnancy
• ASA Score I-IV
• Patients scheduled for breast surgery
• No contraindications (including surgical) to regional (paravertebral) anesthesia
• No previous breast surgery
• No known hereditary or familial cancer syndromes
• No previous cancer anamnesis, radio o chemiotherapy
• Primary breast cancer with Tumor classification 1-3, Nodes 0-2 as determined
• according to the NCI stage definitions (Primary breast cancer without known extension beyond the breast and axillary nodes)
• Free from pain in preoperative period
• Patients who don't use analgesic drugs before surgery
• Patients without cognitive impairment or mental retardation

Exclusion Criteria:

• Women > 18, < 85 years old
• Pregnancy
• ASA Score > IV
• Previous breast surgery
• Contraindications to regional anesthesia
• Known hereditary or familial cancer syndromes
• Previous cancer anamnesis, radio or chemiotherapy
• Tumor classification > 3, Nodes > 2, M > 0 as determined according to the NCI stage
• definitions
• Pain in preoperative period
• Use of analgesic drugs before surgery
• Cognitive impairment or mental retardation
• Patients who did not gave a written informed consent
• Undergoing therapy with alpha (doxazosin) or beta blockers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: General anesthesia; Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)	Procedure: General anesthesia; Sevoflurane and morphine
Experimental: Regional anesthesia; Breast cancer surgery (Tumor Stage 1-3, Nodes 0-2 as determined according to the NCI stage definitions http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page3/print)	Procedure: Regional anesthesia; Paravertebral block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole genome expression by microarray	tumor, biopsy, normal wound tissue	before tumor excision
Whole genome expression by mircoarray	tumor, wound tissue	during surgery (just after tumor excision)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	before tumor excision
cancer recurrence	local or distant metastasis	each 6 months for up to 7 years
survival from cancer	death	each 6 months for up to 7 years
Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at the end of surgery
Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at 24 hours
Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at 168 hours

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera San Gerardo di Monza

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: GENEXAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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