Nerve Grafting for Sensation Restoration After Mastectomy in Breast Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Pregnancy, Planned autologous reconstruction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: Immediate (surgical procedure)

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a nerve graft procedure (neurotization procedure) can restore nipple sensation after a nipple-sparing mastectomy for breast cancer patients. It compares outcomes for patients receiving the nerve graft with those who do not, focusing on quality of life and nipple sensation. The study targets women planning a mastectomy who have not undergone certain breast surgeries or radiation and have a small to medium cup size. The goal is to enhance satisfaction with breast sensation and overall well-being post-surgery. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in breast cancer recovery.

Do I need to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that the neurotization procedure is safe for restoring sensation after mastectomy?

Research shows that neurotization, a surgery to restore feeling in the nipple area after a mastectomy, is usually well-tolerated. Studies on similar surgeries have shown good results in restoring sensation without major safety issues. For example, a review of studies found that patients who underwent nipple-areola complex reinnervation during gender-affirming surgeries experienced significant improvements in sensation. Although direct safety data is limited, the use of this technique in other surgeries suggests it is safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the neurotization procedure because it offers a novel approach to restoring sensation after a mastectomy. Unlike the standard subcutaneous mastectomy, which often leaves patients with reduced sensation due to nerve removal, neurotization involves reconnecting nerves to help regain feeling in the breast area. This technique leverages the body's natural ability to heal and regenerate nerve pathways, potentially improving quality of life for breast cancer survivors. By directly addressing the loss of sensation, neurotization could provide a significant advancement over existing surgical options.

What evidence suggests that neurotization might be an effective treatment for restoring nipple sensation after mastectomy?

This trial will compare two approaches for restoring sensation after mastectomy. Research has shown that a surgical technique called neurotization, which uses nerve grafts, can help restore feeling in patients after a nipple-sparing mastectomy (NSM). Participants in the trial's neurotization arm will undergo this procedure during their standard of care NSM. Studies have found that neurotization improves sensation in the nipple, areola, and nearby breast skin. One study reported a noticeable increase in feeling, with most patients experiencing better outcomes. Additionally, neurotization is associated with high patient satisfaction because it helps restore nipple sensation. While results can vary, many patients regain sensation and enjoy a better quality of life. ^{4 6 7 8 9}

Who Is on the Research Team?

James W Jakub

Principal Investigator

Mayo Clinic

Olivia Ho, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for female breast cancer patients aged 18 or older who are undergoing nipple sparing mastectomy (NSM) with specific criteria: ECOG status of 0-2, A-C cup size, BMI ≤34, ptosis grade ≤2, clinical stage 0-T2N0, and implant volume ≤400cc. Exclusions include prior breast cancer treatments or surgeries on the affected side and active nicotine use.

Inclusion Criteria

My bra cup size is between A and C.

My breast surgery incision is under the breast or on the side.

I am a woman over 18 planning to have nipple-sparing mastectomy.

Exclusion Criteria

I have had breast surgery on the same side as my planned nipple-sparing mastectomy.

I have had a surgery cut around my nipple area longer than 3.1cm.

I am scheduled for radiation therapy after breast removal surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo nipple sparing mastectomy (NSM) with or without neurotization

Immediate (surgical procedure)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visits at 14 days, 6, 12, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Neurotization Procedure
• Subcutaneous Mastectomy

Trial Overview The study tests if adding a neurotization procedure to NSM can restore sensation in the nipple area. It compares patient satisfaction between those who have standard NSM and those who receive additional nerve grafting aimed at improving quality of life and sexual functionality of the breast.

How Is the Trial Designed?

Group I: ARM II (neurotization) Experimental Treatment 3 Interventions

Patients undergo neurotization during standard of care NSM on study.

Group II: ARM I (control) Active Control 2 Interventions

Patients undergo standard of care NSM on study.

Neurotization Procedure is already approved in United States, European Union for the following indications:

Approved in United States as NAC Neurotization for:

• Restoration of nipple sensation after nipple-sparing mastectomy and reconstruction

Approved in European Union as NAC Neurotization for:

• Restoration of nipple sensation after nipple-sparing mastectomy and reconstruction

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Breast neurotization can significantly improve sensory outcomes for postmastectomy patients, addressing the common issue of absent or diminished breast sensation.

The procedure is considered safe with minimal risk of complications, making it a promising area for further research in enhancing patient recovery and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modern Approaches to Breast Neurotization. O'Neill, RC., Spiegel, AJ.[2023]

Neurotization techniques used during immediate DIEP flap breast reconstructions significantly improve breast sensation and sensory recovery compared to delayed reconstructions, highlighting their efficacy in enhancing patient outcomes.

The procedure is described as rapid and simple with minimal morbidity, making it a promising option for restoring breast sensation and increasing patient satisfaction after mastectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-mastectomy sensory recovery and restoration. Hamilton, KL., Kania, KE., Spiegel, AJ.[2021]

In a study of 110 patients undergoing nipple-sparing mastectomy (NSM), no cases of nipple-areolar complex (NAC) necrosis were reported, indicating a high safety profile for this surgical technique.

The use of a specific surgical method involving sharp dissection and careful flap management resulted in only minor complications, such as temporary discoloration or ischemia in six nipples, with all NACs remaining intact after an average follow-up of 30 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Sharp Dissection in Nipple-Sparing Mastectomy: A Safe Procedure with No Necrosis of the Nipple-Areolar Complex. Yang, CQ., Ji, F., Gao, HF., et al.[2022]

In a study of 220 breasts undergoing nipple-sparing mastectomy (NSM) with immediate reconstruction, 64.1% experienced nipple-areolar complex (NAC) ischemia, but only 31.3% required surgical reoperation due to necrosis, indicating a high rate of ischemia but relatively low rates of severe complications.

Factors such as the presence of breast ptosis and the type of surgical incision significantly influenced the risk of NAC necrosis, with lower periareolar incisions being safer for preserving NAC vascularity compared to upper incisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nipple-areolar complex ischemia and necrosis in nipple-sparing mastectomy. Ahn, SJ., Woo, TY., Lee, DW., et al.[2019]

Nipple-sparing mastectomy (NSM) is a safe and effective surgical option for breast cancer treatment, with a low rate of nipple-areola complex (NAC) removal and a median follow-up of 24 months showing only 3 locoregional recurrences among 55 procedures.

Approximately 44% of patients experienced partial recovery of NAC sensation within 6 months post-surgery, indicating that some patients can retain sensation after the procedure, although complete recovery is rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nipple-Areola Complex Sensation after Nipple-sparing Mastectomy. Chirappapha, P., Srichan, P., Lertsithichai, P., et al.[2022]

A novel technique for breast reconstruction after nipple-sparing mastectomy (NSM) was developed, focusing on preserving intercostal nerves and utilizing nerve grafting, which resulted in an impressive 90% rate of preserved sensation in the reconstructed breasts.

Among the 12 women followed for at least 3 months, 87% maintained normal two-point discrimination at the nipple/areolar complex, and all patients reported intact sensation to light touch, indicating that this approach is both safe and effective for improving sensory outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve Preservation and Allografting for Sensory Innervation Following Immediate Implant Breast Reconstruction. Peled, AW., Peled, ZM.[2020]

Delay procedures for nipple-sparing mastectomy (NSM) have a good safety profile, with only 8.9% of patients experiencing partial nipple-areolar complex necrosis and 7.9% experiencing mastectomy flap necrosis among 101 patients studied.

These procedures not only reduce the risk of complications but also allow for retroareolar biopsies to be performed, which can help in planning the surgical approach and reducing the chances of false-negative results during the mastectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delay techniques for nipple-sparing mastectomy: A systematic review. Karian, LS., Therattil, PJ., Wey, PD., et al.[2018]

A new technique for female-to-male mastectomy that preserves and reinnervates the intercostal nerves significantly improves sensation in the nipple-areolar complex (NAC) compared to traditional mastectomy methods, as shown in a study of 10 patients aged 16-19.

Patients who underwent the nerve-sparing technique experienced significant improvements in sensation at the nipple, areola, and surrounding skin, with no loss of sensation compared to preoperative levels, suggesting this method could enhance recovery in similar surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate Targeted Nipple-Areolar Complex Reinnervation: Improving Outcomes in Gender-affirming Mastectomy. Rochlin, DH., Brazio, P., Wapnir, I., et al.[2022]

A new technique for preserving intercostal nerves during mastectomy and using them to reinnervate the nipple areolar complex (NAC) was tested in a study of 14 patients, aged 32 to 61, who underwent immediate autologous breast reconstruction.

The study suggests that this technique may enhance the recovery of sensation in the NAC, although the results did not show a statistically significant difference in sensation compared to a control group that did not receive neurotization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate targeted nipple-areolar complex re-innervation: Improving outcomes in immediate autologous breast reconstruction. Tevlin, R., Brazio, P., Tran, N., et al.[2021]

Women who underwent skin-sparing mastectomy (SSM) reported higher satisfaction with their breasts and overall outcomes compared to those who had nipple-sparing mastectomy (NSM), suggesting SSM may be a more favorable option for patients.

Nipple-areola complex (NAC) sensitivity was significantly lower in the NSM group compared to a non-operated control group, indicating that while NSM preserves the NAC, it may result in reduced sensitivity post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Satisfaction and Nipple-Areola Sensitivity After Bilateral Prophylactic Mastectomy and Immediate Implant Breast Reconstruction in a High Breast Cancer Risk Population: Nipple-Sparing Mastectomy Versus Skin-Sparing Mastectomy. van Verschuer, VM., Mureau, MA., Gopie, JP., et al.[2017]

Citations

1. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1155/tbj/2362697

Nipple Areolar Complex (NAC) Neurotization After ... The authors report reduced NAC sensation in 2 breasts (9%) and reported improvement in one breast (4%). All patients reported intact sensation ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41089735/

Nipple Areolar Complex (NAC) Neurotization After ... Studies demonstrated overall improvement of NAC sensory outcomes and high patient satisfaction after neurotization. However, variability in ...

3. journals.lww.com journals.lww.com/prsgo/fulltext/2025/05000/nipple_areolar_complex_neurotization_following.65.aspx

Nipple–Areolar Complex Neurotization Following... Neurotization of the nipple may restore sensation in NF1 patients who undergo nipple-sparing mastectomy and immediate breast reconstruction for an NAC-sparing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10703124/

Sensory Outcomes after Neurotization in Nipple-sparing ... Performing neurotization during nipple-sparing mastectomy and implant breast reconstruction improves postmastectomy breast and nipple–areolar complex sensation.

5. abs.amegroups.org abs.amegroups.org/article/view/6632/html

superior nipple sensation in gender-affirming mastectomy and ... NAC neurotization patients demonstrated significantly better sensation at the nipple (P=0.0001), areola (P=0.0001) and surrounding breast skin (P=0.0001) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9325332/

Targeted Nipple Areola Complex Reinnervation Despite promising pilot study results, adoption of neurotization of immediate implant-based reconstructions has not occurred.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1748681520306392

Immediate targeted nipple-areolar complex re-innervation We propose a new technique of preserving the intercostal nerves during mastectomy and using them to reinnervate the NAC following mastectomy and immediate ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40877602/

Targeted Nipple-Areola Complex (NAC) Reinnervation (TNR) This study systematically reviews the literature and conducts a meta-analysis to evaluate the efficacy of TNR in both gender-affirming ...

9. link.springer.com link.springer.com/article/10.1007/s00266-025-05179-y

Targeted Nipple-Areola Complex (NAC) Reinnervation (TNR) Meta-analysis of TNR in gender-affirming mastectomy patients demonstrated significantly improved NAC, areola, and peripheral breast skin ...