National Medical Policy

National Medical Policy Subject: Policy Number: Breast Reconstructive Surgery NMP492 Effective Date*: February 2013 Updated: April 2015 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate Medicaid Manuals for coverage guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link X National Coverage Determination (NCD) Breast Reconstruction (140.2): http://www.cms.gov/medicare-coveragedatabase/search/advanced-search.aspx X National Coverage Manual Citation Local Coverage Determination (LCD)* Cosmetic and Reconstructive Surgery; Plastic Surgery: http://www.cms.gov/medicare-coveragedatabase/search/advanced-search.aspx X Article (Local)* Cosmetic vs. Reconstructive Surgery: http://www.cms.gov/medicare-coveragedatabase/search/advanced-search.aspx Other None Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. Breast Reconstructive Surgery Apr 15 1

If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Current Policy Statement (Please Refer to HN NMP 169 Cosmetic and Reconstructive Surgery and HN NMP 323 Lymphedema and Venous Stasis Ulcer Treatments for additional information) and/or state mandates). *Note Women s Health & Cancer Rights Act of 1998 (WHCRA) is a federal law that provides protections to patients who choose to have breast reconstruction in connection with a mastectomy. In accordance with WHCRA, all stages of reconstruction of the breast on which a mastectomy was performed, surgery and reconstruction of the other breast to produce symmetrical appearance, prostheses and treatment of physical complications of the mastectomy, including lymphedema are considered medically necessary. Health Net, Inc. considers reconstructive breast surgery medically necessary after a mastectomy or a lumpectomy which results in a significant deformity. Medically necessary procedures include any of the following: 1. Implantation of U.S. Food and Drug Administration (FDA)-approved internal breast prosthesis; 2. The use of tissue expanders; 3. Use of AlloDerm Regenerative Tissue Matrix, FlexHD Acelluar Hydrated Dermis, AlloMax, NeoForm Dermis; 4. Tissue/muscle reconstruction procedures (e.g. flaps); 5. Oncoplastic reconstruction; 6. Reconstructive surgical revisions; 7. Breast reconstruction of the affected breast, including reconstruction of the nipple and areolar complex; 8. Tattooing in conjunction with reconstructive breast surgery post-mastectomy; 9. Removal of a breast implant, periprosthetic capsulotomy or capsulectomy is considered medically necessary when documentation in the patient s record indicates any of the following mechanical complications of breast prosthesis: Ruptured implant Implant extrusion Painful capsular contracture with disfigurement Infection or inflammatory reaction due to breast prosthesis Siliconoma Granuloma Interference with diagnosis of breast cancer 10. Autologous fat/graft transfer (e.g., lipoinjection, lipofilling, lipopmodelling) postmastectomy, when no native breast tissue is present. Health Net considers breast reconstructive surgery to correct breast asymmetry in the nondiseased, unaffected, or contralateral breast, medically necessary only in the following situations: 1. Surgical correction due to a medically necessary mastectomy or a medically necessary lumpectomy that results in a significant deformity; 2. Repair of breast asymmetry due to trauma. 3. Breast implant for Poland s syndrome (congenital absence of breast). Breast Reconstructive Surgery Apr 15 2

4. Pectus excavatum repair when documented functional impairment exists (i.e., decreased cardiac output and/or abnormal pulmonary function during exercise) or when future cardiovascular compromise is anticipated. Not Medically Necessary Health Net, Inc. considers the following not medically necessary when used in association with breast reconstruction procedures, since there is a lack of randomized, controlled, prospective studies (list may not be all inclusive): 1. Permacol 2. Radiesse Note: Breast reconstruction services following mastectomy and lumpectomy is available to both females and males. In addition, a diagnosis of breast cancer is not required for breast reconstruction services, and the timing of reconstructive services is not a factor. Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures will be replaced by ICD-10 code sets. Health Net National Medical Policies will now include the preliminary ICD-10 codes in preparation for this transition. Please note that these may not be the final versions of the codes and that will not be accepted for billing or payment purposes until the October 1, 2015 implementation date. ICD-9 Codes (not an inclusive list) 170.4-175.9 Malignant neoplasm of breast 198.41 Secondary malignant neoplasm of breast 610.1 Diffuse cystic mastopathy [severe fibrocystic disease] 757.6 Specified anomalies of breast (absence) V10.3 Personal history of malignant neoplasm of breast V45.71 Acquired absence of breast [following medically necessary mastectomy or lumpectomy resulting in significant deformity] ICD-10 Codes (not an inclusive list) C50 Malignant neoplasm of breast N60.1 Diffuse cystic mastopathy(fibrocystic disease) Q83 Congenital malformations of the breast Z85.3 Personal history of malignant neoplasm of breast Z90.1 Acquired absence of breast(s) CPT Codes (not an inclusive list) 11920 Tattooing, intradermal introduction of insoluble opaque pigments to correct color defects of skin, including micropigmentation; 6.0 sq cm or less Breast Reconstructive Surgery Apr 15 3

11921 Tattooing, intradermal introduction of insoluble opaque pigments to correct color defects of skin, including micropigmentation; 6.1 to 20.0 sq cm 11970 Replacement of tissue expander with permanent prosthesis 11971 Removal of tissue expander(s) without insertion of prosthesis 19318 Reduction mammaplasty 19324 Mammaplasty, augmentation; without prosthetic implant 19325 Mammaplasty, augmentation; with prosthetic implant 19328 Removal of intact mammary implant 19330 Removal of mammary implant material 19340 Immediate insertion of breast prosthesis following mastopexy, mastectomy or in reconstruction 19342 Delayed insertion of breast prosthesis following mastopexy, mastectomy or in reconstruction 19350 Nipple/areola reconstruction 19357 Breast reconstruction, immediate or delayed, with tissue expander, Including subsequent expansion 19361 Breast reconstruction with latissimus dorsi flap, with or without prosthetic implant 19364 Breast reconstruction with free flap 19366 Breast reconstruction with other technique 19367 Breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM), single pedicle, including closure of donor site 19368 Breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM), single pedicle, including closure of donor site; with microvascular anastomosis (supercharging) 19369 Breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM), double pedicle, including closure of donor site 19370 Open periprosthetic capsulotomy, breast 19371 Periprosthetic capsulectomy, breast 19380 Revision of reconstructed breast HCPCS Codes (not an all inclusive list) L8600 Implantable breast prosthesis, silicone or equal Q4100 Skin substitute, not otherwise specified Q4116 Skin substitute, alloderm, per square centimeter Q4128 Flex HD, Allopatch HD, Or Matrix HD, Per Square Centimeter Scientific Rationale April 2015 On The U.S. FDA site it is noted that the Biosciences SurgiMend was issued a 510(k) Number of K083898, on 2/4/09. Per the U.S. FDA SurgiMend is intended for implantation to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. SurgiMend is specifically indicated for plastic and reconstructive surgery, muscle flap reinforcement, hernia repair including abdominal, inguinal, femoral, diaphragmatic, scrotal, umbilical, and incisional x`. The FDA site includes 67 adverse events associated with SurgiMend. Per the Manufacturer s site: SurgiMend is a unique acellular collagen matrix derived from fetal and neonatal bovine dermis. SurgiMend offers clear advantages over synthetic and other biologic products for soft tissue repair and reconstruction. Breast Reconstructive Surgery Apr 15 4

There is a Clinical Trial on Acellular Dermal Matrix in Tissue Expander Breast Reconstruction: A Prospective, Randomized, Clinical Trial Comparing SurgiMend PRS and AlloDerm RTU which is currently recruiting participants. The ClinicalTrials.gov Identifier is NCT01781299 and it was last updated June 2013. The purpose of this study is to assess the relative performance and complication rates between the AlloDerm RTU and SurgiMend PRS products as well as the relative economics of these two treatment options. The estimated primary completion date is September 2017. There is another Clinical Trial on SurgiMend in Two-stage Implant-based Breast Reconstruction in Patients With Pre-Mastectomy Radiotherapy, and the study is not yet open for participant recruitment. The ClinicalTrials.gov Identifier is NCT01959867, and it was last updated in October 2013. This is a prospective clinical study comparing two-stage breast reconstruction following mastectomy with and without the use of SurgiMend PRS fetal bovine collagen matrix in patients with premastectomy radiation therapy. The estimated primary completion date is September 2019. The sponsor of the trial is TEI Biosciences Inc., the manufacturer of Surgimend. Scientific Rationale Update April 2013 Autologous fat grafting (AFG) is used as an adjunct to standard breast reconstruction following mastectomy or breast-conserving surgery (lumpectomy or partial mastectomy). Autologous fat grafting consists of 3 phases - harvesting of fat tissue (e.g. lower abdomen, back, or thighs), processing, and application of the graft to the surgical site. Fat harvesting is similar to classic liposuction. In 2009, the American Society of Plastic Surgeons (ASPS) Executive Committee approved Guiding Principles that did not provide specific recommendations for the clinical use of fat grafts, citing a lack of strong data and literature. The review of the scientific evidence by the Task Force indicated that there were no reports suggesting an increased risk of malignancy associated with fat grafting and limited data suggested that fat grafts may not interfere with radiologic imaging for breast cancer detection. In 2011, a joint ASPS & American Society for Aesthetic Plastic Surgery (ASAPS) Position Statement: Stem Cells and Fat Grafting, addressed concerns regarding stem cells and fat grafting in clinical practice. They noted that standard fat grafting procedures which do transfer some stem cells naturally present within the tissue should be described as a fat grafting procedure, not a stem cell procedure. They stated that the marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence. A substantial body of clinical data to assess plastic surgery applications of stem cell therapies still needs to be collected. Until further evidence is available, stem cell therapies in aesthetic and reconstructive surgery should be conducted within clinical studies under Institutional Review Board approval, including compliance with all guidelines for human medical studies. 2012 Post-Mastectomy Fat Graft/Fat Transfer (ASPS) Guiding Principles, provides recommendations regarding fat transfer to the post-mastectomy breast with no native breast tissue present. Per the ASPS, An evaluation of available literature on autologous fat grafting following mastectomy with no remaining native breast tissue indicates that the body of evidence is comprised mostly of case series, and when combined, the studies provide consistent evidence, thus resulting in grade B recommendations. A grade B recommendation encourages clinicians to employ the available information while remaining cognizant of newer, evidence-based findings. Breast Reconstructive Surgery Apr 15 5

The existing evidence suggests autologous fat grafting as an effective option in breast reconstruction following mastectomy while demonstrating moderate to significant aesthetic improvement. In addition, the available evidence also cites autologous fat grafting as a useful modality for alleviating post mastectomy pain syndrome. Furthermore, the evidence suggests autologous fat grafting as a viable option for improving the quality of irradiated skin present in the setting of breast reconstruction. ASPS GUIDING PRINCIPLES 1. Aesthetic Outcome: Studies indicate that breast cancer patients undergoing fat grafting as an adjunct to post-mastectomy breast reconstruction experience moderate to significant aesthetic improvement, particularly for volume, contour and superomedial fullness. The evidence also suggests that cosmetic outcome is significantly enhanced after serial fat grafting and that, overall, patients are satisfied with aesthetic results. 2. Breast Cancer Recurrence: Evidence suggests that in post-mastectomy breast reconstruction patients, fat grafting does not increase the risk of breast cancer recurrence. As surveillance is integral for the management of any breast cancer patient, fat grafting to post-mastectomy reconstructed breasts does not delay diagnosis of breast cancer recurrence. When reviewed by experienced radiologists, the presence of oil cysts and fat necrosis on mammography, ultrasound and MRI imaging is distinguishable from suspicious lesions. Surveillance should continue to be rigorous and it is encouraged that radiologists who are experienced in breast imaging work with plastic surgeons to facilitate imaging accuracy. 3. Complications: Although there is variability in physician technique for fat grafting, the evidence suggests that post-mastectomy breast reconstruction with fat grafting is effective and is associated with a low risk of complications. Furthermore, there is increasing evidence that fat grafting is an effective surgical technique for treating post-mastectomy pain syndrome. 4. Radiation Therapy: There is a growing body of evidence that suggests no increased risk of complications when fat grafting is employed in the presence of previously irradiated tissue. 5. Technique: The number of fat grafting sessions required varies per patient. Studies suggest that a majority of patients require more than one fat grafting session to achieve adequate aesthetic results, and that each additional session will contribute to gradual improvement of the overall outcome Sarfati et al (2013) investigated sixty-eight patients who had mastectomy and breast irradiation who had one or more sessions of lipofilling prior to breast implant reconstruction. These patients were prospectively followed up in order to collect the following data: postoperative complications; cosmetic result; local breast cancer recurrences. The mean number of fat grafting sessions was 2.3 (range 1-6). An average volume of 115mL (70-275) was injected each time. The mean volume of breast implants was 300mL (185-400). The mean follow-up was 23 months. No breast cancer local recurrence was diagnosed during follow-up. Implant explantation was performed in one case (1.47%) The mean cosmetic result was 4.5/5. Investigators concluded fat grafting to the irradiated chest wall prior to implant placement might be an alternative to flap reconstruction for patients who are not suitable or who refuse this option. Irani et al (2012) sought to determine whether fat grafting prior to breast reconstruction could improve thoracic tissue trophicity enough to perform a simple prosthetic reconstruction, avoiding a flap procedure. A total of 25 patients who had undergone a modified radical mastectomy followed by radiotherapy were retrieved. Fat was injected according to Coleman's technique. Prosthetic reconstruction was Breast Reconstructive Surgery Apr 15 6

performed three to six months after the fat grafting procedure. Reconstruction of the nipple-areola complex was performed 3 months after implant positioning. Median follow-up interval was two years. Patient satisfaction was ascertained with a selfassessment questionnaire. Three independent blinded physician observers judged preoperative and postoperative photographs to determine the quality of reconstruction. The mean refined fat injected volume was 160ml. In all cases except two, a unique fat grafting procedure was necessary. Prosthetic reconstruction was achieved in 23 cases. The technique failed in two cases and breast reconstruction was achieved by a latissimus dorsi flap with implant. During the follow-up interval, two complications occurred in two patients presenting with fat necrosis and oil cysts. The mean number of total surgical procedures was 2.5 per patient. Quality of reconstruction was judged as good by both physicians and patients. Authors concluded autologous fat grafting in radiated tissue prior to breast reconstruction is a safe and reliable technique. In selected cases, a simple prosthetic reconstruction can be achieved avoiding a flap procedure. Seth et al (2012) reported that long-term oncologic implications of autologous fat grafting following breast reconstruction remains unclear. The authors evaluated longterm outcomes following tissue expander breast reconstruction with and without fat grafting in a retrospective review of consecutive patients undergoing mastectomy with immediate tissue expander reconstruction. Demographic, operative, oncologic, and postoperative factors were recorded, including the use of fat grafting. Mean follow-up was 42.1 ± 28.8 and 43.6 ± 27.2 months for non-fat-grafting and fatgrafting patients, respectively, including 24.8 ± 5.9 months after the first fatgrafting procedure. Fisher's exact test, t test, and regression analysis were used for statistics. A review of 886 patients (n = 1202 breasts) revealed no significant differences in demographics, operative characteristics, tumor staging, or radiation therapy exposure between fat-grafting (n = 90 breasts) and non-fat-grafting (n = 1112 breasts) patients. Ninety-nine fat-grafting procedures were performed an average of 18.3 months after reconstruction, with one complication (fat necrosis). Grafting did not affect local tumor recurrence or survival when compared with nonfat-grafted breasts. Complication following reconstruction, including a poor cosmetic result, was an independent predictor of undergoing subsequent fat grafting.. The authors concluded the analysis suggests that fat grafting after breast reconstruction does not adversely affect local tumor recurrence or survival on long-term follow-up. Autologous fat grafting can be used as an aesthetic adjunct to prosthetic reconstruction with minimal complications. These results also indicate the need for multi-institutional, prospective studies to definitively establish its oncologic safety. de Blacam et al (2011) reviewed their early experience of fat grafting in the correction of acquired contour deformities after postmastectomy breast reconstruction in a retrospective review of 49 patients who underwent fat grafting to 68 reconstructed breasts was carried out. Clinical outcomes were analyzed and aesthetic results were assessed with objective grading of preoperative and postoperative photographs by two independent, blinded plastic surgeons. On average, 67 cc of fat was injected into each breast per session. There were 111 fat injection procedures, as more than one injection was required in 51.5 percent of cases. Average follow-up time was 2.4 years. Complications occurred in 6.3 percent of procedures, including fat necrosis (3.6 percent), oil cysts (1.8 percent), and infection (0.9 percent). Aesthetic outcome was significantly improved across all measurements, including volume, contour, placement, and superomedial fullness (p<0.001 for all). The reviewers concluded although further studies are required to provide surgeons with definitive guidelines for the implementation of this technique, fat injection is a safe intervention and significantly improves the aesthetic results in patients with contour deformities of the reconstructed breast. Breast Reconstructive Surgery Apr 15 7

Losken et al (2011) reviewed their experience with fat grafting for the correction of acquired breast deformities. A retrospective review was performed on 107 patients with a history of breast cancer between 1996 and 2010, who had autologous fat grafting at the time of secondary breast reconstruction. The indications were for improvement in contour, shape, and volume of the breast following transverse rectus abdominis myocutaneous (TRAM) flap reconstruction (n = 55), latissimus dorsi with or without implant (n = 20), implant reconstruction (n = 20), and breast conservation therapy deformity (n = 12). The average volume of injection was 40 ml (range, 5-150 ml), the most common location being upper and medial quadrants. Fat was harvested mainly from the abdomen, thighs, and flanks. Complications occurred in 11% of the patients, and included fat necrosis, erythema, keloid scarring, and pain. Complications were higher when performed with implant reconstructions. Repeat fat injection was performed in 25% (n = 27/107), which increased with the length of follow-up. Patients with a history of radiation therapy had an increased incidence of repeat injections (36% vs. 18%). Patients with >6 months follow-up reported an improvement of about 83%. The authors concluded autologous fat grafting is a safe and effective tool for secondary breast reconstruction. It is helpful in all types of reconstructions to improve contour, volume, and overall breast shape and symmetry. Repeat injections are often required and this is more common in patients with longer follow-up and in those with a history of radiation therapy. The popularity of this approach in reconstructive breast surgery will likely continue to increase. Rigotti et al (2010) compared the incidence of local and regional recurrence of breast cancer between two contiguous time windows in a homogeneous population of 137 patients who underwent fat tissue transplant after modified radical mastectomy. Median follow-up time was 7.6 years and the follow-up period was divided into two contiguous time windows, the first starting at the date of the radical mastectomy and ending at the first lipoaspirate grafting session and the second beginning at the time of the first lipoaspirate grafting session and ending at the end of the total follow-up time. Although this study did not employ an independent control group, the incidence of local recurrence of breast cancer was found to be comparable between the two periods and in line with data from similar patient populations enrolled in large multicenter clinical trials and who did not undergo postsurgical fat tissue grafting. Statistical comparison of disease-free survival curves revealed no significant differences in relapse rate between the two patient subgroups before fat grafting and after fat grafting. Although further confirmation is needed from multicenter randomized clinical trials, our results support the hypothesis that autologous lipoaspirate transplant combines striking regenerative properties with no or marginal effects on the probability of post-mastectomy locoregional recurrence of breast cancer. Data on long-term outcomes of fat grafting to the breast are lacking. To confirm the safety of lipotransfer in breast cancer patients clinical studies with control group based on long term follow up are needed. Scientific Rationale - Update February 2013 Claro et al (2012) conducted a systematic review of the clinical applicability and safety of autologous fat grafting to the breast for cosmetic and reconstructive purposes. Studies included in the review were original articles of autologous liposuctioned fat grafting to the female breast, with description of clinical complications and/or radiographic changes and/or local breast cancer recurrence. The review included 60 articles with 4601 patients. Thirty studies used fat grafting for augmentation and 41 for reconstructive procedures. The incidence of clinical complications, identified in 21 studies, was 3 9 per cent (117 of 3015); the majority were induration and/or palpable nodularity. Radiographic abnormalities occurred in Breast Reconstructive Surgery Apr 15 8

332 (13 0 per cent) of 2560 women (17 studies); more than half were consistent with cysts. Local recurrence of breast cancer (14 of 616, 2 3 per cent) was evaluated in three studies, of which only one was prospective. Reviewers concluded there is broad clinical applicability of autologous fat grafting for breast reconstruction. Complications were few and there was no evidence of interference with follow-up after treatment for breast cancer. Oncological safety remains unclear. Pérez-Cano et al (2012) reported results of the RESTORE-2, the first prospective clinical trial using autologous adipose-derived regenerative cell (ADRC)-enriched fat grafting for reconstruction of such defects. This single-arm, prospective, multi-center clinical trial enrolled 71 patients post- breast conservation therapy (BCT) with defects 150 ml. Adipose tissue was collected via syringe lipoharvest and then processed during the same surgical procedure using a closed automated system that isolates ADRCs and prepares an ADRC-enriched fat graft for immediate reimplantation. ADRC-enriched fat graft injections were performed in a fan-shaped pattern to prevent pooling of the injected fat. Overall procedure times were less than 4 h. The RESTORE-2 protocol allowed for up to two treatment sessions and 24 patients elected to undergo a second procedure following the six month follow-up visit. Of the 67 patients treated, 50 reported satisfaction with treatment results through 12 months. Using the same metric, investigators reported satisfaction with 57 out of 67 patients. Independent radiographic core laboratory assessment reported improvement in the breast contour of 54 out of 65 patients based on blinded assessment of MRI sequence. There were no serious adverse events associated with the ADRC-enriched fat graft injection procedure. There were no reported local cancer recurrences. Injection site cysts were reported as adverse events in ten patients. Investigators concluded the prospective trial demonstrates the safety and efficacy of the treatment of BCT defects utilizing ADRC-enriched fat grafts. Kijima et al (2012) investigated 22 breasts in 21 patients who underwent partial mastectomy for early breast cancer involving mainly the inner upper quadrant were enrolled in this study. The defect was reconstructed immediately by filling it with an autologous free dermal fat graft (FDFG). At 6 months and 1, 2, 3, 4, and 5 years postoperatively, the width (horizontal length) and thickness (distance perpendicular to skin) of the FDFG on computed tomography (CT) scans were measured. Histologic samples from the implanted FDFG were collected by core needle biopsy (CNB). The correlations between clinical findings and volume of the FDFG on CT and the proportion of fatty tissue in the CNB were examined statistically. Cosmetic results were also evaluated. On CT, the mean width of the FDFG was 95%, 81%, 79%, 73%, 68%, and 47% and the mean thickness were 125%, 121%, 120%, 115%, 104%, and 103% at 6 months, and 1-5 years postoperatively, respectively. In the CNB samples, the mean fatty tissue distribution was 76%, 63%, and 54% at 1 year, 1-4 years, and >4 years postoperatively, respectively. The percent change in the width of the FDFG at 6 months after the operation displayed a significant negative correlation with the postmenopausal period and a significant positive correlation with the maximum surgical margin. On CT, thickness was negatively correlated with the size of the resected breast tissue, and thickness of the implanted FDFG. No clinicopathologic factors or technical factors were related to FDFG outcome and the proportion of fat tissue in the CNB sample, except for axillary dissection. Nineteen of 21 patients had good to excellent cosmesis. Authors concluded FDFG implanted into breast defects after partial mastectomy undergo mild resorption and degeneration to fibrous tissue, but most patients have good to excellent cosmesis. The available evidence on the use of FlexHD to assist one- or two-staged breast reconstruction following mastectomy for breast cancer is very limited. Institutional experiences reported in four retrospective studies address the efficacy and safety of FlexHD and other biologic meshes; however, none of the studies presented or Breast Reconstructive Surgery Apr 15 9

analyzed outcomes separately for FlexHD. The studies included 210 women (258 reconstructed breasts). Reported complications affected 0 to 46% of patients, including infection, necrosis, hematoma, serosa, and pain. The need for reoperation ranged from 0 to 25%. One comparative study (n=119) compared the efficacy of staged biologic mesh-assisted breast reconstruction with breast reconstruction without the use of mesh. In this study, the use of biologic mesh was associated with a significantly higher rate of infection, reoperation, expander explantation, and overall complications, especially in patients with larger breasts (weighing 600 grams) compared with reconstruction without mesh. The patients were generally satisfied after surgery with respect to breast size, shape, and firmness. However, limited evidence showed a discrepancy in patient satisfaction related to symmetry issues between bilateral and unilateral reconstructions. Scientific Rationale Update December 2009 Most breast reconstruction currently performed today utilizes tissue expanders and implants. Breast reconstruction with implants can be performed as a one-step or multiple-step procedure. For example, in a staged procedure, a tissue expander is placed into a surgically created pocket either at the time of mastectomy or after the mastectomy has healed. Over several months, the expander is filled at regular intervals by weekly injections of saline. Tissue expansion is needed to accommodate the permanent implant if an insufficient amount of skin is left after mastectomy. The remaining tissues are stretched over several weeks or months, and the expander is exchanged for a permanent silicone or saline implant during a second surgery when the expansion is complete. Breast reconstruction may also be accomplished in a single stage with the breast implant inserted during a procedure immediately after the mastectomy without tissue expansion, however, the success of this approach depends upon compliance of the subpectoral muscles, adequacy of the subpectoral pocket, and health of the mastectomy flap, etc. Breast reconstruction can be challenging if the patient s skin-pectoral muscle pocket cannot adequately support tissue expansion or if it cannot hold the expander or implant in place. A weakened muscle layer overlying the implant can cause visible rippling and implant extrusion. Autologous flap reconstruction (i.e., a portion of skin and fat, with or without muscle, is harvested from another part of the body and transplanted to the chest where it is shaped into a breast) are generally considered to give a more long-lasting and natural result than implants with fewer revision surgeries and may eliminate the need for a prosthetic implant, however, flap reconstruction is complex, and is associated with longer operating room time, longer recovery period and increased morbidity. In an attempt to improve outcomes following breast reconstruction, AlloDerm (LifeCell Corp.), has been investigated to provide for additional coverage and support of implants and other tissues at the surgical site for either one or two-stage reconstruction procedures. AlloDerm is an acellular dermal matrix derived from human cadaver skin that has been processed and sterilized to remove all cells and antigenic components that could cause inflammation and rejection. This dermal matrix serves as scaffolding for normal tissue ingrowth and cellular repopulation, which promotes tissue regeneration and neovascularization. AlloDerm is available in sheets ranging in size from 4 x 12 to 6 x 16 cm, with a thickness from approximately 0.8 to 3.3 mm. The sheets must be rehydrated in sterile saline before use and trimmed to fit the defect. For breast reconstruction using expanders and/or implants, 1 to 3 sheets of AlloDerm are rehydrated, sized, and cut to match the size and shape of the defect to cover and support the exposed implant beneath the lower edge and to the side of the pectoralis muscle. The allograft is sutured to the pectoralis major muscle superiorly, to the chest wall Breast Reconstructive Surgery Apr 15 10

inferiorly, and to the serratus anterior muscle laterally. The characteristic shape of the AlloDerm graft for this indication is referred to as a hammock or sling. AlloDerm can be used to cover the exposed portion of the implant at the lower pole, which completes and secures the submuscular pocket, and defines the inframammary fold. After completion of expansion and adjuvant therapy if needed, the patient is scheduled for device exchange. Proponents of AlloDerm claim it reduces postoperative pain and musculoskeletal morbidity in breast reconstruction since the allograft eliminates the need for or reduces the extent of dissection and elevation of abdominal muscles during the creation of the inferior-lateral portion of the submuscular pocket for the implant. In addition, the graft may allow for greater and more rapid expansion, and for the immediate placement of a permanent implant. Proposed benefits of Alloderm include supplementation of the pectoralis major muscle deficiency at the breast lower pole, supporting and holding the prosthesis in place and thereby helping to define the shape and contour of the reconstructed breast and serves to cushion the mastectomy skin envelope from direct contact with the implant/expander. Preliminary data indicate that the use of AlloDerm in facilitating breast reconstruction with implant/expander is safe, with no major complications. AlloDerm also contributes to improving the aesthetic outcome of the reconstruction, by achieving good breast projection and symmetry. According to the manufacturer, the following are potential adverse effects, among others, that may result from placement of an implant or graft: wound or systemic infection; seroma; dehiscence; hypersensitive, allergic, or other immune response; sloughing or failure of the graft; and disease transmission. As previously noted in the initial scientific rationale of this policy, published peer review literature evaluating AlloDerm is limited to three nonrandomized comparative studies that includes 2 retrospective studies, Preminger et al (2008), and Becker et al (2009), and 1 prospective study, Spear et al. (2008). Several small case series, one of which evaluated the efficacy of AlloDerm for nipple reconstruction, have also been published. In the comparative studies, no significant differences in tissue expansion measures (fill volume, fill time, etc.) were observed between patients treated with and without AlloDerm. No serious complications or instances of contracture were observed. One study that evaluated aesthetic outcomes found that blinded assessors scored AlloDerm-reconstructed breasts the same as the contralateral breasts. One study found that the revision rate for AlloDerm-treated breasts was significantly lower than that for historical data on breasts that were reconstructed without the graft. The case series found that patients were satisfied with the treatment results and that there were few complications specific to AlloDerm; however, as in the comparative trials, there was little to no objective assessment of clinical outcomes. Although studies have been relatively small, non-randomized studies without long term results, AlloDerm appears to be relatively safe and well tolerated. Histological analysis of tissues showed good incorporation of AlloDerm into the host tissues. No major complications have been reported. According the American Cancer Society, Alloderm is fairly new in breast reconstruction and has been used to extend and support natural tissues and may be used with expanders and implants as well as in nipple reconstruction. The ACS notes that outcome studies are still in progress, but have been promising. Researchers at Memorial Sloan-Kettering Cancer Center are sponsoring a randomized controlled trial assessing the use of Alloderm in two-stage, tissue expander/implant reconstruction. Estimated study completion date is March 2011. Several other Breast Reconstructive Surgery Apr 15 11

clinical trials are currently recruiting patients in an effort to further evaluate Alloderm. Scientific Rationale Initial Breast cancer is the most common malignant neoplasm in women, affecting about 1 in 8 women in the United States. Because it has been conclusively shown that postmastectomy reconstruction does not adversely influence survival outcomes or recurrence rates, preoperative consultation is offered to all individuals desiring breast reconstruction, and the option of not reconstructing the breast is also discussed. Reconstructive breast surgery is defined as surgical procedures that are intended to restore the normal appearance of the breast after surgery, accidental injury, or trauma. The most common indication for reconstructive breast surgery is mastectomy or lumpectomy. These procedures could also be done for chronic, severe fibrocystic breast disease, known as cystic mastitis, unresponsive to medical therapy. Modern breast reconstruction began in 1964 with the introduction of the silicone breast implant. The most common and simplest form of reconstructive breast surgery has been the insertion of a silicone gel-filled or saline-filled breast implant, either inserted immediately at the time of mastectomy, or sometime afterward in conjunction with the previous use of a tissue expander. Significant local complications of breast implants, such as contracture, may require removal of the implant. The art of breast reconstruction has undergone evolution over the last 20 years. Reconstruction selection is based on an assessment of cancer treatment, patient body habitus, smoking history, co-morbidities and patient concerns. Other types of reconstruction include nipple/areola reconstruction, nipple tattooing, and/or the use of autologous tissue, such as a transverse rectus abdominis myocutaneous flap (TRAM procedure), a latissimus dorsi flap, or additional flaps as noted below. In addition, mastopexy, reduction mammoplasty, or implant on the contralateral breast may be performed in order to achieve symmetry with the reconstructed breast. The development of musculocutaneous flaps and microsurgical tissue transplantation paved the way for modern autogenous tissue breast reconstruction. These flaps may be transposed into position with their vascular origin intact ("pedicled" flaps). Tissue flap surgery, or autologous tissue reconstruction, is a way to rebuild the shape of a breast using skin, fat, blood vessels and muscle from another part of the body (upper back, abdomen, or buttocks). This type of flap procedure is usually done to reconstruct the appearance of a breast with a blood supply, after mastectomy. Compared to breast reconstruction with implants, tissue flap procedures require a longer surgery and recovery time but result in a more natural-looking breast. Although there are several different types of tissue flap procedures, the most common are the TRAM flap and the latissimus dorsi flap. Complications can occur with any type of breast reconstruction, however, the most significant effect is delay of initiation of adjuvant therapy. Partial or complete flap loss, wound breakdown, and infection are all reasons why chemotherapy or radiation therapy would be delayed. Complication rates are higher in patients who require radiotherapy postoperatively. In patients who require postoperative radiotherapy, TRAM reconstructions can provide better cosmetic outcomes and lower complication rates than implant reconstructions can. Because postoperative radiotherapy has been recognized to worsen the outcome of an immediate TRAM reconstruction, there has been a movement to delay reconstruction in patients who are expected to need postoperative radiotherapy. However, the advantages of immediate reconstruction outweigh the risk for late complications seen with irradiated immediate TRAM Breast Reconstructive Surgery Apr 15 12

reconstructions. In general, radiotherapy after mastectomy and immediate TRAM flap reconstruction is well tolerated and not associated with an increased rate of acute complications or interruption of radiation therapy. Alloderm AlloDerm Regenerative Tissue Matrix is an acellular dermal matrix derived from human cadaver skin that has been processed and sterilized to remove all cells and antigenic components that could cause inflammation and rejection. Tissue banks procure fresh human cadaveric skin following American Association of Tissue Bank (AATB) guidelines in accordance with the AATB and FDA guidelines. The resulting product contains an extracellular mix of connective tissue components such as collagen, elastin, and hyaluronic acid. When introduced into viable tissue, the matrix serves as scaffolding for normal tissue ingrowth and cellular repopulation, which promotes tissue regeneration and neovascularization. AlloDerm has been proposed as a graft for burn patients, and for reconstructive applications such as facial reconstruction, abdominal wall reconstruction, and breast reconstruction. Prosthetic breast reconstruction with implant or expander is currently the standard in immediate breast reconstruction postmastectomy. Proposed as an alternative to traditional reconstruction, proponents claim AlloDerm reduces postoperative pain and musculoskeletal morbidity since the allograft eliminates the need for or reduces the extent of dissection and elevation of abdominal muscles during the creation of the inferior-lateral portion of the submuscular pocket for the implant. The graft may allow for greater and more rapid expansion, and for the immediate placement of a permanent implant. The evidence base on the efficacy and safety of AlloDerm for postmastectomy breast reconstruction is limited to 3 nonrandomized comparative studies, 2 retrospective studies, (Preminger et al. [2008], and Becker et al. [2009], and 1 prospective study, Spear et al. [2008]), as well as 5 small case series, Breuing et al. [2007], Zienowicz et al. [2007], Salzberg et al. [2006], Gamboa-Bobadilla [2006], and Bindingnavele et al. [2007]. One small case series evaluated the efficacy of AlloDerm for nipple reconstruction. Alloderm has been evaluated and found that patients were satisfied with the treatment results and that there were few complications specific to AlloDerm; however, there was little to no objective assessment of clinical outcomes in any study, and outcomes were undefined or poorly defined. The three-nonrandomized comparative trials (n=30 to 90 patients) and 5 case series (n=11 to 49 patients) evaluated the efficacy and safety of AlloDerm in breast reconstruction following mastectomy for breast cancer and prophylactic mastectomy. In the comparative studies, no significant differences in tissue expansion measures (fill volume, fill time, etc.) were observed between patients treated with and without AlloDerm. No serious complications or instances of contracture were observed. One study that evaluated aesthetic outcomes found that blinded assessors scored AlloDerm reconstructed breasts the same as the contralateral breasts. One study found that the revision rate for AlloDerm-treated breasts was significantly lower than that for historical data on breasts that were reconstructed without the graft. The case series found that patients were satisfied with the treatment results and that there were few complications specific to AlloDerm; however, as in the comparative trials, there was little to no objective assessment of clinical outcomes. AlloDerm appears to be relatively safe and well tolerated. Histological analysis of tissues showed good incorporation of AlloDerm into the host tissues. No major complications have been reported. Reported complications that affected 0 to 25% of patients included infection, necrosis, hematoma, seroma, and flap loss. The studies are all limited by weak designs, lack of randomization, and inadequate follow-up times, Breast Reconstructive Surgery Apr 15 13

which makes it difficult to draw conclusions about the long-term efficacy and safety of AlloDerm in postmastectomy breast reconstruction. Permacol Permacol Porcine Dermal Collagen Surgical Mesh is proposed for use in breast reconstruction. Permacol is comprised of acellular cross-linked porcine dermal collagen and elastin. According to the U.S. Food and Drug Administration (FDA), Permacol is intended for use as a soft tissue patch to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. Evidence in the published, peer-reviewed scientific literature supporting the use of this product in breast reconstruction is lacking and its role is unclear. Radiesse Radiesse injections consist of very small, smooth calcium hydroxylapatite (CaHA) microspheres that are suspended in a water-based gel carrier. Radiesse has been proposed to reshape nipples after reconstruction of the breast following mastectomy. Radiesse has received PMA approval by the FDA as a medical device for subdermal implantation for two indications: correction of moderate to severe facial wrinkles and folds such as nasolabial folds and the correction of facial fat loss in people with human immunodeficiency virus (FDA, 2006). There remains a lack of evidence in the peer-reviewed published literature on the long term outcomes, safety and efficacy of Radiesse in breast reconstructive procedures. Autologous fat transplant (e.g., lipoinjection) Autologous fat grafting to the breast is not a simple procedure and should be performed by well-trained and skilled surgeons. Patients should be informed that it is associated with a risk of calcification, multiple cyst formation, and indurations, and that breast cancer screens will always detect abnormalities. (2008) Autologous fat transplant (i.e., lipoinjection) has been proposed for use in for breast reconstruction procedures. The American Society of Plastic Surgeons (ASPS) and the American Society for Aesthetic Plastic Surgery (ASAPS) state, Although there has been some research on the safety and efficacy of this procedure, more research is needed before concluding that the procedure s benefits outweigh the risks. Symmetry for Contralateral Breast Once reconstruction of the affected breast has begun, the challenge of creating symmetry with the contralateral breast is undertaken. Contralateral breast surgery can be performed at the time of the initial reconstruction or during the second stage. Reduction, augmentation or a combination of procedures can be used both for aesthetic improvement and improved symmetry. As an example, in a woman with very large breasts who undergoes a mastectomy with reconstruction, a contralateral reduction will decrease the size discrepancy, resulting in improved patient comfort and increased symmetry. Reconstruction of the Nipple/ Areolar Complex The final component of breast reconstruction is the creation of the nipple and areola. This is typically performed during the second stage of breast reconstruction, but can also be performed in an office setting. The goal of nipple and areolar reconstruction is to achieve symmetry of position of the nipple-areolar complex in the contralateral breast with comparable appearance and color. There are multiple techniques of local tissue rearrangement for creation of a new nipple. Some are based on skin grafts, while others utilize donor sites that are closed Breast Reconstructive Surgery Apr 15 14

primarily. Nipple projection varies among the different techniques, but adequate results can be achieved with most. Symmetry of position on the breast mound is the most important goal of nipple reconstruction, as even small discrepancies are obvious. Once the projecting papilla has been created, the appearance of the entire nipple-areola complex can be enhanced by the use of tattooing. Poland Syndrome Poland Syndrome is an extremely rare developmental disorder that is congenital. It is characterized by absence or hypoplasia of certain muscles of the chest (e.g., pectoralis major, pectoralis minor, and/or other nearby muscles), and abnormally short, webbed fingers (symbrachydactyly). Additional findings may include underdevelopment or absence of one nipple (including the darkened area around the areola and/or patchy hair growth under the arm (axilla). In females, one breast may also be underdeveloped or absent. In some cases, affected individuals may also exhibit underdeveloped upper ribs and/or an abnormally short arm with underdeveloped forearm bones (i.e., ulna and radius) on the affected side. In most cases, physical abnormalities are confined to one side of the body unilateral. In approximately 75 percent of the cases, the right side of the body is affected. The range and severity of symptoms may vary from case to case. The exact cause of Poland Syndrome is not known. National Comprehensive Cancer Network (NCCN) 2009 Clinical Practice Guidelines in Oncology [Breast Cancer] When breast reconstruction following mastectomy is planned, close prospective evaluation and collaboration between members of the breast cancer treatment team is essential including Oncologic and reconstructive surgeons, as well as other members of multidisciplinary team. Issues related to breast reconstruction also pertain to women who undergo or have undergone lumpectomy, particularly in situations where surgical defects is large and/or expected to be cosmetically unsatisfactory. As with any mastectomy, there is a risk of local and regional cancer recurrence, and evidence suggests skin-sparing mastectomy is probably equivalent to standard mastectomy, in this respect. Proper patient selection for skin-sparing mastectomy is necessary to determine optimal sequencing of reconstructive procedures in relation to adjuvant therapies, and to perform a retention that achieves appropriate surgical margins. Post-mastectomy radiation as noted in the guidelines by NCCN should be applied in cases treated by skin sparing mastectomy. When post-mastectomy radiation is required, delayed reconstruction is generally preferred after completion of radiation therapy in autologous tissue reconstruction, because of reported loss in reconstruction cosmesis (Category 2B*). When implant reconstruction is used, immediate rather than delayed reconstruction is preferred to avoid tissue expansion of radiated skin flaps. Immediate implant reconstruction in patients requiring post-operative radiation has an increased rate of capsular contracture. Surgery to exchange the tissue expanders with permanent implants can be performed prior to radiation or after completion of radiation therapy. Some experienced breast cancer teams have employed protocols in which immediate reconstructions are followed by radiation therapy (Category 2B*). Tissue expansion of irradiated skin can result in a significantly increased risk of capsular contracture, malposition, poor cosmesis and implant exposure. In the previously radiated patients the use of tissue expanders/ implants is relatively contraindicated. Smoking increases the risk of complications for all types of breast reconstruction whether implant or flap. Smoking is therefore considered a relative contraindication Breast Reconstructive Surgery Apr 15 15

to breast reconstruction and patients should be made aware of increased rates of wound healing complications and partial or complete flap failure among smokers. *Note: Category 2B The recommendation is based on lower level evidence and there is nonuniform NCCN consensus (But no major disagreement). Summary In summary, breast reconstruction procedures that are based on established standards of care include insertion of U.S. FDA approved internal breast prosthesis, implantation of tissue expander, tissue/muscle reconstruction procedures (e.g., Flaps), areolar and nipple reconstruction, and areolar and nipple tattooing. In addition, breast reconstruction on the contralateral, unaffected breast to produce symmetry, is considered medically necessary. Breast reconstruction may be carried out immediately after mastectomy or delayed. The advantages of immediate reconstruction include streamlined care, superior cosmetic results, and psychosocial benefits. For women who need postmastectomy radiation therapy (RT), the best way to integrate chest wall RT and breast reconstruction is controversial, and there are no universally agreed upon guidelines. Delayed reconstruction using autologous tissue may be preferred in this setting since it provides the best cosmetic result with the fewest complications. Reconstruction flap selection is based on an assessment of cancer treatment, patient body habitus, smoking history, co-morbidities, discussion between the individual and their physician and patient concerns. The available outcomes data on perforator flaps are limited to single-center reports. One study evaluated sit-up ability three and six months following perforator flap reconstruction. At three months, 95 percent of women were able to return to their preoperative sit-up activity; this was 100 percent by six months postoperatively. Review History September 2009 December 2009 March 2011 February 2013 April 2013 April 2014 April 2015 Medical Advisory Council, initial approval Removed AlloDerm from the investigational section of the policy and added as a medically necessary option in breast reconstruction Policy retired and pertinent information transferred to the Cosmetic and Reconstructive Surgery Medical Policy Reactivated policy and added autologous fat transplantation from Cosmetic and Reconstructive Surgery policy, added FlexHD Revised policy to consider autologous fat transfer/graft as medically necessary. Added information on breast reconstruction from cosmetic/reconstructive policy to this policy. Medicare table added Update no revisions. Codes updated. Update no revisions. Codes updated. This policy is based on the following evidence-based guidelines: 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. V.1.2009. Updated V.1.2011. Updated v.1.2013. Updated v.1.2014. Updated v.2.2015. 2. Hayes Health Technology Brief. Autologous Fat Grafting for Postmastectomy Breast Reconstruction. April 2012. Updated April 30, 2013. Updated April 8, 2014. 3. American Society of Plastic Surgeons. 2012 Post-Mastectomy Fat Graft/Fat Transfer ASPS Guiding Principles. Dec/ 2012. 4. Hayes. Search & Summary. SurgiMend (TEI Biosciences) for Breast Reconstruction. December 30, 2014 Breast Reconstructive Surgery Apr 15 16

References Update April 2015 1. Clinicaltrials.gov. Acellular Dermal Matrix in Tissue Expander Breast Reconstruction: A Prospective, Randomized, Clinical Trial Comparing SurgiMend PRS and AlloDerm RTU. ClinicalTrials.gov Identifier: NCT01781299. June 2013. 2. Clinicaltrials.gov. SurgiMend in Two-stage Implant-based Breast Reconstruction in Patients With Pre-Mastectomy Radiotherapy. ClinicalTrials.gov Identifier: NCT01959867. October 2013. 3. Smit JM, Tielemans HJ, de Vries B, et al. Recurrence of invasive ductal breast carcinoma 10 months after autologous fat grafting. J Plast Reconstr Aesthet Surg. 2014 May;67(5):e127-8. doi: 10.1016/j.bjps.2013.12.043. Epub 2014 Jan 4. 4. Brenelli F, Rietjens M, De Lorenzi F, et al. Oncological safety of autologous fat grafting after breast conservative treatment: a prospective evaluation. Breast J. 2014 Mar;20(2):159-65. doi: 10.1111/tbj.12225. Epub 2014 Jan 23. 5. Ballard TNS, Momoh AO. Advances in Breast Reconstruction of Mastectomy and Lumpectomy Defects. Surgical Oncology Clinics of North America. 23 (3) (pp 525-548), 2014. 6. Kocak E, Nagel TW, Hulsen JH, et al. Biologic matrices in oncologic breast reconstruction after mastectomy. Expert Review of Medical Devices. 11 (1) (pp 65-75), 2014. 7. U.S. FDA. TEI Biosciences. SurgiMend. 510K K08398. February 4, 2009. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf8/k083898.pdf References Update April 2014 1. American Cancer Society: Breast Reconstruction after Mastectomy. Updated 2013. Available at: http://www.cancer.org/cancer/breastcancer/moreinformation/breastreconstruc tionaftermastectomy/index 2. Chaput B, Foucras L, Le Guellec S, et al. Recurrence of an invasive ductal breast carcinoma 4 months after autologous fat grafting. Plast Reconstr Surg. 2013 Jan;131(1):123e-4e. 3. Ibrahim AM, Ayeni OA, Hughes KB, et al. Acellular dermal matrices in breast surgery: A comprehensive review. Ann Plast Surg. 2013 Feb 12. 4. Phillips BT, Bishawi M, Dagum AB, et al. A systematic review of antibiotic use and infection in breast reconstruction: What is the evidence? Plast Reconstr Surg. 2013;131(1):1-13. References Update April 2013 1. Cigna E, Ribuffo D, Sorvillo V, et al. Secondary lipofilling after breast reconstruction with implants. Eur Rev Med Pharmacol Sci. 2012 Nov;16 (12):1729-34. 2. Claro F Jr, Figueiredo JC, Zampar AG, Pinto-Neto AM. Applicability and safety of autologous fat for reconstruction of the breast. Br J Surg. 2012 Jun;99(6):768-80. 3. de Blacam C, Momoh AO, Colakoglu S, et al. Evaluation of clinical outcomes and aesthetic results after autologous fat grafting for contour deformities of the reconstructed breast. Plast Reconstr Surg. 2011 Nov;128(5):411e-418e. 4. Delay E, Garson S, Tousson G, Sinna R. Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J. 2009 Sep-Oct;29(5):360-76. 5. Fraser JK, Hedrick MH, Cohen SR. Oncologic risks of autologous fat grafting to the breast. Aesthet Surg J. 2011 Jan;31(1):68-75. 6. Gentile P, Di Pasquali C, Bocchini I, et al. Breast Reconstruction With Autologous Fat Graft Mixed With Platelet-Rich Plasma. Surg Innov. 2012 Sep 10. Breast Reconstructive Surgery Apr 15 17

7. Gentile P, Orlandi A, Scioli MG, et al..a comparative translational study: the combined use of enhanced stromal vascular fraction and platelet-rich plasma improves fat grafting maintenance in breast reconstruction. Stem Cells Transl Med. 2012 Apr;1(4):341-51. 8. Hyakusoku H, Ogawa R, Ono S, Ishii N, Hirakawa K. Complications after autologous fat injection to the breast. Plast Reconstr Surg. 2009 Jan;123(1):360-70. 9. Illouz YG, Sterodimas A. Autologous fat transplantation to the breast: a personal technique with 25 years of experience. Aesthetic Plast Surg. 2009 Sep;33(5):706-15. 10. Irani Y, Casanova D, Amar E. Autologous fat grafting in radiated tissue prior to breast prosthetic reconstruction: is the technique reliable? Ann Chir Plast Esthet. 2012 Feb;57(1):59-66. 11. Khouri RK, Eisenmann-Klein M, Cardoso E, et al. Brava and autologous fat transfer is a safe and effective breast augmentation alternative: results of a 6- year, 81-patient, prospective multicenter study. Plast Reconstr Surg. 2012 May;129(5):1173-87. 12. Kijima Y, Yoshinaka H, Funasako Y, et al. Immediate breast reconstruction using autologous free dermal fat grafts provides better cosmetic results for patients with upper inner cancerous lesions. Surg Today. 2011 Apr;41(4):477-89. 13. Lohsiriwat V, Curigliano G, Rietjens M, et al. Autologous fat transplantation in patients with breast cancer: "silencing" or "fueling" cancer recurrence? Breast. 2011 Aug;20(4):351-7. 14. Losken A, Pinell XA, Sikoro K, et al. Autologous fat grafting in secondary breast reconstruction. Ann Plast Surg. 2011 May;66(5):518-22. 15. Mestak O, Zimovjanová M. Breast reconstruction by autologous fat transfer. Rozhl Chir. 2012 Jul;91(7):373-7. 16. Missana MC, Laurent I, Barreau L, Balleyguier C. Autologous fat transfer in reconstructive breast surgery: indications, technique and results. Eur J Surg Oncol. 2007 Aug;33(6):685-90. 17. Parikh RP, Doren EL, Mooney B, et al. Differentiating fat necrosis from recurrent malignancy in fat-grafted breasts: an imaging classification system to guide management. Plast Reconstr Surg. 2012 Oct;130(4):761-72. 18. Pérez-Cano R, Vranckx JJ, Lasso JM, et al. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. Eur J Surg Oncol. 2012 May;38(5):382-9. 19. Rigotti G, Marchi A, Stringhini P, et al. Determining the oncological risk of autologous lipoaspirate grafting for post-mastectomy breast reconstruction. Aesthetic Plast Surg. 2010 Aug;34(4):475-80. 20. Salgarello M, Visconti G, Barone-Adesi L. Fat grafting and breast reconstruction with implant: another option for irradiated breast cancer patients. Plast Reconstr Surg. 2012 Feb;129(2):317-29. 21. Sarfati I, Ihrai T, Duvernay A, et al. Autologous fat grafting to the postmastectomy irradiated chest wall prior to breast implant reconstruction: a series of 68 patients. Ann Chir Plast Esthet. 2013 Feb;58(1):35-40. 22. Sarfati I, Ihrai T, Kaufman G, et al. Adipose-tissue grafting to the postmastectomy irradiated chest wall: preparing the ground for implant reconstruction. J Plast Reconstr Aesthet Surg. 2011 Sep;64(9):1161-6. 23. Schultz I, Lindegren A, Wickman M. Improved shape and consistency after lipofilling of the breast: patients' evaluation of the outcome. J Plast Surg Hand Surg. 2012 Apr;46(2):85-90. 24. Seth AK, Hirsch EM, Kim JY, Fine NA. Long-term outcomes following fat grafting in prosthetic breast reconstruction: a comparative analysis. Plast Reconstr Surg. 2012 Nov;130(5):984-90. Breast Reconstructive Surgery Apr 15 18

25. Zheng DN, Li QF, Lei H, et al. Autologous fat grafting to the breast for cosmetic enhancement: experience in 66 patients with long-term follow up. J Plast Reconstr Aesthet Surg. 2008 Jul;61(7):792-8. References Update February 2013 1. Hayes Technology Brief on FlexHD Acellular Dermis (Musculoskeletal Transplant Foundation) for Breast Reconstruction August 2012 2. Buck DW 2nd, Heyer K, DiBardino D, Bethke K, Kim JY. Acellular dermis-assisted breast reconstruction with the use of crescentric tissue expansion: a functional cosmetic analysis of 40 consecutive patients. Aesthet Surg J. 2010a;30(2):194-200. 3. Lanier ST, Wang ED, Chen JJ, et al. The effect of acellular dermal matrix use on complication rates in tissue expander/implant breast reconstruction. Ann Plast Surg. 2010;64(5):674-678 References - Update December 2009 1. Becker S, Saint-Cyr M, Wong C, et al. AlloDerm versus DermaMatrix in immediate expander-based breast reconstruction: a preliminary comparison of complication profiles and material compliance. Plast Reconstr Surg. 2009;123(1):1-6. 2. Bindingnavele V, Gaon M, Ota KS, et al. Use of acellular cadaveric dermis and tissue expansion in postmastectomy breast reconstruction. J Plast Reconstr Aesthet Surg. 2007;60(11):1214-8 3. Breuing KH, Colwell AS. Immediate Breast Tissue Expander-Implant Reconstruction With Inferolateral AlloDerm Hammock and Postoperative Radiation: A Preliminary Report. Eplasty. 2009 May 15;9:e16 4. Breuing KH, Colwell AS. Inferolateral AlloDerm hammock for implant coverage in breast reconstruction. Ann Plast Surg. 2007 Sep;59(3):250-5. 5. Breuing KH, Warren SM. Immediate bilateral breast reconstruction with implants and inferolateral AlloDerm slings. Ann Plast Surg. 2005 Sep;55(3):232-9. 6. Derderian CA, Karp NS, Choi M. Wise-pattern breast reconstruction: modification using AlloDerm and a vascularized dermal-subcutaneous pedicle. Ann Plast Surg. 2009 May;62(5):528-32 7. Gamboa-Bobadilla GM. Implant breast reconstruction using acellular dermal matrix. Ann Plast Surg. 2006;56(1):22-25. 8. Garramone CE, Lam B. Use of AlloDerm in primary nipple reconstruction to improve long-term nipple projection. Plast Reconstr Surg. 2007 May;119(6):1663-8. 9. Glasberg SB, D'Amico RA. Use of regenerative human acellular tissue (AlloDerm) to reconstruct the abdominal wall following pedicle TRAM flap breast reconstruction surgery. Plast Reconstr Surg. 2006 Jul;118(1):8-15 10. Lifecell. Alloderm. Available at: http://www.lifecell.com/alloderm-regenerativetissue-matrix/311/ 11. Namnoum JD. Expander/implant reconstruction with AlloDerm: recent experience. Plast Reconstr Surg. 2009 Aug;124(2):387-94 12. Preminger BA, McCarthy CM, Hu QY, et al. The influence of AlloDerm on expander dynamics and complications in the setting of immediate tissue expander/implant reconstruction: a matched-cohort study. Ann Plast Surg. 2008;60(5):510-513. 13. Salzberg CA. Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm). Ann Plast Surg. 2006;57(1):1-5. 14. Spear SL, Parikh PM, Reisin E, Menon NG. Acellular dermis-assisted breast reconstruction. Aesthetic Plast Surg. 2008;32(3):418-425. 15. Zienowicz RJ, Karacaoglu E. Implant-based breast reconstruction with allograft. Plast Reconstr Surg. 2007 Aug;120(2):373-81 Breast Reconstructive Surgery Apr 15 19

References Initial 1. Wilkins EG, Atisha DM. Breast reconstruction in women with breast cancer. UpToDate. February 13, 2009. 2. Yueh JH, Sumner BA, Slavin A, et al. Impact of Regional Referral Centers for Microsurgical Breast Reconstruction: The New England Perforator Flap Program Experience. J Am Coll Surg. 2009; ;208:246 254. 3. Beier JP, Horch RE, Bach AD, et al. Breast Reconstruction after Breast-Cancer Surgery. New England Journal of Medicine. Volume 360:418-421, January 22, 2009, Number 4. 4. Hyakusoku H, Ogawa R, Ono S, et al. Complications after Autologous Fat Injection to the Breast. Plastic and Reconstructive Surgery: January 2009 - Volume 123 - Issue 1 - pp 360-370. 5. Reuben BC, Manwaring J, Neumayer LA, et al. Recent trends and predictors in immediate breast reconstruction after mastectomy in the United States. The American Journal of Surgery (2009) 198, 237-243. 6. Hayes Health Technology Brief. AlloDerm Regenerative Tissue Matrix (LifeCell Corp.) for Postmastectomy Breast Reconstruction. May 13, 2008. 7. Hayes Search & Summary. Superficial Inferior Epigastric Artery (SIEA) Flap Procedure for Breast Reconstruction. October 2, 2008. 8. Andrades P, Fix RJ, Danilla S, et al. Ischemic complications in pedicle, free, and muscle sparing transverse rectus abdominis myocutaneous flaps for breast reconstruction. Ann Plast Surg. 2008 May;60(5):562-7. 9. Djohan R, Gage E, Bernard S. Breast reconstruction options following mastectomy. Cleve Clin J Med. 2008 Mar;75 Suppl 1:S17-23. 10. DellaCroce FJ. Breast Reconstruction, Perforator Flap. emedicine. February 1, 2007. Available at: http://www.emedicine.com/plastic/topic545.htm. 11. Binder JP. Breast reconstruction by DIEP free flap: a 30 cases experience. Ann Chir Plast Esthet - 01-AUG-2008; 53(4): 318-24 12. Hayes Search & Summary. Inferior Gluteal Artery Perforator (IGAP) Flap Procedure for Postmastectomy Breast Reconstruction. September 8, 2007. 13. Townsend: Sabiston Textbook of Surgery, 18th ed. Chest Wall Reconstruction. 2007. 14. Bajaj AK, Chevray PM, Chang DW. Comparison of donor-site complications and functional outcomes in free muscle-sparing TRAM flap and free DIEP flap breast reconstruction. Plast Reconstr Surg 2006; 117:737. 15. Alderman AK, Kuzon WM Jr, Wilkins EG. A two-year prospective analysis of trunk function in TRAM breast reconstructions. Plast Reconstr Surg. 2006 Jun;117(7):2131-8. 16. Deutsch MF, Robb GL, Talavera F, et al. A. Breast Reconstruction, Other Free Flaps. Updated 2005 June. Available at: http://www.emedicine.com/plastic/topic140.htm 17. Zenn MR, Robb GL, Talavera F, et al. Breast Reconstruction: TRAM, Unipedicled. Updated May 2005. Available at: http://www.emedicine.com/plastic/topic141.htm 18. Gill PS, Hunt JP, Guerra AB, et al. A 10-year retrospective review of 758 DIEP flaps for breast reconstruction. Plast Reconstr Surg. 2004 Apr 1;113(4):1153-60. 19. Craigie JE, Allen RJ, DellaCroce FJ, et al. Autogenous breast reconstruction with the deep inferior epigastric perforator flap. Clin Plast Surg. Jul 2003;30(3):359-69. 20. Celik N. Anteriolateral thigh flap for postmastectomy breast reconstruction. Seminars in Plastic Surgery. 2002;16:45-52. 21. Nahabedian MY, Dooley W, Singh N, et al. Contour abnormalities of the abdomen after breast reconstruction with abdominal flaps: The role of muscle preservation. Plast Reconstr Surg. 2002;109(1):91-101. Breast Reconstructive Surgery Apr 15 20

22. Yap LH, Whiten SC, Forster A, et al. The anatomical and neurophysiological basis of the sensate free TRAM and DIEP flaps. Br J Plast Surg. 2002;55(1):35-45. 23. Guzzetti T, Thione A. Successful breast reconstruction with a perforator to deep inferior epigastric perforator flap. Ann Plast Surg. 2001;46(6):641-643. 24. Kroll SS. Fat necrosis in free transverse rectus abdominis myocutaneous and deep inferior epigastric perforator flaps. Plast Reconstr Surg. 2000;106(3):576-583. 25. Keller A. The deep inferior epigastric perforator free flap for breast reconstruction. Ann Plast Surg. 2001;46(5):474-480. 26. Futter CM, Webster MH, Hagen S, et al. A retrospective comparison of abdominal muscle strength following breast reconstruction with a free TRAM or DIEP flap. Br J Plast Surg 2000; 53:578. 27. Allen RJ, Dupin CL, DellaCroce FJ. Perforator flaps in breast reconstruction. Perspectives in Plastic Surgery. 2000;14:37-54. 28. Your Rights After A Mastectomy. Women's Health & Cancer Rights Act of 1998. http://www.dol.gov/ebsa/publications/whcra.html 29. CMS. Centers for Medicare & Medicaid. Health Insurance Reform for Employers. Overview. 30. CMS. Centers for Medicare & Medicaid. Women's Health & Cancer Rights Act. 31. CMS. Centers for Medicare & Medicaid. NCD for Breast Reconstruction Following Mastectomy (140.2). 1/1/1997. Important Notice General Purpose. Health Net's National Medical Policies (the "Policies") are developed to assist Health Net in administering plan benefits and determining whether a particular procedure, drug, service or supply is medically necessary. The Policies are based upon a review of the available clinical information including clinical outcome studies in the peer-reviewed published medical literature, regulatory status of the drug or device, evidence-based guidelines of governmental bodies, and evidence-based guidelines and positions of select national health professional organizations. Coverage determinations are made on a case-by-case basis and are subject to all of the terms, conditions, limitations, and exclusions of the member's contract, including medical necessity requirements. Health Net may use the Policies to determine whether under the facts and circumstances of a particular case, the proposed procedure, drug, service or supply is medically necessary. The conclusion that a procedure, drug, service or supply is medically necessary does not constitute coverage. The member's contract defines which procedure, drug, service or supply is covered, excluded, limited, or subject to dollar caps. The policy provides for clearly written, reasonable and current criteria that have been approved by Health Net s National Medical Advisory Council (MAC). The clinical criteria and medical policies provide guidelines for determining the medical necessity criteria for specific procedures, equipment, and services. In order to be eligible, all services must be medically necessary and otherwise defined in the member's benefits contract as described this "Important Notice" disclaimer. In all cases, final benefit determinations are based on the applicable contract language. To the extent there are any conflicts between medical policy guidelines and applicable contract language, the contract language prevails. Medical policy is not intended to override the policy that defines the member s benefits, nor is it intended to dictate to providers how to practice medicine. Policy Effective Date and Defined Terms. The date of posting is not the effective date of the Policy. The Policy is effective as of the date determined by Health Net. All policies are subject to applicable legal and regulatory mandates and requirements for prior notification. If there is a discrepancy between the policy effective date and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. * In some states, prior notice or posting on the website is required before a policy is deemed effective. For information regarding the effective dates of Policies, contact your provider representative. The Policies do not include definitions. All terms are defined by Health Net. For information regarding the definitions of terms used in the Policies, contact your provider representative. Policy Amendment without Notice. Health Net reserves the right to amend the Policies without notice to providers or Members. In some states, prior notice or website posting is required before an amendment is deemed effective. No Medical Advice. The Policies do not constitute medical advice. Health Net does not provide or recommend treatment to members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Breast Reconstructive Surgery Apr 15 21

No Authorization or Guarantee of Coverage. The Policies do not constitute authorization or guarantee of coverage of particular procedure, drug, service or supply. Members and providers should refer to the Member contract to determine if exclusions, limitations, and dollar caps apply to a particular procedure, drug, service or supply. Policy Limitation: Member s Contract Controls Coverage Determinations. Statutory Notice to Members: The materials provided to you are guidelines used by this plan to authorize, modify, or deny care for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract. The determination of coverage for a particular procedure, drug, service or supply is not based upon the Policies, but rather is subject to the facts of the individual clinical case, terms and conditions of the member s contract, and requirements of applicable laws and regulations. The contract language contains specific terms and conditions, including pre-existing conditions, limitations, exclusions, benefit maximums, eligibility, and other relevant terms and conditions of coverage. In the event the Member s contract (also known as the benefit contract, coverage document, or evidence of coverage) conflicts with the Policies, the Member s contract shall govern. The Policies do not replace or amend the Member s contract. Policy Limitation: Legal and Regulatory Mandates and Requirements The determinations of coverage for a particular procedure, drug, service or supply is subject to applicable legal and regulatory mandates and requirements. If there is a discrepancy between the Policies and legal mandates and regulatory requirements, the requirements of law and regulation shall govern. Reconstructive Surgery CA Health and Safety Code 1367.63 requires health care service plans to cover reconstructive surgery. Reconstructive surgery means surgery performed to correct or repair abnormal structures of the body caused by congenital defects, developmental abnormalities, trauma, infection, tumors, or disease to do either of the following: (1) To improve function or (2) To create a normal appearance, to the extent possible. Reconstructive surgery does not mean cosmetic surgery," which is surgery performed to alter or reshape normal structures of the body in order to improve appearance. Requests for reconstructive surgery may be denied, if the proposed procedure offers only a minimal improvement in the appearance of the enrollee, in accordance with the standard of care as practiced by physicians specializing in reconstructive surgery. Reconstructive Surgery after Mastectomy California Health and Safety Code 1367.6 requires treatment for breast cancer to cover prosthetic devices or reconstructive surgery to restore and achieve symmetry for the patient incident to a mastectomy. Coverage for prosthetic devices and reconstructive surgery shall be subject to the co-payment, or deductible and coinsurance conditions, that are applicable to the mastectomy and all other terms and conditions applicable to other benefits. "Mastectomy" means the removal of all or part of the breast for medically necessary reasons, as determined by a licensed physician and surgeon. Policy Limitations: Medicare and Medicaid Policies specifically developed to assist Health Net in administering Medicare or Medicaid plan benefits and determining coverage for a particular procedure, drug, service or supply for Medicare or Medicaid members shall not be construed to apply to any other Health Net plans and members. The Policies shall not be interpreted to limit the benefits afforded Medicare and Medicaid members by law and regulation. Breast Reconstructive Surgery Apr 15 22