Clinical trial NCT03779685: GENe EXpression After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer Female
Lead sponsor: Azienda Ospedaliera San Gerardo di Monza
Sponsor class: OTHER
First posted: 2018-12-19
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Whole genome expression by microarray
timeFrame: before tumor excision
measure: Whole genome expression by mircoarray
timeFrame: during surgery (just after tumor excision)
Secondary outcomes:
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
timeFrame: before tumor excision
measure: cancer recurrence
timeFrame: each 6 months for up to 7 years
measure: survival from cancer
timeFrame: each 6 months for up to 7 years
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
timeFrame: at the end of surgery
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
timeFrame: at 24 hours
measure: Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII
timeFrame: at 168 hours
Other outcomes:
Locations:
Study officials:
References: