Regional Anesthesia and Breast Cancer Recurrence
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms; Recurrence
Study type: Interventional
Phase: Phase 3

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.
    

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.
    

Intervention name(s): General anesthesia and opioids; Regional analgesia and propofol
Intervention type(s): Drug; Drug
Intervention description(s): General anesthesia, usually with sevoflurane, and opioid analgesia; Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia
Other intervention name(s): General anesthesia; Regional analgesia
Intervention MeSH terms: Anesthetics; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Breast Cancer; Anesthesia; regional; cancer recurrence; Anesthesia; inhalational; Analgesia; opioid