Nipple Sparing Mastectomy Margaret Thompson MD Breast Surgery Oncology September 25, 2018

HOW FAR HAVE WE COME? Mastectomy pre anesthetic and pre antiseptic era

Radical Mastectomy

Breast Conserving Surgery (BCS) Lumpectomy +/- SLNB/ALND Gold standard for early breast cancer Most commonly performed breast procedure worldwide Provides enhanced cosmetic results Less postoperative pain Shorter recovery time

Why Are More Women Electing Prophylactic Mastectomies? Increasing cancer awareness Expansion of mammographic screening Availability of BRCA 1 & 2 genetic testing Development of statistical models for breast cancer risk stratification

Skin-Sparing Mastectomy (SSM) Described in 1991 Resection of Nipple-areola complex (NAC) Any existing biopsy scars Breast parenchyma +/- SLNB/ALND TOTAL BILATERAL MASTECTOMY WITH RECONSTRUCTION IN PROGRESS

Total Skin-Sparing Mastectomy (TSSM) = Nipple Sparing Mastectomy NAC significant to woman’s body image & QOL Growing public & surgeon interest in < radical & > cosmetic approaches Conservation of breast skin & NAC Provides best natural envelope for reconstruction Preserving nipple, inframammary fold, & breast contour ↓ need for contralateral breast procedures to achieve symmetry Preop 8 mths postop

Clinical arguments for & against the adoption of nipple sparing mastectomy (NSM) Oncological safety & equivalency not defined in RCTs No defined/standard incision, operative technique, or intra- op nipple assessment High rate of nipple loss/sensitivity Paucity of data XRT Unproven appropriateness in BRCA 1/2 For Scarcity of TDL Cosmetic benefit ↓surgical procedures / anesthesia Intraop XRT ↓ necrotic NAC No difference in OS Surveillances of reconstructed breast w/mammo & breast MRI

Oncologic Safety of NSM in Therapeutic Setting No prospective randomized controlled trials evaluating safety & oncological effectiveness of NSM vs traditional breast surgery.

Opponents of NSM argue that nipple involvement in mastectomy specimens is high , ranging from 0-58%. And as such removal of th NAC is obligatory in all cases.

Sappey’s drawing of the superficial lymphatics of upper torso & female breast (1874) This belief is primarily based on Sappey’s theory of centripetal lymphatic drainage which states all breast tissue drains toward the subareolar plexus. If indeed Sappeys theory is correct, NSM would leave prominent retroareolar draining lymphatics behind and is oncologically unsound.

However, Turner-Warwich in 1959 demonstrated that lymphatic drainage of the breast is not towards the nipple but rather downwards towards the deep pectoral lymphatic plexus implying that preseration of the NAC may be safe.

TDLUs in the nipple? TDLU TDLU’s in the nipple? When TDLUs present Basic reacting unit in all dysplastic, metaplastic, hyperplastic, anaplastic & neoplastic lesions of human breast is terminal duct lobular unit Wellings Path Res Pract 1980 TDLU’s in the nipple? Montagna failed to ID TDLUs in nipple Br J Der 1970 TDLUs in up to 9% mastectomy specimens Love, Cancer 2004; Taneri, EurSurgRes2005 When TDLUs present Mostly located near base of nipple No TDLUs found at tip when biopsy performed Base of nipple intra-op biopsy NAC preservation may not necessarily ↑ LRR Wellings et al utilized who mount methodology and su gross microscopic exam to analyze 196 breaste specimens and concluded “the basic reacting unit in practically all dysplastic, metaplastic, hyperplastic, anaplastic, and neoplastic lesios of the human beast is the terminal duct lobular unit”. Which rasies the ?, does leaving behind the NAC in NSM necessarily imply risk of LRR is increased? Yes if there were TDLUs w/in the nipple . Histological studies performed by Montana et al failed to ID any TDLUs in the nipple , Yet other authors have IDs TDLUs in up to 9% of mastectomy specimens. Perhaps more importantly, when TDLUs were present, they were universally located near the base of the nipple and no TDLUS were found at the tip whenever bx was performed. These findings suggest that as long as an I/O bx of the base of nipple is performed, NAC preservation may not increase rate of LRR.

Going back to table showing nipple involvement in mastectomy specimens is high , ranging from 0-58%. Unfortunately lack of uniformity of these studies in regard to pt selection , tumor characteristics and sampling of specimens makes results highly variable.

Retrospective analysis of LRR patterns in pts who have undergone NSM show that LRR rates 0-8.5% are comparable to those following BCS and these recurrences are NOT centered around the NAC

N= 2,182 NSM, 2007 – 2016 w/cancer or risk reduction Long term outcomes 311 NSM 2007- 2012 for Stages 0-3 BCs 240 (77%) NSM were for invasive cancer 71 (23%) DCIS At 51m f/u 17 developed a recurrence 11 (3.7%) LRR & 8 (2.7%) DR 2 patients had simultaneous LRR & DR 2 breast cancer-related deaths in patients with isolated distant recurrences Smith et al, JAmCollSurg.2017

Smith et al, JAmCollSurg.2017 DFS 95.7% @ 3 yrs & 92.3% @ 5 yrs

Smith et al JAmCollSurg.2017 No patient in 2,182 NSM cohort had recurrence in retained NAC Smith et al JAmCollSurg.2017

Smith et al, JAmCollSurg.2017 The Smith results are c/w those of other recent NSM series. LRR range from 0 to 4.6% at 10 to 60 months. Only 2 modern studies report any NAC recurrrences, and their rates are quite low at 0.7% and 0.8%.

TSSM & Immediate Breast Reconstruction Wang et al, 2014 Reviewed all cases 2005 - 2012 Comorbidities, treatment, postop complications, & outcomes LR, DR, OS analyzed 633 patients (981 cases) Median f/u time 29 m (14-54) Imm breast recon: TEI (89%), pedicleTRAM (5%), free flap (5%), perm implant (0.3%), lat flap (0.2%) Post op complications ↓ over time

3% Overall 5-year cumulative incidences of recurrence were 3.0 %(locoregional) and 4.2 %(distant), and there were no recurrences in the NAC skin

4.2% Overall 5-year cumulative incidences of recurrence were 3.0 %(locoregional) and 4.2 %(distant), and therewere no recurrences in the NAC skin

Overall Survival after TSSM by Clinical Stage 93% Overall 5 year survival was 93% Specifically 97% for stage 0; 98% stage I; 96% for stage II; 74% stage III ds, and 33% for stage IV ds

Indications for NSM High risk BRCA carriers Small tumors Tumors > 2 cm (?) from NAC No skin / NAC involvement Smaller / non ptotic breast No LVI, axillary LN+, EIC

Contraindications of NSM Inflammatory breast cancer Large / ptotic breast Delayed reconstruction Smokers/diabetics Tumor < 2 cm (?) from NAC NAC involvement

Complications Bleeding Seroma Infection Tissue necrosis Capsular contracture

Follow up after NSM Same as simple & skin sparing mastectomy No screening imaging needed No mammogram , no US, no MRI Consider US / MRI for +complaints/findings F/u according to ASCO recommendations based on primary diagnosis

NSSM Summary For most women with breast cancer BCS is the preferred option. The coordinated use of systemic therapy can maximize the odds of BCS in most women. NSSM is an ideal option for prophylactic mastectomy and for well selected CA patients who have no choice but mastectomy.

NSSM Summary Oncologically safe in well selected patients with invasive cancer or DCIS An excellent option for prophylactic mastectomy All of the well established BCS data has suggested that nipple removal does not confer a survival advantage NAC recurrence as sole site of LR is very rare LR in mastectomy flaps with or without NAC preservation is comparable in selected patient trials Cosmetic results particularly in prophylactic mastectomy cases are superior Psychological benefit may be substantial

Thank You