Clinical study of the feasibility, complications, and cosmetic outcomes of immediate autologous fat grafting during breast-conserving surgery for early-stage breast cancer in China.

BACKGROUND: The resection of tumors in small breasts or in areas such as the upper and inner parts of the breast may have disabling cosmetic results. Tumor resection reduces the volume of the breast and may result in asymmetry or distortion of the nipple-areola complex. Autologous fat transfer/grafting has been shown to be a reliable technique for improving these poor cosmetic results. This study aimed to evaluate the feasibility, complications, and cosmetic outcomes of immediate autologous fat grafting during breast-conserving surgery (BCS) in Chinese patients with early-stage breast cancer. METHODS: This retrospective study included 58 patients with early breast cancer treated by the same surgical team from October 2016 to May 2017. The patients were divided into two groups: BCS with lipofilling (experiment group, n=30) and BCS without lipofilling (control group, n=28). All patients received the recommended breast cancer treatment with complementary radiotherapy. The follow-up period after the completion of radiotherapy ranged from 36-44 months. The resected and grafted volumes, complications, esthetic results, patient satisfaction, and recurrence rate within 3 years were compared between the groups. RESULTS: The average resected and grafted volumes in the lipofilled group were 47 and 74 mL, respectively, with only one seroma and no other complications. Regarding physician evaluation, BCS with lipofilling resulted in better cosmetic outcomes than BCS without lipofilling (33% versus 15%, respectively). Poor responses occurred in only 7% of patients with lipofilling, compared with 15% without lipofilling. Regarding patient self-evaluation, Breast-Q scores including patient satisfaction with their breasts and psychosocial well-being, were significantly higher in patients who received lipofilling compared with non-lipofilled patients. Regional recurrence occurred in one patient (case 21) (3.7%) in the lipofilling group and systemic recurrence occurred in one patient (case 12) (3.8%) in the control group. CONCLUSIONS: Immediate autologous fat grafting is a promising, effective, and convenient technique for partial breast reconstruction after BCS, with potentially higher levels of patient and physician satisfaction compared with traditional BCS. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ONN-17010514. Registered 24 January 2017.

Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study.

BACKGROUND: Fat grafting has been widely indicated for postmastectomy and postlumpectomy breast reconstruction. The literature emphasizes the clinical efficacy of fat grafting, but experimental studies raise important questions about the recurrence risk because of the stimulation of remaining cancer cells by progenitor or adult adipocytes. Because breast conservative treatment provides a higher risk of residual cancer cells in the breast tissue compared with mastectomy, the authors set up a matched case-control study of fat grafting versus no fat grafting after breast conservative treatment. METHODS: The authors collected data from 322 consecutive patients operated on for a primary invasive breast cancer who subsequently underwent fat grafting for breast reshaping from 2006 to 2013. All patients were free of recurrence before fat grafting. For each patient, the authors selected one patient with similar characteristics who did not undergo fat grafting. RESULTS: After a mean follow-up of 4.6 years (range, 0.1 to 10.2 years) after fat grafting, or a corresponding time for controls, the authors observed no difference in the incidence of local events (fat grafting, n = 14; controls, n = 16; p = 0.49), axillary nodes metastasis (fat grafting, n = 3; controls, n = 6; p = 0.23), distant metastases (fat grafting, n = 14; controls, n = 15; p = 0.67), or contralateral breast cancer (fat grafting, n = 4; controls, n = 4; p = 0.51). CONCLUSION: Fat grafting seems to be a safe procedure after breast conservative treatment for breast cancer patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Total Breast Reconstruction With Fat Grafting After Internal Expansion and Expander Removal.

INTRODUCTION: The development of fat grafting techniques both in cosmetic and reconstructive breast surgery has highlighted the need to recreate a breast mound using similar tissues and without visible scarring. Our technique combines skin expansion by conventional expanders and breast volume replacement by serial fat grafting and final expander removal. MATERIALS AND METHODS: Fat grafting had been performed both by Coleman technique and Bodyjet system. We report a series of 12 cases enrolled between 2008 and 2013. Each case has been presented in this article, focusing on received treatment, observed complications, and results. RESULTS: Satisfactory results were observed 6 months after the last session in most of the concluded reconstructions with a low complication rate.

Conservative mastectomy versus nipple-sparing mastectomy: preliminary considerations of oncological safety on 30 patients not receiving intra-operative radiotherapy.

BACKGROUND: For several years, there has been broad consensus that nipple-sparing mastectomy is a safe surgical treatment for breast cancer. However, the technique is associated with a relatively high risk of local recurrence (LR) behind the nipple-areola complex (NAC). It is for this reason that some years ago we introduced intraoperative radiotherapy with electrons (ELIOT) targeted specifically to the NAC to reduce the probability of recurrence there. However, in some cases we preferred to avoid ELIOT when the NAC appears to have a poor blood supply to ensuring the best chance of NAC survival. METHODS: From July 2003 to April 2010 at our institute, 30 patients received nipple-sparing mastectomy but neither ELIOT nor external radiotherapy, as the surgeon considered the irradiation would markedly compromise the chances of NAC survival, because of sub-optimal vascularization. RESULTS: After a median follow-up of 5 years there were no LRs with minor post-operative complications. CONCLUSIONS: This preliminary case series indicates that the presented technique can be a safe procedure in breast cancer surgery, but requires greater number of cases and a longer follow-up to confirm the oncological safety.

Technique for Minimizing Donor-site Morbidity after Pedicled TRAM-Flap Breast Reconstruction: Outcomes by a Single Surgeon's Experience.

BACKGROUND: Breast reconstruction with pedicled transverse rectus abdominis myocutaneous (TRAM) flap can result in significant abdominal wall donor-site morbidity. We present our technique of transversely dividing the anterior fascia and rectus abdominis combined with reinforcement above the arcuate line for closure of the anterior abdominal wall defect to prevent contour deformities performed by a single senior surgeon and compare these results with those of our prior series. METHODS: We described our new technique of closure of the abdominal wall defect and retrospectively performed the comparison between the results of pedicled TRAM flaps using the new closure technique and those of 420 pedicled TRAM flaps from our 2003 publication in terms of abdominal bulging and hernia. RESULTS: Sixty-seven pedicled TRAM flaps in 65 patients were compared with 420 pedicled TRAM flaps of the 2003 series. The new technique was associated with 5 partial TRAM flap necroses (8%). There was no total flap loss with the new technique. The median follow-up period was 13 months (range, 4-36 months). There were no instances of abdominal hernia and bulge during follow-up in the new series. Compared with the previous 2003 series, the new technique was superior in terms of occurrence of abdominal wall hernia or bulging. CONCLUSIONS: We are still performing pedicled TRAM flap for autologous breast reconstruction. Using the technique of transversely dividing the anterior fascia and rectus abdominis combined with reinforcement above the arcuate line can reduce the occurrence of abdominal bulging and hernia.

Evaluation of Lipofilling Safety in Elderly Patients with Breast Cancer.

BACKGROUND: Lipofilling is widely used in breast reconstruction after mastectomy with reconstruction or breast conserving surgery in patients with breast cancer. The aim of this study is focused on complications associated with lipofilling in elderly breast cancer patients with breast defects after breast conserving surgery or reconstruction. METHODS: A total of 137 patients older than 60 years who underwent 153 lipofilling procedures were included. All patients had undergone breast lipofilling using Coleman's technique. Estimated breast defect volume, lipofilling volume, and complications after lipofilling were obtained for analysis. RESULTS: Most patients (67%) had only 1 lipofilling procedure. The median lipofilling volume to breast defect volume ratio was 1.5. No severe complications were found after treatment. Liponecrosis was detected in 10 of 153 breasts (7%) or 9 of 137 patients within 2 weeks after lipofilling and required surgical drainage in 2. No local recurrences were noted. CONCLUSIONS: The incidence of liponecrosis after lipofilling in elderly patients was relatively high, requiring surgical drainage in some cases. As a rough guide, the lipofilling volume should not exceed 1.5 times the defect volume, and close postoperative follow-up within the first 2 weeks is suggested for these patients.

Safety of Lipofilling in Patients with Breast Cancer.

Lipotransfer represents a technical revolution in plastic surgery and is increasingly used worldwide. Although known for several decades, lipofilling has only recently found widespread use in patients with breast cancer to improve the results of breast reconstructions and to correct deformities after conservative treatment. The plastic surgery literature underlines the technique's versatility and the quality of the results, showing lipofilling as an effective cosmetic procedure and proposing it as a safe, neutral biological material that is able to restore the body contour. Several studies underline the power of transferred fat to regenerate blood supply in skin disorders following radiotherapy.

Outcome of Immediate Breast Reconstruction in Patients With Nonendocrine-Responsive Breast Cancer: A Monoinstitutional Case-Control Study.

BACKGROUND: The long-term prognostic relevance of immediate breast reconstruction (IBR) for patients with estrogen receptor (ER)-negative breast cancer (BC) has not been fully elucidated. PATIENTS AND METHODS: The study population included 444 patients with ER-negative BC who underwent total mastectomy with complete axillary dissection between 1995 and 2006, 339 patients with and 105 patients without IBR. The median follow-up was 8.6 years. RESULTS: Patients treated with IBR were younger (P < .001) and received surgery more recently (2003-2006: 53.1% vs. 39%; P = .0003), and had a lower number of metastatic lymph nodes (>4 lymph nodes involvement: 29.5% vs. 45.7%; P = .0026), smaller tumors (pT1/2: 15% vs. 26.7%; P = .0007), and lower extent of peritumoral vascular invasion (15.9% vs. 21%; P = .032). The 5-year cumulative incidence of locoregional recurrence was 7.1% in the IBR group and 11.7% in the no IBR group (hazard ratio [HR], 0.81; P = .63). The 5-year cumulative incidence of distant metastases were similar in the 2 groups (P = .79). The 5-year overall and disease-free survival proportions were 79.9% versus 69.5% (HR, 1.11; P = .67) and 66.6% versus 54.1% (HR, 1.04; P = .83) in the IBR group and no IBR group, respectively. CONCLUSION: IBR intervention does not significantly affect prognosis of ER-negative BC patients.

Poly implant prothèse asymmetrical anatomical breast implants: a product recall study.

BACKGROUND: In 2010 high rupture rates were unexpectedly found among prostheses produced by the French manufacturer Poly Implant Prothèse. Since then, several studies have been performed concerning the round implants, but there are still few data available on anatomical implants. METHODS: From 2003 to 2006 Poly Implant Prothèse implants were employed at the authors' institute for immediate or delayed reconstruction after mastectomy. All implants were anatomical and asymmetrical. In November of 2010, the authors began offering free consultation with a plastic surgeon and radiologist. Demographic data, type of reconstruction, implant lifespan, indications for implant removal, and rupture rate were recorded. RESULTS: A total of 578 women underwent postmastectomy immediate or delayed reconstruction with 658 Poly Implant Prothèse implants from 2003 to 2006 at the authors' institute. The authors explanted 409 of 443 prostheses, and 34 were explanted at other centers. Eighty-nine patients died and 120 are alive with the implants in place. The mean implant lifespan was 57.5 months, 76 ruptured implants were explanted (18.5 percent), and in 22 cases (5.4 percent), leakage of silicone gel was detected. CONCLUSIONS: Poly Implant Prothèse implant failure is to be ascribed to shell structure, although the primary safety issue concerned the gel (an industrial-grade and low-cohesive silicone). These issues produce the known rupture rates in the manufacturer's round implants. The authors' use of only anatomical and asymmetrical implants, with their more cohesive silicone gel and more rigid shell allowing a stable form and projection along with a natural feel and touch, probably reduces the rupture rate and silicone spread, although these events remain unacceptably high compared with similar products of other brands. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Does immediate breast reconstruction after mastectomy and neoadjuvant chemotherapy influence the outcome of patients with non-endocrine responsive breast cancer?

BACKGROUND/AIM: In breast cancer (BC) patients, breast surgery followed by immediate breast reconstruction (IBR) might favour recurrences and metastases due to extensive surgical manipulation. We retrospectively investigated whether IBR after mastectomy and neoadjuvant chemotherapy (NT) influenced the outcome in patients with early and locally advanced oestrogen receptor (ER)-negative BC. PATIENTS AND METHODS: Between 1995 and 2006, 133 BC patients received NT followed by total mastectomy, 59 of whom underwent IBR. Patients receiving IBR (IBR group) were compared to patients who did not receive IBR (no-IBR group) over a prolonged median follow-up time (8.2 years). RESULTS: Patients receiving IBR were on average younger than patients not receiving IBR (p<0.001). The percentage of patients with positive clinical nodal status (cN) was 19% in the IBR group and 7% in no-IBR group (p=0.036), whereas patients without IBR were more frequently diagnosed as clinical T4 (59% vs. 15%, p<0.001). The 5-year cumulative incidence of locoregional recurrences were 14% in the no-IBR group and 21% in the IBR group. The hazard of locoregional events, adjusted for age, clinical T and cN, was significantly greater in the IBR group than in the no-IBR group (hazard ratio (HR)=2.77, p=0.045). The 5-year cumulative incidences of distant metastases were similar in the two groups (p=0.414). CONCLUSION: IBR following total mastectomy in patients with ER-negative disease after NT is associated with a worse rate of local relapses. More insight in mechanisms of wound healing and extent of surgery is required to further investigate this observation.

Obesity, proinflammatory mediators, adipose tissue progenitors, and breast cancer.

PURPOSE OF REVIEW: There is emerging evidence that obesity is associated with an increase in the incidence, severity, and mortality from different types of cancer, including postmenopausal breast cancer. Here, we discuss the role of white adipose tissue (WAT) cells and of related soluble factors in the local and metastatic growth of this neoplastic disease. Moreover, we discuss the recent increase in the use of WAT-derived progenitor cells in breast cancer patients to enhance the quality of breast reconstruction and the related risks. RECENT FINDINGS: In several murine models, WAT cells and progenitors were found to have cooperative roles in promoting local breast cancer. Moreover, they were found to contribute to adipocytes and pericytes supporting the cancer vasculature, and stimulated the metastatic progression of breast cancer. There are some clinically retrospective data showing a significant increase in the frequency of intraepithelial neoplasia in patients who received a lipofilling procedure for breast reconstruction compared with controls. SUMMARY: Preclinical models and clinical studies are urgently needed to investigate how to inhibit the tumor-promoting activity of WAT cells and progenitors. The risks associated with the use of WAT cells for breast reconstructions should be better investigated retrospectively and prospectively.

Nipple sparing mastectomy: does breast morphological factor related to necrotic complications?

BACKGROUND: Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated. METHOD: We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients. RESULTS: Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk. CONCLUSIONS: Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.

Appropriate use of magnetic resonance imaging and ultrasound to detect early silicone gel breast implant rupture in postmastectomy reconstruction.

BACKGROUND: Implant rupture is one of the most important sequelae of breast reconstruction after mastectomy. The primary aim of this study was to compare magnetic resonance imaging and ultrasound evaluation with intraoperative findings and provide a reliable description of the occurrence of each radiological sign. METHODS: The authors prospectively recruited a consecutive series of 102 postmastectomy patients requiring implant change for aesthetic purposes. Magnetic resonance imaging and ultrasound evaluation results were compared with intraoperative findings. Sensitivity, specificity, positive predictive value, negative predictive value, and the overall accuracy of magnetic resonance imaging and ultrasound in detecting ruptured implants were calculated, along with their corresponding 95 percent confidence intervals. RESULTS: Magnetic resonance imaging performs better than ultrasound for diagnosis of breast implant rupture, with overall accuracies of 94 and 72 percent, respectively. The negative predictive value of ultrasound was 85 percent, meaning that in the case of negative ultrasound findings, magnetic resonance imaging may be avoided. Teardrop sign and water droplets are the most common findings on magnetic resonance imaging. CONCLUSIONS: Magnetic resonance imaging should be considered the method of choice for investigating silicone gel implant rupture in postmastectomy patients, and the standardization of magnetic resonance imaging criteria may improve magnetic resonance imaging accuracy. The authors therefore suggest a strategy of screening asymptomatic women with ultrasound every year and with magnetic resonance imaging every 5 years. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer.

Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.

Free nipple graft technique to correct nipple and areola malposition after breast procedures.

SUMMARY: Secondary correction of nipple areola complex (NAC) malposition represents a major concern after breast reconstructive procedures. It is frequently requested by patients complaining about asymmetric areolas impairing the whole reconstructive procedure and asking for improved cosmetic outcomes. Several methods have been described to achieve a good symmetry between the 2 areolas, either natural or reconstructed. We describe our correction technique with free NAC graft. A total of 16 patients were treated with free NAC grafts between April 2010 and April 2013 at the European Institute of Oncology, Milan, Italy. This series focused on the surgical technique and its postoperative outcomes. Three cases of partial graft loss (18%) were observed in the postoperative period. No total NAC necrosis occurred. No infection was observed. All the complications were managed with a conservative treatment, not requiring any further surgery. NAC malposition following breast reconstructive procedures can be corrected using the technique of free NAC graft with reliable and satisfactory results.

Do clinicopathological features of the cancer patient relate with nipple areolar complex necrosis in nipple-sparing mastectomy?

BACKGROUND: The selections of nipple-sparing mastectomy (NSM) are principally depending on oncologic indication and oncologic safety. The main complication of NSM is nipple areolar complex (NAC) necrosis, and it is usually related to surgical technique. However, the patients' clinicopathological factors should be also considered. METHOD: We retrospectively reviewed 934 consecutive NSM patients during 2002-2007 at the European Institute of Oncology, Milan, Italy. We identified a group of patient who had NAC excision because of NAC necrosis and compared this group with those who had successful NAC conservation. We analyzed the association between the risk of NAC necrosis and the clinicopathological features of the patients. RESULTS: Among 934 NSM, 772 were invasive cancers and 162 were in situ cancers. Of the 934, 40 NAC (4.2%) were removed during the postoperative period because of necrosis. When we considered age, BMI, menopausal status, smoking status, tumor size, axillary lymph node status, in situ or invasive cancer histology, presence of extensive situ component, grading, estrogen receptor, progesterone receptor, HER2/neu overexpression, Ki-67 proliferative index, and peritumoral vascular invasion, no association was observed between patients' clinicopathological features and NAC necrosis incidence. CONCLUSIONS: In our study, clinicopathological features have no significant impact on necrosis complication in therapeutic NSMs. Positive retroareolar margin is the risk of necrosis. Further studies are required to avoid bias due to the different cancer treatments such as different reconstruction techniques and intraoperative radiation protocols. The correlation between breast morphology and NAC necrosis should also be investigated in the future.

Risk of locoregional recurrence in patients with false-negative frozen section or close margins of retroareolar specimen in nipple-sparing mastectomy.

BACKGROUND: Our purpose was to evaluate the locoregional recurrence (LRR) of patients with false-negative, frozen-section or close margins of retroareolar specimen in nipple-sparing mastectomy (NSM) procedure. METHODS: From 2002-2008, we recruited patients who had atypia or presence of cancer cells in definitive histology of retroareolar tissue despite of absence of tumor cell in intraoperative retroareolar frozen section. We also included the close margin cases defined as the presence of tumor cells at the first frozen section, but after deeper core out of retroareolar tissue were revealed free of malignancy. The incidence of LRR and NAC recurrence were reported, and the factors associated were analyzed. RESULTS: Of 948 NSM procedures, there were 88 false-negative, frozen-sections and 10 close margin cases. The 5-year cumulative incidence of LRR and NAC recurrence was 11.2 % (10/98 patients) and 2.4 % (2/98 patients), respectively. Analyzing the definitive results of retroareolar tissue, the 5-year cumulative incidence of LRR was 42.9 % (n = 4) for atypia, 10 % (n = 2) for lobular carcinoma in situ (LCIS), 10 % (n = 1) for close margins, 8.7 % (n = 3) for ductal carcinoma in situ (DCIS), and 0 % for invasive carcinoma. In situ carcinoma as a primary tumor was a significant predictor of NAC recurrence (P < 0.01). CONCLUSIONS: Despite a high reliability of frozen section, there is still a minority of false-negative results. Nevertheless, the LRR is considerably low. This fact suggests the possibility of preservation of the NAC after discussion with the patient.