Botulinum Toxin A (Botox) in Tissue Expander Breast Reconstruction
Condition: Breast Cancer; Pain, Postoperative; BRCA1 Mutation; BRCA2 Mutation; Breast Diseases; Neoplasms
MeSH terms: Breast Diseases; Pain, Postoperative
Intervention: Botulinum Toxin Type A; Placebo
Intervention description: 5 mL 0.9% NaCl solution to mimic Botulinum Toxin Type A
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 131.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Mastectomy; Mammaplasty; Breast reconstruction; Tissue expansion; Botulinum toxins, Type A; Quality of Life; Acellular dermal matrix

Summary:

      Each year, the number of breast cancer survivors who choose post-mastectomy breast
      reconstruction keeps rising. Among women who elect to pursue breast reconstruction,
      approximately 75% will choose prosthetic breast reconstruction. Implant-based breast
      reconstruction is frequently achieved in two-stages. The first stage consists of the
      placement of a tissue expander after mastectomy. This is followed by a period of biweekly
      tissue expansions that can last several months. In the second stage, the tissue expander is
      removed in a surgical procedure and replaced with a permanent breast implant. Tissue
      expansion is a well-established breast reconstruction technique characterized by high success
      rates and high patient satisfaction. Despite the well-recognized advantages of this
      successful breast reconstruction technique, the subpectoral placement of a tissue expander is
      associated with significant pain and discomfort in the immediate post-operative period and
      during the phase of tissue expansion. Pectoralis major muscle spasm is a frequently reported
      problem during tissue expansion. Legeby et al. recently showed that women who underwent
      prosthetic breast reconstruction had higher pain scores and took more analgesics that those
      who did not choose post-mastectomy reconstruction.

      In the past 10 years, publications on the use of botulinum toxin A (BTX-A) for pain relief in
      a wide array of clinical conditions have increased tremendously. BTX-A is one of the
      neurotoxins produced by Clostridium botulinum bacteria. By reversibly inhibiting
      neurotransmitter release, BTX-A has both analgesic and paralytic properties. The analgesic
      action of BTX-A was initially thought to be related to its effects on muscular contraction.
      However, a recent in vitro study of embryonic rat dorsal neurons did confirm that BTX-A
      inhibits release of substance P, a neurotransmitter associated with pain and inflammatory
      reactions. The presence of analgesic properties of BTX-A is increasingly supported by several
      clinical observations: pain relief with BTX-A injections has been reported for migraine
      headaches, chronic pelvic, chronic tennis elbow, and post-operative pain control for lower
      limb lengthening correction, among others.

      This aspect has never been studied in breast cancer survivors who elect to pursue breast
      reconstruction with tissue expanders. Furthermore, physical function outcomes are important
      to consider with BTX-A use because the link between temporary muscle paralysis and
      improvements in participation in daily activities is not a given.

      The investigators propose to complete a double-blinded prospective randomized controlled
      trial of women undergoing unilateral and bilateral mastectomies with immediate placement of
      tissue expanders, to establish the efficacy and safety of BTX-A in alleviating pain and in
      improving physical well-being during the expansion period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women at least 18 years of age, who will undergo immediate unilateral or bilateral
             tissue expander breast reconstruction following therapeutic skin-sparing or
             nipple-sparing mastectomy

          -  Women at least 18 years of age, who will undergo immediate bilateral tissue expanders
             breast reconstruction following risk-reduction (prophylactic) skin-sparing or
             nipple-sparing mastectomy

        Exclusion Criteria:

          -  Subjects who are unable to read or speak English

          -  Breast reconstruction using the latissimus dorsi flap combined with a tissue expander

          -  Documented diagnosis of chronic pain, upper limb spasticity, cervical dystonia,
             axillary hyperhidrosis, strabismus or blepharospasm

          -  Hypersensitivity to any botulinum toxin preparation or to any of the components in the
             formulation

          -  Infection at the proposed site of injection

          -  Pre-existing neuromuscular disorders (including diagnosed myasthenia gravis,
             Eaton-Lambert syndrome, or amyotrophic lateral sclerosis)

          -  Aminoglycosides intake at the time of surgery (these antibiotics can potentiate the
             effect of BTX-A)

          -  Women who are pregnant or breast feeding

          -  Presence of breast implants from previous breast surgery

          -  Reported use of Botox within 4 months prior to planned surgical date