Kevin S Hughes

• MD, FACS
• Professor at Medical University of South Carolina

Background: Current cancer prevention guidelines recommend assessing breast cancer risk using validated risk calculators such as Tyrer-Cuzick and assessing genetic testing eligibility with Women at high-risk of breast cancer may be recommended to undergo additional or earlier screening. Risk assessment is not consistently implemented in the primary...

Purpose Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination. Methods Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with t...

Purpose: The Tyrer-Cuzick lifetime risk score (TC LR) is used to estimate the probability of an unaffected female patient developing breast cancer as well as their likelihood of carrying a BRCA1/BRCA2 pathogenic variant (PV), considering factors such as family history, personal history, and breast density. The purpose of this study is to determine...

Background Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of...

Introduction With the expansion of guidelines for germline genetic testing, more patients are eligible for testing. Unfortunately, many remain untested. Testing is critical, as patients with pathogenic variants (and their families) can benefit from more aggressive screening and preventative strategies, as well as targeted therapies (e.g., poly (ade...

Published biomedical information has and continues to rapidly increase. The recent advancements in Natural Language Processing (NLP), have generated considerable interest in automating the extraction, normalization, and representation of biomedical knowledge about entities such as genes and diseases. Our study analyzes germline abstracts in the con...

Objectives Natural language processing (NLP) algorithms can interpret unstructured text for commonly used terms and phrases. Pancreatic pathologies are diverse and include benign and malignant entities with associated histologic features. Creating a pancreas NLP algorithm can aid in electronic health record coding as well as large database creation...

This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon’s practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a refer...

e13524 Background: Lynch Syndrome (LS), the most common form of hereditary colorectal cancer (CRC), is due to germline pathogenic variant (PV) in mismatch repair genes (MMR). Since 2009, the National Comprehensive Cancer Network (NCCN) recommends MMR screening for LS for all CRCs regardless of age. The American College of Medical Genetics and Genom...

Purpose: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristi...

Simple Summary BRCAPRO is a widely used breast cancer risk prediction model based on family history. A major limitation of this model is that it does not consider non-genetic risk factors. We expand BRCAPRO by combining it with another popular model, BCRAT, that uses mostly non-genetic risk factors, and show that the expanded model can achieve impr...

Background: Gastric adenocarcinoma (GAC) is the fifth most common cancer in the world, and the presence of germline pathogenic variants has been linked with approximately 5% of gastric cancer diagnoses. Multiple GAC susceptibility genes have been identified, but information regarding the risk associated with pathogenic variants in these genes rema...

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal tes...

Background: Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefi...

10577 Background: Germline genetic testing for cancer susceptibility has proven to be a powerful tool in cancer risk assessment, screening, and prevention but a huge gap exists between the number of germline genetic testing candidates and the number of patients actually tested. This study aimed to evaluate the impact of mainstreamed genetic testing...

551 Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for...

e13592 Background: NLP (artificial intelligence) can automate the identification of records in large datasets. The purpose of this study was to evaluate the feasibility of NLP to identify breast cancer-associated lung metastases to understand clinical characteristics and challenges posed by this common site of breast cancer recurrence. Methods: Pat...

Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for gBR...

Introduction: Magnetic seeds have emerged as an alternative to wires for localization of nonpalpable breast lesions. The purpose of this study was to evaluate the utility of magnetic seeds compared to wires for preoperative localization. Materials and methods: A retrospective cohort analysis of magnetic seed localization (MSL) and wire localizat...

Purpose Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance...

Screening programs must balance the benefit of early detection with the cost of overscreening. Here, we introduce a novel reinforcement learning-based framework for personalized screening, Tempo, and demonstrate its efficacy in the context of breast cancer. We trained our risk-based screening policies on a large screening mammography dataset from M...

(1) Background: The purpose of this study is to compare the performance of four breast cancer risk prediction models by race, molecular subtype, family history of breast cancer, age, and BMI. (2) Methods: Using a cohort of women aged 40–84 without prior history of breast cancer who underwent screening mammography from 2006 to 2015, we generated bre...

PURPOSE Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demo...

Genetic testing offers providers a potentially life saving tool for identifying and intervening in high-risk individuals. However, disparities in receipt of genetic testing have been consistently demonstrated and undoubtedly have significant implications for the populations not receiving the standard of care. If correctly used, there is the potenti...

Background Nipple-sparing mastectomy (NSM) is an oncologically safe alternative to skin-sparing mastectomy (SSM). This study evaluated whether NSM patients were more satisfied than SSM patients in short- and long-term follow-up.Methods Women who underwent NSM or SSM between 2009 and 2019 completed a postoperative BREAST-Q survey at least 1 year aft...

Background Breast cancer is a heterogeneous disease, divided into subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Subtypes have different biology and prognosis, with accumulating evidence of different risk factors. The purpose of this study was to compare b...

Background Genetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes. Objective The aim of this study was to understa...

Background Fewer than 1% of all breast cancers occur in men. As a result, a distinct lack of data exists regarding the management and outcomes in this cohort.Methods Any male patient with pathologically confirmed breast cancer diagnosed between August 2000 and October 2017 at either Massachusetts General Hospital or Brigham and Women’s Hospital/Dan...

Background Nipple-sparing mastectomy (NSM) is now routinely offered to BRCA mutation carriers for risk reduction. We assessed the rates of ipsilateral cancer events after prophylactic and therapeutic NSM in BRCA1 and BRCA2 mutation carriers.MethodsBRCA1 and BRCA2 mutation carriers undergoing NSM from October 2007 to June 2019 were identified in a s...

Objective Second breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments. Me...

Purpose Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20–40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact o...

Pathogenic variants in germline cancer susceptibility genes can increase the risk of a large number of diseases. Our study aims to assess the disease spectrum of gastric cancer susceptibility genes and to develop a comprehensive resource of gene–disease associations for clinicians. Twenty-seven potential germline gastric cancer susceptibility genes...

Background Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases, which clinicians must manage for their patients. We evaluated the disease spectrum of breast cancer susceptibility genes (BCSGs) with the aim of developing a comprehensive resource of gene-disease associations for clinicians. Methods Twel...

BACKGROUND Genetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes. OBJECTIVE The aim of this study was to underst...

Background: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better can...

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guideline...

Background Determining how many female patients who underwent breast imaging meet the eligibility criteria for genetic testing for familial pancreatic cancer (FPC).MethodsA total of 42,904 patients seen at the Newton-Wellesley Hospital between 2007 and 2009 were retrospectively reviewed. The first four categories were based on pancreatic cancer-ass...

Background: Molecular characterization of breast tumors has revealed four subtypes which differ in expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Breast cancer subtypes have different prognosis and unique risk factors. Breast cancer risk assessment models mainly reflect risk of...

Background: Family history is one of the strongest predisposing factors for male breast cancer (MBC). Several MBC susceptibility genes have been identified, but the risk of MBC for individuals with a pathogenic variant in these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susc...

Improved breast cancer risk models enable targeted screening strategies that achieve earlier detection and less screening harm than existing guidelines. To bring deep learning risk models to clinical practice, we need to further refine their accuracy, validate them across diverse populations, and demonstrate their potential to improve clinical work...

Purpose We evaluated the risk of cardiac mortality in older patients who receive adjuvant radiotherapy (RT) for stage I breast cancer to determine if this risk persists in the modern era. Methods Using the 2000-2015 Surveillance, Epidemiology, and End Results Program (SEER) data, we performed a population-based cohort study to evaluate the associa...

Screening programs must balance the benefits of early detection against the costs of over screening. Achieving this goal relies on two complementary technologies: (1) the ability to assess patient risk, (2) the ability to develop personalized screening programs given that risk. While methodologies for assessing patient risk have significantly impro...

Purpose: Literature on clinical note mining has highlighted the superiority of machine learning (ML) over hand-crafted rules. Nevertheless, most studies assume the availability of large training sets, which is rarely the case. For this reason, in the clinical setting, rules are still common. We suggest 2 methods to leverage the knowledge encoded i...

Background Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases. We aim to evaluate the disease spectrum of breast cancer susceptibility genes (BCSGs) to develop a comprehensive resource of gene-disease associations for clinicians. Methods Thirteen genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1,...

Background The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID‐19) on breast cancer screening, breast surgery, and genetics consultations. Methods User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the...

Background Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes.Methods We identified biopsy-proven, node-positive breast cancer patients tr...

Accurate risk stratification is key to reducing cancer morbidity through targeted screening and preventative interventions. Numerous breast cancer risk prediction models have been developed, but they often give predictions with conflicting clinical implications. Integrating information from different models may improve the accuracy of risk predicti...

Unstructured: Modern Artificial Intelligence (AI) technologies can play a key role in preventing and monitoring the present and the future epidemics. Here, we provide an overview of recently published literature on the COVID-19 pandemics in four strategic areas: (1) triage, diagnosis and risk prediction; (2) drug repurposing and development; (3) p...

UNSTRUCTURED Artificial intelligence (AI) technologies can play a key role in preventing, detecting, and monitoring epidemics. In this paper, we provide an overview of the recently published literature on the COVID-19 pandemic in four strategic areas: (1) triage, diagnosis, and risk prediction; (2) drug repurposing and development; (3) pharmacogeno...

Objective: The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients. Materials: Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emissi...

1520 Background: It is critical for oncologists to be aware of unbiased and interpretable cancer risks (i.e., penetrance) in carriers with germline pathogenic variants in cancer susceptibility genes. However, relevant literature is large and varies significantly in study design, patient ascertainment, and types of risk estimates reported. This hete...

In this work, we consider the exponentially growing subarea of genetics in cancer. The need to synthesize and centralize this evidence for dissemination has motivated a team of physicians to manually construct and maintain a knowledge base that distills key results reported in the literature. This is a laborious process that entails reading through...

PurposeThe classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset. MethodsA total of 7496 variants sequenced between 1996 and 2019 were collected...

Background: Use of risk-reducing Salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian and breast cancer for women who carry a BRCA1/2 mutation. It is important to adjust for RRSO use in the estimation of BRCA1/2 penetrance of breast and ovarian cancer. Methods: We searched PubMed for penetrance estimates of breast and ovarian c...

Background: Lynch syndrome, the most common colorectal cancer (CRC) syndrome, is caused by germline mismatch repair (MMR) genes. Precise estimates of age-specific risks are crucial for sound counseling of individuals managing a genetic predisposition to cancer, but published risk estimates vary. The objective of this work is to provide gene-, sex-...

Purpose The goal of breast cancer surgery is to remove all of the cancer with a minimum of normal tissue, but absence of full 3-dimensional information on the specimen makes this difficult to achieve. Method Micro-CT is a high resolution, X-ray, 3D imaging method, widely used in industry but rarely in medicine. Results We imaged and analyzed 173...

p>Background: The goal of breast cancer surgery is to remove all cancer with a minimum of normal tissue, but the absence of full 3-dimensional information on the surgical specimen makes this difficult to achieve. Method: Micro CT is a high resolution, X-ray, 3D imaging method, used principally in material science and industry but little used in med...

Background: Guideline-concordant care (GCC) for DCIS includes surgery, radiation, and endocrine treatment. Active surveillance (AS) is a strategy under study for management of low risk DCIS. The PORTAL Study was designed to evaluate patient reported outcomes (PROs) after GCC for DCIS compared to women who received AS for DCIS combined with women wi...

Background: HBOC testing guidelines were established to identify patients with clinically actionable variants and limit economic burden. We report the impact of germline results on health outcome based on clinical decision making and treatment interventions, regardless of guidelines, in a multi-center registry. Methods: 20 community-based and acade...

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The medical literature has been growing exponentially, and its size has become a barrier for physicians to locate and extract clinically useful information. As a promising solution, natural language processing (NLP), especially machine learning (ML)‐based NLP is a technology that potentially provides a promising solution. ML‐based NLP is based on t...

PURPOSE: The popularity of germline genetic panel testing has led to a vast accumulation of variant-level data. Variant names are not always consistent across laboratories and not easily mappable to public variant databases such as ClinVar. A tool that can automate the process of variants harmonization and mapping is needed to help clinicians ensur...

Background: We previously reported that breast conservation was feasible for women with large or irregularly shaped breast cancers when tumor resection was guided by multiple localizing wires. We now report long-term outcomes of multiple-wire versus single-wire localized lumpectomies for breast cancer. Patients and methods: We retrospectively re...

Purpose Radiofrequency identification (RFID) tag localization (TL) is a technique of localizing non-palpable breast lesions that can be performed prior to surgery. We sought to evaluate whether TL is comparable to wire localization (WL) in regard to specimen size, operative time, and re-excision rate. Methods A retrospective cohort analysis was pe...

Introduction Bilateral reduction mammoplasty is one of the most common plastic surgery procedures performed in the U.S. This study examines the incidence, management, and prognosis of incidental breast cancer identified in reduction specimens from a large cohort of reduction mammoplasty patients. Methods Breast pathology reports were retrospective...

Background: This study examined the effects of an enhanced recovery program on inpatient opioid requirements and hospital length of stay (LOS) for mastectomy patients undergoing immediate reconstruction. Methods: An enhanced recovery program for patients undergoing mastectomy with immediate tissue expander (TE) or implant reconstruction was eval...

Background: Several breast cancer risk-assessment models exist. Few studies have evaluated predictive accuracy of multiple models in large screening populations. Methods: We evaluated the performance of the BRCAPRO, Gail, Claus, Breast Cancer Surveillance Consortium (BCSC), and Tyrer-Cuzick models in predicting risk of breast cancer over 6 years...

Purpose: The medical literature relevant to germline genetics is growing exponentially. Clinicians need tools that help to monitor and prioritize the literature to understand the clinical implications of pathogenic genetic variants. We developed and evaluated two machine learning models to classify abstracts as relevant to the penetrance-risk of c...

Purpose: Quantifying the risk of cancer associated with pathogenic mutations in germline cancer susceptibility genes-that is, penetrance-enables the personalization of preventive management strategies. Conducting a meta-analysis is the best way to obtain robust risk estimates. We have previously developed a natural language processing (NLP) -based...

Background The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. Methods Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary...

Background Increased use of contralateral prophylactic mastectomy (CPM) as treatment for ductal carcinoma in situ (DCIS) in the US was first noted in the early 2000s. Optimization of treatment guidelines for DCIS requires an understanding of current surgical treatment trends, particularly as they may differ by patient sociodemographic and community...

Purpose: Natural language processing (NLP) techniques have been adopted to reduce the curation costs of electronic health records. However, studies have questioned whether such techniques can be applied to data from previously unseen institutions. We investigated the performance of a common neural NLP algorithm on data from both known and heldout...

Objective: Differentiation between gynecomastia, a common cause of male breast enlargement, and breast cancer is crucial for appropriate management. Fine-needle aspiration biopsy has been shown to be sensitive and specific in assessing female breast lesions, comparable to core needle biopsy. Few such studies have been conducted in men. We assessed...

1561 Background: Proliferative breast lesions with atypia (atypical hyperplasia and lobular carcinoma in-situ (LCIS)) increase the risk of breast cancer (BC). Most cases are diagnosed in the context of an abnormal mammogram. Little is known about BC risk for patients with these lesions who are asymptomatic. Mammoplasty specimens allow us to study b...

1583 Background: HBOC testing guidelines were established to identify patients with clinically actionable variants and limit economic burden. We report the impact of germline results on health outcome based on clinical decision making and treatment interventions, regardless of guidelines, in a multi-center registry. Methods: 20 community-based and...

Background Screening breast MRI is recommended for women with BRCA mutation or a history of chest radiation, but guidelines are equivocal for MRI screening of women with a personal history of breast cancer or high-risk lesion. Purpose To evaluate screening breast MRI performance across women with different elevated breast cancer risk indications. M...

Purpose Atypical ductal hyperplasia (ADH) significantly increases the risk of breast cancer in women. However, little is known about the implications of ADH in men. Methods Review of 932 males with breast pathology was performed to identify cases of ADH. Patients were excluded if ADH was upgraded to cancer on excision, or if they had contralateral...

PURPOSE: The medical literature relevant to germline genetics is growing exponentially. Clinicians need tools monitoring and prioritizing the literature to understand the clinical implications of the pathogenic genetic variants. We developed and evaluated two machine learning models to classify abstracts as relevant to the penetrance (risk of cance...

Purpose The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. Methods A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop...

Background: Nipple-sparing mastectomies (NSMs) preserve the intact nipple, including nipple duct orifices. Retained orifices might remain patent and communicate with the underlying reconstruction. We report the incidence and outcomes of nipple discharge after NSM in pregnant and nonpregnant women. Patients and methods: Retrospective review of al...

Background: The addition of pertuzumab to trastuzumab and chemotherapy significantly improves the pathologic complete response (pCR) rate in HER2+ localized breast cancer in the preoperative setting. Although many patients are converted to breast conserving therapy (BCT) candidates by neoadjuvant HER2-directed therapy, a significant proportion opt...

Background: The rising incidence of ductal carcinoma in situ (DCIS) since the widespread enactment of mammography screening has been well documented. Patterns in DCIS incidence among women of various ages and across different racial and ethnic groups have not been well described. Study design: The Surveillance, Epidemiology, and End Results publ...

Purpose Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. Methods We...

To the Editor The article by Katz and colleagues¹ recently published in an issue of JAMA Surgery contains factual errors that are concerning. We would agree that rates of genetic testing are suboptimal, with many patients who should have genetic testing not receiving it, and we also agree that surgeon skill, attitude, and practice factor significan...

Purpose: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer N...