GENe EXpression in Tissues From Operating Field After Regional or General ANesthesia in Patients Undergoing Breast Cancer Surgery. The GENEXAN Randomized Controlled Genomic Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Cancer Female
- Sponsor
- Azienda Ospedaliera San Gerardo di Monza
- Enrollment
- 100
- Primary Endpoint
- Whole genome expression by mircoarray
- Last Updated
- 5 years ago
Overview
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.
Investigators
Zhirajr Mokini M.D.
Principal Investigator
Azienda Ospedaliera San Gerardo di Monza
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)
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
Outcomes
Primary Outcomes
Whole genome expression by mircoarray
Time Frame: during surgery (just after tumor excision)
tumor, wound tissue
Whole genome expression by microarray
Time Frame: before tumor excision
tumor, biopsy, normal wound tissue
Secondary Outcomes
- Immune progenitors (MDBCs, GMPs, HPSCs), Natural Killer, T regulatory Lymphocytes, PentraxinIII(at 168 hours)
- cancer recurrence(each 6 months for up to 7 years)
- survival from cancer(each 6 months for up to 7 years)