Neurotization of the Nipple Areolar Complex to Restore Sensation for Patients With Breast Cancer Undergoing Nipple Sparing Mastectomy and Reconstruction

Study Overview
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Brief Summary
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This phase II trial tests the willingness of patients undergoing nipple sparing mastectomy (NSM) to enroll in a randomized study of NSM with or without neurotization of the nipple areolar complex (NAC). This trial also compares patient reported outcomes, including quality of life and breast and NAC sexual functionality, for patients undergoing NSM with or without neurotization of the NAC. NSM is a standard practice option for patients undergoing preventative mastectomy, but many report dissatisfaction with decreased nipple sensation. Neurotization is a surgical technique using a nerve graft in an attempt to restore NAC sensation. Neurotization during NSM and reconstruction may restore NAC sensation and improve quality of life in breast cancer patients.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine willingness of patients undergoing NSM to enroll in a randomized trial of NSM with or without neurotization. SECONDARY OBJECTIVES: I. To compare patient reported outcomes, including quality of life and breast and NAC sexual functionality, for patients undergoing NSM with or without neurotization. II. To compare NAC sensation at 12 months in patients undergoing NSM with or without neurotization. III To determine rate of mastectomy skin flap necrosis following NSM via the skin ischemia and necrosis (SKIN) score. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care NSM on study. ARM II: Patients undergo neurotization during standard of care NSM on study. After completion of study intervention, patients are followed at 14 days and at 6, 12 and 24 months postoperatively.

Official Title
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Randomized Feasibility Study to Determine the Feasibility of Neurotization of the Nipple Areolar Complex at the Time of Nipple Sparing Mastectomy and Prosthetic Based Reconstruction

Conditions
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Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8

Intervention / Treatment
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* Procedure: Neurotization Procedure
* Other: Questionnaire Administration
* Procedure: Subcutaneous Mastectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients age >= 18 undergoing NSM Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Cup size A-C Body mass index (BMI) =< 34 Ptosis grade =< 2 Clinical stage 0 - T2N0 Final planned implant volume =< 400cc Inframammary or lateral mammary incision Exclusion Criteria: Prior history of breast cancer on side of planned NSM Prior breast reduction, augmentation or mastopexy on side of planned NSM Prior periareolar incision >= 3.1cm on side of planned NSM Prior breast radiation (mantle field radiation also excluded) on side of planned NSM Planned autologous reconstruction (immediate or delayed) Tumor =< 0.9cm from NAC (including suspicious calcifications or magnetic resonance imaging (MRI) enhancement) Clinically node positive Planned post mastectomy radiation (PMRT) Planned breast splitting incision Active nicotine use (within 4 weeks of surgical date)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM I (control)<br>Patients undergo standard of care NSM on study. | Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Subcutaneous Mastectomy<br>* Undergo standard of care NSM<br>* Other names: Nipple-Sparing Mastectomy;|
| Experimental: ARM II (neurotization)<br>Patients undergo neurotization during standard of care NSM on study. | Procedure: Neurotization Procedure<br>* Undergo placement of nerve graft<br>* Other names: Nerve Regeneration Procedure;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Subcutaneous Mastectomy<br>* Undergo standard of care NSM<br>* Other names: Nipple-Sparing Mastectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients undergoing nipple sparing mastectomy (NSM) to enroll in a randomized trial of NSM with or without neurotization | Will calculate the proportion of eligible patients who opt to take part in the study. Additionally, will descriptively analyze and report the specific factors that influenced patients' decisions to participate, with the aim of identifying and addressing any obstacles encountered. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest physical well-being | Measured using the BREAST- Q (copyright) scored on a 5-point Likert scale. Results will be reported descriptively. | At baseline and up to 12 months | 
| Psychosocial well-being | Measured using the BREAST- Q scored on a 5-point Likert scale. Results will be reported descriptively. | At baseline and up to 12 months | 
| Sexual well-being | Measured using the BREAST- Q scored on a 5-point Likert scale. Results will be reported descriptively. | At baseline and up to 12 months | 
| Patient reported amount of sensation in nipple areolar complex (NAC) and breast | Patient reported amount of sensation in nipple areolar complex (NAC) and breast will be will be assessed using a 5-item sensation questionnaire with 5 options to answer each question. Results will be reported descriptively. | At baseline and up to 12 months | 
| Patient reported significance of breast or NAC for sexuality | Patient reported significance of breast or NAC for sexuality will be assessed using a 5-item Significance of Breast or Nipple Areolar Complex for Sexuality Questionnaire with 5 options to answer each question. Results will be reported descriptively. | At baseline and up to 12 months | 
| Tactile sensitivity scores | Measured using Semmes Weinstein monofilament test. Scores will be averaged for each patient across all breast/ NAC measurements and summarized in terms of mean, standard deviation, median, and range. The ordinal score at each of the sites will also be summarized in terms of median and range. Frequency and type of missing data will be summarized. | At baseline and up to 12 months | 
| Incidence of adverse events (AEs) | AEs, using National Cancer Institute Common Terminology Criteria for Adverse Events, will be summarized within arms by reporting the number and percentage of patients. The maximum grade for each type of AEs will be recorded for each patient and frequency tables will be reviewed to determine overall patterns. The frequency and type of solicited AEs experienced in each arm will also be reported. | At 12 months | 
| Mastectomy skin flap necrosis | Incidence of mastectomy skin flap necrosis will be assessed using the skin ischemia necrosis (SKIN) score, as recorded by clinical staff. Necrosis is defined as any depth SKIN score of C or D and surface area >1. | At 12 months |