The success of breast conservation protocols BREAST. Implant Reconstruction in Breast Cancer Patients Treated with Radiation Therapy

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1 BREAST Implant Reconstruction in Breast Cancer Patients Treated with Radiation Therapy Jeffrey A. Ascherman, M.D. Matthew M. Hanasono, M.D. Martin I. Newman, M.D. Duncan B. Hughes, M.D. New York, N.Y. Background: Implant reconstruction in breast cancer patients treated with radiation therapy is controversial. Prior studies are limited by older prosthetic devices, reconstructive techniques, and radiation therapy protocols. Methods: A retrospective review was performed of patients who underwent tissue expansion and implant breast reconstruction performed by a single surgeon after mastectomy for breast cancer from 1996 to Complications and aesthetic results were compared between patients who received radiation therapy and those who did not. Results: A total of 104 patients (123 breasts) who underwent mastectomy and implant breast reconstruction were included in the study. Twenty-seven patients (27 breasts) received either premastectomy or postmastectomy radiation therapy for breast cancer. All patients who received radiation therapy did so before completion of their implant reconstruction. Complications ultimately requiring prosthetic device removal or replacement, as well as total complications (those requiring prosthetic removal or replacement and those not requiring prosthetic removal or replacement), were more frequent in breasts that received radiation than breasts that did not (18.5 percent versus 4.2 percent for complications requiring prosthetic removal or replacement, p 0.025, and 40.7 percent versus 16.7 percent for total complications, p 0.01). Breast symmetry was significantly better in patients who did not receive radiation compared with those who did (p 0.01). Conclusions: Implant breast reconstruction in patients who receive radiation therapy is possible but associated with more frequent complications and decreased aesthetic results. However, the present results compare favorably to those reported in prior studies. Improved results in the present study may be attributable to the use of newer prostheses, staged breast reconstruction with initial tissue expansion, total muscular coverage of the implant, and modern radiation therapy protocols. (Plast. Reconstr. Surg. 117: 359, 2006.) The success of breast conservation protocols with lumpectomy and local radiation therapy has led to a dramatic increase in the use of radiation for breast cancer during the past two decades. 1 3 As a result, greater numbers of patients with a history of breast irradiation are presenting to plastic surgeons for breast reconstruction following mastectomy for recurrent or residual breast cancer. In addition, the use of radiation therapy as an adjuvant treatment to From the Department of Surgery, Division of Plastic Surgery, Columbia University Medical Center. Received for publication August 5, 2004; revised August 1, Presented at the 73rd Annual Scientific Meeting of the American Society of Plastic Surgeons, the Plastic Surgery Educational Foundation, and the American Society of Maxillofacial Surgeons, in Philadelphia, Pennsylvania, October 9 to 13, Copyright 2006 by the American Society of Plastic Surgeons DOI: /01.prs mastectomy has also increased. The need or potential need for postsurgical radiation to the reconstructed breast mound should therefore be considered when the method of breast reconstruction is being selected. 3,4 However, the selection of autologous versus implant breast reconstruction after mastectomy in patients who have received or are expected to receive radiation treatment for breast cancer is controversial. Several authors have suggested that aesthetic results with autologous tissue breast reconstruction are superior and that complication rates are lower. 5 9 However, complication rates are still higher in radiated breasts, even with autologous tissue, and some patients prefer reconstruction with implants, while others are not candidates for autologous tissue reconstruction. 7,10,11 In addition, it is not always possible to predict which patients will need postoperative radiation therapy before mastectomy. Spear and Maxwell

2 Plastic and Reconstructive Surgery February 2006 have suggested that breast reconstruction using tissue expansion followed by permanent implant placement with modern prostheses and contemporary radiation therapy protocols may result in lower complication rates and improved aesthetic outcomes in patients who receive radiation than reported in previous series. The present study was undertaken to critically analyze the outcome of breast reconstruction using newer tissue expanders, permanent implants, and placement techniques in recently treated patients who have received radiation therapy for breast cancer before the completion of their implant breast reconstruction. The goal of this study was to provide the plastic surgeon with relevant data needed to appropriately counsel patients in their choice between autologous and implant breast reconstruction, as well as to identify risk factors for complications or suboptimal implant reconstruction results. PATIENTS AND METHODS Surgical Technique All patients underwent a staged breast reconstruction. Tissue expansion was first performed with a textured, anatomically shaped expansion device, either McGhan 133 series (Inamed, Santa Barbara, Calif.) tissue expanders (including 133, 133LV, 133MV, and 133FV) or Mentor 1400 and 2500 series (Mentor, Santa Barbara, Calif.) tissue expanders. McGhan tissue expansion devices were exchanged after the appropriate volume was achieved (see Tissue Expansion Protocol, below) for either McGhan 68, 168, 363, or 468 series salinefilled devices or McGhan 10 or 153 series silicone gel-filled devices; Mentor devices were used as permanent implants after port removal. Tissue expanders were placed submuscularly in a space created beneath the pectoralis major and above the pectoralis minor and chest wall. Laterally, the tissue expanders were placed beneath the anterior insertions of the serratus anterior muscle. Before tissue expander placement, the cavity was pulse lavaged with bacitracin irrigation. The muscle pocket was closed using interrupted Polysorb (glycolide/lactide copolymer; United States Surgical Corp., Norwalk, Conn.) absorbable braided sutures. A single, 10-mm flat Jackson-Pratt drain was placed and brought through the skin via a separate incision in the lateral inframammary fold crease. The skin and subcutaneous tissues were closed in layers using absorbable Polysorb sutures. Tissue Expansion Protocol Expansion was initiated approximately 1 month postoperatively and continued at intervals of 2 to 3 weeks until completion. In patients undergoing chemotherapy, expansion was performed within 3 days before or 3 days after chemotherapy to avoid expansion during periods in which the white blood cell count was maximally suppressed. Expansion was either completed before or held during radiation therapy to avoid changes in breast volume and surface area that would affect the designated radiation field. In all patients, radiation therapy was completed before the final surgery for either expander removal (McGhan prostheses) and placement of a permanent implant or removal of the expander port (Mentor prostheses). This final surgery was usually performed 1 to 2 months after the completion of expansion. Patient Data A retrospective review was conducted of consecutive patients who underwent tissue expansion and implant breast reconstruction following mastectomy performed by a single surgeon, the senior author (J.A.A.). Patients who received radiation before total mastectomy (i.e., patients undergoing salvage mastectomy after failed lumpectomy combined with radiation therapy) were identified. A second group of patients who received radiation following total mastectomy with adjuvant radiation therapy for high-stage disease or close/positive surgical margins was also identified. Three patients who had received mantle radiation for Hodgkin s disease before mastectomy for breast cancer were excluded from the analysis. Symmetry was graded by the surgeon on a three-point scale: unsatisfactory, satisfactory, and optimal. Patient satisfaction with the final breast reconstruction was rated using a three-point scale: dissatisfied, partially satisfied, or fully satisfied. The control group was composed of all patients treated during the study period who underwent tissue expansion and implant reconstruction following total mastectomy but did not receive radiation therapy. Data were analyzed using the chi-square test, the Student t test, or the Mann- Whitney U test where appropriate. A p value less than 0.05 was considered significant. As indicated in Tables 1 to 3, some statistics apply to patients (n 104) and others apply to breasts (n 123). The p values that apply to breasts may therefore not be precise for data where two breasts in the same patient are not independent of each other, such as with regard to pulmonary embolism. 360

3 Volume 117, Number 2 Implant Reconstruction after Radiation Table 1. Demographics and Reconstruction Information Radiation No Radiation p No. of patients (104 total) No. of breasts (123 total) No. of bilateral mastectomy and implants 6 (22%) 13 (17%) NS* Average age, years (SD) (range, 32-75) 52.0 (11.8) 52.7 (11.6) NS Chemotherapy Patients (n 56) 23 (85%) 33 (43%) 0.001* Breasts (n 69) 22 (81%) 47 (49%) 0.01* Smokers Patients (n 14) 3 (11%) 11 (14%) NS* Breasts (n 16) 3 (11%) 13 (14%) NS* Diabetes Patients (n 6) 1 (4%) 5 (6%) NS* Breasts (n 7) 1 (4%) 6 (6%) NS* Average follow-up, months (SD) (range, 1-36) 14.2 (8.6) 16.0 (13.4) NS Tissue expanders Mentor (16 devices) 7 (26%) 9 (9%) 0.025* McGhan (107 devices) 20 (74%) 87 (91%) 0.025* Average tissue expander volume, ml (SD) 449 (237) 402 (171) NS Average permanent implant volume, ml (SD) 398 (230) 363 (136) NS NS, not significant. *Chi-square test. Student t test. Mentor 1400 and 2500 series tissue expanders (Mentor, Santa Barbara, Calif.) with removable remote filling port. McGhan 133, 133 LV, 133MV, and 133FV series tissue expanders (Inamed, Santa Barbara, Calif.). Range of manufacturer s maximum recommended expander fill volumes is 150 to 850 cc. Range of permanent implant volumes is 120 to 825 cc. Table 2. Outcomes in Breasts Receiving Radiation versus Breasts That Did Not Radiated (n 27) Controls (n 96) p* Complications resulting in removal or replacement 5 (18.5%) 4 (4.2%) Infection 1 (4.0%) 0 (0%) NS Extrusion 4 (14.8%) 0 (0%) Port malfunction 0 (0%) 1 (1.0%) NS Capsular contracture 0 (0%) 1 (1.0%) NS Pain 0 (0%) 1 (1.0%) NS Rippling 0 (0%) 1 (1.0%) NS Complications not resulting in removal or replacement 6 (22.2%) 12 (12.5%) NS Pulmonary embolism 0 (0%) 2 (2.1%) NS Seroma 4 (14.8%) 7 (7.3%) NS Skin necrosis 1 (3.7%) 2 (2.1%) NS Cellulitis 1 (3.7%) 0 (0%) NS Pain 0 (0%) 1 (1.0%) NS Total complications 11 (40.7%) 16 (16.7%) 0.01 Symmetry (1-3, SD) 2.1 (0.7) 2.6 (0.5) 0.01 Patient satisfaction (1-3, SD) 2.4 (0.8) 2.7 (0.6) NS NS, not significant. *Comparison of radiated breasts and controls (breasts that did not receive radiation). Chi-square test. Symmetry was graded on a three-point scale, with 1 unsatisfactory, 2 satisfactory, and 3 optimal. Mann-Whitney U test, two-tailed. Patient satisfaction was graded on a three-point scale, with 1 dissatisfied, 2 partially satisfied, and 3 fully satisfied. RESULTS A total of 107 consecutive female patients who underwent 127 postmastectomy breast reconstructions with implants were identified over a 7-year period, from July of 1996 to June of Three of these patients had received mantle radiation for Hodgkin s disease and were excluded from the study, leaving the 104 patients who underwent 123 breast reconstructions with implants (85 unilateral and 19 bilateral) who comprise this study group (Table 1). Twenty-seven patients received radiation therapy for breast cancer, compared with 77 who did not receive radiation therapy. Of these 123 reconstructions, 120 (97.6 percent) were immediate and three (2.4 percent) were delayed (13 months to 22 years). None of the patients with delayed reconstructions received radiation treatment. 361

4 Plastic and Reconstructive Surgery February 2006 Table 3. Complications in Patients as a Function of Tobacco Use, Diabetes Mellitus, and Chemotherapy No. Complications* p Smokers 14 2 (14%) NS Nonsmokers (26%) Diabetics 6 2 (33%) NS Nondiabetics (24%) Chemotherapy (33%) 0.01 No chemotherapy 49 8 (16%) NS, not significant. *Total complications (complications requiring prosthetic device removal or replacement and complications not requiring prosthetic device removal or replacement). Chi-square comparison of complications in smokers versus nonsmokers, diabetics versus nondiabetics, and patients who received chemotherapy versus patients who did not receive chemotherapy. Chi-square test. There were no statistically significant differences in the proportion of smokers, diabetics, or patients who received bilateral mastectomy and breast reconstruction between the group that received radiation therapy and the control group (Table 1). There was a significant difference in the proportion of patients who received chemotherapy (excluding tamoxifen) for breast cancer, with a greater proportion of radiated patients also receiving chemotherapy (p 0.001). There were no significant differences in the average tissue expander size (recommended maximum expansion volume) or average permanent implant size (actual final implant volume) between the two groups. Of the 27 breasts that received radiation, eight received radiation before mastectomy and 19 received radiation after mastectomy. Of these latter 19, radiation therapy was finished before complete expansion in 15 and after expansion but before permanent implant placement (McGhan devices) or port removal (Mentor devices) in four. All patients received radiation before the exchange of a tissue expander for a permanent implant, or before removal of the implant port. A significantly greater proportion of patients receiving radiation therapy were reconstructed with the Mentor 1400 and 2500 series prostheses, which served as both tissue expanders and permanent implants after the remote port was removed (26 percent radiated versus 9 percent not radiated, p 0.025) (Table 1). Outcome data are presented in Table 2. Extrusion requiring implant or tissue expander removal or replacement was the only complication significantly more common in patients who received radiation therapy (p 0.001), although the number of events in each category of complication was small. To increase statistical power, complications were grouped into those that ultimately required removal or replacement of a tissue expander or implant and those that did not. Complications resulting in prosthetic device removal or replacement included infection that did not resolve with antibiotic treatment alone, tissue expander or implant extrusion, tissue expander port malfunction, severe (grade IV) capsular contracture, intractable pain, and severe rippling. Complications that did not require prosthetic device removal or replacement included pulmonary embolism, seroma, skin edge necrosis, superficial skin cellulitis successfully treated with antibiotics alone, and prolonged postoperative discomfort. There was a significantly higher incidence of complications requiring removal or replacement of a tissue expander or implant in the radiated group, which included patients radiated before and after mastectomy (18.5 percent, versus 4.2 percent in controls, p 0.025). Total complications, which included complications requiring prosthetic device removal or replacement and those that did not, were also significantly higher in breasts receiving radiation (40.7 percent, versus 16.7 percent in controls, p 0.01). There was no statistically significant difference in the proportion of radiated and nonradiated patients experiencing complications that did not require implant removal or replacement (22.2 percent for radiated breasts versus 12.5 percent for controls). Breast symmetry scores were significantly higher in the group that did not receive radiation (p 0.01), whereas the difference in patient satisfaction between radiated and control patients was not statistically significant. When the timing of radiation therapy was taken into account by comparing breast reconstructions in patients who received radiation before mastectomy to those in patients who received radiation after mastectomy and tissue expander placement but before implant exchange or port removal, no statistically significant differences were observed in the number of complications requiring tissue expander or implant removal, complications not requiring tissue expander or implant removal, or total complications. Differences in symmetry ratings and patient satisfaction scores were also not statistically significant between patients who received radiation before mastectomy and patients who received radiation after mastectomy and tissue expander placement. Breast reconstructions performed with tissue expander placement followed by exchange of the expander for a permanent implant after the completion of expansion and breast reconstructions with devices with remote ports that were subsequently removed after expansion was complete 362

5 Volume 117, Number 2 Implant Reconstruction after Radiation (Mentor 1400 and 2500 series devices) were analyzed together, because both reconstructions require a similar expansion process and both require two operative procedures. When Mentor and McGhan tissue expansion devices were compared separately, there were no statistically significant differences in the rates of complications requiring tissue expander or implant removal, complications not requiring tissue expander or implant removal, or total complications. Tobacco usage, diabetes mellitus, and chemotherapy were examined as independent risk factors (Table 3). Tobacco usage and diabetes mellitus were not associated with a statistically significant increase in complication rates. However, a statistically higher percentage of complications did occur in patients who received chemotherapy compared with those who did not (33 percent versus 16 percent, p 0.01). Of note, as mentioned previously and listed in Table 1, a statistically significantly greater proportion of patients who received chemotherapy also received radiation therapy compared with chemotherapy patients who did not receive radiation. DISCUSSION Several authors have recommended against implant placement in patients who have received or are expected to receive radiation therapy. 7 9 Forman et al. 8 reported their experience from 1976 to 1993 with tissue expansion and implant reconstruction in nine patients (10 breasts) who underwent salvage mastectomy for recurrent breast cancer initially treated with lumpectomy and radiation. They reported two patients who experienced difficultly with expansion and poor positioning that required revision surgery, one patient who developed an infection that required implant removal, and two patients with grade III or IV capsular contracture who required revision surgery. They cited use of outdated implants and radiation therapy protocols as limitations of their study. Evans et al. 7 reported five complications that resulted in implant removal or replacement, including severe capsular contracture, implant exposure, and implant rupture, in 12 patients (14 implants) who received radiotherapy before or after breast reconstruction treated over a 19-year period, from 1975 to They also noticed an increased incidence of complications (10 complications) in 25 patients who received radiation and had implants placed beneath transverse rectus abdominis musculocutaneous or latissimus dorsi flaps. They advocated autogenous breast reconstruction alone in patients who either had received or were about to receive radiotherapy. Vandeweyer and Deraemaecker 9 presented a series of six out of 124 immediate breast reconstructions with implants performed in patients who received postoperative radiation therapy. All of their patients developed grade III or IV capsular contracture, compared with 3.4 percent of their control group. All implants were placed without initial tissue expansion and without muscular coverage of the implants laterally beneath the serratus anterior. It was not mentioned how many of these patients required revision surgery. Spear and Onyewu 3 reported their experience with postmastectomy breast reconstruction performed from 1990 to 1997 in patients who received radiation for breast cancer. As in the present study, their breast reconstruction technique involved initial tissue expansion, because this had previously been demonstrated to be superior to single-stage implant reconstruction. 13 In their series of 40 breast reconstructions, of which 33 were initially performed without a simultaneous latissimus dorsi or rectus abdominis muscle or myocutaneous flap and are comparable to our series, 12 complications resulting in prosthetic device removal or replacement were noted. These complications included severe capsular contracture, implant extrusion, and threatened extrusion requiring reoperation. Unlike the present study, their most common complication was capsular contracture requiring revision surgery (nine of 40 patients). It is difficult to compare the findings of these prior studies to those presented here because of differences in reporting both subjective and objective data. The decision to group complications based on whether they resulted in prosthetic device removal or replacement provides an objective criterion that facilitates comparison of our experience with the experiences of prior investigators. The rate of complications requiring tissue expander or implant removal or replacement in patients receiving radiation observed in the present study (18.5 percent) compares favorably to the rates reported in previous series. This may be attributed to differences in technique, such as staged reconstruction that includes initial tissue expansion or total muscular coverage, newer prosthetics, or differences in radiotherapy protocols. Cordeiro et al. 14 recently presented a series of 81 patients who received radiation therapy after undergoing implant breast reconstruction. Their series includes nine patients (11 percent) who experienced complications resulting in removal or replacement of their implant. However, patients in their study differ from those in the 363

6 Plastic and Reconstructive Surgery February 2006 present study in that all of their patients received radiation after the permanent implant was placed, whereas all patients in our study received radiation before placement of the permanent implant (McGhan devices) or removal of the implant port (Mentor devices). One can conclude from comparing these two studies that radiation therapy is best given after the completion of implant breast reconstruction, but this is not always possible. Strengths of the present study include consistency of surgical technique and postoperative management, including the protocol for expansion during chemotherapy and radiation therapy. Although not documented, it can be presumed that since patients were treated over a relatively short time period, the oncologic treatment methods, including oncologic surgery, chemotherapy, and radiation therapy, were kept relatively constant compared with previous studies that analyzed data from patients over a study period as long as 19 years. The present study includes reconstruction with modern expansion and implant devices rather than with a broad range of implants that are no longer in current use. One possible confounding issue is that multiple radiation therapy centers were used to treat the patients who received radiation therapy, and thus radiation treatment protocols were not standardized. Data for the dosage of radiation given were not consistently available, and thus a doseresponse relationship could not be evaluated by the present study. Future studies that do examine the relationship between radiation dosages and implant complications will be helpful. The delivery of radiation therapy to the postmastectomy chest wall in the presence of partially or totally full tissue expanders is also controversial in some centers. Some radiation oncologists are concerned about the possibility of interference from the expansion device resulting in impaired delivery of radiation to the internal mammary nodes, or the possibility of increased tangential field radiation of lung and cardiac tissues when increasing the delivery of radiation to breasts in which an implant mound is present. 15 Others believe that the presence of a tissue expander results in negligible attenuation of radiation delivered based on dosimetric measurements. 16,17 A recent ex vivo study also suggests that metallic ports that are integrated into some tissue expansion devices do not result in a significant amount of scatter around the port, and as a result, there is no evidence of consistently increased radiation doses at the surface of the expander. 18 The need for postmastectomy radiation therapy cannot always be predicted accurately before surgery. Current recommendations for postmastectomy radiation include advanced primary tumors or four or more positive lymph nodes, based on recent guidelines from the American Society for Therapeutic Radiology and Oncology and the American Society of Clinical Oncology. 19,20 The inability to accurately stage breast cancer, particularly with regard to nodal metastases, presents a challenge for surgeons in preoperative decision making and patient counseling with regard to planning autologous or implant breast reconstruction. Kronowitz and Robb 21 believe that implants should be avoided if at all possible in patients who will receive postoperative radiation and have introduced an algorithm for staging breast reconstruction if postoperative radiation is likely. They recommend placement of a tissue expander to preserve the skin envelope in patients in whom there is a reasonable likelihood but not a certainty that radiation therapy will be needed postoperatively. The tissue expander is deflated before radiation therapy then re-expanded after radiation therapy before delayed breast reconstruction with autologous tissue. If radiation therapy is not performed, the patient remains a candidate for either implant or autologous reconstruction. In every case of breast reconstruction with implants, and particularly in patients with a history of radiation treatment to the breast or in whom postoperative radiation therapy is likely, informed consent from the patient is critical. As mentioned, it is often not possible to predict which patients will need postoperative radiation nor the specific type of radiotherapy that will be needed (e.g., radiation therapy for positive margins, radiation for lymphatic invasion, and so on). Every patient, therefore, needs to be appropriately counseled preoperatively regarding the adverse effects of possible postoperative radiation on breast reconstruction. The patient should be informed of the increased risks, particularly for extrusion, and of the possibility of decreased symmetry associated with implant reconstruction in irradiated breasts when compared with implant reconstruction in breasts without radiation or autologous reconstruction. During the expansion process in patients who have previously received radiation therapy, we recommend observing the skin flaps carefully for excessive tension, soft-tissue atrophy, telangiectasia formation, and color changes. Should the flaps develop signs of compromise during the expansion, we recommend slowing down the expansion process, either with decreased expansion volumes or less frequent expansions. If necessary, ceasing expansion before achieving the desired volume is also an option when performing reconstruction with tissue ex- 364

7 Volume 117, Number 2 Implant Reconstruction after Radiation pansion and implants. The possibility of not fully achieving the desired breast size due to decreased tolerance of radiated tissues should also be discussed with the patient preoperatively. The majority of radiated patients in our series received radiation before completion of expansion. If signs of skin flap compromise were observed when expansion was resumed, expansion was halted for time periods of up to 2 to 3 months, allowing the flaps to accommodate to the increased tension. An increased complication rate compared with patients who received radiation after expansion was complete but before exchange for permanent implant, or port removal in the case of Mentor 1400 and 2500 series devices, was not observed in this group. CONCLUSIONS Outcome data must be periodically re-evaluated, as both oncologic treatment and breast reconstruction materials and techniques continue to evolve. Data from our series demonstrate a lower rate of complications and better aesthetic results in patients who had not received radiation therapy before implant breast reconstruction compared with those who did receive radiation therapy before completing implant reconstruction. Although the literature and our own experience suggest that breast reconstruction with autologous tissue is preferred when possible in patients who have previously been radiated, for technical, medical, or personal reasons, not every patient is an appropriate candidate for reconstruction with autologous tissue. In addition, the need for postoperative radiation treatment cannot always be evaluated accurately before mastectomy. Furthermore, comparison of the current series to previous studies suggests that staged reconstruction with initial tissue expansion, complete coverage of the implant with muscle, and modern radiation therapy protocols do contribute to a reduction in complications when implant reconstruction is undertaken in radiated patients. Jeffrey A. Ascherman, M.D. Columbia University Medical Center 161 Fort Washington Avenue New York, N.Y jaa7@columbia.edu REFERENCES 1. Fisher, B., Anderson, S., Redmond, C., et al. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N. Engl. J. Med. 333: 1456, Overgaard, M., Hansen, P. S., Overgaard, J., et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N. Engl. J. Med. 337: 949, Spear, S. L., and Onyewu, C. Staged breast reconstruction with saline-filled implants in the irradiated breast: Recent trends and therapeutic implications. Plast. Reconstr. Surg. 105: 930, Ragaz, J., Jackson, S. M., Le, N., et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N. Engl. J. Med. 337: 956, Dickson, M. G., and Sharpe, D. T. The complications of tissue expansion in breast reconstruction: A review of 75 cases. Br. J. Plast. Surg. 40: 629, Von Smitten, K., and Sundell, B. The impact of adjuvant radiotherapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy for breast cancer. Eur. J. Surg. Oncol. 18: 119, Evans, G. R., Schusterman, M. A., Kroll, S. S., et al. Reconstruction and the radiated breast: Is there a role for implants? Plast. Reconstr. Surg. 96: 1111, Forman, D. L., Chiu, J., Restifo, R. J., Ward, B. A., Haffty, B., and Ariyan, S. Breast reconstruction in previously irradiated patients using tissue expanders and implants: A potentially unfavorable result. Ann. Plast. Surg. 40: 360, Vandeweyer, E., and Deraemaecker, R. Radiation therapy after immediate breast reconstruction with implants. Plast. Reconstr. Surg. 106: 56, Hartrampf, C. R., Jr., Bennett, G. K. Autogenous tissue reconstruction in the mastectomy patient: A critical review of 300 patients. Ann. Surg. 205: 508, Kroll, S. S., Schusterman, M. A., Reece, G. P., Miller, M. J., and Smith, B. Breast reconstruction with myocutaneous flaps in previously irradiated patients. Plast. Reconstr. Surg. 93: 460, Spear, S. L., and Maxwell, G. P. Reconstruction and the radiated breast: Is there a role for implants? (Discussion) Plast. Reconstr. Surg. 96: 1116, Spear, S. L., and Majidian, A. Immediate breast reconstruction in two stages using textured integrated-valve tissue expanders and breast implants: A retrospective review of 171 consecutive breast reconstructions from 1989 to Plast. Reconstr. Surg. 101: 53, Cordeiro, P. G., Pusic, A. L., Disa, J. J., McCormick, B., and VanZee, K. Irradiation after immediate tissue expander/ implant breast reconstruction: Outcomes, complications, aesthetic results, and satisfaction among 156 patients. Plast. Reconstr. Surg. 113: 877, Buchholz, T. A., Kronowitz, S. J., and Kuerer, H. M. Immediate breast reconstruction after skin-sparing mastectomy for treatment of advanced breast cancer: Radiation oncology considerations. Ann. Surg. Oncol. 9: 820, Jackson, W. B., Goldson, A. L., and Staud, C. Postoperative irradiation following immediate breast reconstruction using a temporary tissue expander. J. Natl. Med. Assoc. 86: 538, Shankar, R. A., Nibhanupudy, J. R., Sridhar, R., Ashton, C., and Goldson, A. L. Immediate breast reconstruction: Impact on radiation management. J. Natl. Med. Assoc. 95: 286, Moni, J., Graves-Ditman, M., Cederna, P., et al. Dosimetry around metallic ports in tissue expanders in patient receiving postmastectomy radiation therapy: An ex vivo evaluation. Med. Dosimetry 29: 49, Harris, J., Halpin-Murphy, P. S., McNeese, M., et al. Consensus statement on postmastectomy radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 44: 989, Recht, A., Edge, S. B., Solin, L. J., et al. Postmastectomy radiotherapy: Clinical practice guidelines of the American Society of Clinical Oncology. J. Clin. Oncol. 19: 1539, Kronowitz, S. J., and Robb, G. L. Breast reconstruction with postmastectomy radiation therapy: Current issues. Plast. Reconstr. Surg. 114: 950,