Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Breast Diseases

Skin Diseases

Disease Attributes

Central Nervous System Depressants

All Drugs and Chemicals

Platelet Aggregation Inhibitors

Analgesics

Anesthetics

Propofol

Sevoflurane

Analgesics, Opioid

Hypnotics and Sedatives

Anesthetics, Intravenous

Anesthetics, General

General anesthesia followed by opioid administration

Regional anesthesia and analgesia (either epidural or paravertebral) combined with propofol

General anesthesia, usually with sevoflurane, and opioid analgesia

General anesthesia and opioids

Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia

Regional analgesia and propofol

Daniel I Sessler, MD

In this multi-center trial, Stage 1-3 patients having mastectomies or isolated lumpectomy with axillary node dissection will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and morphine analgesia. Participants will be followed for up to 10 years to determine the rate of cancer recurrence or metastasis.

Surgery is the primary and most effective treatment of breast cancer, but residual disease in the form of scattered micrometastases and tumor cells are usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. At least three perioperative factors shift the balance toward progression of minimal residual disease:

1. Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGF, and releases growth factors that promote local and distant growth of malignant tissue.
2. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.
3. Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents.

However, regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia, and minimizing opioid requirement. Animal studies indicate that regional anesthesia and optimum postoperative analgesia independently reduce the metastatic burden in animals inoculated with breast adenocarcinoma cells following surgery. Preliminary data in cancer patients are also consistent: paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis approximately four-fold (95% CI of estimated hazard ratio is 0.71 - 0.06) during a 2.5 to 4-year follow-up period compared to opioid analgesia. The investigators will thus test the hypothesis that recurrence after breast cancer surgery is lower with regional anesthesia/analgesia than with general anesthesia and opioid analgesia.

In this multi-center trial, Stage 1-3 patients having mastectomies will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and opioid analgesia. As with all time-to-event trials, interim and final analyses are based on the number of outcome events (recurrences in this case) rather than enrollment. The number of patients required is just an estimate and varies based on actual recurrence rates which in turn depend on patients' stage and grade, and ancillary treatments. There will be three evenly spaced interim analyses and a final analysis at 351 recurrences. Confirming our hypothesis will indicate that a minor modification to anesthetic management, one that can be implemented with little risk or cost, will reduce the risk of cancer recurrence - a complication that is often ultimately lethal.

Regional Anesthesia and Breast Cancer Recurrence

time to breast cancer recurrence from the end of surgery.

Brief Pain Inventory is used to evaluate with values of any pain vs. no pain (binary)

neuropathic pain is a binary outcome: any pain vs. no pain

Physical and Mental Health Composite Scores (PCS \& MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

The Cleveland Clinic

Principal Investigator

General anesthesia followed by opioid administration

General anesthesia and opioids: General anesthesia, usually with sevoflurane, and opioid analgesia

General Anesthesia and Opioid

Regional anesthesia and analgesia (either epidural or paravertebral) combined with propofol

Regional analgesia and propofol: Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia

Regional Analgesia and Propofol

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Daniel Sessler, MD

Number of Participants Who Had Breast Cancer Recurrence After Breast Cancer Surgery

at 6-month

1-year

data was not available/collected for all participants due to lost follow up or miss phone call.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Regional Anesthesia and Breast Cancer Recurrence	NCT00418457	Breast Neoplasm...	General anesthe... Regional analge...	18 Years - 85 Years	The Cleveland Clinic
Regional Anesthesia and Breast Cancer Recurrence	NCT00418457	Breast Neoplasm...	General anesthe... Regional analge...	18 Years - 85 Years	The Cleveland Clinic

Spots Global Cancer Trial Database for general anesthesia and opioids