PROJECT SUMMARY/ABSTRACT Millions of women worldwide have undergone mastectomy and breast reconstruction procedures. Simple (also called total) mastectomy, the most common mastectomy procedure for women with breast cancer, amputates all of the breast tissue, including the third through sixth intercostal nerves, leaving the breast numb. Loss of sensation is a distressing symptom (affecting more than 60%) that leads to major adverse effects, including elevated risk of injury, disembodiment (a feeling that the breasts no longer are part of one's body), loss of touch- based affective communication (e.g., the feel of an embrace), and loss of erogenous sensation. Mastectomy also often results in chronic neuropathic pain (25-60%), a costly and burdensome condition that standard interventions cannot reliably alleviate. Our solution, the Bionic Breast Device (BBD), combines a neural stimulation approach (successfully deployed to restore touch in bionic hands and feet in limb amputees) with a novel tissue-like stretchable sensor that detects pressure applied to the nipple-areolar complex. The BBD will trigger stimulation of intercostal nerves, evoking a sensation experienced on the otherwise insensate breast. The objective of the present Phase 0 trial is to characterize, for the first time, the sensory consequences of electrically activating the intercostal nerves that innervate the breast in women who have recently undergone a mastectomy. In this study, we will implant cuff electrodes on intercostal nerves T3 and T4 in women during their mastectomy procedure. Participants will all be women undergoing bilateral mastectomy with two stage alloplastic (implant) reconstruction for early breast cancer (unilateral in situ or T1N0, <2cm) or breast cancer risk reduction. Following a 4-6 week recovery period after mastectomy with electrode implantation, participants will undergo twice-weekly psychophysical testing sessions during which electrical stimulation will be applied to the nerves through the electrodes via percutaneous leads. Participants will have the electrodes and percutaneous leads removed during their planned second stage reconstructive surgery 12-20 weeks after mastectomy. The specific aims of this research are to: (1) Establish the parameters of electrical stimulation of the intercostal nerves that evoke perceptible and distinguishable sensations and characterize the projected fields on the body; (2) Characterize the features of the sensations evoked via activation of the intercostal nerves, including their quality and perceived naturalness; and (3) Gauge the short (during implantation) and longer-term (6 months following explantation) impact of intermittent electrical stimulation of the intercostal nerves on post-mastectomy pain. This trial will establish that touch sensation can be restored to the breast via neural stimulation. Data will also be obtained to inform future feasibility (including safety), efficacy, and acceptability trials. The Bionic Breast Project proposes enormous benefit at relatively low cost and risk and thus has the potential to be truly transformative.

PROJECT NARRATIVE Simple mastectomy amputates all of the breast tissue, including the third through sixth intercostal nerves, leaving the breast numb. The resulting deafferentation leads to major adverse effects, including a disembodiment of the breasts, loss of touch-based affective communication, abolition of breast-centered erogenous touch, and, in many women, the development of chronic pain. Our objective is to lay the groundwork for a neuroprosthetic solution to the negative sensory sequelae of mastectomy by establishing that touch sensation can be restored to the breast via bionics.