BREAST Evaluating Long-Term Outcomes following Nipple-Sparing Mastectomy and Reconstruction in the Irradiated Breast Scott L. Spear, M.D. John Shuck, M.D. Lindsay Hannan, M.D., M.S.P.H. Frank Albino, M.D. Ketan M. Patel, M.D. Washington, D.C.
Background: Although it is well established that reconstruction of the irradiated breast is associated with diminished cosmetic results and more frequent complications, little is known about the specific effects of radiation therapy on the reconstructive outcomes after nipple-sparing mastectomy. Methods: Patients who had nipple-sparing mastectomy and had either previous radiation therapy for breast-conservation therapy or postmastectomy radiation therapy were reviewed. Patient demographics, reconstructive details, and postoperative outcomes were analyzed. Patient photographs were used to evaluate aesthetic parameters. Fisher’s exact and t tests were used for comparison of groups, with a value of p < 0.05 considered significant. Results: Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy (72.2 percent) or before postmastectomy radiation therapy (27.8 percent), with an average follow-up of 3 years. First-stage complications occurred in six patients (33.3 percent). Nipple position was classified as high-riding in 55.6 percent of patients. Average time to revision was 13.3 months. Most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and h igh-riding nipple (22.4 percent). Capsular contracture occurred more commonly in patients who needed postmastectomy radiation therapy compared with those who had previously undergone breast-conservation therapy (40 percent versus 7.8 percent). Maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent). Conclusions: Nipple-sparing mastectomy and implant reconstruction should be approached cautiously in the setting of radiation therapy. When early complications are present, significant morbidity may occur. Late revision surgery is common in this subset of patients. Implant malposition and a high-riding nipple occur most frequently. (Plast. Reconstr. Surg. 133: 605e, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
T
he evolution of techniques in breast reconstruction has resulted in dramatically improved aesthetic results following implantbased reconstruction.1–8 Nipple-sparing mastectomy has been a major contributing factor for these improvements. Despite the positive impact of this valuable option, patient selection continues to eliminate this choice for many patients. The ideal candidate for nipple-areola complex preservation is one with small, nonptotic or minimally From the Department of Plastic Surgery, Georgetown University Hospital. Received for publication July 16, 2013; accepted November 13, 2013. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000098
ptotic breasts and a single small peripheral tumor. Concerns over blood supply and vascularity are minimized with shorter flaps and a smaller dissection area. In addition, with the improved techniques related to breast implants, acellular tissue matrices, and fat grafting, nipple-sparing techniques coupled with reconstruction can result in remarkable aesthetic results.1,2,4,9,10 Despite early concerns with the oncologic efficacy and risk for recurrence in nipple-sparing mastectomy, there Disclosure: Dr. Spear is a consultant for LifeCell Corp. (Branchburg, N.J.) and A llergan, Inc. (Irvine, Calif.). None of the other authors has any disclosures. No funding was used for the preparation of this article.
www.PRSJournal.com
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Plastic and Reconstructive Surgery • May 2014 is a growing body of evidence demonstrating its safety in the properly selected patient.11–16 Drawbacks to choosing nipple-sparing techniques are typically related to anatomical and surgical technical challenges. Wound healing complications and nipple necrosis are reported to be as high as 20 percent.9,12,17,18 Often, wound healing issues following nipple-sparing mastectomy and implant reconstruction result in early complications and occasionally reconstruction failure and explantation. Although the anatomical criteria for nipple-sparing mastectomy have been expanded and have been shown to be a viable option in patients who have undergone prior mastopexy or reduction, the effects of radiation therapy remain unclear.19–21 This lack of information and the uncertainty regarding nipple-sparing mastectomy in the irradiated breast understandably have made clinicians hesitant to pursue this reconstructive modality, given the possibility of increased complication rates. The long-term effects of radiation therapy have traditionally resulted in suboptimal implant-based breast reconstruction in many centers.22 Late capsular contracture rates with possible revision reconstruction or reconstructive failure have led many centers to abandon implant reconstruction when radiation therapy has already occurred or is likely to be needed. Recently, studies have shown some success with reconstruction using implants in the irradiated breast.23–26 The senior author (S.L.S.) has found that, in select patients, pursuing implant-based reconstruction can result in successful outcomes.23 Newer adjuncts— namely, the use of acellular dermal matrices and some forms of adjuvant radiation therapy—have resulted in an increase in acceptable outcomes following radiation therapy. However, until now, no study has looked specifically at outcomes when reconstruction is performed after nipple-sparing mastectomy in the breast that has been or will be irradiated. Therefore, the aim of this study was to investigate the outcomes of patients who underwent nipple-sparing mastectomy and who either had previous radiation therapy as part of breast conservation or who had postmastectomy radiation therapy.
PATIENTS AND METHODS Study Design An institutional review board–approved retrospective analysis was performed of all patients who underwent nipple-sparing mastectomy and implantbased reconstruction performed by the senior
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surgeon (S.L.S.) from 2002 to 2012. Patients who either had radiation therapy before mastectomy as a part of previous breast-conservation therapy or underwent postmastectomy radiation therapy were identified. Eighteen patients were identified who met the inclusion criteria of this study. Reconstructive Technique The technique of two-stage immediate expander-to-implant reconstruction with AlloDerm (LifeCell Corp., Branchburg, N.J.) has been described previously by the senior author (S.L.S.).27 In patients with a history of b reast-conservation therapy, an immediate implant-based reconstructive option was given to patients who (1) would otherwise be a candidate for nipple-sparing mastectomy and reconstruction and (2) have supple tissue with minimal radiation-induced soft-tissue/ skin damage (Figs. 1 and 2). In the later portion of this study, if postmastectomy radiation therapy was expected, implant exchange was attempted before the initiation of radiation therapy. If postmastectomy radiation therapy was performed before implant exchange, a minimum of 6 weeks was allowed before attempting exchange. Also, later during the study period, if postmastectomy radiation therapy was planned before surgery and neoadjuvant chemotherapy had already occurred, direct-to-implant reconstruction was the preferred option when feasible rather than a two-stage expander/implant approach. Incisions for nipple-sparing mastectomy were chosen in collaboration between the surgical oncologist and plastic surgeon. Periareolar, lateral, and inframammary incisions were used for all patients and were determined based on the tumor location and overall breast characteristics. All expanders/implants were placed in the partial subpectoral plane, and since 2004, this has included acellular dermal matrix lower pole support. Postoperative antibiotics were administered until drain removal, which occurred at approximately 2 weeks, when drainage had tapered off to less than 30 cc per 24 hours. Tissue expansion was resumed at approximately 2 weeks after reconstruction and was performed at intervals until the desired volume was obtained. Exchange to a permanent implant was highly dependent on other circumstances such as chemotherapy and the timing and need for postmastectomy radiation therapy. Capsulotomies and other pocket adjustments were performed to create the desired position and shape of the reconstruction.
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy
Fig. 1. Appropriate candidates for nipple-sparing mastectomy based on breast size, tumor size, and disease location. (Above) A 47-year-old, otherwise healthy woman with a history of left breast estrogen receptor/progesterone receptor–positive, Her-2–negative invasive ductal carcinoma treated with partial mastectomy and radiation therapy. The patient presented 8 years after her initial treatment with recurrence of her invasive breast cancer for bilateral mastectomies. There are minimal skin changes following radiation therapy, with relatively symmetric breasts and a minimally widened left breast scar. (Below) A 49-year-old woman with a history of left estrogen receptor/ progesterone receptor/Her2–positive invasive ductal carcinoma of her left breast treated with partial mastectomy notable for a negative sentinel lymph node biopsy followed by chemotherapy and irradiation. She was found to have a palpable mass 10 years after her initial carcinoma corresponding with disease recurrence on biopsy. Recent genetic testing confirms that she is a BRCA1 gene mutation carrier. The left breast is minimally contracted, with no radiation-related skin changes observed.
Data Collection and Analysis Patient information was collected from office charts and operative reports. First-stage reconstruction was defined by the immediate reconstruction occurring at the time of mastectomy. Primary outcomes of interest included mastectomy
Fig. 2. A high-riding nipple-areola complex may occur after nipple-sparing mastectomy and reconstruction; however, the severity of this displacement is variable. (Above) Mild case of left superior nipple displacement in a 51-year-old woman following nipple-sparing mastectomy and radiation therapy for invasive left breast cancer. (Center) Moderately high-riding nipple-areola complex in a 47-year-old woman following bilateral nipple-sparing mastectomy and adjuvant chemotherapy and irradiation for left invasive breast cancer. (Below) Severe left nipple displacement and moderate right nipple elevation in a 42-year-old woman following bilateral nipple-sparing mastectomy and adjuvant radiation therapy for left invasive breast cancer.
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Plastic and Reconstructive Surgery • May 2014 skin necrosis, return to the operating room, infection requiring antibiotics, and infection requiring explantation. Second-stage reconstruction was defined for patients who had an implant exchanged after an initial tissue expander placed at the time of mastectomy. Primary outcomes of second-stage surgery were related to implant characteristics, timing of reconstruction, revisions, and complications. Revision surgery was analyzed for the defined follow-up period. Capsular contracture, malposition correction, implant exchange, and nipple position were critically evaluated. Analyses were performed using SAS for Windows, Version 9.2 (SAS Institute, Inc., Cary, N.C.). Categorical demographic variables were analyzed by means of Fisher’s exact test because of the small sample size. Means and standard deviations were calculated for continuous variables. The t test was used for comparison between groups. An a priori value of p < 0.05 was considered significant. Nipple Position Analysis Determination of a high-riding nipple was determined based on the location of the nipple along the vertical axis of the breast in a three-quarters oblique view as recently described.28 Relative percentage height was used to classify the high-riding nipple as mild, moderate, or severe (Fig. 2).
RESULTS Patient Characteristics Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy [13 of 18 (72.2 percent)] or before postmastectomy radiation therapy [five of 18 (27.8 percent)], with an average follow-up of 3 years. Average patient age and body mass index were 47.5 years and 21.1 kg/m2, respectively (Tables 1 and 2). Average mastectomy weight was 271 g. Previous smoking history was reported in three of 18 patients (16.7 percent). No patients had previous breast augmentations or implants. Precise radiation dosimetry schedules were unavailable for analysis because of the variations in treating institutions. First-Stage Outcomes Two-stage expander-implant reconstruction was planned in a majority of patients [17 of 18 (94.4 percent)]. One patient underwent direct-to-implant reconstruction following mastectomy. This patient had neoadjuvant chemotherapy
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before mastectomy and was scheduled to undergo postmastectomy radiation therapy. In this scenario, direct-to-implant reconstruction was chosen to avoid the necessity of an implant exchange following postmastectomy radiation therapy. Firststage complications occurred in six of 18 patients (33.3 percent), with most (four of six) occurring in patients who had previously undergone breastconservation therapy, for a complication rate of 30.8 percent (four of 13) in that group (Table 3). Sixty-seven percent of complications were related to skin ischemic changes, with one patient developing partial nipple necrosis. All ischemic changes healed without full-thickness skin loss. Infection developed in one patient, which was successfully treated with antibiotic therapy alone. One hematoma occurred requiring operative washout. No expander/implant loss occurred following the first-stage reconstruction. Average expander/ implant volume was 356 ml, with an average initial fill volume of 258 ml. Second-Stage Outcomes Of the 17 patients who underwent a t wo-stage reconstruction, the average time to implant exchange was 167 days (Table 4). Radiation therapy occurred before implant exchange in 14 of 17 patients (82.4 percent) and after implant exchange in three of 17 patients (17.6 percent). Shaped anatomical gel implants were placed in seven of 17 patients (41 percent), whereas round smooth gel implants were placed in the remaining 10 patients (59 percent). Average final implant volume was 421 ml. Three patients (17.6 percent) underwent fat grafting at the second stage, and capsular modification occurred in 13 of 17 patients (76.5 percent). Complications occurred in one patient (5.9 percent) at the time of exchange. An infection occurred following implant exchange resulting in eventual implant loss (Figs. 3 and 4). This patient had a history of previous breast-conservation therapy 5 years before mastectomy. Revision Surgery and Long-Term Outcomes Additional revision surgery occurred in nine of 18 patients (50 percent) (Table 5). Four patients underwent multiple revisions (average, 3.0). Average time to revision was 13.3 months. The most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and high-riding nipple (55.6 percent). Interventions during revision included implant exchange (37.5 percent), malposition correction with capsular modification (31.2 percent),
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy Table 1. Overall Demographics Value (%)* No. of patients Average age, yr Average BMI, kg/m2 History of smoking Single-stage reconstruction Two-stage reconstruction PMRT History of BCT
18 47.5 21.13 3 (16.7) 1 (5.6) 17 (94.4) 5 (27.8) 13 (72.2)
BMI, body mass index; PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy.
Table 2. Breast-Conservation Therapy versus Postmastectomy Radiation Therapy Age, yr BMI, kg/m2 Percent Weeks until exchange
PMRT
BCT
p
37.2 ± 8.4 21.7 ± 3.9 37.0 ± 9.2 32.0 ± 13.6
51.5 ± 9.1 20.9 ± 3.4 41.6 ± 11.4 21.1 ± 5.9
0.01 0.61 0.44 0.2
PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy; BMI, body mass index.
Table 3. First-Stage Reconstruction Details Mean (n)* Average mastectomy weight, g Incision types Superoareolar with lateral extension Inferoareolar with lateral extension Lateral IMF Direct-to-implant Usage of ADM Complications Nipple necrosis Infection Expander/implant loss Average fill volume, ml Average interval between XRT and first-stage reconstruction, mo†
271 10 6 1 1 5.6 (1) 83 (15) 33.3 (6) 5.6 (1) 5.6 (1) 0 (0) 258 112.4
IMF, inframammary fold; ADM, acellular dermal matrix; XRT, radiation therapy. *All values are mean (n) unless otherwise specified. †Reported for breast-conservation therapy cohort only.
Table 4. Second-Stage Reconstruction Details % (n)* Average time to exchange, days XRT performed after exchange† XRT performed before exchange† Average implant size, ml Contoured implants used Round implants used Revision during exchange ADM used Fat grafting Complications
capsulectomy for capsular contracture (18.8 percent), and surgical correction of a high-riding nipple (25 percent). When cohorts were separated on whether radiation therapy was delivered in the setting of breastconservation therapy or postmastectomy radiation therapy, differing outcomes were seen (Table 6). In the premastectomy radiation therapy cohort, patients had a lower long-term rate of significant capsular contracture (7.8 percent) compared with the postmastectomy radiation therapy cohort (40 percent; p = 0.17), although statistical significance was not achieved. When nipple position was evaluated, similar results were seen across both cohorts. Both cohorts had over half of patients with either grade 2 or grade 3 nipple elevation (53.9 percent and 60 percent, respectively; p = 0.99). There appeared to be no association between incision type and degree of nipple elevation (Table 7). In addition, similar rates of correction for implant malposition occurred between groups (20 percent and 30.8 percent, respectively; p = 1.0). Overall, maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent).
167 60 (3) 40 (2) 421 41.2 (7) 61.1 (11) 72.2 (13) 23.5 (4) 17.6 (3) 5.6 (1)
XRT, radiation therapy; ADM, acellular dermal matrix. *All values are percentages (n) unless otherwise specified. †Represents the PMRT cohort only.
DISCUSSION Rates of implant-based breast reconstruction continue to rise.29,30 These increases in volume are paralleled by innovations and technical improvements in surgical techniques. One of the most influential of these methods, n ipple-sparing mastectomy, allows for preservation of the n ipple-areola complex and can result in superior aesthetic results. Nipplesparing mastectomy has now become an integral part of the reconstructive process. Nevertheless, despite being a highly desirable oncologic option, it is a technically challenging procedure offered to only select patients. As the collective experience with nipple-sparing mastectomy and implant reconstruction has continued to grow, refinements have allowed for better cosmetic results. Implant-based reconstructive outcomes in the setting of radiation therapy remain inferior to those in the nonirradiated breast but have gradually improved over recent years.31 In partial breast reconstruction, intraoperative radiotherapy minimizes collateral tissue damage, which may likely improve reconstruction attempts if future reconstruction is needed.32 Following mastectomy, early literature supports potential beneficial effects with the use of acellular dermal matrix during implant reconstruction. Seth et al. found that acellular dermal matrix may have a protective effect on
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Fig. 3. (Above, left) A 55-year-old woman with left breast invasive lobular carcinoma who (above, right) underwent bilateral nipple-sparing mastectomies with tissue expander placement followed by chemotherapy and radiation. Seven months later, she had an exchange to implants (McGhan Style 20, 500 ml) with left breast dermal fat grafting for a contour deformity. Unfortunately, she developed a postoperative infection with device exposure notable for methicillin-sensitive Staphylococcus aureus necessitating explantation of her left implant 2 months later (below).
postradiation pain/tightness and implant extrusion compared with no acellular dermal matrix.33 Similarly, Vardanian et al. evaluated acellular dermal matrix–assisted implant reconstruction and found statistically significant decreases in capsular contracture rates and mechanical shift.34 All patients in our series received acellular dermal matrix during the first-stage reconstructive operation. In addition, acellular dermal matrix was used in 24 percent of patients during the second-stage reconstruction. When faced with radiation therapy, early complications following mastectomy can lead to prolonged morbidity requiring explantation. Conversely, late complications related to tightness, distortion, and capsular contracture lead patients to
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seek revision surgery.35,36 Although we found low early complication rates with nipple-sparing mastectomy in the irradiated breast, late revision surgery occurred in 50 percent of patients during the follow-up period. Not surprisingly, capsular contracture was more common in patients who received postmastectomy radiation therapy compared with those who previously had breast-conservation therapy. This finding is likely related to different protocols of radiotherapy commonly used in the setting of breast-conservation therapy compared with postmastectomy radiation therapy.37,38 In addition, the lack of an implant during radiation therapy in breast-conservation therapy patients eliminates any direct capsular damage caused by radiation.
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy Table 5. Reconstructive Outcomes % (n)* Average no. of revisions per patient Average time to revision, mo Malposition requiring correction Capsular contracture Change of implant Eventual implant loss High-riding nipple Nipple corrective surgery Average follow-up, yr
0.89 13.3 27.8 (5) 16.7 (3) 33.3 (6) 11.1 (2) 55.6 (10) 22.2 (4) 3
*All values are percentages (n) unless otherwise specified.
Table 6. Complications of Postmastectomy Radiation Therapy versus Breast-Conservation Therapy
Fig. 4. The patient in Figure 3 ultimately required a latissimus dorsi flap and implant reconstruction to achieve stable closure.
The occurrence of nipple elevation, or the “high-riding nipple,” is a complication specific to implant reconstruction after nipple-sparing mastectomy, and is a more significant risk with reconstruction after nipple-sparing mastectomy of the irradiated breast. Recently, the senior author (S.L.S.) described the occurrence of a high-riding nipple and a classification system. The authors found that one-third of patients with an excessively high nipple-areola complex had undergone nipple-sparing mastectomy.28 In reconstruction after nipple-sparing mastectomy of the irradiated breast, nipple elevation seems to occur more frequently. We found that a majority of the patients in this retrospective review had some degree of nipple elevation, with nearly half desiring corrective surgery. Although the exact mechanism of radiation therapy and its effect on nipple position and surrounding skin is not known, a proposed mechanism based on superior pole skin contraction against firm attachment in the region of the clavicle may explain the upward migration commonly seen following implant reconstruction.
High-riding nipple 0 1 2 High-riding nipple Low (grade 0, 1) High (grade 2, 3) Capsular contracture No Yes Malposition correction No Yes Any complication No Yes
PMRT (%)
BCT (%)
p
1 (20.0) 2 (40.0) 2 (40.0)
5 (38.6) 3 (23.1) 5 (38.5)
0.82
2 (40.0) 3 (60.0)
6 (46.2) 7 (53.9)
0.99
3 (60.0) 2 (40.0)
12 (92.3) 1 (7.8)
0.17
4 (80.0) 1 (20.0)
1 (69.2) 4 (30.8)
1 (20.0) 4 (80.0)
6 (46.2) 7 (53.9)
0.99 0.6
PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy.
The topic of prosthetic reconstruction of the irradiated breast has long been mired in controversy, with some arguing that implants should not be used and others favoring their use in selected, more favorable cases. When considering implant reconstruction of the irradiated breast, our position has been that thoughtful patient selection is important to achieve a reasonable likelihood of a successful outcome. When breast-conservation therapy has previously been performed, there is a legitimate hesitancy with pursuing implant reconstruction because of (1) wound healing complications that can lead to early implant failure and (2) late capsular contracture rates with potential for extensive revision surgery and possible late implant failure. This risk is potentially magnified with nipple-sparing mastectomy because of the already increased risk with that procedure of wound healing issues related to either partial- or full-thickness necrosis.12–14,17,18 Long skin flaps and wide undermining make this technique prone to
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Plastic and Reconstructive Surgery • May 2014 Table 7. Nipple Position by Incision Type Incision Type
Low-Riding Nipple (%)
High-Riding Nipple (%)
Inferoareolar Lateral Lateral IMF Superoareolar
2 (25.0) 0 (0.0) 1 (12.5) 5 (62.5)
4 (40.0) 1 (10.0) 0 (0.0) 5 (50.0)
p 0.69
IMF, inframammary fold.
wound healing complications.9,10,12,13 A history of breast radiotherapy necessarily compounds that risk, making careful patient selection all the more important. In addition to consideration of the oncologic issues of nipple-sparing mastectomy after breast-conservation therapy, we use selection criteria based mostly on physical examination. In patients with very large or ptotic breasts, significant skin changes, substantial breast distortion, malposition of the nipple, and/or scar contracture, nipple-sparing techniques are generally not offered. Although we found a 33 percent early complication rate following nipple-sparing mastectomy after radiation therapy, no patient required operative intervention for flap necrosis or ischemia, illustrating the importance of conservative patient selection and careful surgical technique. Increasing patient demand for the nipple-sparing mastectomy in conjunction with a growing comfort with the procedure on the part of oncologic surgeons will likely result in the even more widespread implementation of nipple-sparing mastectomy as an option for patients. In addition, the increased frequency of postmastectomy radiation therapy will likely result in more patients needing postmastectomy radiation therapy after nipple-sparing mastectomy. Although it is clear that irradiation following postmastectomy implant reconstruction diminishes the quality of the results and causes an increase in symptomatic capsular contractures, infections, and reconstruction failure, the safety and efficacy of implant reconstruction and nipple-sparing mastectomy followed by postmastectomy radiation therapy remain less clearly defined. With these patients in mind, a better understanding of their outcomes will allow them and their surgeons to make more informed decisions related to treatment. In patients who received postmastectomy radiation therapy after implant reconstruction and nipple-sparing mastectomy, we found a 40 percent capsular contracture rate, resulting in a number of revisions for capsular contracture. The average time to revision related to capsular contracture in this subset of patients was 18 months. One patient
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underwent two separate revision operations and later elected for implant removal and autologous flap reconstruction because of painful capsular contracture. In addition, nipple malposition was found in 60 percent of this subset of patients, with a majority obtaining corrective surgery. Looking at both cohorts over the long term, revision surgery related to malposition and a high-riding nipple was performed in half of the patients. In addition, a significant proportion of these patients needed additional revision operations. The key findings of our review are a high degree of success (88.9 percent) overall with implant reconstruction after nipple-sparing mastectomy in the irradiated breast. Despite a 30 percent complication rate at the first-stage reconstruction of nipple-sparing mastectomy after breast-conservation therapy/radiation therapy, there were no failures at the first stage in those patients. Because postmastectomy radiation therapy follows the first stage of nipple-sparing mastectomy, the first stage in those patients was similar to other nonirradiated patients. Capsular contracture resulting in revision occurred in both irradiated groups but was more common in the postmastectomy radiation therapy group. The finding that is new and unique to this cohort of patients is the frequency of nipple malposition seen after nipple-sparing mastectomy in an irradiated breast, which can occur whether the irradiation precedes (53.9 percent) or follows (60 percent) the nipple-sparing mastectomy. Although some patients had revisions specifically designed to correct or improve their nipple position, no patient has so far chosen to have their displaced nipple removed. As our understanding of this subject expands, we should be able to make better and more informed decisions about treatment strategies. We now have an additional issue to consider when contemplating implant reconstruction and nipplesparing mastectomy following radiation therapy or before postmastectomy radiation therapy. The oncologic issues and radiation morbidity have previously been described, but the issue of nipple malposition poses an additional problem to be considered. That said, so far, our impression is that patients prefer their misplaced nipple to no nipple at all. This may not be much different than the patient after breast-conservation therapy, where some displacement of the nipple seems to often be well accepted. In the meantime, we now have reason to inform patients of this additional issue and, at the same time, contemplate whether there are any steps we can take to prevent this occurrence. As
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy this is an early report, it remains to be seen whether others have findings similar to ours. We also plan to compare this experience with our experience with the larger population of nipple-sparing mastectomy patients who have not been irradiated. The authors acknowledge a number of limitations to the current study. In this series, breast-conservation therapy and postmastectomy radiation therapy patients are grouped when overall early and late complications are reported. Although the irradiation timing is disparate, we feel that once postmastectomy radiation therapy has been delivered, the effects on the breast are similar, particularly with regard to late revision surgery. Finally, our sample size is small and therefore may not adequately represent the early and late complication rates in this broadening population of patients. However, given the relative lack of data available in the literature regarding this subject, along with the rapidly expanding popularity of the nipplesparing mastectomy, we feel that the reporting of the inherent complication rates in nipple-sparing mastectomy patients is of paramount importance.
CONCLUSIONS In patients undergoing nipple-sparing mastectomy, early complication rates are relatively low and may be managed nonoperatively in most cases. In this subset of patients, the need for late revision surgery is high as a result of radiation-induced effects. Nipple-sparing mastectomy and implant reconstruction can be successfully performed in the irradiated breast; however, revision surgery is common secondary to implant malposition, capsular contracture, and/or a high-riding nipple. Scott L. Spear, M.D. Department of Plastic Surgery Georgetown University Hospital 3800 Reservoir Road, NW Washington, D.C. 20007 [email protected]
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4. Wellisch DK, Schain WS, Noone RB, Little JW III. The psychological contribution of nipple addition in breast reconstruction. Plast Reconstr Surg. 1987;80:699–704. 5. Spear SL, Schwarz KA, Venturi ML, Barbosa T, Al-Attar A. Prophylactic mastectomy and reconstruction: Clinical outcomes and patient satisfaction. Plast Reconstr Surg. 2008;122:1–9. 6. Ueda S, Tamaki Y, Yano K, et al. Cosmetic outcome and patient satisfaction after skin-sparing mastectomy for breast cancer with immediate reconstruction of the breast. Surgery 2008;143:414–425. 7. Isern AE, Tengrup I, Loman N, Olsson H, Ringberg A. Aesthetic outcome, patient satisfaction, and health-related quality of life in women at high risk undergoing prophylactic mastectomy and immediate breast reconstruction. J Plast Reconstr Aesthet Surg. 2008;61:1177–1187. 8. Salgarello M, Barone-Adesi L, Terribile D, Masetti R. Update on one-stage immediate breast reconstruction with definitive prosthesis after sparing mastectomies. Breast 2011;20:7–14. 9. Salgarello M, Visconti G, Barone-Adesi L. Nipple-sparing mastectomy with immediate implant reconstruction: Cosmetic outcomes and technical refinements. Plast Reconstr Surg. 2010;126:1460–1471. 10. Blechman KM, Karp NS, Levovitz C, et al. The lateral inframammary fold incision for nipple-sparing mastectomy: Outcomes from over 50 immediate implant-based breast reconstructions. Breast J. 2013;19:31–40. 11. Mallon P, Feron JG, Couturaud B, et al. The role of nipple-sparing mastectomy in breast cancer: A com prehensive review of the literature. Plast Reconstr Surg. 2013;131:969–984. 12. Spear SL, Willey SC, Feldman ED, et al. Nipple-sparing mastectomy for prophylactic and therapeutic indications. Plast Reconstr Surg. 2011;128:1005–1014. 13. Spear SL, Hannan CM, Willey SC, Cocilovo C. Nipple-sparing mastectomy. Plast Reconstr Surg. 2009;123:1665–1673. 14. Rusby JE, Smith BL, Gui GP. Nipple-sparing mastectomy. Br J Surg. 2010;97:305–316. 15. Chung AP, Sacchini V. Nipple-sparing mastectomy: Where are we now? Surg Oncol. 2008;17:261–266. 16. Spear SL, Carter ME, Schwarz K. Prophylactic mastectomy: Indications, options, and reconstructive alternatives. Plast Reconstr Surg. 2005;115:891–909. 17. Djohan R, Gage E, Gatherwright J, et al. Patient satisfaction following nipple-sparing mastectomy and immediate breast reconstruction: An 8-year outcome study. Plast Reconstr Surg. 2010;125:818–829. 18. Chen CM, Disa JJ, Sacchini V, et al. Nipple-sparing mastectomy and immediate tissue expander/implant breast reconstruction. Plast Reconstr Surg. 2009;124:1772–1780. 19. Spear SL, Rottman SJ, Seiboth LA, Hannan CM. Breast reconstruction using a staged nipple-sparing mastectomy following mastopexy or reduction. Plast Reconstr Surg. 2012;129:572–581. 20. Rivolin A, Kubatzki F, Marocco F, et al. Nipple-areola complex sparing mastectomy with periareolar pexy for breast cancer patients with moderately ptotic breasts. J Plast Reconstr Aesthet Surg. 2012;65:296–303. 21. Alperovich M, Tanna N, Samra F, et al. Nipple-sparing mastectomy in patients with a history of reduction mammaplasty or mastopexy: How safe is it? Plast Reconstr Surg. 2013;131:962–967. 22. Israeli R, Feingold RS. Acellular dermal matrix in breast reconstruction in the setting of radiotherapy. Aesthet Surg J. 2011;31(Suppl):51S–64S.
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Plastic and Reconstructive Surgery • May 2014 23. Spear SL, Seruya M, Rao SS, et al. Two-stage prosthetic breast reconstruction using AlloDerm including outcomes of different timings of radiotherapy. Plast Reconstr Surg. 2012;130:1–9. 24. Clemens MW, Kronowitz SJ. Acellular dermal matrix in irradiated tissue expander/implant-based breast reconstruction: Evidence-based review. Plast Reconstr Surg. 2012;130(Suppl 2):27S–34S. 25. Colwell AS, Damjanovic B, Zahedi B, Medford-Davis L, Hertl C, Austen WG Jr. Retrospective review of 331 consecutive immediate single-stage implant reconstructions with acellular dermal matrix: Indications, complications, trends, and costs. Plast Reconstr Surg. 2011;128:1170–1178. 26. Spear SL, Boehmler JH, Bogue DP, Mafi AA. Options in reconstructing the irradiated breast. Plast Reconstr Surg. 2008;122:379–388. 27. Spear SL, Parikh PM, Reisin E, Menon NG. Acellular dermis-assisted breast reconstruction. Aesthetic Plast Surg. 2008;32:418–425. 28. Spear SL, Albino FP, Al-Attar A. Classification and management of the post-operative, high-riding nipple. Plast Reconstr Surg. 2013;131:1413–1421. 29. Albornoz CR, Bach PB, Mehrara BJ, et al. A paradigm shift in U.S. breast reconstruction: Increasing implant rates. Plast Reconstr Surg. 2013;131:15–23. 30. Cemal Y, Albornoz CR, Disa JJ, et al. A paradigm shift in U.S. breast reconstruction: Part 2. The influence of changing mastectomy patterns on reconstructive rate and method. Plast Reconstr Surg. 2013;131:320e–326e.
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31. Lam TC, Hsieh F, Boyages J. The effects of post-mastectomy adjuvant radiotherapy on immediate two-staged prosthetic breast reconstruction: A systematic review. Plast Reconstr Surg. 2013;132:511–518. 32. Veronesi U, Orecchia R, Luini A, et al. Intraoperative radiotherapy during breast conserving surgery: A study on 1,822 cases treated with electrons. Breast Cancer Res Treat. 2010;124:141–151. 33. Seth AK, Hirsch EM, Fine NA, Kim JY. Utility of acellu lar dermis-assisted breast reconstruction in the setting of radiation: A comparative analysis. Plast Reconstr Surg. 2012;130:750–758. 34. Vardanian AJ, Clayton JL, Roostaeian J, et al. Comparison of implant-based immediate breast reconstruction with and without acellular dermal matrix. Plast Reconstr Surg. 2011;128:403e–410e. 35. Cordeiro PG, Pusic AL, Disa JJ, McCormick B, VanZee K. Irradiation after immediate tissue expander/implant breast reconstruction: Outcomes, complications, aesthetic results, and satisfaction among 156 patients. Plast Reconstr Surg. 2004;113:877–881. 36. Percec I, Bucky LP. Successful prosthetic breast reconstruction after radiation therapy. Ann Plast Surg. 2008;60:527–531. 37. Wilkinson JB, Vicini FA, Shah C, et al. Twenty-year outcomes after breast-conserving surgery and definitive radiotherapy for mammographically detected ductal carcinoma in situ. Ann Surg Oncol. 2012;19:3785–3791. 38. Beitsch PD, Shaitelman SF, Vicini FA. Accelerated partial breast irradiation. J Surg Oncol. 2011;103:362–368.
Background: Although it is well established that reconstruction of the irradiated breast is associated with diminished cosmetic results and more frequent complications, little is known about the specific effects of radiation therapy on the reconstructive outcomes after nipple-sparing mastectomy. Methods: Patients who had nipple-sparing mastectomy and had either previous radiation therapy for breast-conservation therapy or postmastectomy radiation therapy were reviewed. Patient demographics, reconstructive details, and postoperative outcomes were analyzed. Patient photographs were used to evaluate aesthetic parameters. Fisher’s exact and t tests were used for comparison of groups, with a value of p < 0.05 considered significant. Results: Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy (72.2 percent) or before postmastectomy radiation therapy (27.8 percent), with an average follow-up of 3 years. First-stage complications occurred in six patients (33.3 percent). Nipple position was classified as high-riding in 55.6 percent of patients. Average time to revision was 13.3 months. Most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and h igh-riding nipple (22.4 percent). Capsular contracture occurred more commonly in patients who needed postmastectomy radiation therapy compared with those who had previously undergone breast-conservation therapy (40 percent versus 7.8 percent). Maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent). Conclusions: Nipple-sparing mastectomy and implant reconstruction should be approached cautiously in the setting of radiation therapy. When early complications are present, significant morbidity may occur. Late revision surgery is common in this subset of patients. Implant malposition and a high-riding nipple occur most frequently. (Plast. Reconstr. Surg. 133: 605e, 2014.) CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
T
he evolution of techniques in breast reconstruction has resulted in dramatically improved aesthetic results following implantbased reconstruction.1–8 Nipple-sparing mastectomy has been a major contributing factor for these improvements. Despite the positive impact of this valuable option, patient selection continues to eliminate this choice for many patients. The ideal candidate for nipple-areola complex preservation is one with small, nonptotic or minimally From the Department of Plastic Surgery, Georgetown University Hospital. Received for publication July 16, 2013; accepted November 13, 2013. Copyright © 2014 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000000098
ptotic breasts and a single small peripheral tumor. Concerns over blood supply and vascularity are minimized with shorter flaps and a smaller dissection area. In addition, with the improved techniques related to breast implants, acellular tissue matrices, and fat grafting, nipple-sparing techniques coupled with reconstruction can result in remarkable aesthetic results.1,2,4,9,10 Despite early concerns with the oncologic efficacy and risk for recurrence in nipple-sparing mastectomy, there Disclosure: Dr. Spear is a consultant for LifeCell Corp. (Branchburg, N.J.) and A llergan, Inc. (Irvine, Calif.). None of the other authors has any disclosures. No funding was used for the preparation of this article.
www.PRSJournal.com
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Plastic and Reconstructive Surgery • May 2014 is a growing body of evidence demonstrating its safety in the properly selected patient.11–16 Drawbacks to choosing nipple-sparing techniques are typically related to anatomical and surgical technical challenges. Wound healing complications and nipple necrosis are reported to be as high as 20 percent.9,12,17,18 Often, wound healing issues following nipple-sparing mastectomy and implant reconstruction result in early complications and occasionally reconstruction failure and explantation. Although the anatomical criteria for nipple-sparing mastectomy have been expanded and have been shown to be a viable option in patients who have undergone prior mastopexy or reduction, the effects of radiation therapy remain unclear.19–21 This lack of information and the uncertainty regarding nipple-sparing mastectomy in the irradiated breast understandably have made clinicians hesitant to pursue this reconstructive modality, given the possibility of increased complication rates. The long-term effects of radiation therapy have traditionally resulted in suboptimal implant-based breast reconstruction in many centers.22 Late capsular contracture rates with possible revision reconstruction or reconstructive failure have led many centers to abandon implant reconstruction when radiation therapy has already occurred or is likely to be needed. Recently, studies have shown some success with reconstruction using implants in the irradiated breast.23–26 The senior author (S.L.S.) has found that, in select patients, pursuing implant-based reconstruction can result in successful outcomes.23 Newer adjuncts— namely, the use of acellular dermal matrices and some forms of adjuvant radiation therapy—have resulted in an increase in acceptable outcomes following radiation therapy. However, until now, no study has looked specifically at outcomes when reconstruction is performed after nipple-sparing mastectomy in the breast that has been or will be irradiated. Therefore, the aim of this study was to investigate the outcomes of patients who underwent nipple-sparing mastectomy and who either had previous radiation therapy as part of breast conservation or who had postmastectomy radiation therapy.
PATIENTS AND METHODS Study Design An institutional review board–approved retrospective analysis was performed of all patients who underwent nipple-sparing mastectomy and implantbased reconstruction performed by the senior
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surgeon (S.L.S.) from 2002 to 2012. Patients who either had radiation therapy before mastectomy as a part of previous breast-conservation therapy or underwent postmastectomy radiation therapy were identified. Eighteen patients were identified who met the inclusion criteria of this study. Reconstructive Technique The technique of two-stage immediate expander-to-implant reconstruction with AlloDerm (LifeCell Corp., Branchburg, N.J.) has been described previously by the senior author (S.L.S.).27 In patients with a history of b reast-conservation therapy, an immediate implant-based reconstructive option was given to patients who (1) would otherwise be a candidate for nipple-sparing mastectomy and reconstruction and (2) have supple tissue with minimal radiation-induced soft-tissue/ skin damage (Figs. 1 and 2). In the later portion of this study, if postmastectomy radiation therapy was expected, implant exchange was attempted before the initiation of radiation therapy. If postmastectomy radiation therapy was performed before implant exchange, a minimum of 6 weeks was allowed before attempting exchange. Also, later during the study period, if postmastectomy radiation therapy was planned before surgery and neoadjuvant chemotherapy had already occurred, direct-to-implant reconstruction was the preferred option when feasible rather than a two-stage expander/implant approach. Incisions for nipple-sparing mastectomy were chosen in collaboration between the surgical oncologist and plastic surgeon. Periareolar, lateral, and inframammary incisions were used for all patients and were determined based on the tumor location and overall breast characteristics. All expanders/implants were placed in the partial subpectoral plane, and since 2004, this has included acellular dermal matrix lower pole support. Postoperative antibiotics were administered until drain removal, which occurred at approximately 2 weeks, when drainage had tapered off to less than 30 cc per 24 hours. Tissue expansion was resumed at approximately 2 weeks after reconstruction and was performed at intervals until the desired volume was obtained. Exchange to a permanent implant was highly dependent on other circumstances such as chemotherapy and the timing and need for postmastectomy radiation therapy. Capsulotomies and other pocket adjustments were performed to create the desired position and shape of the reconstruction.
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy
Fig. 1. Appropriate candidates for nipple-sparing mastectomy based on breast size, tumor size, and disease location. (Above) A 47-year-old, otherwise healthy woman with a history of left breast estrogen receptor/progesterone receptor–positive, Her-2–negative invasive ductal carcinoma treated with partial mastectomy and radiation therapy. The patient presented 8 years after her initial treatment with recurrence of her invasive breast cancer for bilateral mastectomies. There are minimal skin changes following radiation therapy, with relatively symmetric breasts and a minimally widened left breast scar. (Below) A 49-year-old woman with a history of left estrogen receptor/ progesterone receptor/Her2–positive invasive ductal carcinoma of her left breast treated with partial mastectomy notable for a negative sentinel lymph node biopsy followed by chemotherapy and irradiation. She was found to have a palpable mass 10 years after her initial carcinoma corresponding with disease recurrence on biopsy. Recent genetic testing confirms that she is a BRCA1 gene mutation carrier. The left breast is minimally contracted, with no radiation-related skin changes observed.
Data Collection and Analysis Patient information was collected from office charts and operative reports. First-stage reconstruction was defined by the immediate reconstruction occurring at the time of mastectomy. Primary outcomes of interest included mastectomy
Fig. 2. A high-riding nipple-areola complex may occur after nipple-sparing mastectomy and reconstruction; however, the severity of this displacement is variable. (Above) Mild case of left superior nipple displacement in a 51-year-old woman following nipple-sparing mastectomy and radiation therapy for invasive left breast cancer. (Center) Moderately high-riding nipple-areola complex in a 47-year-old woman following bilateral nipple-sparing mastectomy and adjuvant chemotherapy and irradiation for left invasive breast cancer. (Below) Severe left nipple displacement and moderate right nipple elevation in a 42-year-old woman following bilateral nipple-sparing mastectomy and adjuvant radiation therapy for left invasive breast cancer.
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Plastic and Reconstructive Surgery • May 2014 skin necrosis, return to the operating room, infection requiring antibiotics, and infection requiring explantation. Second-stage reconstruction was defined for patients who had an implant exchanged after an initial tissue expander placed at the time of mastectomy. Primary outcomes of second-stage surgery were related to implant characteristics, timing of reconstruction, revisions, and complications. Revision surgery was analyzed for the defined follow-up period. Capsular contracture, malposition correction, implant exchange, and nipple position were critically evaluated. Analyses were performed using SAS for Windows, Version 9.2 (SAS Institute, Inc., Cary, N.C.). Categorical demographic variables were analyzed by means of Fisher’s exact test because of the small sample size. Means and standard deviations were calculated for continuous variables. The t test was used for comparison between groups. An a priori value of p < 0.05 was considered significant. Nipple Position Analysis Determination of a high-riding nipple was determined based on the location of the nipple along the vertical axis of the breast in a three-quarters oblique view as recently described.28 Relative percentage height was used to classify the high-riding nipple as mild, moderate, or severe (Fig. 2).
RESULTS Patient Characteristics Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy [13 of 18 (72.2 percent)] or before postmastectomy radiation therapy [five of 18 (27.8 percent)], with an average follow-up of 3 years. Average patient age and body mass index were 47.5 years and 21.1 kg/m2, respectively (Tables 1 and 2). Average mastectomy weight was 271 g. Previous smoking history was reported in three of 18 patients (16.7 percent). No patients had previous breast augmentations or implants. Precise radiation dosimetry schedules were unavailable for analysis because of the variations in treating institutions. First-Stage Outcomes Two-stage expander-implant reconstruction was planned in a majority of patients [17 of 18 (94.4 percent)]. One patient underwent direct-to-implant reconstruction following mastectomy. This patient had neoadjuvant chemotherapy
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before mastectomy and was scheduled to undergo postmastectomy radiation therapy. In this scenario, direct-to-implant reconstruction was chosen to avoid the necessity of an implant exchange following postmastectomy radiation therapy. Firststage complications occurred in six of 18 patients (33.3 percent), with most (four of six) occurring in patients who had previously undergone breastconservation therapy, for a complication rate of 30.8 percent (four of 13) in that group (Table 3). Sixty-seven percent of complications were related to skin ischemic changes, with one patient developing partial nipple necrosis. All ischemic changes healed without full-thickness skin loss. Infection developed in one patient, which was successfully treated with antibiotic therapy alone. One hematoma occurred requiring operative washout. No expander/implant loss occurred following the first-stage reconstruction. Average expander/ implant volume was 356 ml, with an average initial fill volume of 258 ml. Second-Stage Outcomes Of the 17 patients who underwent a t wo-stage reconstruction, the average time to implant exchange was 167 days (Table 4). Radiation therapy occurred before implant exchange in 14 of 17 patients (82.4 percent) and after implant exchange in three of 17 patients (17.6 percent). Shaped anatomical gel implants were placed in seven of 17 patients (41 percent), whereas round smooth gel implants were placed in the remaining 10 patients (59 percent). Average final implant volume was 421 ml. Three patients (17.6 percent) underwent fat grafting at the second stage, and capsular modification occurred in 13 of 17 patients (76.5 percent). Complications occurred in one patient (5.9 percent) at the time of exchange. An infection occurred following implant exchange resulting in eventual implant loss (Figs. 3 and 4). This patient had a history of previous breast-conservation therapy 5 years before mastectomy. Revision Surgery and Long-Term Outcomes Additional revision surgery occurred in nine of 18 patients (50 percent) (Table 5). Four patients underwent multiple revisions (average, 3.0). Average time to revision was 13.3 months. The most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and high-riding nipple (55.6 percent). Interventions during revision included implant exchange (37.5 percent), malposition correction with capsular modification (31.2 percent),
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy Table 1. Overall Demographics Value (%)* No. of patients Average age, yr Average BMI, kg/m2 History of smoking Single-stage reconstruction Two-stage reconstruction PMRT History of BCT
18 47.5 21.13 3 (16.7) 1 (5.6) 17 (94.4) 5 (27.8) 13 (72.2)
BMI, body mass index; PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy.
Table 2. Breast-Conservation Therapy versus Postmastectomy Radiation Therapy Age, yr BMI, kg/m2 Percent Weeks until exchange
PMRT
BCT
p
37.2 ± 8.4 21.7 ± 3.9 37.0 ± 9.2 32.0 ± 13.6
51.5 ± 9.1 20.9 ± 3.4 41.6 ± 11.4 21.1 ± 5.9
0.01 0.61 0.44 0.2
PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy; BMI, body mass index.
Table 3. First-Stage Reconstruction Details Mean (n)* Average mastectomy weight, g Incision types Superoareolar with lateral extension Inferoareolar with lateral extension Lateral IMF Direct-to-implant Usage of ADM Complications Nipple necrosis Infection Expander/implant loss Average fill volume, ml Average interval between XRT and first-stage reconstruction, mo†
271 10 6 1 1 5.6 (1) 83 (15) 33.3 (6) 5.6 (1) 5.6 (1) 0 (0) 258 112.4
IMF, inframammary fold; ADM, acellular dermal matrix; XRT, radiation therapy. *All values are mean (n) unless otherwise specified. †Reported for breast-conservation therapy cohort only.
Table 4. Second-Stage Reconstruction Details % (n)* Average time to exchange, days XRT performed after exchange† XRT performed before exchange† Average implant size, ml Contoured implants used Round implants used Revision during exchange ADM used Fat grafting Complications
capsulectomy for capsular contracture (18.8 percent), and surgical correction of a high-riding nipple (25 percent). When cohorts were separated on whether radiation therapy was delivered in the setting of breastconservation therapy or postmastectomy radiation therapy, differing outcomes were seen (Table 6). In the premastectomy radiation therapy cohort, patients had a lower long-term rate of significant capsular contracture (7.8 percent) compared with the postmastectomy radiation therapy cohort (40 percent; p = 0.17), although statistical significance was not achieved. When nipple position was evaluated, similar results were seen across both cohorts. Both cohorts had over half of patients with either grade 2 or grade 3 nipple elevation (53.9 percent and 60 percent, respectively; p = 0.99). There appeared to be no association between incision type and degree of nipple elevation (Table 7). In addition, similar rates of correction for implant malposition occurred between groups (20 percent and 30.8 percent, respectively; p = 1.0). Overall, maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent).
167 60 (3) 40 (2) 421 41.2 (7) 61.1 (11) 72.2 (13) 23.5 (4) 17.6 (3) 5.6 (1)
XRT, radiation therapy; ADM, acellular dermal matrix. *All values are percentages (n) unless otherwise specified. †Represents the PMRT cohort only.
DISCUSSION Rates of implant-based breast reconstruction continue to rise.29,30 These increases in volume are paralleled by innovations and technical improvements in surgical techniques. One of the most influential of these methods, n ipple-sparing mastectomy, allows for preservation of the n ipple-areola complex and can result in superior aesthetic results. Nipplesparing mastectomy has now become an integral part of the reconstructive process. Nevertheless, despite being a highly desirable oncologic option, it is a technically challenging procedure offered to only select patients. As the collective experience with nipple-sparing mastectomy and implant reconstruction has continued to grow, refinements have allowed for better cosmetic results. Implant-based reconstructive outcomes in the setting of radiation therapy remain inferior to those in the nonirradiated breast but have gradually improved over recent years.31 In partial breast reconstruction, intraoperative radiotherapy minimizes collateral tissue damage, which may likely improve reconstruction attempts if future reconstruction is needed.32 Following mastectomy, early literature supports potential beneficial effects with the use of acellular dermal matrix during implant reconstruction. Seth et al. found that acellular dermal matrix may have a protective effect on
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Fig. 3. (Above, left) A 55-year-old woman with left breast invasive lobular carcinoma who (above, right) underwent bilateral nipple-sparing mastectomies with tissue expander placement followed by chemotherapy and radiation. Seven months later, she had an exchange to implants (McGhan Style 20, 500 ml) with left breast dermal fat grafting for a contour deformity. Unfortunately, she developed a postoperative infection with device exposure notable for methicillin-sensitive Staphylococcus aureus necessitating explantation of her left implant 2 months later (below).
postradiation pain/tightness and implant extrusion compared with no acellular dermal matrix.33 Similarly, Vardanian et al. evaluated acellular dermal matrix–assisted implant reconstruction and found statistically significant decreases in capsular contracture rates and mechanical shift.34 All patients in our series received acellular dermal matrix during the first-stage reconstructive operation. In addition, acellular dermal matrix was used in 24 percent of patients during the second-stage reconstruction. When faced with radiation therapy, early complications following mastectomy can lead to prolonged morbidity requiring explantation. Conversely, late complications related to tightness, distortion, and capsular contracture lead patients to
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seek revision surgery.35,36 Although we found low early complication rates with nipple-sparing mastectomy in the irradiated breast, late revision surgery occurred in 50 percent of patients during the follow-up period. Not surprisingly, capsular contracture was more common in patients who received postmastectomy radiation therapy compared with those who previously had breast-conservation therapy. This finding is likely related to different protocols of radiotherapy commonly used in the setting of breast-conservation therapy compared with postmastectomy radiation therapy.37,38 In addition, the lack of an implant during radiation therapy in breast-conservation therapy patients eliminates any direct capsular damage caused by radiation.
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy Table 5. Reconstructive Outcomes % (n)* Average no. of revisions per patient Average time to revision, mo Malposition requiring correction Capsular contracture Change of implant Eventual implant loss High-riding nipple Nipple corrective surgery Average follow-up, yr
0.89 13.3 27.8 (5) 16.7 (3) 33.3 (6) 11.1 (2) 55.6 (10) 22.2 (4) 3
*All values are percentages (n) unless otherwise specified.
Table 6. Complications of Postmastectomy Radiation Therapy versus Breast-Conservation Therapy
Fig. 4. The patient in Figure 3 ultimately required a latissimus dorsi flap and implant reconstruction to achieve stable closure.
The occurrence of nipple elevation, or the “high-riding nipple,” is a complication specific to implant reconstruction after nipple-sparing mastectomy, and is a more significant risk with reconstruction after nipple-sparing mastectomy of the irradiated breast. Recently, the senior author (S.L.S.) described the occurrence of a high-riding nipple and a classification system. The authors found that one-third of patients with an excessively high nipple-areola complex had undergone nipple-sparing mastectomy.28 In reconstruction after nipple-sparing mastectomy of the irradiated breast, nipple elevation seems to occur more frequently. We found that a majority of the patients in this retrospective review had some degree of nipple elevation, with nearly half desiring corrective surgery. Although the exact mechanism of radiation therapy and its effect on nipple position and surrounding skin is not known, a proposed mechanism based on superior pole skin contraction against firm attachment in the region of the clavicle may explain the upward migration commonly seen following implant reconstruction.
High-riding nipple 0 1 2 High-riding nipple Low (grade 0, 1) High (grade 2, 3) Capsular contracture No Yes Malposition correction No Yes Any complication No Yes
PMRT (%)
BCT (%)
p
1 (20.0) 2 (40.0) 2 (40.0)
5 (38.6) 3 (23.1) 5 (38.5)
0.82
2 (40.0) 3 (60.0)
6 (46.2) 7 (53.9)
0.99
3 (60.0) 2 (40.0)
12 (92.3) 1 (7.8)
0.17
4 (80.0) 1 (20.0)
1 (69.2) 4 (30.8)
1 (20.0) 4 (80.0)
6 (46.2) 7 (53.9)
0.99 0.6
PMRT, postmastectomy radiation therapy; BCT, breast-conservation therapy.
The topic of prosthetic reconstruction of the irradiated breast has long been mired in controversy, with some arguing that implants should not be used and others favoring their use in selected, more favorable cases. When considering implant reconstruction of the irradiated breast, our position has been that thoughtful patient selection is important to achieve a reasonable likelihood of a successful outcome. When breast-conservation therapy has previously been performed, there is a legitimate hesitancy with pursuing implant reconstruction because of (1) wound healing complications that can lead to early implant failure and (2) late capsular contracture rates with potential for extensive revision surgery and possible late implant failure. This risk is potentially magnified with nipple-sparing mastectomy because of the already increased risk with that procedure of wound healing issues related to either partial- or full-thickness necrosis.12–14,17,18 Long skin flaps and wide undermining make this technique prone to
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Plastic and Reconstructive Surgery • May 2014 Table 7. Nipple Position by Incision Type Incision Type
Low-Riding Nipple (%)
High-Riding Nipple (%)
Inferoareolar Lateral Lateral IMF Superoareolar
2 (25.0) 0 (0.0) 1 (12.5) 5 (62.5)
4 (40.0) 1 (10.0) 0 (0.0) 5 (50.0)
p 0.69
IMF, inframammary fold.
wound healing complications.9,10,12,13 A history of breast radiotherapy necessarily compounds that risk, making careful patient selection all the more important. In addition to consideration of the oncologic issues of nipple-sparing mastectomy after breast-conservation therapy, we use selection criteria based mostly on physical examination. In patients with very large or ptotic breasts, significant skin changes, substantial breast distortion, malposition of the nipple, and/or scar contracture, nipple-sparing techniques are generally not offered. Although we found a 33 percent early complication rate following nipple-sparing mastectomy after radiation therapy, no patient required operative intervention for flap necrosis or ischemia, illustrating the importance of conservative patient selection and careful surgical technique. Increasing patient demand for the nipple-sparing mastectomy in conjunction with a growing comfort with the procedure on the part of oncologic surgeons will likely result in the even more widespread implementation of nipple-sparing mastectomy as an option for patients. In addition, the increased frequency of postmastectomy radiation therapy will likely result in more patients needing postmastectomy radiation therapy after nipple-sparing mastectomy. Although it is clear that irradiation following postmastectomy implant reconstruction diminishes the quality of the results and causes an increase in symptomatic capsular contractures, infections, and reconstruction failure, the safety and efficacy of implant reconstruction and nipple-sparing mastectomy followed by postmastectomy radiation therapy remain less clearly defined. With these patients in mind, a better understanding of their outcomes will allow them and their surgeons to make more informed decisions related to treatment. In patients who received postmastectomy radiation therapy after implant reconstruction and nipple-sparing mastectomy, we found a 40 percent capsular contracture rate, resulting in a number of revisions for capsular contracture. The average time to revision related to capsular contracture in this subset of patients was 18 months. One patient
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underwent two separate revision operations and later elected for implant removal and autologous flap reconstruction because of painful capsular contracture. In addition, nipple malposition was found in 60 percent of this subset of patients, with a majority obtaining corrective surgery. Looking at both cohorts over the long term, revision surgery related to malposition and a high-riding nipple was performed in half of the patients. In addition, a significant proportion of these patients needed additional revision operations. The key findings of our review are a high degree of success (88.9 percent) overall with implant reconstruction after nipple-sparing mastectomy in the irradiated breast. Despite a 30 percent complication rate at the first-stage reconstruction of nipple-sparing mastectomy after breast-conservation therapy/radiation therapy, there were no failures at the first stage in those patients. Because postmastectomy radiation therapy follows the first stage of nipple-sparing mastectomy, the first stage in those patients was similar to other nonirradiated patients. Capsular contracture resulting in revision occurred in both irradiated groups but was more common in the postmastectomy radiation therapy group. The finding that is new and unique to this cohort of patients is the frequency of nipple malposition seen after nipple-sparing mastectomy in an irradiated breast, which can occur whether the irradiation precedes (53.9 percent) or follows (60 percent) the nipple-sparing mastectomy. Although some patients had revisions specifically designed to correct or improve their nipple position, no patient has so far chosen to have their displaced nipple removed. As our understanding of this subject expands, we should be able to make better and more informed decisions about treatment strategies. We now have an additional issue to consider when contemplating implant reconstruction and nipplesparing mastectomy following radiation therapy or before postmastectomy radiation therapy. The oncologic issues and radiation morbidity have previously been described, but the issue of nipple malposition poses an additional problem to be considered. That said, so far, our impression is that patients prefer their misplaced nipple to no nipple at all. This may not be much different than the patient after breast-conservation therapy, where some displacement of the nipple seems to often be well accepted. In the meantime, we now have reason to inform patients of this additional issue and, at the same time, contemplate whether there are any steps we can take to prevent this occurrence. As
Volume 133, Number 5 • Outcomes after Nipple-Sparing Mastectomy this is an early report, it remains to be seen whether others have findings similar to ours. We also plan to compare this experience with our experience with the larger population of nipple-sparing mastectomy patients who have not been irradiated. The authors acknowledge a number of limitations to the current study. In this series, breast-conservation therapy and postmastectomy radiation therapy patients are grouped when overall early and late complications are reported. Although the irradiation timing is disparate, we feel that once postmastectomy radiation therapy has been delivered, the effects on the breast are similar, particularly with regard to late revision surgery. Finally, our sample size is small and therefore may not adequately represent the early and late complication rates in this broadening population of patients. However, given the relative lack of data available in the literature regarding this subject, along with the rapidly expanding popularity of the nipplesparing mastectomy, we feel that the reporting of the inherent complication rates in nipple-sparing mastectomy patients is of paramount importance.
CONCLUSIONS In patients undergoing nipple-sparing mastectomy, early complication rates are relatively low and may be managed nonoperatively in most cases. In this subset of patients, the need for late revision surgery is high as a result of radiation-induced effects. Nipple-sparing mastectomy and implant reconstruction can be successfully performed in the irradiated breast; however, revision surgery is common secondary to implant malposition, capsular contracture, and/or a high-riding nipple. Scott L. Spear, M.D. Department of Plastic Surgery Georgetown University Hospital 3800 Reservoir Road, NW Washington, D.C. 20007 [email protected]
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