Nipple-Sparing Mastectomy: Are WeCompromising Oncologic Safety forCosmesis?

Bridget A. Oppong, MD, and Virgilio Sacchini, MD

THEEVOLUTIONOFMASTECTOMYTECHNIQUES

Randomized trials, such as the National Surgical AdjuvantBreast and Bowel Project B-04 and B-06 clinical trials,1,2

provided a foundation for a minimally invasive approach tothe surgical management of early breast cancers. Data fromthese trials resulted in women being offered breast conserva-tion surgery rather than mastectomy. However, there willalways be women who are not candidates for conservationsurgery or who simply prefer mastectomy. For such patients,the surgical approach to mastectomy has shifted from the dis-figuring radical mastectomy of old to skin-sparing mastec-tomy. Out of the skin-sparing technique evolved thesubcutaneous mastectomy, described by Freeman in 1962.3

Today, the nipple-sparing mastectomy (NSM), as subcuta-neous mastectomy is now called, offers an even bettercosmetic outcome and has garnered much attention as mastec-tomy rates overall continue to increase in many parts of theUnited States.4 However, the question remains: Does NSMadequately accomplish the goal of mastectomy, which is toremove the entire mammary gland for maximum therapeuticbenefit for those with cancer or prophylaxis for those at risk?

PROPHYLACTIC SURGERY

Historically, it has been reported that bilateral prophylacticmastectomy (BPM) results in an approximately 90% reduc-tion in the risk of developing subsequent cancer.5 This figurewas based on a retrospective analysis of 639 women witha family history of breast cancer undergoing BPMs between1960 and 1993. The current standard of care for prophylacticmastectomy is total mastectomy (with or without reconstruc-tion) performed in the same way as a therapeutic mastec-tomy. In this well-known Mayo Clinic report, there was nosignificant difference in outcomes based on whether themastectomy included the nipple or not.5 This providedsome early assurance of the safety of non-standard mastec-tomy techniques, including NSM, for surgical prophylaxis.

At Memorial Sloan-Kettering Cancer Center (MSKCC),3.5% of all mastectomies performed from 2000 to 2010 wereNSMs.6 This rate has increased from 1% sincewe first reportedour initial experience from 2000 to 2005.7 In 2011, we pub-lished an updated analysis of 353 NSM procedures, performedin 200 patients from 2000 to 2010, of which 196 (56%) werefor prophylactic risk reduction.6 While none of the women

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has developed cancer, we admittedly have had a limitedmedian follow-up of only 10 months. However, there areseveral other large retrospective studies that have suggestedthe oncologic safety of NSMs for prophylactic indications(Table 1).6,8-11 In one report, data from 4 large centers showedthat for 55 prophylactic NSMs, breast cancer developed in 2patients at a median follow-up of 24.6 months.8 Additionally,in a recent report by Spear and colleagues, 162 NSMs wereperformed between 1989 and 2010 in 101 women, of which70% were for risk reduction. No patients developed canceranywhere in the breast or nipple-areola complex (NAC) aftera mean follow-up of 3 years, 7 months.12

While we await updates from these studies of long-termoutcomes for those undergoing prophylactic NSMs, there isconsistent interest and demand in this procedure. The desirefor nipple preservation in the risk-reduction setting hasbecome increasingly common, as it results in improvedcosmesis and patient satisfaction.12

ONCOLOGIC UTILITY

While NSMs are performed disproportionately for prophy-laxis in most reports, the number of NSM therapeutic proce-dures has increased. At MSKCC, of the NSMs performedafter 2006, 48.2% were for therapeutic indications, eitherductal carcinoma in situ (DCIS) or invasive cancer.6 In earlierstudies, European centers spearheaded the use of NSM forcancer therapy and published several series.7,13-15 Whilemost did not have long-term follow-up, short-term datashowed a risk of recurrence similar to that for more acceptedskin-sparing mastectomies. These studies also outlined selec-tion criteria for optimal candidates for NSM, including tumorsize, location, and patient factors. In keeping with the criteriaestablished in these reports, since 2000 we have offered NSMat MSKCC to carefully selected patients who have clinicallynegative axillas and tumors less than 3 cm in size and morethan 1 cm from the NAC (Table 2).6

We employ a surgical technique that is largely the samefor both prophylactic and therapeutic NSMs. The majorexception is that in the therapeutic cases we perform a biopsyof the retroareolar ducts and analyze the frozen sections intra-operatively. If neoplasia is identified intraoperatively, or uponfinal pathologic examination, the NAC is removed. In ourseries published in 2011,6 of 157 therapeutic NSMs per-formed, 74 had DCIS (20.8%), 82 had invasive carcinoma(23.2%), and 1 had phyllodes tumor. Of the 82 invasivecancers, the median tumor size was 1.1 cm (range, 0.1-5.0 cm). On intraoperative frozen section assessment, weidentified involvement of the NAC in 11 of the 157 patients,with subsequent removal. Preservation of the NAC resultedin good surgical outcomes for 97% of the patients. Somedegree of skin desquamation or necrosis was experienced by

TABLE 1.dReported Series of Nipple-Sparing Mastectomies

Series NSMs Prophylactic, % Therapeutic, %

Nipple-Sparing Mastectomy

Follow-Up(Months)

No. of LocalRecurrences (%)

No. of LocalRecurrences at NAC

Gerber et al, 20037 61 0 100 59 1 (1.6%) 1Caruso et al, 200613 50 0 100 66 1 (2%) 1Sacchini et al, 20068 192 45 55 24.6 2 (2%) 0Crowe et al, 20089 140 27 73 41 2 (3.4%) 0Benediktsson et al, 200814 216 0 100 156 52 (8.5% with RT and

28.4% without RT)0

Sookhan et al, 200810 18 45 55 10.8 0 0Voltura et al, 200811 51 33 67 18 2 (5.9%) 0Petit et al, 2012*15 934 0 100 50 37 (4%) 11Kim et al, 201016 152 0 100 60 3 (2%) 2Spear et al, 201112 162 70 30 30 0 0de Alcantara et al, 20116 353 60 40 10 0 0

NSM, nipple-sparing mastectomy; NAC, nipple-areola complex; RT, radiotherapy*NSMs performed with intraoperative radiation.

TABLE 2.dPatient Selection for Nipple-Sparing Mastectomy

Inclusion CriteriaClinically negative axillaTumor < 3 cm in any of the 4 quadrants of the breastTumors > 1 cm from the nipple and areola complex (prior to 2005 > 2 cm)Exclusion CriteriaTumor Factors

Peripheral locationMultifocalityPatient Factors

Grade 4 ptosis of the breastOversized breastsDiabetic patientsHeavy smokersObese patients

19.5% of patients, but only 3.3% of patients required opera-tive debridement.6 There were no reported local recurrences,albeit with a limited median follow-up period of 10.38 months(range, 0-109 months). One patient developed a brain metas-tasis and died because of metastatic disease.

Reports from other institutions also show that a nipple-sparing approach could be considered for properly selectedpatients with early disease, especially when a subareolar

biopsy is performed. These studies suggest minimal onco-logic sequelae when clear margins are obtained under theNAC, with overall local recurrence rates ranging from1.6% to 28.4% (Table 1).6,8-12 Benediktsson and Perbeckpublished the only prospective trial on NSM with a primaryendpoint of survival,14 and while they showed the highestlocal recurrence rate (28.4% over 156 months) among non-irradiated patients, the overall survival rate of 76.4% wascomparable to that of conventional mastectomy reported inother trials.

In conclusion, NSM, while still not accepted as standardof care owing to the dearth of long-term data, remains anincreasingly popular option. The interest in this techniquewill continue as mastectomy rates increase. At MSKCC,the rate of contralateral prophylactic mastectomy over thepast few years was 13.8%, increasing from 6.7% in 1997 to24.2% in 2005.17 With an undoubtedly superior cosmeticresult when compared to standard techniques, NSM hasa high patient satisfaction rate, which also confers a psycho-logical benefit.12 While patients may be content with NSM,whether their surgeons are satisfied with the oncologic safetyremains another issue. Many remain uneasy about thismastectomy technique over concerns of residual breast tissuethat may harbor tumor in women with known cancer orresidual breast tissue that may develop malignancy in thesubset of women undergoing prophylactic mastectomy.While the current data do not provide enough evidence tomake NSM the new standard, the limited short-term data

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do suggest that it is probably not inferior to the moreaccepted skin-sparing mastectomy. Most poignantly, all theretrospective series show no significant increase in localrecurrence, with an especially minimal risk of local recur-rence to the NAC.

References1. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER,

Wolmark N. Twenty-five-year follow-up of a randomizedtrial comparing radical mastectomy, total mastectomy, andtotal mastectomy followed by irradiation. N Engl J Med.2002;347:567-575.

2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up ofa randomized trial comparing total mastectomy, lumpectomy,and lumpectomy plus irradiation for the treatment of invasivebreast cancer. N Engl J Med. 2002;347:1233-1241.

3. Freeman BS. Subcutaneous mastectomy for benign breastlesions with immediate or delayed prosthetic replacement.Plast Reconstr Surg Transplant Bull. 1962;30:676-682.

4. Damle S, Teal CB, Lenert JJ, Marshall EC, Pan Q,McSwain AP. Mastectomy and contralateral prophylacticmastectomy rates: an institutional review. Ann Surg Oncol.2011;18:1356-1363.

5. Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy ofbilateral prophylactic mastectomy in women with a familyhistory of breast cancer. N Engl J Med. 1999;340:77-84.

6. de Alcantara Filho P, Capko D, Barry JM, Morrow M,Pusic A, Sacchini VS. Nipple-sparing mastectomy for breastcancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience. Ann Surg Oncol. 2011;18:3117-3122.

7. Gerber B, Krause A, Reimer T, et al. Skin-sparing mastectomywith conservation of the nipple-areola complex and autologousreconstruction is an oncologically safe procedure. Ann Surg.2003;238:120-127.

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8. Sacchini V, Pinotti JA, Barros AC, et al. Nipple-sparingmastectomy for breast cancer and risk reduction: oncologicor technical problem? J Am Coll Surg. 2006;203:704-714.

9. Crowe JP, Patrick RJ, Yetman RJ, Djohan R. Nipple-sparingmastectomy update: one hundred forty-nine procedures andclinical outcomes. Arch Surg. 2008;143:1106-1110.

10. Sookhan N, Boughey JC, Walsh MF, Degnim AC. Nipple-sparing mastectomydinitial experience at a tertiary center.Am J Surg. 2008;196:575-577.

11. Voltura AM, Tsangaris TN, Rosson GD, et al. Nipple-sparingmastectomy: critical assessment of 51 procedures andimplications for selection criteria. Ann Surg Oncol. 2008;15:3396-3401.

12. Spear SL, Willey SC, Feldman ED, et al. Nipple-sparingmastectomy for prophylactic and therapeutic indications.Plast Reconstr Surg. 2011;128:1005-1014.

13. Caruso F, Ferrara M, Castiglione G, et al. Nipple sparingsubcutaneous mastectomy: sixty-six months follow-up. Eur JSurg Oncol. 2006;32:937-940.

14. Benediktsson KP, Perbeck L. Survival in breast cancer afternipple-sparing subcutaneous mastectomy and immediatereconstruction with implants: a prospective trial with 13years median follow-up in 216 patients. Eur J Surg Oncol.2008;34:143-148.

15. Petit JY, Veronesi U, Orecchia R, et al. Risk factors associatedwith recurrence after nipple-sparing mastectomy for invasiveand intraepithelial neoplasia [published online ahead of printJanuary 9, 2012]. Ann Oncol. 10.1093/annonc/mdr566.

16. Kim HJ, Park EH, Lim WS, et al. Nipple areola skin-sparingmastectomy with immediate transverse rectus abdominismusculocutaneous flap reconstruction is an oncologicallysafe procedure: a single center study. Ann Surg. 2010;251:493-498.

17. King TA, Sakr R, Patil S, et al. Clinical management factorscontribute to the decision for contralateral prophylacticmastectomy. J Clin Oncol. 2011;29:2158-2164.

Is Breast Conservation Therapy UnderSiege?

Todd M. Tuttle, MD, MS

After the National Institutes of Health Consensus Statementwas released in 1990, the rates of breast-conserving surgery(BCS) increased in the United States throughout the 1990s

and 2000s.1,2 However, in 2009, 2 single-institution studiesreported that mastectomy rates had markedly increased, witha corresponding decrease in BCS rates.3,4 In a study of 5865patients treated at the Moffitt Cancer Center, McGuire andcolleagues reported that the mastectomy rates increased from35% in 2004 to 60% in 2007; young age (<40 years), largertumor size, and lymphovascular invasion were independentpredictors of mastectomy.3 In another study of 5405 patientstreated at theMayoClinic, Katipamula and colleagues reported