Browsing by Author "Hwang, E Shelley"

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    Clinical and pathological stage discordance among 433,514 breast cancer patients.
    (American journal of surgery, 2019-10) Plichta, Jennifer K; Thomas, Samantha M; Sergesketter, Amanda R; Greenup, Rachel A; Fayanju, Oluwadamilola M; Rosenberger, Laura H; Tamirisa, Nina; Hyslop, Terry; Hwang, E Shelley
    BACKGROUND:We aim to determine clinical and pathological stage discordance rates and to evaluate factors associated with discordance. METHODS:Adults with clinical stages I-III breast cancer were identified from the National Cancer Data Base. Concordance was defined as cTN = pTN (discordance: cTN≠pTN). Multivariate logistic regression was used to identify factors associated with discordance. RESULTS:Comparing clinical and pathological stage, 23.1% were downstaged and 8.7% were upstaged. After adjustment, factors associated with downstaging (vs concordance) included grade 3 (OR 10.56, vs grade 1) and HER2-negative (OR 3.79). Factors associated with upstaging (vs concordance) were grade 3 (OR 10.56, vs grade 1), HER2-negative (OR 1.25), and lobular histology (OR 2.47, vs ductal). ER-negative status was associated with stage concordance (vs downstaged or upstaged, OR 0.52 and 0.87). CONCLUSIONS:Among breast cancer patients, nearly one-third exhibit clinical-pathological stage discordance. This high likelihood of discordance is important to consider for counseling and treatment planning.
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    Implications of missing data on reported breast cancer mortality
    (Breast Cancer Research and Treatment) Plichta, Jennifer K; Rushing, Christel N; Lewis, Holly C; Rooney, Marguerite M; Blazer, Dan G; Thomas, Samantha M; Hwang, E Shelley; Greenup, Rachel A
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    Nodal Response to Neoadjuvant Chemotherapy Predicts Receipt of Radiation Therapy after Breast Cancer Diagnosis.
    (International journal of radiation oncology, biology, physics, 2019-10-31) Fayanju, Oluwadamilola M; Ren, Yi; Suneja, Gita; Thomas, Samantha M; Greenup, Rachel A; Plichta, Jennifer K; Rosenberger, Laura H; Force, Jeremy; Hyslop, Terry; Hwang, E Shelley
    BACKGROUND:Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in breast-cancer patients, but it is unclear how post-NACT response influences radiotherapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiotherapy among patients experiencing nodal pCR is associated with improved OS. METHODS:cN1 female breast cancer patients diagnosed 2010-2015 who were ypN0 (i.e., nodal pCR, n=12,341) or ypN1 (i.e., residual disease, n=13,668) post-NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiotherapy. Cox proportional hazards modeling was used to estimate the association between radiotherapy and adjusted OS. RESULTS:26,009 patients were included. 43.9% (n=5,423) of ypN0 and 55.3% (n=7,556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test p=0.29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test p<0.001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease, both p<0.01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients but approached significance for ypN1 patients (hazard ratio [HR] 0.83, 95% CI 0.69-0.99, p=0.04, overall p-value=0.11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR 0.38, 95% CI 0.22-0.66) and ypN1 patients (HR 0.44, 95% CI 0.30-0.66, both p<0.001), but this improvement was not significantly greater than that associated with breast-only radiation. CONCLUSIONS:ypN0 patients were less likely to receive nodal radiation than ypN1 patients, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.
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    Perspectives on Inflammatory Breast Cancer (IBC) Research, Clinical Management and Community Engagement from the Duke IBC Consortium.
    (Journal of Cancer, 2019-01) Devi, Gayathri R; Hough, Holly; Barrett, Nadine; Cristofanilli, Massimo; Overmoyer, Beth; Spector, Neil; Ueno, Naoto T; Woodward, Wendy; Kirkpatrick, John; Vincent, Benjamin; Williams, Kevin P; Finley, Charlotte; Duff, Brandi; Worthy, Valarie; McCall, Shannon; Hollister, Beth A; Palmer, Greg; Force, Jeremy; Westbrook, Kelly; Fayanju, Oluwadamilola; Suneja, Gita; Dent, Susan F; Hwang, E Shelley; Patierno, Steven R; Marcom, P Kelly
    Inflammatory breast cancer (IBC) is an understudied and aggressive form of breast cancer with a poor prognosis, accounting for 2-6% of new breast cancer diagnoses but 10% of all breast cancer-related deaths in the United States. Currently there are no therapeutic regimens developed specifically for IBC, and it is critical to recognize that all aspects of treating IBC - including staging, diagnosis, and therapy - are vastly different than other breast cancers. In December 2014, under the umbrella of an interdisciplinary initiative supported by the Duke School of Medicine, researchers, clinicians, research administrators, and patient advocates formed the Duke Consortium for IBC to address the needs of patients in North Carolina (an ethnically and economically diverse state with 100 counties) and across the Southeastern United States. The primary goal of this group is to translate research into action and improve both awareness and patient care through collaborations with local, national and international IBC programs. The consortium held its inaugural meeting on Feb 28, 2018, which also marked Rare Disease Day and convened national research experts, clinicians, patients, advocates, government representatives, foundation leaders, staff, and trainees. The meeting focused on new developments and challenges in the clinical management of IBC, research challenges and opportunities, and an interactive session to garner input from patients, advocates, and community partners that would inform a strategic plan toward continuing improvements in IBC patient care, research, and education.
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    The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution.
    (Cell, 2020-04) Rozenblatt-Rosen, Orit; Regev, Aviv; Oberdoerffer, Philipp; Nawy, Tal; Hupalowska, Anna; Rood, Jennifer E; Ashenberg, Orr; Cerami, Ethan; Coffey, Robert J; Demir, Emek; Ding, Li; Esplin, Edward D; Ford, James M; Goecks, Jeremy; Ghosh, Sharmistha; Gray, Joe W; Guinney, Justin; Hanlon, Sean E; Hughes, Shannon K; Hwang, E Shelley; Iacobuzio-Donahue, Christine A; Jané-Valbuena, Judit; Johnson, Bruce E; Lau, Ken S; Lively, Tracy; Mazzilli, Sarah A; Pe'er, Dana; Santagata, Sandro; Shalek, Alex K; Schapiro, Denis; Snyder, Michael P; Sorger, Peter K; Spira, Avrum E; Srivastava, Sudhir; Tan, Kai; West, Robert B; Williams, Elizabeth H; Human Tumor Atlas Network
    Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.
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    The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions.
    (The Journal of surgical research, 2019-09) Sergesketter, Amanda R; Thomas, Samantha M; Fayanju, Oluwadamilola M; Menendez, Carolyn S; Rosenberger, Laura H; Greenup, Rachel A; Hyslop, Terry; Parrilla Castellar, Edgardo R; Hwang, E Shelley; Plichta, Jennifer K
    BACKGROUND:Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age. METHODS:Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis: <50 y, 50-70 y, and >70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis. RESULTS:A total of 530 patients with atypia were identified: 31.1% < 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% > 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41). CONCLUSIONS:Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.
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    Unmasking the immune microecology of ductal carcinoma in situ with deep learning.
    (NPJ breast cancer, 2021-03) Narayanan, Priya Lakshmi; Raza, Shan E Ahmed; Hall, Allison H; Marks, Jeffrey R; King, Lorraine; West, Robert B; Hernandez, Lucia; Guppy, Naomi; Dowsett, Mitch; Gusterson, Barry; Maley, Carlo; Hwang, E Shelley; Yuan, Yinyin
    Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial variability within ductal carcinoma in situ (DCIS) samples and its association with progression are not well understood. To characterise tissue spatial architecture and the microenvironment of DCIS, we designed and validated a new deep learning pipeline, UNMaSk. Following automated detection of individual DCIS ducts using a new method IM-Net, we applied spatial tessellation to create virtual boundaries for each duct. To study local TIL infiltration for each duct, DRDIN was developed for mapping the distribution of TILs. In a dataset comprising grade 2-3 pure DCIS and DCIS adjacent to invasive cancer (adjacent DCIS), we found that pure DCIS cases had more TILs compared to adjacent DCIS. However, the colocalisation of TILs with DCIS ducts was significantly lower in pure DCIS compared to adjacent DCIS, which may suggest a more inflamed tissue ecology local to DCIS ducts in adjacent DCIS cases. Our study demonstrates that technological developments in deep convolutional neural networks and digital pathology can enable an automated morphological and microenvironmental analysis of DCIS, providing a new way to study differential immune ecology for individual ducts and identify new markers of progression.