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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage 0 Breast Cancer AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Subcutaneous Mastectomy; Procedure: Neurotization Procedure

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: James W. Jakub, M.D.
      • Principal Investigator: Olivia S. Ho, M.D., M.S.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Planned nipple sparing mastectomy (NSM)

• Ideal NSM candidates would meet the following criteria:

  • Cup size A-C
  • BMI <34
  • Ptosis grade < 2
  • Clinical stage 0 - T2N0
  • Final planned implant volume < 400cc
  • Inframammary or lateral mammary incision
  • Tumor > 0.5cm from the nipple areolar complex (NAC)
  • No prior breast reduction, mastopexy, or periareolar incisions on side of planned NSM
  • No prior breast radiation on side of planned NSM
  • Tumor <0.5cm from NAC (including suspicious calcifications or MRI enhancement)
  • No planned post mastectomy radiation (PMRT)
  • No nicotine use within 4 weeks of surgical date

Exclusion Criteria:

• Planned autologous reconstruction (immediate or delayed)
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
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
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
Chest physical well-being	Measured using the BREAST-Q© scored on a 3-point Likert scale where 1=None of the time and 3=All of the time. Higher scores indicate poorer chest physical well-being.	At baseline and up to 12 months
Psychosocial well-being	Measured using the BREAST-Q© scored on a 5-point Likert scale where 1=None of the time and 5=All of the time. Higher scores indicate poorer psychosocial well-being.	At baseline and up to 12 months
Sexual well-being	Measured using the BREAST-Q© scored on a 5-point Likert scale where 1=None of the time and 5=All of the time. Higher scores indicate poorer sexual well-being.	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. Examples of answers include a range from Very unpleasant to Very pleasant or Unimportant to Very Important. 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: Not at all, A little bit, Somewhat, Quite a bit, or Very much. Results will be reported descriptively.	At baseline and up to 12 months
Incidence of adverse events (AEs)	AEs will be scored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and will be summarized within arms by reporting the number and percentage of patients for each AE. 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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: James W. Jakub, M.D., Mayo Clinic; Principal Investigator: Olivia S. Ho, M.D., M.S., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2023
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): November 10, 2026

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Carcinoma; Breast Neoplasms; Carcinoma in Situ; Skin and Connective Tissue Diseases; Breast Carcinoma In Situ; Surgical Procedures, Operative; Mastectomy; Mastectomy, Subcutaneous
• Other Study ID Numbers: MC230302 (Other Identifier: Mayo Clinic); NCI-2023-09574 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 23-004411 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No