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

Breast Cancer Female Clinical Trial

— GENEXAN  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03779685
• Other study ID #: GENEXAN
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: August 2020
• Source: Azienda Ospedaliera San Gerardo di Monza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms

Intervention

Procedure:
• General anesthesia
Sevoflurane and morphine
• Regional anesthesia
Paravertebral block

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera San Gerardo di Monza

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Whole genome expression by microarray	tumor, biopsy, normal wound tissue	before tumor excision
Primary	Whole genome expression by mircoarray	tumor, wound tissue	during surgery (just after tumor excision)
Secondary	Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	before tumor excision
Secondary	cancer recurrence	local or distant metastasis	each 6 months for up to 7 years
Secondary	survival from cancer	death	each 6 months for up to 7 years
Secondary	Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at the end of surgery
Secondary	Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at 24 hours
Secondary	Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII	in blood	at 168 hours