Regional Anesthesia and Breast Cancer Recurrence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00418457
Recruitment Status : Recruiting
First Posted : January 4, 2007
Last Update Posted : January 26, 2018
Information provided by (Responsible Party):
d sessler, The Cleveland Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: General anesthesia and opioids Drug: Regional analgesia and propofol Phase 3

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2076 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Regional Anesthesia and Breast Cancer Recurrence
Study Start Date : January 2007
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: General anesthesia and opioid
General anesthesia followed by opioid administration
Drug: General anesthesia and opioids
General anesthesia, usually with sevoflurane, and opioid analgesia
Other Name: General anesthesia
Active Comparator: Regional analgesia and propofol
Regional anesthesia and analgesia (either epidural or paravertebral) combined with propofol
Drug: Regional analgesia and propofol
Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia
Other Name: Regional analgesia

Primary Outcome Measures :
  1. Cancer recurrence rate [ Time Frame: up to 10 years ]

Secondary Outcome Measures :
  1. post-surgical pain [ Time Frame: 1 year ]
    Chronic post-surgical pain is reduced by paravertebral or thoracic epidural analgesia.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Primary breast cancer without known extension beyond the breast and axillary nodes (i.e. believed to be Tumor Stage 1-3, Nodes 0-2)
  • Scheduled for unilateral or bilateral mastectomy with or without implant (isolated "lumpectomy" will not qualify)
  • Isolated "lumpectomy" with axillary node dissection (anticipated removal of at least five nodes)
  • Written informed consent, including willingness to be randomized to morphine or regional analgesia

Exclusion Criteria:

  • Previous surgery for breast cancer (except diagnostic biopsies)
  • Inflammatory breast cancer
  • Age < 18 or > 85 years old
  • Scheduled free flap reconstruction
  • ASA Physical Status ≥ 4
  • Any contraindication to epidural or paravertebral anesthesia and analgesia (including coagulopathy, abnormal anatomy)
  • Any contraindication to midazolam, propofol, sevoflurane, fentanyl, or morphine
  • Other cancer not believed by the attending surgeon to be in long-term remission
  • Systemic disease believed by the attending surgeon to present ≥ 25% two-year mortality

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00418457

Contact: Roberta Johnson 216-444-9950

United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Roberta Johnson    216-444-9950   
Medical University of Vienna Recruiting
Vienna, Austria
Contact: Edith Fleischmann, MD   
Principal Investigator: Edith Fleischmann, MD         
Peking Union Medical College Hospital Recruiting
Beijing, China
Contact: Lijian Pei         
University of Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Contact: Tanja A. Meyer-Treschan, M.D.    49 (0) 211 81 17491   
Contact: Kathrin Domagala   
Principal Investigator: Tanja A Meyer-Treschan, M.D.         
Mater Misericordiae Hospital Recruiting
Dublin, Ireland, 7
Contact: Donal J Buggy, MD,FRCPI    35-31-830-9568   
Principal Investigator: Donal J Buggy, MD         
Tan Tock Seng Hospital Recruiting
Singapore, Singapore
Contact: Ern Yu Tan         
Contact: John Tey         
Sponsors and Collaborators
The Cleveland Clinic
Principal Investigator: Daniel I Sessler, MD The Cleveland Clinic

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: d sessler, Principal Investigator, The Cleveland Clinic Identifier: NCT00418457     History of Changes
Other Study ID Numbers: 06-692
First Posted: January 4, 2007    Key Record Dates
Last Update Posted: January 26, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by d sessler, The Cleveland Clinic:
Breast Cancer
Anesthesia; regional
cancer recurrence
Anesthesia; inhalational
Analgesia; opioid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Disease Attributes
Pathologic Processes
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Sensory System Agents
Peripheral Nervous System Agents