Behaviour, barriers and facilitators of shared decision making in breast cancer surgical treatment: A qualitative systematic review using a 'Best Fit' framework approach.

BACKGROUND: Due to the diversity and high sensitivity of the treatment, there were difficulties and uncertainties in the breast cancer surgical decision-making process. We aimed to describe the patient's decision-making behaviour and shared decision-making (SDM)-related barriers and facilitators in breast cancer surgical treatment. METHODS: We searched eight databases for qualitative studies and mixed-method studies about breast cancer patients' surgical decision-making process from inception to March 2021. The quality of the studies was critically appraised by two researchers independently. We used a 'best fit framework approach' to analyze and synthesize the evidence. RESULTS: Twenty-eight qualitative studies and three mixed-method studies were included in this study. Four themes and 10 subthemes were extracted: (a) struggling with various considerations, (b) actual decision-making behaviours, (c) SDM not routinely implemented and (d) multiple facilitators and barriers to SDM. CONCLUSIONS: Patients had various considerations of breast surgery and SDM was not routinely implemented. There was a discrepancy between information exchange behaviours, value clarification, decision support utilization and SDM due to cognitive and behavioural biases. When individuals made surgical decisions, their behaviours were affected by individual-level and system-level factors. Therefore, healthcare providers and other stakeholders should constantly improve communication skills and collaboration, and emphasize the importance of decision support, so as to embed SDM into routine practice. PATIENT AND PUBLIC CONTRIBUTION: This systematic review was conducted as part of a wider research entitled: Breast cancer patients' actual participation roles in surgical decision making: a mixed method research. The results of this project helped us to better analyze and generalize patients' views.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases.

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Ultrasonography is an effective tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

BACKGROUND: Individuals with severe motor and intellectual disabilities have become an aging population, and high cancer morbidity and mortality are critical issues affecting their survival. Cancer screening is a crucial method of resolving this issue; however, a suitable screening method for them has not been established. METHODS: We used ultrasonography alone and performed breast cancer screening for women over 30 years old in our facility from 2016 to 2023. We observed the outcomes and calculated the recall/detection rate in this screening. RESULTS: Three cases among 379 tested positive in this screening, all of which underwent radical surgery. They are alive and well without relapse present. We detected these breast cancer cases with a low recall rate. CONCLUSION: We were able to successfully detect breast cancer cases using ultrasonography alone. Ultrasonography is an effective and feasible tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

The PI3K/AKT/mTOR signaling pathway in breast cancer: Review of clinical trials and latest advances.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer mortality in women. As the phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a wide range of physiological functions of cells including growth, proliferation, motility, and angiogenesis, any alteration in this axis could induce oncogenic features; therefore, numerous preclinical and clinical studies assessed agents able to inhibit the components of this pathway in BC patients. To the best of our knowledge, this is the first study that analyzed all the registered clinical trials investigating safety and efficacy of the PI3K/AKT/mTOR axis inhibitors in BC. Of note, we found that the trends of PI3K inhibitors in recent years were superior as compared with the inhibitors of either AKT or mTOR. However, most of the trials entering phase III and IV used mTOR inhibitors (majorly Everolimus) followed by PI3K inhibitors (majorly Alpelisib) leading to the FDA approval of these drugs in the BC context. Despite favorable efficacies, our analysis shows that the majority of trials are utilizing PI3K pathway inhibitors in combination with hormone therapy and chemotherapy; implying monotherapy cannot yield huge clinical benefits, at least partly, due to the activation of compensatory mechanisms. To emphasize the beneficial effects of these inhibitors in combined-modal strategies, we also reviewed recent studies which investigated the conjugation of nanocarriers with PI3K inhibitors to reduce harmful toxicities, increase the local concentration, and improve their efficacies in the context of BC therapy.

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A-to-I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs.

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.

Preclinical Efficacy of Cabazitaxel Loaded Poly(2-alkyl cyanoacrylate) Nanoparticle Variants.

Background: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect. Methods: Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry. Results: In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment. Conclusion: We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response.

Comparative Analysis of Recurrence-Free Survival and Mortality in Postmastectomy Patients: Insights From Multidecade, Multiinstitutional Propensity Score Matching.

INTRODUCTION: Disparities in postmastectomy reconstructive care are widely acknowledged. However, there is limited understanding regarding the impact of reconstructive services on cancer recurrence and breast cancer-related mortality. Therefore, this study aims to examine how patient-specific factors and breast reconstruction status influence recurrence-free survival and mortality rates in breast cancer patients. METHODS: Retrospective chart review was performed to collect data on patients who underwent mastectomy at 2 institutions within the New York-Presbyterian system from 1979 to 2019. Sociodemographic information, medical history, and the treatment approach were recorded. Propensity score matching, logistic regression, unpaired t test, and chi-square test were used for statistical analysis. RESULTS: Overall, cancer recurrence occurred in 6.62% (317) of patients, with 16.8% (803) overall mortality rate. For patients who had relapsed disease, completion of the reconstruction sequence was correlated with an earlier detection of cancer recurrence and improved survival odds (P < 0.05). Stratified analysis of the reconstruction group alone showed mortality benefit among patients who underwent free flap procedures (P < 0.05). CONCLUSION: Patients undergoing breast reconstruction after mastectomy are likely to have better access to follow-up care and improved interfacing with the healthcare system. This may increase the speed at which cancer recurrence is detected. This study highlights the need for consistent plastic surgery referral and continued monitoring by all members of the breast cancer care team for cancer recurrence among patients.

Assessing Long-Term Volume Retention in Breast Fat Grafting: A Comparative Study of Lipoaspirate Processing Techniques.

INTRODUCTION: Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery. METHODS: A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change. RESULTS: The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05). DISCUSSION: Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis.

An Evolving Landscape: Return of Breast Sensation After Mastectomy Varies by Anatomic Region and Reconstructive Method.

PURPOSE: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time. METHODS: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests. RESULTS: One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively. CONCLUSIONS: Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast.

Minimizing Nipple-Areolar Complex Complications in Prepectoral Breast Reconstruction After Nipple-Sparing Mastectomy.

PURPOSE: Nipple-areolar complex (NAC) viability remains a significant concern following prepectoral tissue expander (TE) reconstruction after nipple-sparing mastectomy (NSM). This study assesses the impact of intraoperative TE fill on NAC necrosis and identifies strategies for mitigating this risk. METHODS: A chart review of all consecutive, prepectoral TEs placed immediately after NSM was performed between March 2017 and December 2022 at a single center. Demographics, mastectomy weight, intraoperative TE fill, and complications were extracted for all patients. Partial NAC necrosis was defined as any thickness of skin loss including part of the NAC, whereas total NAC necrosis was defined as full-thickness skin loss involving the entirety of the NAC. P < 0.05 was considered statistically significant. RESULTS: Forty-six patients (83 breasts) with an average follow-up of 22 months were included. Women were on average 46 years old, nonsmoker (98%), and nondiabetic (100%) and had a body mass index of 23 kg/m2. All reconstructions were performed immediately following prophylactic mastectomies in 49% and therapeutic mastectomies in 51% of cases. Three breasts (4%) were radiated, and 15 patients (33%) received chemotherapy. Mean mastectomy weight was 346 ± 274 g, median intraoperative TE fill was 150 ± 225 mL, and median final TE fill was 350 ± 170 mL. Partial NAC necrosis occurred in 7 breasts (8%), and there were zero instances of complete NAC necrosis. On univariate analysis, partial NAC necrosis was not associated with any patient demographic or operative characteristics, including intraoperative TE fill. In multivariable models controlling for age, body mass index, mastectomy weight, prior breast surgery, and intraoperative TE fill, partial NAC necrosis was associated with lower body mass index (odds ratio, 0.53; confidence interval [CI], 0.29-0.98; P < 0.05) and higher mastectomy weight (odds ratio, 1.1; CI, 1.01-1.20; P < 0.05). Prior breast surgery approached significance, as those breasts had a 19.4 times higher odds of partial NAC necrosis (95% CI, 0.88-427.6; P = 0.06). CONCLUSIONS: Nipple-areolar complex necrosis following prepectoral TE reconstruction is a rare but serious complication. In this study of 83 breasts, 7 (8%) developed partial NAC necrosis, and all but one were able to be salvaged.

Impact of Comorbidities on Sensory Return After Breast Reconstruction.

PURPOSE: Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling. METHODS: This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests. RESULTS: A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction. CONCLUSIONS: Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration.

Proliferation Patterns of MCF-7 Breast Cancer Cells in Lipoaspirate Conditioned Media.

INTRODUCTION: Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment. METHODS: Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT. RESULTS: The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05). DISCUSSION: Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.

Continuing Insurance Coverage for Flap-Based Breast Reconstruction: Is There a Reservation Cost Related to a Woman's Abdominal Flap Choice?

BACKGROUND: The recent proposed alterations to the Centers for Medicare and Medicaid Services regulations, although subsequently reversed on August 21, 2023, have engendered persistent concerns regarding the impact of insurance policies on breast reconstruction procedures coverage. This study aimed to identify factors that would influence women's preferences regarding autologous breast reconstruction to better understand the possible consequences of these coverage changes. METHODS: A survey of adult women in the United States was conducted via Amazon Mechanical Turk to assess patient preferences for breast reconstruction options, specifically deep inferior epigastric perforator (DIEP) and transverse rectus abdominis myocutaneous (TRAM) flap surgery. The Cochrane-Armitage test evaluated trends in flap preferences concerning incremental out-of-pocket payment increases. RESULTS: Of 500 total responses, 485 were completed and correctly answered a verification question to ensure adequate attention to the survey, with respondents having a median (interquartile range) age of 26 (25-39) years. When presented with the advantages and disadvantages of DIEP versus TRAM flaps, 78% of respondents preferred DIEP; however, as DIEP's out-of-pocket price incrementally rose, more respondents favored the cheaper TRAM option, with $3804 being the "indifference point" where preferences for both procedures converged (P < 0.001). Notably, respondents with a personal history of breast reconstruction showed a higher preference for DIEP, even at a $10,000 out-of-pocket cost (P = 0.04). CONCLUSIONS: Out-of-pocket cost can significantly influence women's choices for breast reconstruction. These findings encourage a reevaluation of emergent insurance practices that could potentially increase out-of-pocket costs associated with DIEP flaps, to prevent cost from decreasing equitable patient access to most current reconstructive options.

Simultaneous Free Flap Breast Reconstruction Combined With Contralateral Mastopexy or Breast Reduction: A Propensity-Matched National Surgical Quality Improvement Program Study on Postoperative Outcomes.

BACKGROUND: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can increase patient satisfaction and minimize the need for a second procedure. Surgeon concerns of increases in operative time, postoperative complications, and final breast symmetry may decrease the likelihood of these procedures being done concurrently. This study analyzed postoperative outcomes of simultaneous contralateral mastopexy or breast reduction with free flap breast reconstruction. METHODS: By using the American College of Surgeons National Surgical Quality Improvement Program database (2010-2020), we analyzed 2 patient cohorts undergoing (A) free flap breast reconstruction only and (B) free flap breast reconstruction combined with contralateral mastopexy or breast reduction. The preoperative variables assessed included demographic data, comorbidities, and perioperative data. Using a neighbor matching algorithm, we performed a 1:1 propensity score matching of 602 free flap breast reconstruction patients and 621 with concurrent contralateral operation patients. Bivariate analysis for postoperative surgical and medical complications was performed for outcomes in the propensity-matched cohort. RESULTS: We identified 11,308 cases who underwent microsurgical free flap breast reconstruction from the American College of Surgeons National Surgical Quality Improvement Program database from the beginning of 2010 to the end of 2020. A total of 621 patients underwent a free flap breast reconstruction combined with contralateral mastopexy or breast reduction. After propensity score matching, there were no significant differences in patient characteristics, perioperative variables or postoperative medical complications between the 2 cohorts. CONCLUSIONS: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can be performed safely and effectively without an increase in postoperative complication rates. This can improve surgeon competence in offering this combination of procedures as an option to breast cancer survivors, leading to better patient outcomes in terms of symmetrical and aesthetically pleasing results, reduced costs, and elimination of the need for a second operation.

Disparities in Breast Reconstruction: An Analysis of Treatment Choices.

BACKGROUND: Breast reconstruction methods vary based on factors such as medical history, breast size, and personal preferences. However, disparities in healthcare exist, and the role race plays in accessing to different reconstruction methods is unclear. This study aimed to investigate the influence of race and/or ethnicity on the type of breast reconstruction chosen. METHODS: This retrospective cohort study analyzed the University of Pittsburgh Medical Center Magee Women's Hospital database, including patients who underwent breast cancer surgery from 2011 to 2022. Multivariate analysis examined race, reconstruction, and reconstruction type (P < 0.05). RESULTS: The database included 13,260 women with breast cancer; of whom 1763 underwent breast reconstruction. We found that 91.8% of patients were White, 6.8% Black, and 1.24% were of other races (Asian, Chinese, Filipino, Vietnamese, unknown). Reconstruction types were 46.8% implant, 30.1% autologous, and 18.7% combined. Among Black patients, autologous 36.3%, implant 32.2%, and combined 26.4%. In White patients, autologous 29.5%, implant 48%, and combined 18.2%. Among other races, autologous 36.3%, implant 40.9%, and combined 22.7%. In patients who underwent breast reconstruction, 85.2% underwent unilateral and 14.7% of patients underwent bilateral. Among the patients who had bilateral reconstruction, 92.3% were White, 6.1% were Black, and 1.5% were of other ethnicities. CONCLUSIONS: Our analysis revealed differences in breast reconstruction methods. Autologous reconstruction was more common among Black patients, and implant-based reconstruction was more common among Whites and other races. Further research is needed to understand the cause of these variations.

Alternative Lymphatic Drainage Pathways in the Trunk Following Oncologic Therapy.

BACKGROUND: Anatomic and functional descriptions of trunk and breast lymphedema following breast cancer treatment are emerging as indicators of lymphatic dysfunction. Indocyanine green-lymphangiography has been instrumental in characterizing this dysfunction in the extremity and can be applied to other regions. Previous work has established a validated Pittsburgh Trunk Lymphedema Staging System to characterize such affected areas. This study aims to identify risk and protective factors for the development of truncal and upper extremity lymphedema using alternative lymphatic drainage, providing implications for medical and surgical treatment. METHODS: Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between 12/2014 and 3/2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated for axillary and inguinal lymphatic flow. A linear-weighted Cohen's kappa statistic was calculated comparing alternative drainage evaluation. Binomial regression was used to compute relative risks (RRs). Significance was assessed at alpha = 0.05. RESULTS: Eighty-six sides (46 patients) were included. Twelve sides underwent no treatment and were considered controls. Eighty-eight percent of the noncontrols had alternative lymphatic flow to the ipsilateral axillae (64%), ipsilateral groins (57%), contralateral axillae (20.3%), and contralateral groins (9.3%). Cohen's kappa for alternative drainage was 0.631 ± 0.043. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of developing truncal lymphedema [RR 0.78, confidence interval (CI) 0.63-0.97, P = 0.04; RR 0.32, CI 0.13-0.79, P = 0.01, respectively]. Radiation therapy increased risk of truncal and upper extremity lymphedema (RR 3.69, CI 0.96-14.15, P = 0.02; RR 1.92, CI 1.09-3.39, P = 0.03, respectively). Contralateral axillary drainage and axillary lymph node dissection were associated with increased risk of upper extremity lymphedema (RR 4.25, CI 1.09-16.61, P = 0.01; RR 2.83, CI 1.23-6.52, P = 0.01, respectively). CONCLUSIONS: Building upon previous work, this study shows risk and protective factors for the development of truncal and upper extremity lymphedema. Most prevalent alternative channels drain to the ipsilateral axilla and groin. Ipsilateral axillary and contralateral inguinal drainage were associated with reduced risk of truncal lymphedema. Patients with radiation, axillary dissection, and contralateral axillary drainage were associated with increased risk of upper extremity lymphedema. These findings have important clinical implications for postoperative manual lymphatic drainage and for determining eligibility for lymphovenous bypass surgery.

Out-of-Pocket Costs and Payments in Autologous and Implant-Based Breast Reconstruction: A Nationwide Analysis.

BACKGROUND: Many factors influence a patient's decision to undergo autologous versus implant-based breast reconstruction, including medical, social, and financial considerations. This study aims to investigate differences in out-of-pocket and total spending for patients undergoing autologous and implant-based breast reconstruction. METHODS: The IBM MarketScan Commercial Databases were queried to extract all patients who underwent inpatient autologous or implant-based breast reconstruction from 2017 to 2021. Financial variables included gross payments to the provider (facility and/or physician) and out-of-pocket costs (total of coinsurance, deductible, and copayments). Univariate regressions assessed differences between autologous and implant-based reconstruction procedures. Mixed-effects linear regression was used to analyze parametric contributions to total gross and out-of-pocket costs. RESULTS: The sample identified 2079 autologous breast reconstruction and 1475 implant-based breast reconstruction episodes. Median out-of-pocket costs were significantly higher for autologous reconstruction than implant-based reconstruction ($597 vs $250, P < 0.001) as were total payments ($63,667 vs $31,472, P < 0.001). Type of insurance plan and region contributed to variable out-of-pocket costs (P < 0.001). Regression analysis revealed that autologous reconstruction contributes significantly to increasing out-of-pocket costs (B = $597, P = 0.025) and increasing total costs (B = $74,507, P = 0.006). CONCLUSION: The US national data demonstrate that autologous breast reconstruction has higher out-of-pocket costs and higher gross payments than implant-based reconstruction. More study is needed to determine the extent to which these financial differences affect patient decision-making.

[Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases].

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

[Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma].

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features.

Everolimus is widely used in patients with advanced ER-positive, HER2-negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER-positive, HER2-negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers were included. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1 genes. An immunochemical analysis was conducted to evaluate expression of PTEN, INPP4B, STK11, p4EBP1, and pS6. We analyzed 71 patients (44 primary tumors; 27 metastatic tissues). Median age was 63 years [58-69]. All patients had heavily pretreated advanced disease. A mutation in the PIK3CA pathway was observed in 32 samples (PIK3CA exons 10 and 21 and AKT1 exon 4 in 15.5%, 24.0%, and 5.6% of samples), and in ESR1 in 5 samples (7.0%), respectively. Most samples showed cytoplasmic expression of the PIK3CA pathway proteins. Progression-free survival was longer in patients with a pS6 or p4EBP1 histoscore ≥ median value (6.6 versus 3.7 months, p = 0.037), and in patients with a PTEN histoscore ≤ median value (7.1 versus 5.3 months, p = 0.02). Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.