Areola Preservation in NSM With Nipple Involvement (APRESERVE-1)

April 19, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

Oncologic Safety and Aesthetic Outcomes of Areola Preservation With Simultaneous Nipple Reconstruction in Nipple-Sparing Mastectomy With Intraoperative Nipple Involvement: A Single-Center, Prospective, Exploratory Study

Background:

During nipple-sparing mastectomy (a surgery that removes breast tissue but keeps the nipple and areola), doctors test the tissue behind the nipple right away. If cancer cells are found in this nipple tissue, current guidelines say the entire nipple and areola must be removed. However, research suggests that when the nipple is involved, the surrounding pigmented skin (the areola) is very rarely affected by cancer. Removing it might be unnecessary and leads to a worse cosmetic outcome, which can impact a woman's self-image and quality of life. Currently, there is no prospective study to guide whether the areola can be safely preserved in this specific situation.

Purpose:

This is a pilot study that aims to explore the feasibility, safety, and early outcomes of a new surgical procedure: preserving the areola and performing immediate nipple reconstruction when cancer is found in the nipple during surgery.

Study Plan:

This is a single-arm, single-center, prospective, exploratory study. Women with early-stage breast cancer who are scheduled for a nipple-sparing mastectomy will be invited. Only if cancer is confirmed in the nipple during their surgery will they be enrolled into the single test group. In this group:

The nipple is removed.

A small ring of tissue from under the areola is tested immediately (second frozen section). If this ring shows no cancer, the areola skin is preserved.

A new nipple is created during the same operation using a local skin flap technique (purse-string suture).

All patients will have immediate breast reconstruction.

We plan to include about 40-60 patients at one hospital. Patients will be closely followed for 3 years with regular check-ups and scans to monitor for any cancer recurrence or complications.

What We Will Measure (Exploratory Endpoints):

Safety & Feasibility: The success rate of areola preservation (based on negative second frozen section), surgical complication rates (e.g., infection, tissue necrosis).

Early Effectiveness: The rate of cancer returning in the breast/chest wall area within 3 years (local recurrence).

Patient-Reported Outcomes: Patient satisfaction with their breasts and well-being, measured by the BREAST-Q questionnaire before and after surgery.

Why This Study is Important:

This is the first prospective study to systematically evaluate this new surgical approach. The results will provide crucial preliminary data on safety and early outcomes. If the findings are promising, they will form the foundation for designing a larger, controlled trial in the future. Ultimately, this research could lead to a new option that offers women better cosmetic results and improved quality of life after mastectomy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study evaluates the oncological safety and aesthetic outcomes of areola preservation with simultaneous nipple reconstruction in breast cancer patients undergoing nipple-sparing mastectomy who have nipple involvement but negative areolar margins on intraoperative frozen section. The intervention involves removing the nipple while preserving the areolar skin flap and performing immediate nipple reconstruction using a purse-string suture technique. This single-arm, prospective, exploratory study will enroll 45 patients. Primary outcome is technical success rate; secondary outcomes include 3-year local recurrence, complications, BREAST-Q scores, and nipple projection maintenance.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • The Second Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Female, age ≥ 18 years.
  2. Pathologically confirmed primary invasive breast carcinoma or ductal carcinoma in situ (DCIS).
  3. Clinical tumor stage cTis-2, N0-2, M0 (AJCC 8th Edition).
  4. Planned for therapeutic nipple-sparing mastectomy (NSM) with immediate reconstruction.
  5. Intraoperative frozen section confirms involvement of the nipple core tissue by invasive carcinoma or DCIS.
  6. ECOG performance status 0-1.
  7. Willing and voluntarily provide written informed consent.

Exclusion Criteria:

  1. Clinical or radiological suspicion of areola or skin involvement.
  2. Inflammatory breast cancer.
  3. Pregnancy or lactation.
  4. Any severe medical or psychiatric condition that, in the investigator's judgment, would preclude safe participation or compliance.
  5. Severe uncontrolled comorbidities with a life expectancy of less than 5 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Areola Preservation & Nipple Reconstruction Group
Patients with intraoperatively confirmed nipple involvement during nipple-sparing mastectomy, who receive areola-preserving surgery (pending negative second frozen section of the peri-areolar margin) combined with immediate nipple reconstruction via a local flap technique (e.g., purse-string suture), followed by immediate breast reconstruction.
Procedure: Areola-Preserving Nipple-Sparing Mastectomy with Immediate Nipple Reconstruction
This is a combined surgical procedure for patients with intraoperative nipple involvement during nipple-sparing mastectomy. After resection of the involved nipple, a full-thickness peri-areolar tissue margin is harvested for a second intraoperative frozen section. If the margin is negative for carcinoma, the areola skin is preserved. An immediate nipple reconstruction is then performed using a local skin flap technique (e.g., purse-string suture). This is followed by standard immediate breast reconstruction (implant-based or autologous).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Local Recurrence Rate
Time Frame: 3 years post-surgery
The incidence of local recurrence in the ipsilateral chest wall/skin or residual breast tissue, assessed by clinical examination and imaging (breast ultrasound and/or MRI), with pathological confirmation for suspected cases.
3 years post-surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Successful Areola Preservation
Time Frame: Intraoperative
The proportion of patients in whom the areola is successfully preserved, defined as having a negative result on the second intraoperative frozen section of the peri-areolar margin.
Intraoperative
Incidence of Postoperative Complications
Time Frame: Within 90 days post-surgery
The rate of surgical complications, including but not limited to areolar skin necrosis (partial/full), infection, seroma, hematoma, and implant loss/failure.
Within 90 days post-surgery
Change in Patient-Reported Satisfaction and Well-being
Time Frame: Baseline, 6, 12, 24, and 36 months post-surgery
Change in scores from baseline as measured by the validated BREAST-Q questionnaire modules (Satisfaction with Breasts, Psychosocial, Sexual, and Physical Well-being).
Baseline, 6, 12, 24, and 36 months post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigators

  • Principal Investigator: Ke Wang, MD, Department of Breast Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

January 15, 2029

Study Completion (Estimated)

January 15, 2030

Study Registration Dates

First Submitted

January 5, 2026

First Submitted That Met QC Criteria

April 19, 2026

First Posted (Actual)

April 22, 2026

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 19, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APRESERVE-2025-1471

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study is a single-center exploratory trial. Data sharing is not planned because the sample size is small (n=45) and the study is primarily designed to generate preliminary parameter estimates for future multi-center trials.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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