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Low Cancer Occurrence Rate following Prophylactic Nipple-Sparing Mastectomy

Boyd, Carter J; Ramesh, Sruthi; Bekisz, Jonathan M; Guth, Amber A; Axelrod, Deborah M; Shapiro, Richard L; Hiotis, Karen; Schnabel, Freya R; Karp, Nolan S; Choi, Mihye
BACKGROUND:Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS:All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS:A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS:Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, IV.
PMID: 36999997
ISSN: 1529-4242
CID: 5613282

No Cancer Occurrences in 10-year Follow-up after Prophylactic Nipple-sparing Mastectomy

Boyd, Carter J.; Bekisz, Jonathan M.; Ramesh, Sruthi; Hemal, Kshipra; Guth, Amber A.; Axelrod, Deborah M.; Shapiro, Richard L.; Hiotis, Karen; Schnabel, Freya R.; Choi, Mihye; Karp, Nolan S.
Background: Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-Term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years. Methods: Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate. Results: Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort. Conclusions: The long-Term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established.
ISSN: 2169-7574
CID: 5548712

Long-Term Cancer Recurrence Rates Following Nipple-Sparing Mastectomy: A 10-year Follow-up Study

Boyd, Carter J; Salibian, Ara A; Bekisz, Jonathan M; Axelrod, Deborah M; Guth, Amber A; Shapiro, Richard L; Schnabel, Freya R; Karp, Nolan S; Choi, Mihye
BACKGROUND:Despite the increased utilization of nipple-sparing mastectomies (NSM), there is limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who received therapeutic NSM with a median of 10 years of follow-up. METHODS:All patients undergoing NSM at a single institution were retrospectively reviewed temporally to obtain a median of 10-years of follow up. Patient demographic factors, mastectomy specimen pathology, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence. RESULTS:126 therapeutic NSM were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4%) and ductal carcinoma in situ (38.1%). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0% and 10.3% of NSM specimens, respectively. Sentinel lymph node biopsy was performed in 84.9% of NSM and 17.8% were positive. The rate of positive frozen subareolar biopsy was 7.3% (n=82) and permanent subareolar pathology was 9.5% (n=126). The most frequently observed pathologic tumor stages was stage I (44.6%) and stage 0 (33.9%). Incidence of recurrent disease was 3.17% per mastectomy and 3.33% per patient. Upon univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence. CONCLUSIONS:Overall recurrence rates are low in patients undergoing NSM at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence.
PMID: 35943969
ISSN: 1529-4242
CID: 5286852

Macrophage density is an adverse prognosticator for ipsilateral recurrence in ductal carcinoma in situ

Darvishian, Farbod; Wu, Yinxiang; Ozerdem, Ugur; Chun, Jennifer; Adams, Sylvia; Guth, Amber; Axelrod, Deborah; Shapiro, Richard; Troxel, Andrea B; Schnabel, Freya; Roses, Daniel
INTRODUCTION/BACKGROUND:There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood. METHODS:We queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables. RESULTS:The analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (>50) and high CD68/CD163 ratio (>0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24-19, p = 0.023) and 10.32 (95% CI: 1.34-80, p = 0.025), respectively]. CONCLUSIONS:macrophage density and CD68/CD163 ratio also predict a shorter time to recurrence.
PMID: 35489232
ISSN: 1532-3080
CID: 5217782

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

Lee, Ann Y; Friedman, Erica B; Sun, James; Potdar, Aishwarya; Daou, Hala; Farrow, Norma E; Farley, Clara R; Vetto, John T; Han, Dale; Tariq, Marvi; Shapiro, Richard; Beasley, Georgia; Contreras, Carlo M; Osman, Iman; Lowe, Michael; Zager, Jonathan S; Berman, Russell S
PMID: 33893602
ISSN: 1534-4681
CID: 4889162

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

Cen, Cindy; Chun, Jennifer; Kaplowitz, Elianna; Axelrod, Deborah; Shapiro, Richard; Guth, Amber; Schnabel, Freya
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/CONCLUSIONS: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.
PMID: 33635409
ISSN: 1534-4681
CID: 4802382

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

Chou, Margaret; Illa-Bochaca, Irineu; Minxi, Ben; Darvishian, Farbod; Johannet, Paul; Moran, Una; Shapiro, Richard L; Berman, Russell S; Osman, Iman; Jour, George; Zhong, Hua
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.
PMID: 33005020
ISSN: 1530-0285
CID: 4617292

Lentigo Maligna Melanoma In-Situ with Neurotropism [Case Report]

Occidental, Michael; Shapiro, Richard; Jour, George
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 suggests 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. This article is protected by copyright. All rights reserved.
PMID: 32557727
ISSN: 1600-0560
CID: 4485292

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

Lee, Ann Y; Friedman, Erica B; Sun, James; Potdar, Aishwarya; Daou, Hala; Farrow, Norma E; Farley, Clara R; Vetto, John T; Han, Dale; Tariq, Marvi; Shapiro, Richard; Beasley, Georgia; Contreras, Carlo M; Osman, Iman; Lowe, Michael; Zager, Jonathan S; Berman, Russell S
PURPOSE/OBJECTIVE: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.
PMID: 32529271
ISSN: 1534-4681
CID: 4489782

Preliminary analysis of distinct clinical and biologic features of bone metastases in melanoma

Wilson, Melissa A; Zhong, Judy; Johannet, Paul; Lee, Yesung; Masub, Natasha; Wechter, Todd; Moran, Una; Berman, Russell S; Shapiro, Richard L; Weber, Jeffrey; Pavlick, Anna; Osman, Iman
Melanoma disseminates to the skeletal system where it is then difficult to treat. Yet, there remains limited research investigating metastatic bone disease (MBD) in melanoma. Here, we evaluate whether there are distinct clinicopathologic variables at the time of primary melanoma diagnosis that predispose metastases to engraft bone, and we test the hypothesis that patients with MBD have different responses to treatment. Cutaneous melanoma patients enrolled in a prospective database were studied. Individuals with metastatic melanoma and bone metastases (M-Bone) were compared to those with metastatic disease but no M-Bone. Of the 463 (42.7%) patients, 198 with unresectable metastatic melanoma had M-Bone and 98 developed bone metastasis (bone mets) as first site. Progression-free survival and overall survival were significantly worse in patients with M-Bone compared to those without M-Bone (P < 0.001) independent of treatment modalities, and in patients whose melanoma spread to bone first, compared to those who developed first mets elsewhere (P < 0.001). Interestingly, patients with bone mets presented with primary tumors that had more tumor infiltrating lymphocytes (P < 0.001) and less often a nodular histologic subtype compared to patients without M-Bone (P < 0.001). Our data suggest that melanoma bone metastasis is a distinct clinical and biological entity that cannot be explained by generalized metastatic phenotype in all patients. The observed dichotomy between more favorable primary histopathologic characteristics and a grave overall prognosis requires more studies to elucidate the molecular processes by which melanomas infiltrate bone and to build a mechanistic understanding of how melanoma bone metastases yield such detrimental outcomes.
PMID: 32804707
ISSN: 1473-5636
CID: 4573002