This clinical trial aims to evaluate whether direct neurotization using fully autologous components during autologous breast reconstruction improves postoperative breast sensation and sensory-related quality of life in women undergoing unilateral mastectomy. Direct neurotization involves coapting the recipient intercostal nerve to an autologous nerve graft placed within the flap to facilitate reinnervation.

The study's primary questions are:

1. Does direct neurotization using fully autologous nerve grafts improve cutaneous sensory recovery, as assessed by Semmes-Weinstein monofilament thresholds measured at standardized breast locations?
2. Does neurotization enhance patient-reported sensory outcomes and quality of life, as assessed by the BREAST-Q Sensation Module?

As secondary objectives, the study will assess whether biological predictors of nerve regeneration correlate with sensory outcomes. These include:

1. Neuregulin-1 (NRG1) expression in flap tissue biopsy;
2. Cross-sectional area of the recipient nerve fibres;
3. Breast morphometry measured at baseline and follow-up;
4. Intraepidermal nerve fibre density (IENFD) on skin biopsy.

Participants will be randomly assigned to receive either:

1. Neurotized autologous breast reconstruction using fully autologous graft components, or
2. Standard (non-neurotized) autologous breast reconstruction.

The study will compare these groups to determine whether neurotization accelerates or enhances the return of breast sensation over a 6-month follow-up period, with evaluations at 1 month, 3 months, and 6 months after surgery.

Participants will undergo:

1. Autologous breast reconstruction with or without direct neurotization as part of their planned cancer surgery.
2. Sensory testing using Semmes-Weinstein monofilaments at baseline, 1, 3, and 6 months.
3. Completion of BREAST-Q questionnaires evaluating breast sensation, symptoms, and quality of life at each follow-up visit.

3. Intraoperative tissue sampling for NRG1 analysis and nerve morphometry. 4. Skin biopsy (if applicable) to assess intraepidermal nerve fibre density. 5. Breast morphometry assessment using a breast morphometry measurement software tool.

This study seeks to provide high-quality evidence on the effectiveness of direct neurotization using fully autologous components in restoring breast sensation and to explore biological predictors that may influence sensory recovery after autologous breast reconstruction.

Inclusion Criteria:

• Female patients aged ≥18 years.
• Patients with unilateral breast cancer who have undergone or will undergo unilateral mastectomy.
• Patients undergoing breast reconstruction.
• Patients with unilateral breast cancer regardless of adjuvant therapy status (receiving radiotherapy and/or chemotherapy or receiving no adjuvant therapy).
• Willing to comply with all scheduled examinations and tissue sampling procedures.
• Able and willing to provide written informed consent.

Exclusion Criteria:

• History of peripheral neuropathy (e.g., diabetes mellitus with neuropathic complications).
• Bilateral mastectomy.
• Presence of skin or soft-tissue conditions of the breast that may interfere with sensory assessment.
• Active smokers (use of tobacco, vape, or other nicotine products within 14 days prior to neurotization).
• Refusal or inability to attend follow-up evaluations.

Individual participant data will not be shared due to concerns regarding participant confidentiality and the potential risk of re-identification in a small surgical trial with detailed clinical and biomarker data.