The Modified Frailty Index Predicts Major Complications in Oncoplastic Reduction Mammoplasty.

BACKGROUND: An important component of preoperative counseling and patient selection involves surgical risk stratification. There are many tools developed to predict surgical complications. The Modified Frailty Index (mFI) calculates risk based on the following five elements: hypertension, chronic obstructive pulmonary disease, congestive heart failure, diabetes, and functional status. Recent literature demonstrates the efficacy of the mFI across multiple surgical disciplines. We elected to investigate its utility in oncoplastic reductions (OCR). METHODS: A retrospective review of all patients with breast cancer who underwent OCR from 1998 to 2020 was queried from a prospectively maintained database. Patient demographics, comorbidities, and surgical details were reviewed. The mFI was computed for each patient. The primary clinical outcome was the development of complications. RESULTS: 547 patients were included in the study cohort. The average age was 55 and the average body mass index was 33.5. The overall complication rate was 19% (n = 105) and the major complication rate was 9% (n = 49). Higher frailty scores were significantly associated with the development of major complications (P < 0.05). mFI scores of 0 had a major complication rate of 5.7%; scores of 1, 13%; and scores of 2, 15.1%. The relative risk of a major complication in patients with elevated mFI (>0) was 2.2. Age, body mass index, and resection weights were not associated with complications (P = 0.15, P = 0.87, and P = 0.30 respectively) on continuous analysis. CONCLUSIONS: Elevated mFI scores are associated with an increased major complication profile in patients who are undergoing OCR. Hypertension and diabetes are the most common comorbidities in our population, and this tool may assist with preoperative counseling and risk stratification. Benefits of this risk assessment tool include its ease of calculation and brevity. Our study is the first to demonstrate its utility in OCR; however, further study in high-risk patients would strengthen the applicability of this frailty index.

Impact of Oncoplastic Surgery on Oncologic Outcomes in Patients with Breast Cancer.

Background: For patients with breast cancer, oncoplastic surgery (OPS) serves as a valuable technique that allows for immediate reconstruction at the time of resection. While the aim of OPS is to improve breast cosmesis, it is critical to ensure OPS does not negatively impact appropriate cancer treatment. Methods: Based on current literature, this study provides a broad overview on the potential oncologic advantages of OPS for patients diagnosed with breast cancer. Results: OPS has been shown to be a safe and reliable approach with oncologic advantages. More specifically, OPS broadens the indications for breast conservation therapy (BCT); allows for a more generous margin of resection, thus decreasing rates of re-excision; and provides the opportunity to sample additional breast tissue, which may detect occult disease. Reduction mammaplasty may also decrease the risk for developing breast cancer. Importantly, in the era of multimodality therapy, long-term oncologic outcomes and postoperative surveillance algorithms appear to be similar when comparing patients who undergo OPS and BCT. Conclusions: For patients with breast cancer, oncoplastic surgery has emerged as a valuable technique to improve breast cosmesis while achieving optimal oncologic outcomes. As the landscape of breast oncology continues to evolve, it is critical for a multidisciplinary team to be involved to guide management and reconstructive strategies.

Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Time to Radiation after Oncoplastic Reduction versus After Lumpectomy.

Prior studies contrasting oncoplastic reduction (OCR) to traditional lumpectomy have validated oncoplastic reduction surgery with similar survival and oncological outcomes. The purpose of this study was to evaluate if there was a significant difference in the time to initiation of radiation therapy after OCR in comparison with the standard breast-conserving therapy (lumpectomy). Methods: The patients included were from a database of breast cancer patients who all underwent postoperative adjuvant radiation after either OCR or lumpectomy at a single institution between 2003 and 2020. Patients who experienced delays in radiation for nonsurgical reasons were excluded. Comparisons were made between the groups in the time to radiation and complication rates. Results: A total of 487 patients underwent breast-conserving therapy, with 220 having undergone OCR and 267 lumpectomy patients. There was no significant difference in days to radiation between patient cohorts (60.5 OCR, 56.2 lumpectomy, P = 0.059). There was a significant difference in the number of complications between OCR and lumpectomy patients (20.4% OCR, 2.2% lumpectomy, P < 0.001). However, of patients who had complications, there was no significant difference in the number of days to radiation (74.3 OCR, 69.3 lumpectomy, P = 0.732). Conclusions: Compared with lumpectomy, OCR was not associated with an increased time to radiation but was associated with higher complications. Statistical analysis did not reveal surgical technique or complications to be independent, significant predictors of increased time to radiation. Surgeons should be aware that although complications may remain higher in OCR, this does not necessarily translate to delays in radiation.

A Discordant Pattern of Uptake on 68 Ga-PSMA PET/CT Versus 18 F-Fluciclovine PET/CT in Radiation-Induced Hepatitis : Implications for Early Postradiotherapy Imaging-Based Response Assessment.

ABSTRACT: A 62-year-old woman with right-sided invasive lobular breast carcinoma completed external beam radiotherapy 6 weeks before undergoing a 68 Ga-PSMA PET/CT and 18 F-fluciclovine PET/CT scan as part of an ongoing clinical trial (NCT04750473) assessing the performance of these molecular imaging modalities in invasive lobular breast carcinoma. The 68 Ga-PSMA PET/CT demonstrated a band-like area of increased radiotracer uptake in the dome of the right lobe of the liver anteriorly, whereas 18 F-fluciclovine PET/CT done a day later revealed photopenia in the corresponding area of the liver. The external beam radiotherapy plan confirmed that the radiotherapy field overlaid the region of the hepatic discordant radiotracer uptake on the PET/CT scans.

Outcomes of the same-day discharge following mastectomy before, during and after COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The majority of patients undergoing mastectomy before the COVID-19 pandemic were admitted for 23-h observation to the hospital. Indications for observation included drain care education, pain control and observation for possible early surgical complications. This study compared the rates of outpatient mastectomy before, during, and after the COVID-19 pandemic and indirectly evaluated the safety of same-day discharge. METHODS: We retrospectively analyzed patients undergoing mastectomy using Current Procedural Terminology code 19303. RESULTS: A total of 357 patients were included: 113 were treated pre-COVID-19, 82 patients during COVID-19 and 162 post-COVID-19. The rate of outpatient mastectomies tripled during the pandemic from 17% to 51% (p < 0.001); after the pandemic remain high at 48%. The rate of bilateral mastectomies decreased during the pandemic to 30% from 48% prepandemic (p = 0.015). Pectoralis muscle block utilization increased during the COVID-19 period from 36% to 59% (p = 0.002). No difference in complication rates, including surgical site infections, hematomas, and readmissions, pre and during COVID. CONCLUSIONS: The rate of outpatient mastectomy increased during the COVID-19 pandemic. During this timeframe, perioperative complications did not increase, suggesting the safety of this practice. After the pandemic, the rate of outpatient mastectomy continued to be significantly higher than pre-COVID.

A Tale of 3 Tracers: Contrasting Uptake Patterns of 18F-Fluciclovine, 68Ga-PSMA, and 18F-FDG in the Uterus and Adnexa.

ABSTRACT: A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.

Inhibition of NADPH Oxidase-ROS Signal using Hyaluronic Acid Nanoparticles for Overcoming Radioresistance in Cancer Therapy.

Upregulation of NADPH oxidases (NOXs) in cancer cells leads to chronic increase in intracellular reactive oxygen species (ROS) and adaptation to a high ROS level for cell survival and, thereby, low sensitivity to radiotherapy. To overcome resistance to radiotherapy, we have developed a bioactive and CD44 targeted hyaluronic acid nanoparticle encapsulated with an NOX inhibitor, GKT831 (HANP/GKT831). We found that HANP/GKT831 had stronger inhibitory effects on ROS generation and cell proliferation than that of GKT831 alone in cancer cells. Systemic delivery of HANP/GKT831 led to the targeted accumulation in breast cancer patient derived xenograft (PDX) tumors in nude mice. Importantly, the combination of systemic delivery of HANP/GKT831 with a low dose of local radiotherapy significantly enhanced tumor growth inhibition in breast cancer PDX models. Our results showed that HANP/GKT831 primed tumor cells to radiation-induced DNA damage and cell death by downregulation of DNA repair function and oncogenic signal pathways.

The Impact Oncoplastic Reduction Has on Long-Term Recurrence in Breast Conservation Therapy.

BACKGROUND: The use of oncoplastic reduction techniques have many proven benefits over lumpectomy alone in the management of women with breast cancer. The impact it has on tumor recurrence is unclear. The purpose of this review was to evaluate the incidence of recurrence in patients who underwent oncoplastic reduction techniques compared to lumpectomy alone. METHODS: A prospectively maintained database of patients at Emory Hospital who underwent oncoplastic reduction techniques at the time of tumor resection was queried. These patients were compared to a series of patients who had lumpectomy alone over a similar period. For inclusion in the study, patients were at least 10 years since the time of the tumor resection. The main outcome of interest was tumor recurrence. RESULTS: There were 97 patients in the lumpectomy-only group and 95 patients in the oncoplastic reduction group, with an average follow-up of 7.8 years and 8.5 years, respectively. Patients in the oncoplastic group were younger (lumpectomy only, 61.4 years; oncoplastic reduction, 51.6 years; p < 0.001) and had larger tumors (lumpectomy only, 1.1 cm; oncoplastic reduction, 1.6 cm; p < 0.001). Local recurrence was 13 percent in the lumpectomy-only group and 9 percent in the oncoplastic reduction group (p = 0.34), and overall recurrence rates were similar (lumpectomy only, 15 percent; oncoplastic reduction, 24 percent; p = 0.13). Overall, surgical intervention (lumpectomy alone versus oncoplastic reduction) was not associated with local recurrence or any recurrence on univariate and multivariate analyses. CONCLUSION: Despite the oncoplastic reduction patients having a higher risk of recurrence and a more generous tumor resection, the long-term recurrence rates were equivalent when compared to breast-conserving therapy alone. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Incidence and Outcomes of Completion Mastectomy following Oncoplastic Reduction: A Case Series.

Background: Patients occasionally need completion mastectomy (CM) following oncoplastic reduction for various reasons necessitating definitive reconstructive techniques. The purpose of this study was to evaluate those patients who required CM following oncoplastic reduction and evaluate indications, technique, and outcomes. Methods: Patients who underwent a completion mastectomy at some time point following the oncoplastic reduction were identified. Factors that influenced CM and additional reconstruction were analyzed. All statistical analysis was conducted using the IBM SPSS Statistics 27.0 (IBM Corp.). Results: A total of 29 patients (5.3%) underwent CM during the study period with an average follow-up of 3 years since the original procedure. The most common reasons were positive margins (20/29, 69.0%) and recurrence (8/29, 27.6%). Twenty-two had reconstructive procedures (75.9%) and seven did not (24.1%). The patients who underwent CM and reconstruction were significantly younger (49.2 years) than those who had no reconstruction (64.3 years, P = 0.004). The most common type of reconstruction was transverse rectus abdominis myocutaneous (TRAM)/deep inferior epigastric perforator (DIEP) flap (12/22, 54.5%), followed by latissimus (6/22, 27.3%) and tissue expander (3/22, 13.6%). The complication rate in the CM group was 24% (N = 7/29), which included two seromas (6.9%), followed by infection, fat necrosis, mastectomy skin necrosis, and donor site necrosis (3.4% each). Conclusions: Completion mastectomy is indicated typically for positive margins or recurrence. Reconstruction is performed more frequently in younger patients, with the TRAM/DIEP flap and latissimus dorsi reconstruction being the most common technique.

Preoperative Body Image Factors Are Associated with Complications after Breast Reconstruction.

BACKGROUND: Psychological factors are broadly understood to contribute to overall health, but their contribution to wound healing is less well defined. Limited data exist on the association of preoperative psychological factors such as body image and postoperative complications. The present study analyzed the association between preoperative body image factors and postoperative complications following breast reconstruction. METHODS: This was a prospective cohort study of 302 breast cancer patients undergoing breast reconstruction from 2011 to 2015. All patients completed the BREAST-Q; demographics, surgical details, and postoperative complications were recorded. The association of body image factors by means of the BREAST-Q and postoperative complications was analyzed. RESULTS: On univariate analysis, patients who reported lower preoperative satisfaction with how they appeared in the mirror unclothed, or felt less self-confident or attractive, were significantly more likely to develop an infection postoperatively. Preoperative satisfaction scores were not associated with complications when analyzed in a multivariate fashion. On binomial logistic regression analysis, after controlling for age, body mass index, reconstruction technique, and use of radiotherapy, patients who reported less preoperative satisfaction with how comfortably bras fit or how they appeared in a mirror unclothed were at an increased risk for delayed wound healing. CONCLUSIONS: Patients with lower preoperative body satisfaction were found to have an increased incidence of infections and delayed wound healing. Although postoperative outcomes are multifactorial, the data suggest that baseline psychological factors such as body image may play a role in postoperative outcomes. Broader use of prehabilitative therapies, targeted at psychosocial factors, may warrant further investigation to optimize postoperative outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Management of high-risk breast lesions diagnosed on core biopsies and experiences from prospective high-risk breast lesion conferences at an academic institution.

BACKGROUND: The management of high-risk breast lesions diagnosed on image-guided core biopsy remains controversial. We implemented a high-risk breast conference attended by breast pathologists, imagers, and surgeons to prospectively review all contemporary cases in order to provide a consensus recommendation to either surgically excise or follow on imaging at 6-month intervals for a minimum of 2 years. METHODS: Between May, 2015 and June, 2019, 127 high-risk lesions were discussed. Of these 127 cases, 116 had concordant radiology-pathology (rad-path) findings. The remaining 11 patients had discordant rad-path findings. Of the 116 concordant cases, 6 were excluded due to lack of the first imaging follow-up until analysis. Of the remaining 110 patients, 43 had atypical ductal hyperplasia (ADH), 12 had lobular carcinoma in situ (LCIS), 19 had atypical lobular hyperplasia (ALH), 33 had radial scar (RS), 2 had flat epithelial atypia (FEA), and 1 had mucocele-like lesion (ML). We recommended excision for ADH if there were > 2 ADH foci or < 90% of the associated calcifications were removed. For patients with LCIS or ALH, we recommended excision if the LCIS or ALH was associated with microcalcifications or the LCIS was extensive. We recommended excision of RS when < 1/2 of the lesion was biopsied. We recommended all patients with FEA and ML for 6-month follow-up. RESULTS: Following conference-derived consensus for excision, of the 27 ADH excised, 9 were upgraded to invasive carcinoma or ductal carcinoma in situ. Of the six LCIS cases recommended for excision, none were upgraded. Nine excised radial scars revealed no upgrades. Additionally, 3 patients with ADH, 2 with ALH, 1 with LCIS, and 2 with RS underwent voluntary excision, and none were upgraded. All other patients (13 with ADH, 5 LCIS, 17 ALH, 22 RS, 2 FEA and 1 ML) were followed with imaging, and none revealed evidence of disease progression during follow-up (187-1389 days). All 11 rad-path discordant cases were excised with 2 upgraded to carcinoma. CONCLUSIONS: The results of this prospective study indicate that high-risk breast lesions can be successfully triaged to surgery versus observation following establishment of predefined firm guidelines and performance of rigorous rad-path correlation.

The impact of axillary node surgery on outcomes following immediate breast reconstruction.

Immediate breast reconstruction (IBR) has become the most common method for postmastectomy reconstruction. Axillary lymph node dissection is performed for the staging of patients, but the impact of IBR with nodal surgery on postoperative complications remains elusive. The present study aims to investigate the impact of concomitant axillary lymph node surgery on postoperative complications. We conducted a retrospective study of patients who underwent IBR from 2000 to 2014. We recorded and analyzed patient data to determine the association between nodal surgery and postsurgical complications. Univariate and multivariate analyses were utilized to elucidate the risk of a complication given nodal surgery, sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), and type of incision for nodal access. A total of 986 breast reconstructions were included for analysis. Overall incidence of postoperative complications per breast that received nodal surgery was 35.9% (n = 230/642), compared to 25.6% (n = 88/344) in breasts that did not have concomitant nodal surgery (P = .001). Nodal surgery was found to increase risk of all complications with an odds ratio of 1.62 (P = .001). Moreover, complications were significantly higher in patients whose nodes were accessed via mastectomy incision (39.4%) when compared to a separate incision (33.5%). Multivariate analysis showed that nodal sampling through the mastectomy incision is a significant risk factor for seroma, with an odds ratio of 3.60 (P = .002). We did not observe differences in breast complications in patients who underwent SLNB vs ALND. These factors should be taken into account in the approach to breast reconstruction during lymphadenectomy.

Patients with benign papilloma diagnosed on core biopsies and concordant pathology-radiology findings can be followed: experiences from multi-specialty high-risk breast lesion conferences in an academic center.

BACKGROUND: To determine whether patients with benign papilloma diagnosed on core biopsy can be spared from surgery. METHODS: We prospectively reviewed 150 consecutive core biopsy-diagnosed papilloma cases at a multi-specialty high-risk breast lesion conference to determine whether surgical excision was necessary. Of these 150 cases, 148 had concordant radiologic-pathologic features. Six were excluded due to lack of the first imaging follow-up until analysis. 112 were benign papillomas; 17 were papillomas involved by atypical ductal hyperplasia (atypical papilloma); 6 papillomas had ADH in adjacent tissue but not involving the papilloma; 2 papillomas were involved by atypical lobular hyperplasia (ALH); and 5 papillomas had ALH in adjacent tissue. Two were radiology-pathology (rad-path) discordant. RESULTS: Thirty-nine of the 112 benign papillomas were excised with no upgrade to carcinoma; 73 were followed with no disease progression during follow-up (185-1279 days). Fifteen of 17 atypical papillomas were surgically excised with 4 (26.7%) upgraded to carcinoma. Four of the 6 patients with ADH adjacent to a benign papilloma underwent excision with 2 upgrades to carcinoma. None of the patients with papilloma, which was either involved by ALH or had ALH in adjacent tissue had upgrade or disease progression during follow-up (204-1159 days). Finally, the two cases with discordant path-rad discordant were excised with no upgrade. CONCLUSIONS: Our data confirm that rad-path concordant benign papillomas diagnosed on core biopsy do not require surgery. It also supports the value of a formal multi-specialty review of all benign papilloma cases to create a consensus management plan.

Time to Radiation After Oncoplastic Reduction.

BACKGROUND: Partial breast reconstruction with reduction mammaplasty is an accepted option for women with breast cancer who wish to receive breast conserving therapy. With additional surgery and potential postoperative complications, the impact this approach has on the timely initiation of adjuvant radiation therapy has been raised as a concern. The purpose of this study was to determine if any postoperative complications after oncoplastic reduction (OCR) are associated with a delay in time to radiation. METHODS: All patients undergoing OCR with postoperative adjuvant radiation at a single institution between 1997 and 2015 were included in the analysis. Women who received adjuvant chemotherapy or experienced delays in radiation therapy due to nonsurgical reasons were excluded from our analysis. Comparisons were made between the time to radiation for patients with surgical complications and those without. RESULTS: One hundred eighteen patients were included. Twenty-six (22.0%) experienced a surgical complication. Complications included cellulitis, delayed healing, seroma, wound breakdown, and wound dehiscence. Postoperative complications resulted in a significantly different median time interval for initiation of radiation (74 days vs 54 days, P < 0.001) compared to those without a complication. Among the entire cohort, 5% of patients required a second operative procedure due to complications. (n = 6/118 patients) including hematoma, infection, seroma, open wounds, wound dehiscence, and nipple necrosis. There was no difference in median time to radiation therapy in those with complications who returned to the operating room (73 days) compared to those who did not (74 days, P = 0.692). CONCLUSION: Postoperative complications following OCR procedures were associated with an increased time to initiation of adjuvant radiation therapy regardless of whether or not the complication required reoperation. This needs to be taken into consideration when planning these combined procedures with every attempt made to minimize complications through patient selection and surgical technique.

The Expanded Use of Autoaugmentation Techniques in Oncoplastic Breast Surgery.

BACKGROUND: Autoaugmentation techniques have been applied to oncoplastic reductions to assist with filling larger, more remote defects, and to women with smaller breasts. The purpose of this report is to describe the use of autoaugmentation techniques in oncoplastic reduction and compare the results with those of traditional oncoplastic reduction. METHODS: The authors queried a prospectively maintained database of all women who underwent partial mastectomy and oncoplastic reduction between 1994 and October of 2015. The autoaugmentation techniques were defined as (1) extended primary nipple autoaugmentation pedicle, and (2) primary nipple pedicle and secondary autoaugmentation pedicle. Comparisons were made to a control oncoplastic group. RESULTS: There were a total of 333 patients, 222 patients (67.7 percent) without autoaugmentation and 111 patients (33 percent) with autoaugmentation (51 patients with an extended autoaugmentation pedicle, and 60 patients with a secondary autoaugmentation pedicle). Biopsy weight was smallest in the extended pedicle group (136 g) and largest in the regular oncoplastic group (235 g; p = 0.017). Superomedial was the most common extended pedicle, and lateral was the most common location. Inferolateral was the most common secondary pedicle for lateral and upper outer defects. There were no significant differences in the overall complication rate: 15.5 percent in the regular oncoplastic group, 19.6 percent in the extended pedicle group, and 20 percent in the secondary pedicle group. CONCLUSIONS: Autoaugmentation techniques have evolved to manage complex defects not amenable to standard oncoplastic reduction methods. They are often required for lateral defects, especially in smaller breasts. Autoaugmentation can be performed safely without an increased risk of complications, broadening the indications for breast conservation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer.

Heterogeneous tumor cells, high incidence of tumor recurrence, and decrease in overall survival are the major challenges for the treatment of chemo-resistant breast cancer. Results of our study showed differential chemotherapeutic responses among breast cancer patient derived xenograft (PDX) tumors established from the same patients. All doxorubicin (Dox)-resistant tumors expressed higher levels of cancer stem-like cell biomarkers, including CD44, Wnt and its receptor LRP5/6, relative to Dox-sensitive tumors. To effectively treat resistant tumors, we developed an ultra-small magnetic iron oxide nanoparticle (IONP) drug carrier conjugated with peptides that are dually targeted to Wnt/LRP5/6 and urokinase plasminogen activator receptor (uPAR). Our results showed that simultaneous binding to LRP5/6 and uPAR by the dual receptor targeted IONPs was required to inhibit breast cancer cell invasion. Molecular analysis revealed that the dual receptor targeted IONPs significantly inhibited Wnt/ß-catenin signaling and cancer stem-like phenotype of tumor cells, with marked reduction of Wnt ligand, CD44 and uPAR. Systemic administration of the dual targeted IONPs led to nanoparticle-drug delivery into PDX tumors, resulting in stronger tumor growth inhibition compared to non-targeted or single-targeted IONP-Dox in a human breast cancer PDX model. Therefore, co-targeting Wnt/LRP and uPAR using IONP drug carriers is a promising therapeutic approach for effective drug delivery to chemo-resistant breast cancer.

An atypical presentation of Paget's Disease of the breast without nipple involvement: Case report and review of the literature.

We present a case of a 63 year-old Caucasian female who developed a right breast skin lesion discrete from the nipple that was subsequently diagnosed as Paget's Disease of the breast (PDB). Imaging did not reveal an underlying breast cancer or involvement of the nipple. The patient underwent a segmental mastectomy preserving the nipple and final pathology demonstrated residual Paget's disease of the skin and did not reveal any additional underlying breast carcinoma. To our knowledge, this case represents the first reported diagnosed case of isolated PDB without nipple involvement.

Neoadjuvant Therapy Combined With Oncoplastic Reduction for High-Stage Breast Cancer Patients.

OBJECTIVE: Oncoplastic surgery has been shown to be a good alternative to breast conservation surgery (BCS) alone for patients with breast cancer. Its role in patients with advanced disease is unclear. In this study, we evaluate the safety of oncoplastic BCS (OBCS) in patients who received neoadjuvant therapy (NT) for high stage breast cancer. METHODS: The oncologic outcomes of consecutive patients classified as high stage (>T2 or at least N1) who received NT followed by BCS at EUH by a single breast surgeon (T.M.S.) from September 2004 until June 2015 were compared with those who received BCS combined with an oncoplastic reduction. Patients were surveyed using the BREAST-Q to determine their satisfaction after surgery. RESULTS: A total of 87 patients were included in this series. The mean initial tumor size (4.37 vs 2.56 cm), the weight of the surgical specimen, and the post-NT tumor size were all larger in the OBCS group as compared with BCS alone (1.54 vs 1.29 cm). The mean follow-up was 44 months. The average percent reduction in tumor size in response to NT was slightly greater in the OBCS group (61 vs 52%). Oncologic outcomes were similar for OBCS reduction and BCS groups, respectively: positive margin rate, reexcision rate, completion mastectomy rate, local recurrence rate, and 5-year DSS. Patient satisfaction was similar between the 2 groups. CONCLUSIONS: The oncoplastic approach in high stage patients treated with neoadjuvant systemic Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation therapy appears to be as safe and effective when compared to BCS alone. Oncoplastic BCS paired with NT broadens the indication for BCS for patients with larger tumor size.

Oncoplastic Breast Reduction Technique and Outcomes: An Evolution over 20 Years.

BACKGROUND: Reduction mammaplasty at the time of lumpectomy is a good option in women with breast cancer and macromastia. We critically evaluated refinements and outcomes of this technique. METHODS: A prospectively maintained database was reviewed of all women with breast cancer who received lumpectomy and reduction mammaplasty at our institution from 1994 to 2015. Patients' demographics were reviewed. Preoperative and postoperative patient satisfaction (BREAST-Q) was determined. Comparisons were made between early and recent cases. RESULTS: There were 353 patients included. Average age was 54 (range, 21 to 80 years), with the largest number having stage I disease [n = 107 of 246 (43.5 percent)]. Average lumpectomy specimen was 207 g (range, 11.6 to 1954 g) and total reduction weight averaged 545 g (range, 21 to 4102 g). Tumor size averaged 2.02 cm (range, 0.00 to 15.60 cm). The positive margin rate was 6.2 percent (n = 22). Completion mastectomy rate was 9.9 percent (n = 35). Overall complication rate was 16 percent. The recurrence rate was 5.2 percent (n = 10 of 192) at a mean follow-up of 2 years (range, 2 months to 15 years). Resection weights greater than 1000 g were associated with having a positive margin (16.7 percent versus 5.0 percent; p = 0.016), and tended to be associated with having a completion mastectomy (p = 0.069). Positive margin and completion mastectomy rates have been lower in the past 10 years. Over 1 year postoperatively, women reported increased self-confidence (p = 0.020), feelings of attractiveness (p = 0.085), emotional health (p = 0.037), and satisfaction with sex life (p = 0.092). CONCLUSIONS: The oncoplastic reduction technique is effective and results in improved patient-reported outcomes. Resections over 1000 g are associated with a higher incidence of positive margins and may increase the risk for completion mastectomy. Outcomes have improved with experience and refinement in technique.