Results of Magnetic Resonance Imaging (MRI) Screening in Patients at High Risk for Breast Cancer.

BACKGROUND: Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. METHODS: Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. RESULTS: A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. CONCLUSIONS: Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.

Optimization of an automated tumor-infiltrating lymphocyte algorithm for improved prognostication in primary melanoma.

Tumor-infiltrating lymphocytes (TIL) have potential prognostic value in melanoma and have been considered for inclusion in the American Joint Committee on Cancer (AJCC) staging criteria. However, interobserver discordance continues to prevent the adoption of TIL into clinical practice. Computational image analysis offers a solution to this obstacle, representing a methodological approach for reproducibly counting TIL. We sought to evaluate the ability of a TIL-quantifying machine learning algorithm to predict survival in primary melanoma. Digitized hematoxylin and eosin (H&E) slides from prospectively enrolled patients in the NYU melanoma database were scored for % TIL using machine learning and manually graded by pathologists using Clark's model. We evaluated the association of % TIL with recurrence-free survival (RFS) and overall survival (OS) using Cox proportional hazards modeling and concordance indices. Discordance between algorithmic and manual TIL quantification was assessed with McNemar's test and visually by an attending dermatopathologist. In total, 453 primary melanoma patients were scored using machine learning. Automated % TIL scoring significantly differentiated survival using an estimated cutoff of 16.6% TIL (log-rank P < 0.001 for RFS; P = 0.002 for OS). % TIL was associated with significantly longer RFS (adjusted HR = 0.92 [0.84-1.00] per 10% increase in % TIL) and OS (adjusted HR = 0.90 [0.83-0.99] per 10% increase in % TIL). In comparison, a subset of the cohort (n = 240) was graded for TIL by melanoma pathologists. However, TIL did not associate with RFS between groups (P > 0.05) when categorized as brisk, nonbrisk, or absent. A standardized and automated % TIL scoring algorithm can improve the prognostic impact of TIL. Incorporation of quantitative TIL scoring into the AJCC staging criteria should be considered.

Margin Assessment and Re-excision Rates for Patients Who Have Neoadjuvant Chemotherapy and Breast-Conserving Surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has enabled more patients to be eligible for breast-conservation surgery (BCS). Achieving negative lumpectomy margins, however, is challenging due to changes in tissue composition and potentially scattered residual carcinoma in the tumor bed. Data regarding BCS after NAC have shown variable re-excision rates. MarginProbe (Dilon Technologies, Newport News, VA, USA) has been shown to identify positive resection margins intraoperatively and to reduce the number of re-excisions in primary BCS, but has not been studied in NAC+BCS cases. This study aimed to investigate the clinicopathologic characteristics, margin status, and re-excision rates for NAC+BCS patients with and without the use of MarginProbe. METHODS: The Institutional Breast Cancer Database was queried for patients who received NAC and had BCS from 2010 to 2019. The variables of interest were demographics, tumor characteristics, pathologic complete response (pCR), MarginProbe use, and re-excision rates. RESULTS: The study population consisted of 214 patients who had NAC, 61 (28.5 %) of whom had NAC+BCS. The median age of the patients was 53.5 years. A pCR was achieved for 19 of the patients (31.1 %). Of the remaining 42 patients, 9 (21 %) had close or positive margins that required re-excision. Re-excision was associated with a larger residual tumor size (p = 0.025) and estrogen receptor (ER)-positive disease before NAC (p = 0.041). MarginProbe use was associated with a lower re-excision rate for the patients who had NAC+BCS (6 % vs. 31 %, respectively). CONCLUSION: The patients with a larger residual tumor burden and ER-positive disease had a greater risk for inadequate margins at surgery. MarginProbe use was associated with a lower re-excision rate. Techniques to reduce the need for re-excision will support the use of BCS after NAC.

The Devil's in the Details: Discrepancy Between Biopsy Thickness and Final Pathology in Acral Melanoma.

PURPOSE: We hypothesized that initial biopsy may understage acral lentiginous melanoma (ALM) and lead to undertreatment or incomplete staging. Understanding this possibility can potentially aid surgical planning and improve primary tumor staging. METHODS: A retrospective review of primary ALMs treated from 2000 to 2017 in the US Melanoma Consortium database was performed. We reviewed pathology characteristics of initial biopsy, final excision specimens, surgical margins, and sentinel lymph node biopsy (SLNB). RESULTS: We identified 418 primary ALMs (321 plantar, 34 palmar, 63 subungual) with initial biopsy and final pathology results. Median final thickness was 1.8 mm (range 0.0-19.0). There was a discrepancy between initial biopsy and final pathology thickness in 180 (43%) patients with a median difference of 1.6 mm (range 0.1-16.4). Final T category was increased in 132 patients (32%), including 47% of initially in situ, 32% of T1, 39% of T2, and 28% of T3 lesions. T category was more likely to be increased in subungual (46%) and palmar (38%) melanomas than plantar (28%, p = 0.01). Among patients upstaged to T2 or higher, 71% had ≤ 1-cm margins taken. Among the 27 patients upstaged to T1b or higher, 8 (30%) did not have a SLNB performed, resulting in incomplete initial staging. CONCLUSIONS: In this large series of ALMs, final T category was frequently increased on final pathology. A high index of suspicion is necessary for lesions initially in situ or T1 and consideration should be given to performing additional punch biopsies, wider margin excisions, and/or SLNB.

Metastasectomy for melanoma is associated with improved overall survival in responders to targeted molecular or immunotherapy.

BACKGROUND AND OBJECTIVES: Metastasectomy for melanoma provides durable disease control in carefully selected patients. Similarly, BRAF-targeted and immune checkpoint inhibition has improved median overall survival (OS) in metastatic patients. We hypothesized that there is an increasing role for metastasectomy in melanoma patients responding to these therapies. METHODS: Retrospective analysis of a prospectively maintained database identified 128 patients with stage IV melanoma who received targeted molecular and/or checkpoint inhibitors at an academic institution from 2006 to 2017. Records were reviewed to characterize clinicopathologic characteristics, response to treatment, and intent of surgery for those who underwent metastasectomy. OS was analyzed by the Kaplan-Meier method. RESULTS: Median OS from stage IV diagnosis was 31.3 months. A total of 81 patients received checkpoint inhibitors, 11 received targeted inhibitors, and 36 received both. A total of 73 patients underwent metastasectomy. Indications for surgery included the intent to render disease-free (54%), palliation (34%), and diagnostic confirmation (11%). Responders to systemic therapy who underwent metastasectomy had improved OS compared to responders who did not (84.3 vs. 42.9 months, P = .018). CONCLUSIONS: Metastasectomy for melanoma is associated with improved OS in patients that respond to targeted molecular or immunotherapy. Resection should be strongly considered in this cohort as multimodality treatment results in excellent OS.

Lentigo maligna melanoma in situ with neurotropism.

Perineural invasion, or neurotropism, is defined by the presence of cancer cells either within the neuronal sheath or found along the nerves. In melanoma, it is most commonly associated with invasive desmoplastic melanoma, a melanoma that is most commonly associated with malignant melanoma in situ, lentigo maligna type. Initially, perineural invasion was included in the reported Breslow thickness; however, recent data suggest that it should not be included. In this report, we describe a case of malignant melanoma in situ, lentigo maligna type, with associated neurotropism in the absence of invasive component.

Pregnancy-associated breast cancer in a contemporary cohort of newly diagnosed women.

Pregnancy-associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy, lactation, or in the postpartum period. There is evidence that PABC is associated with a poorer prognosis, and that the development of the disease is influenced by the unique hormonal milieu of pregnancy. The purpose of this study was to investigate the clinicopathologic characteristics associated with PABC in a contemporary cohort of women with newly diagnosed BC. Our institutional Breast Cancer Database was queried for women diagnosed with BC between 2009-2018 who had at least one full-term pregnancy (FTP). Variables of interest included patient demographics and clinical and tumor characteristics. PABC was defined as breast cancer diagnosed within 24 months of delivery. Statistical analyses included Pearson's chi-square and logistic regression. Out of a total of 2202 women, 46 (2.1%) had PABC. Median follow-up in the total cohort was 5.5 years. After adjusting for age at first FTP, PABC was associated with younger age at diagnosis, older age at first FTP, non-Caucasian race, BRCA positivity, presentation with a palpable mass, higher pathologic stage, higher histologic grade, and ER-negative and triple-negative receptor status. The association of PABC with non-Caucasian race may be reflected in the increased proportion of triple-negative breast cancers in the PABC group. PABC was also associated with older age at first FTP. As more women delay childbearing, risk for PABC may increase. Our findings suggest that women who become pregnant at older ages should be followed carefully during pregnancy and the postpartum period, especially if they are BRCA mutation carriers. The optimal approach for monitoring older women during pregnancy and the postpartum period is unclear.

Sentinel lymph node positivity in patients undergoing mastectomies for ductal carcinoma in situ (DCIS).

Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico-pathologic variables were analyzed using Pearson's chi-squared, Wilcoxon Rank-Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P = .0289), palpability (P < .0001), extent of disease on imaging (P = .0121), mass on preoperative imaging (P = .0003), multifocality (P = .0231) and multicentricity (P = .0395). In multivariate analysis, palpability (P = .0080), extent of disease on imaging (P = .0074) and mass on preoperative imaging (P = .0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.

A Nomogram to Predict Factors Associated with Lymph Node Metastasis in Ductal Carcinoma In Situ with Microinvasion.

INTRODUCTION: Ductal carcinoma in situ (DCIS) with foci of invasion measuring ≤ 1 mm (DCISM), represents < 1% of all invasive breast cancers. Sentinel lymph node biopsy (SLNB) has been a standard component of surgery for patients with invasive carcinoma or extensive DCIS. We hypothesize that selective performance of SLNB may be appropriate given the low incidence of sentinel node (SN) metastasis for DCISM. We investigated the clinicopathologic predictors for SN positivity in DCISM, to identify which patients might benefit from SLNB. METHODS: A retrospective review of the National Cancer Database was performed for cases from 2012 to 2015. Clinical and tumor characteristics, including SN results, were evaluated, and Pearson's Chi square tests and logistic regression were performed. RESULTS: Of 7803 patients with DCISM, 306 (4%) had at least one positive SN. Patients with positive SNs were younger, more often of Black race, had higher-grade histology and larger tumor size, and were more likely to have lymphovascular invasion (LVI; all p < 0.001). In an adjusted model, the presence of LVI was associated with the highest odds ratio (OR) for node positivity (OR 8.80, 95% confidence interval 4.56-16.96). CONCLUSIONS: Among women with DCISM, only 4% had a positive SN. Node positivity was associated with more extensive and higher-grade DCIS, and the presence of LVI was strongly correlated with node positivity. Our data suggest that LVI is the most important factor in determining which patients with DCISM will benefit from SN biopsy.

The Relationship of Breast Density and Positive Lumpectomy Margins.

BACKGROUND: A positive lumpectomy margin after breast-conserving surgery (BCS) is a significant predictor for ipsilateral cancer recurrence. The MarginProbe, a Food and Drug Administration (FDA)-approved device for intraoperative assessment of lumpectomy margins, is associated with a reduction in re-excision surgery. This study aimed to evaluate the relationship of mammographic breast density (MBD) and clinicopathologic characteristics with margin status in women undergoing BCS with the MarginProbe. METHODS: The institutional database was queried for patients with breast cancer who had BCS with the MarginProbe from 2013 to 2017. Clinicopathologic characteristics were collected. The study defined MBD as less dense (Breast Imaging Reporting and Data System [BI-RADS] A and B) and more dense (BI-RADS C and D). A positive margin was defined as smaller than 1 mm. Pearson Chi square and uni- and multivariate logistic regression were performed. RESULTS: Of 1734 patients, 341 met the study criteria. The median patient age was 63 years. The patients with higher mammographic density were younger (p < 0.0001) and had a lower body mass index (BMI) (p < 0.0001). The patients with higher MBD were more likely to present with a palpable mass (p = 0.0360). Of the 341 patients, 135 (39.6%) had one or more positive margins on the main specimen, and 101 (74.8%) were converted to final negative margins after the MarginProbe directed re-excisions. Positive final margins were associated with larger tumor size (p = 0.0242) and more advanced stage of disease at diagnosis (p = 0.0255). CONCLUSIONS: In this study of patients undergoing BCS, breast density was not correlated with the likelihood of a positive margin. The presence of positive final lumpectomy margins was associated with older age and more extensive disease.

Tumor-Infiltrating Lymphocytes in a Contemporary Cohort of Women with Ductal Carcinoma In Situ (DCIS).

BACKGROUND: Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. METHODS: Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. RESULTS: Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (< 45%) or dense (≥ 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5 months compared with four patients with sparse TILs with mean time to recurrence of 97.9 months (p = 0.003). CONCLUSIONS: Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.

cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING.

Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS-/-), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found cGAS-/- mice had significantly increased liver injury compared with WT or STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING. Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to anoxia/reoxygenation (A/R). We confirmed a previously published finding that hepatocytes do not express STING under normoxic conditions or after A/R. Hepatocytes and liver from cGAS-/- mice had increased cell death and reduced induction of autophagy under hypoxic conditions as well as increased apoptosis. Protection could be restored in cGAS-/- hepatocytes by overexpression of cGAS or by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a novel protective role for cGAS in the regulation of autophagy during liver I/R injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the first to document the important role of cGAS in the acute setting of sterile injury induced by I/R. Specifically, we provide evidence that cGAS protects liver from I/R injury in a STING-independent manner.

Redox-dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice.

Sterile liver inflammation, such as liver ischemia-reperfusion, hemorrhagic shock after trauma, and drug-induced liver injury, is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here, we identify a mechanism for redox-mediated regulation of absent in melanoma 2 (AIM2) inflammasome activation in hepatocytes after redox stress in mice, which occurs through interaction with cytosolic high mobility group box 1 (HMGB1). We show that in liver during hemorrhagic shock in mice and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA. Activation of caspase-1 through AIM2 leads to subsequent hepatoprotective responses such as autophagy. HMGB1 binds to AIM2 at a non-DNA-binding site on the hematopoietic interferon-inducible nuclear antigen domain of AIM2 to facilitate inflammasome and caspase-1 activation in hepatocytes. Furthermore, binding of HMGB1 to AIM2 is stronger with fully reduced all-thiol HMGB1 than with partially oxidized disulfide-HMGB1, and binding strength corresponds to caspase-1 activation. These data suggest that HMGB1 redox status regulates AIM2 inflammasome activation. CONCLUSION: These findings suggest a novel and important mechanism for regulation of AIM2 inflammasome activation in hepatocytes during redox stress and may suggest broader implications for how this and other inflammasomes are activated and how their activation is regulated during cell stress, as well as the mechanisms of inflammasome regulation in nonimmune cell types. (Hepatology 2017;65:253-268).

Association between Ki-67 expression and clinical outcomes among patients with clinically node-negative, thick primary melanoma who underwent nodal staging.

BACKGROUND: Patients with thick primary melanomas (≥4 mm) have highly variable survival outcomes. Cell proliferation marker Ki-67 has been identified as promising biomarker in thick melanoma but has not been evaluated since the wide spread adoption of sentinel lymph node biopsy. We revisit its prognostic relevance in the sentinel node era. METHODS: We studied patients with thick (≥4 mm) primary melanoma prospectively enrolled in a clinicopathological biospecimen database from 2002 to 2015, and evaluated the prognostic value of Ki-67 expression while controlling for features included in the existing staging criteria. RESULTS: We analyzed 68 patients who underwent lymph node sampling and who had an available tumor for Ki-67 immunohistochemical (IHC) staining. The median tumor thickness was 6.0 mm; the median follow-up was 2.6 years. In multivariable analysis including nodal status and primary tumor ulceration, Ki-67 expression was an independent predictor of worse recurrence-free survival (HR 2.19, P = 0.024) and overall survival (HR 2.49, P = 0.028). Natural log-transformed tumor thickness (ln [thickness]) was also significantly associated with worse OS (HR 2.39, P = 0.010). CONCLUSION: We identify Ki-67 and ln (thickness) as potential biomarkers for patients with thick melanoma who have undergone nodal staging. If validated in additional studies, these biomarkers could be integrated into the staging criteria to improve risk-stratification.

Treatment Outcomes for Metastatic Melanoma of Unknown Primary in the New Era: A Single-Institution Study and Review of the Literature.

BACKGROUND: Metastatic melanoma of unknown primary (MUP) is uncommon, biologically ill defined, and clinically understudied. MUP outcomes are seldom reported in clinical trials. In this study, we analyze responses of MUP patients treated with systemic therapy in an attempt to inform treatment guidelines for this unique population. METHODS: New York University (NYU)'s prospective melanoma database was searched for MUP patients treated with systemic therapy. PubMed and Google Scholar were searched for MUP patients treated with immunotherapy or targeted therapy reported in the literature, and their response and survival data were compared to the MUP patient data from NYU. Both groups' response data were compared to those reported for melanoma of known primary (MKP). RESULTS: The MUP patients treated at NYU had better outcomes on immunotherapy but worse on targeted therapy than the MUP patients in the literature. The NYU MUP patients and those in the literature had worse outcomes than the majority-MKP populations in 10 clinical trial reports. CONCLUSIONS: Our study suggests that MUP patients might have poorer outcomes on systemic therapy as compared to MKP patients. Our cohort was small and limited data were available, highlighting the need for increased reporting of MUP outcomes and multi-institutional efforts to understand the mechanism behind the observed differences.

Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care.

OBJECTIVES: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population. METHODS: 182 patients diagnosed with stage IV melanoma from July 2006 to December 2013 and treated with BRAF- and/or MEK-targeted therapy or ICI were prospectively studied. Outcomes and clinicopathologic differences between trial and commercial cohorts were assessed. RESULTS: Patients receiving commercial therapy (vs. on trial) had poorer prognostic features (i.e., brain metastases) and lower median overall survival (mOS) when assessed across all treatments (9.2 vs. 17.5 months, p = 0.0027). While toxicity within trial and commercial cohorts did not differ, patients who experienced toxicity had increased mOS (p < 0.001), irrespective of stratification by trial status or therapy. CONCLUSION: Metastatic melanoma patients receiving commercial treatment may represent a different clinical population with poor prognostic features compared to trial patients. Toxicity may prognosticate treatment benefit.

Cost Analysis of Intraoperative Subareolar Frozen Section During Nipple-Sparing Mastectomy.

BACKGROUND: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy (NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative subareolar frozen section can provide earlier detection intraoperatively. Cost analysis for intraoperative subareolar frozen section has never been performed. METHODS: NSM cases from 2006-2013 were reviewed. Patient records including financial charges were analyzed. RESULTS: Of 480 subareolar biopsies for NSM from 2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with 7 of 12 detected on intraoperative frozen section. The median baseline charge for an intraoperative subareolar frozen section was $309 for an estimated total cost of $94,863 in 307 breasts. The median baseline charge for interval operative resection of a nipple-areolar complex following an abnormal subareolar pathology result was $11,021. Intraoperative subareolar biopsy avoided an estimated six return trips to the operating room for savings of $66,126. At our institution, routine use of intraoperative frozen section resulted in an additional $28,737 in healthcare charges or $95 per breast. CONCLUSIONS: We present the first cost analysis to evaluate intraoperative subareolar frozen section in NSM. This practice obviated an estimated six return trips to the operating room. With our institutional frequency of abnormal subareolar pathology, intraoperative frozen sections resulted in a marginal increased charge per mastectomy.

Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients.

OBJECTIVES: The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. METHODS: We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the χ² test and multivariate logistic regression. We compared survival distributions using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard ratios. RESULTS: Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. CONCLUSION: Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background.