BREAST Breast Reconstruction Outcomes after NippleSparing Mastectomy and Radiation Therapy Richard G. Reish, M.D. Alex Lin, B.S. Nicole A. Phillips, M.D. Jonathan Winograd, M.D. Eric C. Liao, M.D., Ph.D. Curtis L. Cetrulo, Jr., M.D. Barbara L. Smith, M.D. William G. Austen, Jr., M.D. Amy S. Colwell, M.D. Boston, Mass.
Background: Few studies in the literature examine outcomes of immediate breast reconstruction after mastectomy with nipple preservation and radiation therapy. Methods: Retrospective analysis of multisurgeon consecutive implant-based reconstructions after nipple-sparing mastectomy from June of 2007 to December of 2012 was conducted at a single institution. Results: Six hundred five immediate breast reconstructions were performed following nipple-sparing mastectomy, of which 88 were treated with radiation therapy. There was a trend toward more complications in patients with radiation (19.3 percent versus 12.8 percent; p = 0.099) associated with a higher rate of implant loss (6.8 percent versus 1.0 percent; p = 0.001). Preoperative radiotherapy had a higher risk of total complications (p = 0.04; OR, 2.225; 95 percent CI, 1.040 to 4.758) and postoperative radiotherapy had a higher risk of explantation (p = 0.015; OR, 5.634; 95 percent CI, 1.405 to 22.603). There were no significant differences in nipple removal secondary to malposition or positive oncologic margins in patients with radiation compared to those without radiation. Patients with radiation did have a higher incidence of secondary procedures for capsular contracture (12.5 percent versus 2.3 percent; p < 0.001) and fat grafting (13.6 percent versus 3.9 percent; p < 0.001). The total nipple retention rate in patients with radiation therapy was 90 percent (79 of 88), and the reconstruction failure rate was 8 percent. Conclusions: Nipple-sparing mastectomy and immediate reconstruction in patients who had or will receive radiation therapy is associated with a higher incidence of complications and operative revisions compared with patients without radiation. However, most patients have successful reconstructions with nipple retention and no recurrences. (Plast. Reconstr. Surg. 135: 959, 2015.) CLINICAL QUESTION/ LEVEL OF EVIDENCE: Therapeutic, III.
mmediate implant-based breast reconstruction remains the most common type of breast reconstruction after mastectomy in the United States.1 Nipple-sparing mastectomy has had a profound impact on the potential for improved cosmetic results and has significantly increased in prevalence in recent years. There is abundant evidence in the literature that nipple-sparing mastectomy provides both cosmetic and quality-oflife benefits for patients, with reduced need for From the Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School. Received for publication March 11, 2014; accepted October 9, 2014. Presented at the 93rd Annual Meeting of the American Association of Plastic Surgeons, in Miami, Florida, April 5 through 8, 2014. Copyright © 2015 by the American Society of Plastic Surgeons DOI: 10.1097/PRS.0000000000001129
additional nipple reconstruction and tattooing,2,3 and provides an acceptable level of oncologic safety.4–7 Adjuvant radiation therapy is the standard of care for breast cancer treatment following lumpectomy and, concomitantly, chest wall irradiation is becoming increasingly common for mastectomy patients who have opted for immediate implant-based breast reconstruction.8 As the indications for radiation therapy in the treatment of breast cancer increase, surgeons are encountering more patients who have had or will have radiation therapy.
Disclosure: Dr. Colwell is a consultant for LifeCell Corp. and Allergan, Inc. The other authors have no financial interest to declare in relation to the content of this article.
Plastic and Reconstructive Surgery • April 2015 Nipple reconstruction following skin-sparing mastectomy in patients with radiation therapy has limited success in the authors’ combined experience. The vast majority of nipple reconstructions in these patients flatten entirely. In the worstcase scenario, the incisions may not heal and lead to implant exposure. Thus, if oncologically feasible, nipple preservation at the time of mastectomy may offer these patients the opportunity to maintain a nipple with their breast reconstruction. Although there have been recent studies investigating the effects of radiation therapy on implant-based breast reconstruction after skinsparing mastectomy, few studies in the literature have examined outcomes of immediate breast reconstruction after mastectomy with nipple preservation and radiation therapy. We present a single-institution experience with over 2 years of follow-up.
PATIENTS AND METHODS After obtaining approval from the Massachusetts General Hospital Institutional Review Board, a retrospective analysis of multisurgeon consecutive implant-based reconstructions after nipple-sparing mastectomy from June of 2007 to December of 2012 was conducted at a single institution. Delayed reconstructions and those involving primary autologous flaps were excluded from this analysis. Only reconstructions with at least 1 full year of follow-up were included in the study. Patients’ medical records were reviewed for complications. Complications included infection requiring intravenous antibiotics and/or operative washout, seroma requiring aspiration or operative drainage, skin necrosis requiring surgical excision, nipple necrosis requiring surgical excision, hematoma, and explantation. Demographics including patient age, body mass index, active tobacco use, history of chemotherapy, exposure to radiation therapy, and use of acellular dermal matrix were assessed. A smoker was defined as someone who was smoking at the time of the initial consultation for mastectomy and reconstruction. For patients with preoperative radiation therapy, if there were no noticeable skin changes and the breast was soft, they were considered a candidate for immediate alloplastic reconstruction. If the skin envelope was healthy at the time of surgery, the patient was considered a candidate for direct-to-implant reconstruction. If the skin envelope was not healthy, or if the patient had significant asymmetry or wanted a significantly larger
breast size, a tissue expander/implant reconstruction was planned. Acellular dermal matrix or mesh was used if the pectoralis muscle was released inferiorly to prevent pectoralis retraction and maintain implant or expander position. If the skin envelope was threatened, total or nearly total submuscular positioning was performed. If the patient had donor sites available for autologous reconstruction, they were considered a candidate for immediate autologous reconstruction. Patients who met both criteria were allowed to choose their type of reconstruction. Patients with visible radiation-induced changes of the skin and/or hard fibrous breasts were not considered candidates for immediate or delayed alloplastic reconstruction. For patients receiving postoperative radiation therapy, all were considered candidates for immediate alloplastic reconstruction. If the skin envelope was healthy at the time of surgery, the patient was a candidate for direct-toimplant reconstruction. If the skin envelope was unhealthy or if the patient wanted a significant increase in breast size, tissue expander/implant reconstruction was planned. Tissue expanders that were placed at the time of mastectomy were exchanged for silicone implants either before or after radiation therapy, depending on the urgency and preference of the radiation oncologist, surgeon, and patient. If the patient desired autologous reconstruction, they were offered either delayed reconstruction or immediatedelayed reconstruction with placement of an implant or tissue expander at the time of mastectomy. Autologous reconstruction was then performed after radiation therapy. Surgical technique and patient outcomes including nippleareola complex necrosis, nipple-areola complex removal because of either asymmetry or close oncologic margins, breast asymmetry requiring revision, and capsular contracture requiring open capsulotomy were analyzed to compare outcomes of irradiated patients with nonirradiated patients. For statistical assessment, all statistical calculations were performed using Stata version 12.0 (StataCorp., College Station, Texas). The p values for continuous variables were calculated using a two-sample t test. Categorical variables were analyzed using either the chi-square test or Fisher’s exact test. Significance level was set at p < 0.05. Multivariate logistic regression analysis was performed to control for confounding variables while identifying significant predictors for clinical outcome measures.
Volume 135, Number 4 • Outcomes of Breast Reconstruction RESULTS Six hundred five immediate breast reconstructions were performed following nipplesparing mastectomy. Of the reconstructions, 88 were treated with radiation therapy and 517 had no radiation therapy. Preoperative radiation therapy was administered in 43, and 45 received postmastectomy radiation therapy to the site of reconstruction (Figs. 1 and 2). Of the reconstructions with preoperative radiation therapy, eight were mantle irradiation for Hodgkin disease. Of the reconstructions with postoperative radiation therapy, 10 received neoadjuvant chemotherapy and 35 received postmastectomy chemotherapy. Radiation therapy was administered to the tissue expander (10 reconstructions) or final silicone implant (35 reconstructions). The mean followup period for all patients was 686 days. In comparing the group of patients with radiation therapy to the group without radiation therapy, the irradiated patients were older (49.8 years versus 45.9 years; p < 0.001) but were similar with regard to body mass index and smoking status (Table 1). There was a trend toward more total complications (19.3 percent versus 12.8 percent; p = 0.099) and infections (6.8 percent versus 2.9 percent; p = 0.064) in patients with radiation therapy, and there was a significantly higher rate of implant loss (6.8 percent versus 1.0 percent; p = 0.001). Complications requiring explantation included infections and skin flap necrosis in both the irradiated and nonirradiated groups. In comparing preoperative radiation therapy to no radiation therapy, there were more singlestage reconstructions (p = 0.014) with lower mean implant volume (300 cc versus 386 cc; p < 0.001) in patients with preoperative radiation therapy (Table 2). With multivariate logistic regression
analysis, reconstructions with preoperative radiation therapy had a higher risk of total complications (p = 0.04; OR, 2.225; 95 percent CI, 1.040 to 4.758). In comparing postoperative radiation therapy to no radiation therapy, the mean implant volume was higher with postoperative radiation therapy (Table 3). With regression analysis, postoperative radiation therapy was associated with a higher risk of explantation (p = 0.015; OR, 5.634; 95 percent CI, 1.405 to 22.603). There were no significant differences in nipple removal secondary to malposition or positive oncologic margins in patients who received radiation compared to those who did not receive radiation therapy. Patients with radiation therapy did have a higher incidence of secondary procedures for capsular contracture (12.5 percent versus 2.3 percent; p < 0.001), which was significant for both preoperative and postoperative radiation therapy. There was also a higher incidence of fat grafting (13.6 versus 3.9 percent; p < 0.001), primarily in the patients who had preoperative radiation therapy. The total nipple retention rate in patients with radiation therapy and nipple-sparing mastectomy was 90 percent (79 of 88), and the reconstruction failure rate (number of explantations for immediate complications plus explantations for capsular contracture) was 8 percent.
DISCUSSION Chest wall/breast irradiation is the standard adjuvant therapy for lumpectomy patients who may later need mastectomy, and it is becoming increasingly more common as adjuvant treatment for mastectomy patients who have opted for breast reconstruction. In this series, we analyzed the outcomes of immediate breast reconstruction
Fig. 1. This 50-year-old woman had right breast cancer treated with a lumpectomy and radiation therapy. Four years later, she developed recurrent invasive ductal carcinoma in the lateral breast (left). She had a right mastectomy with a single-stage reconstruction and is shown 3 months (center) postoperatively. The patient then had a prophylactic left mastectomy with single-stage reconstruction and is shown 2 years after her initial surgery (right).
Plastic and Reconstructive Surgery • April 2015
Fig. 2. This 44-year-old woman developed a left breast cancer in the upper outer quadrant (left). She had neoadjuvant chemotherapy followed by left mastectomy and single-stage reconstruction (center). She then had radiation therapy and is shown 1 year after radiation therapy (right).
following nipple-sparing mastectomy in patients with radiation therapy compared to no radiation therapy and found that the majority of our patients with radiation therapy retained their nipples and had successful reconstructions. Not surprisingly, we found a trend toward higher rates of complications in our patients with radiation therapy, as we have seen before.9 In this series, we also saw a higher rate of grade III/IV capsular contracture requiring capsulotomy in the reconstructions with radiation therapy. It is difficult to compare rates of fat grafting in a multisurgeon study because the rate of fat grafting is largely influenced by the surgeon. Nonetheless, we did observe a higher rate of fat grafting in patients with preoperative radiation therapy compared with no radiation therapy, which may be related to the larger number of single-stage reconstructions with smaller, more conservative implant size. Nipple retention with mastectomy for the treatment of breast cancer has been controversial because of concerns regarding cancer recurrence. However, with nipple-sparing mastectomy procedures evolving to remove the ductal tissue from the nipple, more patients have become candidates for this procedure. Numerous series in the literature have supported the oncologic safety of nipple-sparing mastectomy compared with skin-sparing mastectomy,4–7,10 and these patients continue to be followed on an institutional review board protocol at our institute. We have previously reported that, at 22 months’ mean followup, local recurrence has occurred in four of 156 breasts (2.6 percent) operated on for cancer through 2011. There were no recurrences involving the nipple.
In this relatively high-risk group of patients, the question may arise: Why take any chances and attempt nipple preservation? There are two reasons. One is that nipple reconstruction following implant-based reconstruction and radiation therapy is typically unsuccessful. In the best cases, a small projection is maintained after the inevitable shrinkage that occurs following a reconstruction; in the worst cases, the donor sites from the nipple reconstruction do not heal, leading to implant infection, exposure, and/or loss. The second reason is that with nipple preservation, more patients are candidates for single-stage reconstruction with implants because of the extra skin of the breast. In our institute, the complication rate is lower for patients with preoperative radiation therapy and direct-to-implant reconstruction compared with tissue expander/implant reconstruction. For patients who will receive postoperative radiation therapy, a surgical procedure is spared. In addition to the oncologic concerns, some surgeons may avoid nipple-sparing procedures in patients who they know will receive radiation therapy because of concerns over where the nipple placement will be following radiation therapy. In our series, it was common to see grade II contracture following radiation therapy; however, nipple malposition leading to removal was not observed in any of the postoperative radiation therapy reconstructions, suggesting that the nipple is maintained in an acceptable position. We did not perform any type of mastopexy or pedicled nipple transposition on any irradiated breast. We did perform contralateral mastopexy on two patients with bilateral implants and one patient at the time of bilateral tissue expander exchange to remove
Volume 135, Number 4 • Outcomes of Breast Reconstruction Table 1. Breast Reconstructions with Preoperative or Postoperative Radiation Therapy (Total Radiation Therapy) Compared to No Radiation Therapy Demographics Total no. of cases Age, yr Mean Range BMI Mean Range Active smoker Follow-up period, yr Mean Range Reconstruction Single-stage DTI reconstruction Two-stage TE reconstruction Implant volume, cc Mean Range Initial TE fill volume, cc Mean Range Acellular dermal matrix Complications Nipple-areola complex necrosis Mastectomy skin flap necrosis Infection Hematoma Seroma Explant secondary to complications Additional procedures Nipple removal Malposition Oncologic margins Capsular contracture Fat grafting
Total Radiation Therapy (%)
No Radiation Therapy (%)
23.6 17.1–34.5 4 (4.6)
23.9 16.9–38.0 29 (5.6)
62 (70.5) 24 (27.3)
311 (60.2) 196 (37.9)
107.1 0–275 61 (69.3)
126.4 0–500 370 (71.6)
4 (4.6) 7 (8.0) 6 (6.8) 1 (1.1) 1 (1.1) 6 (6.8)
20 (3.9) 28 (5.4) 15 (2.9) 9 (1.7) 9 (1.7) 5 (1.0)
0.767 0.346 0.064 1.000 1.000 0.001
1 (1.1) 4 (4.6) 11 (12.5) 12 (13.6)
7 (1.4) 15 (2.9) 12 (2.3) 20 (3.9)