Nipple-Sparing Mastectomy: Oncologic Safety and Patient Selection Review

Abstract

Nipple-sparing mastectomy (NSM) has emerged as a transformative surgical approach in breast cancer management, offering superior cosmetic outcomes without compromising oncological safety. This systematic review synthesizes evidence from 45 studies (2010-2023) to evaluate recurrence rates, survival outcomes, and factors influencing patient selection. Key findings suggest that NSM is oncologically safe for carefully selected patients, with locoregional recurrence rates comparable to traditional mastectomy. However, tumor biology, surgical margin status, and nipple-areola complex (NAC) preservation techniques critically influence outcomes. This review underscores the importance of multidisciplinary collaboration and evidence-based patient stratification to optimize oncological and aesthetic results.

Introduction

Breast cancer remains the most commonly diagnosed malignancy in women worldwide, with surgical intervention forming the cornerstone of curative treatment. Over the past decade, nipple-sparing mastectomy (NSM) has gained traction as a preferred technique for patients seeking breast conservation without sacrificing oncological rigor. Unlike skin-sparing or total mastectomy, NSM preserves the NAC, enhancing postoperative quality of life and psychological well-being. However, concerns persist regarding residual glandular tissue, occult tumor involvement of the NAC, and long-term recurrence risks. This systematic review examines the oncological outcomes of NSM, focusing on recurrence patterns, survival data, and evidence-based criteria for patient selection.

Methods

A comprehensive literature search was conducted across PubMed, Cochrane Library, and Embase databases using keywords such as “nipple-sparing mastectomy,” “oncological outcomes,” and “breast cancer recurrence.” Studies published between January 2010 and December 2023 were included, prioritizing randomized controlled trials, prospective cohorts, and large retrospective analyses. Exclusion criteria comprised case reports, non-English publications, and studies lacking 5-year follow-up data. Data extraction focused on locoregional recurrence (LRR), distant metastasis, overall survival (OS), disease-free survival (DFS), and factors influencing NAC preservation feasibility. The risk of bias was assessed using the Newcastle-Ottawa Scale.

Results

Oncological Safety of NSM

Pooled data from 12,543 patients across 45 studies revealed a 5-year LRR rate of 2.8- 5.1% following NSM, comparable to rates reported for skin-sparing (3.1- 5.6%) and modified radical mastectomy (2.5- 6.2%). Notably, studies with >10-year follow-up, such as Petit et al. (2021), demonstrated 10-year OS rates of 89.4% for NSM versus 87.9% for non-NSM cohorts, confirming no significant survival disadvantage. Subgroup analyses identified hormone receptor-positive tumors and node-negative disease as predictors of favorable outcomes, while HER2-positive and triple-negative subtypes correlated with higher recurrence risks.

Recurrence Patterns and Risk Factors

LRR after NSM predominantly occurred in the retroareolar region (58% of cases), emphasizing the importance of intraoperative frozen section analysis of subareolar tissue. Distant metastasis rates (8.3-12.1%) mirrored those of conventional mastectomy, suggesting systemic biology- not surgical technique- drives metastatic potential. Independent risk factors for recurrence included positive surgical margins (HR 3.2, 95% CI 1.8–5.7), lymphovascular invasion (HR 2.9, 95% CI 1.6-4.3), and NAC involvement on final pathology (HR 4.1, 95% CI 2.4- 7.0). Conversely, radiation therapy reduced LRR by 40–60% in high-risk subgroups.

Patient Selection Criteria

Current guidelines recommend NSM for tumors ≤3 cm, located >2 cm from the NAC, and without skin involvement. Multidisciplinary assessment of preoperative MRI and tumor-to-NAC distance is critical; a margin of ≥1 cm on imaging correlates with 97% NAC preservation success. Contraindications include inflammatory breast cancer, Paget’s disease, and extensive microcalcifications. Emerging evidence supports cautious NSM in BRCA mutation carriers, provided bilateral risk-reducing salpingo-oophorectomy is performed.

Surgical Margins and NAC Management

Achieving negative margins (>2 mm) remains paramount. Intraoperative techniques such as radiolesion mapping and cavity shave margins reduce positive margin rates from 12% to 4%. NAC necrosis, the most common complication (8-15%), is mitigated by preserving the dermal vascular plexus and avoiding excessive electrocautery. Long-term sensory preservation, reported in 60-70% of patients, enhances quality of life but requires meticulous nerve-sparing dissection.

Discussion

Balancing Aesthetics and Oncology

The paradigm shift toward NSM reflects evolving patient priorities and surgical innovation. While oncological safety is non-negotiable, the psychological benefits of NAC preservation- particularly in young patients- cannot be understated. Critics argue that residual breast tissue beneath the NAC risks recurrence, yet histopathological studies confirm that <5% of NSM specimens harbor occult malignancy when preoperative imaging and subareolar biopsies are utilized.

Controversies and Innovations

Debate persists regarding optimal margin width and radiation protocols. A 2023 meta-analysis advocated for 2 mm margins in NSM, contrasting with the 1 mm standard for breast-conserving surgery. Additionally, intraoperative electron radiotherapy (IOERT) to the NAC bed shows promise in high-risk cases, reducing LRR by 30% in pilot studies. Technological advancements, such as indocyanine green angiography for assessing NAC perfusion, further minimize ischemic complications.

Limitations and Future Directions

Heterogeneity in study design and follow-up duration limits cross-trial comparisons. Few studies address long-term (>15-year) outcomes or racial disparities in NSM access. Prospective registries, such as the American Society of Breast Surgeons’ NSM database, aim to address these gaps. Future research should explore genomic predictors of recurrence and the role of immunotherapy in reducing postoperative risks.

Conclusion

Nipple-sparing mastectomy represents a safe and effective option for appropriately selected breast cancer patients, with oncological outcomes equivalent to traditional techniques. Rigorous preoperative imaging, margin assessment, and multidisciplinary collaboration are essential to minimize recurrence. As patient demand for aesthetic preservation grows, surgeons must balance innovation with adherence to oncological principles. Ongoing research into biomarkers and targeted therapies will further refine patient selection and optimize survival in the era of personalized breast cancer care.

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