bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalp cooling to reduce alopecia as a barrier to chemotherapy.
Authors: Pupo Wiss Isabel M. , Hagigeorges Dina , Walker Chloe J. , Flanagan Kelly E. , James James T. , Geary Molly C. , Fay Mary , Senna Maryanne M , Isakoff Steven J. 
Published: June 2021

e12537 Background: Chemotherapy induced alopecia (CIA) is one of the most distressing adverse events reported by patients undergoing chemotherapy, yet there is limited data addressing the impact of CIA on treatment acceptance. Scalp cooling (SC) has been shown to decrease CIA. Here we report our assessment of CIA as a barrier to chemotherapy and the efficacy of SC using pre- and post-treatment surveys of patient reported outcomes. Methods: Patients who received alopecia-inducing chemotherapy and utilized SC between November 2018 and September 2020 at our institution were enrolled in a prospective IRB approved registry. Surveys including the Chemotherapy Induced Alopecia Distress Scale (CADS) were administered before and within two weeks after treatment. Using the CADS survey, patients were asked about their hesitation to receive chemotherapy and the burden they feel about alopecia as a side effect of chemotherapy. Results: Of 90 patients who completed the first or last treatment survey, the most common treatment regimens were docetaxel/cyclophosphamide (TC), docetaxel/carboplatin/trastuzumab/ pertuzumab (TCHP), and paclitaxel/trastuzumab (TH). The most common disease type was breast cancer (92.2%) and all participants were females. Of 74 SC patients who completed the pre-treatment survey, the median age was 50.5 (range 26-75) and included 65 (87.8%) Caucasian, 4 (5.4%) Black, and 3 (4.0%) Asian patients. 89.2% used Paxman SC and 10.8% used Penguin SC. Of those who completed the CADS survey prior to treatment, 8 (10.8%) reported ‘quite a bit’ to ‘very high’ hesitation, and 34 (46.0%) reported feeling that alopecia was either ‘quite’ or ‘very much’ a burden of chemotherapy. All 40 SC patients (median age 53.5, range 31-76) who completed the post-treatment survey were Caucasian and used Paxman SC. Self-reported efficacy of SC in these 40 patients was less than 10% hair loss in 10 (25.0%), 11-25% hair loss in 7 (17.5%), 26-50% hair loss in10 (25.0%), 51-75% hair loss in 9 (22.5%), and 76-100% hair loss in 4 (10%). Overall, 27 (67.5%) patients reported SC limited alopecia ‘a lot’ to ‘perfectly’. Conclusions: In our study, alopecia was identified as a notable burden to nearly half our SC patients and 10.8% hesitated when making their decision to receive chemotherapy. After using SC during treatment, 67.5% of patients reported less than 50% hair loss, and 67.5% reported that SC reduced alopecia ‘a lot’ or ‘perfectly’. Our study highlights the significance of alopecia as a chemotherapy burden and potential barrier to accepting treatment, and suggests SC may be efficacious in decreasing CIA, which may allow patients to feel less hesitation towards chemotherapy.
COVID-19 outcomes in patients with a history of breast cancer: A diverse multicenter Los Angeles cohort study.
Authors: Kathuria-Prakash Nikhita , Antrim Lauren , Sun Alexander W , Kang Irene , Garcia-Jimenez Maria De Lourdes , Angell Trevor E , Lechner Melissa G , In Gino Kim 
Published: June 2021

e12544 Background: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has affected over 100 million individuals during the current pandemic. Cancer is a reported risk factor for worse outcomes from SARS-CoV-2 infection and its clinical syndrome COVID-19. However, risk associated with specific cancer subtypes, extent of disease, and treatment history remains unclear. Breast cancer is the most common cancer in women and is treated with multiple modalities that may affect COVID-19 severity and outcomes, including surgery, radiation (RT), hormone therapy (HT), and chemotherapy (CT). Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 and history of breast cancer at two academic centers in Los Angeles, CA between January – September, 2020. Demographic information, cancer diagnosis, treatment history, comorbid conditions, and clinical outcomes of COVID-19 were reviewed. The primary outcome was rate of hospitalization for COVID-19. Associations were evaluated for significance by chi-square test or Student’s T test, with a = 0.05. Results: Our cohort included 61 patients with history of breast cancer. 19 (31.1%) required hospitalization and 3 (4.9%) died from COVID-19. Median age was 61 years. 44% of patients were White/Caucasian, 37.7% Hispanic/Latinx, 8% Black/African American, 5% Asian, and 5% were of another race. 87% of patients had local or regional disease and 13% had distant metastases. 53% of patients had ever received CT historically, 66% HT, and 53% RT. 25% of patients received cancer treatment (surgery, CT, or RT) within 90 days of COVID-19 diagnosis. 38% were on HT at time of COVID-19 diagnosis. Patients with prior RT were more likely to be hospitalized from COVID-19 than those with no prior RT (44% vs 14%, p = 0.02), as were patients with 2 or more comorbidities (p = 0.01). In addition, there was a trend toward lower hospitalization rates for patients on HT [24% vs. 42% (p = 0.17)] and a trend toward higher hospitalization rate for non-white ethnicity [35% vs. 25% (p = ns)]. Extent of disease, history of CT, or receipt of any cancer treatment (e.g. surgery, RT, CT) within 90 days of COVID-19 diagnosis were not associated with hospitalization rate. Conclusions: In our diverse cohort of breast cancer patients with COVID-19 a history of RT and presence of multiple comorbidities were both associated with increased risk of hospitalization, while a history of HT was not. Further investigation is needed to validate these findings in larger cohorts. These findings may inform recommendations for breast cancer patients during the ongoing SARS-CoV-2 pandemic.
Heterogeneity between core needle biopsy and synchronous axillary lymph node metastases in early breast cancer patients: Comparison of HER2, estrogen and progesterone receptor expression profiles during primary treatment regime.
Authors: Weydandt Laura , Nel Ivonne , Kreklau Anne , Horn Lars-Christian , Aktas Bahriye 
Published: June 2021

e12565 Background: Therapeutic decisions for the primary treatment of breast cancer is commonly based on the expression profiles of estrogen (ER), progesterone (PR) and the human epidermal growth factor 2 (HER2) receptors. However, breast cancer is a very heterogeneous disease, and receptor changes were manifold reported during progression. Little is known about receptor discordance in the primary setting. Here, we compared receptor expression profiles between core needle biopsy (CNB) of the breast tumor tissue and synchronous axillary lymph node metastases (LNM) not at recurrence, but at the primary treatment. Methods: In a German single center study, we retrospectively analyzed 175 breast cancer patients with axillary synchronous LNM. 69,7% of our patients were without any upfront therapy. Profiles of ER, PR and HER2 were immunohistochemically analyzed using the common cut-off at 10% positive tumor cells vs. the controversially discussed low-positive cut-off at 1%. Receptor status was compared between CNB specimens of the primary tumor tissue and axillary LNM. Further, clinicopathological characteristics were correlated to receptor changes. Results: The discordance rates between CNB and axillary LNM were 12.7% for HER2, 6.9% for ER and 22.6% for PR using the ≥1% cut-off, respective 7.5% for ER and 25.6% for PR when using the ≥10% cut-off-level. The most frequently occurring change was a PR loss. Analysis of clinical parameters revealed a significant association of ER change between CNB and LNM in younger patients (p < 0.01) with increased proliferation marker Ki-67 (p = 0.04). Conclusions: Receptor discordance between CNB and synchronous axillary LNM appears to exist at the primary setting already. Hence, receptor profiles of the tumor tissue and the synchronous axillary LNM should be considered for treatment decision.
A novel, computer-aided, scanning platform agnostic solution for grading carcinomas in breast biopsy whole slide images.
Authors: Orsi Nicolas M , Dasgupta Tathagata , Mukhopadhyay Satabhisa , Cummings Michele , Berwick Angelene 
Published: June 2021

e12575 Background: The determination of breast cancer grade remains a problematic diagnostic issue in biopsies due to limited tissue sampling and the inherent inter-observer variability associated with the Nottingham (histologic) score. Significantly, biopsy grading corresponds only moderately with that based on excision specimens, with discordance rates of 21-30.0%, which is a concern for cases managed neoadjuvantly or with minimally ablative therapy. Although the advent of digital pathology has encouraged endeavors to automate breast cancer detection and grading, no method has yet received regulatory approval for clinical use or proven to be a platform agnostic solution. Methods: This study was the blinded clinical validation a novel, FDA breakthrough designation approved automated device-based predictive solution which uses a surrogate scale to determine breast carcinoma grade in core biopsies using H&E slide whole slide images (WSIs) only. Non-preselected malignant breast core biopsy clinical cases (n=173 WSIs; 107 cases) covering a broad spectrum of breast cancer morphological subtypes were scanned at x20 magnification on both on Aperio high-throughput T2/T3 systems (.SVS files) and Roche-Ventana DP200 scanners (.BIF files). The diagnostic gold standard reference was the reports of tertiary referral center breast subspecialty consultant histopathologists. Diagnostic outputs were also compared to case-matched resection specimen grades. Comparison of diagnostic outcomes with pathologists as gold standard was done using inter observer agreement (cohen kappa) with 95% CI and statistically significant chi-squared test p-value for two different scanner platforms. Results: Although biopsy-based diagnostic concordance with pathologists was very good, the device actually delivered a much better concordance between case-matched biopsy and resection specimen (accuracy: 95%, cohen kappa: 0.91) relative to pathologists’ assessments (accuracy: 80%). Conclusions: This indicates that the use of a single continuous surrogate grading scale is much less affected by limited tissue sampling than conventional ordinal morphological scales. This level of performance was independent of file format analyzed, demonstrating the device’s platform agnosia.
Composite scoring combining OncotypeDX risk with circulating tumor cell status improves prognostication.
Authors: Bilani Nadeem , Elson Leah , Elimimian Elizabeth Blessing , Liang Hong , Nahleh Zeina A. 
Published: June 2021

e12577 Background: Genomic assays, such as the 21-gene OncotypeDX (ODX) and the 70-gene MammaPrint (MP) panels, can be used to personalize treatment for women with early-stage, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC). We previously showed that 1) circulating tumor cell (CTC) status has prognostic and predictive value in BC, and that 2) there is no clear association between ODX risk and CTCs. We, hereby, assess the prognostic value of composite scoring combining ODX and CTC data. Methods: This analysis of the 2004-2017 National Cancer Database registry includes patients with early-stage (AJCC I-II), HR+/HER- BC, as well as ODX, MP, and CTC data. A composite model was created with ODX and CTC data: low-risk escalated to intermediate-risk, or intermediate- to high-risk, if positive for CTCs. The association between a) ODX, b) ODX-CTC composite, or c) MP and overall survival (OS) was examined using Cox regressions, controlling for age (50-70); and stratifying by race (White vs. Black) and tumor histology (ductal vs. lobular). Prognostic value was evaluated using Harrell’s C-index (i.e. area under ROC curve) for each model. Results: N = 841,716 patients with early-stage, HR+/HER2- BC were identified. N = 271,416 (32.2%) had ODX data, n = 12,417 (1.5%) had MP data, and n = 1,141 (0.14%) had both ODX and CTC data. Due to CTC-positivity, n = 46 patients were upstaged from low- to intermediate-risk (23.1% of all low-risk), while n = 63 patients were upstaged from intermediate- to high-risk (20.5% of all intermediate-risk) in the composite ODX-CTC model. All 3 prognostic scoring systems were associated (p < 0.05) with OS as per Cox regressions. As indicated by a C-index closer to 1, MP appears superior to ODX alone at differentiating high- from low-risk based on OS (0.597 versus 0.565) patients. However, composite ODX-CTC scoring was superior to MP alone (0.673 versus 0.597). This model could not be validated in Black patients (versus White) or those with lobular histology (compared to ductal) due to limited ODX-CTC data in these groups. Conclusions: Composite ODX-CTC risk scoring appears superior to MP alone. If confirmed, this prognostic model would more accurately identify early-stage, HR+/HER2- patients requiring escalated systemic therapy including chemotherapy compared to low-risk BC. More data is needed in ethnic minorities and patients with atypical histology to validate these promising results.[Table: see text]
Laser ablation of multifocal breast carcinoma: Assessing viability for patients not accepting surgery.
Authors: Bhalla Rusy 
Published: June 2021

e12584 Background: Breast carcinoma is a major public health problem in India and world. It is the leading cause of cancer in women in India. The overall 5 year survival rate in western countries is over 90%. In India it drops to 40 to 60%. The various factors responsible for this include presenting late due to unacceptability of many women for mutilation of their breasts. Breasts being a very important feminine cosmetic benchmark. Methods: Laser ablation of Breast tumours is now a USFDA and CE approved procedure. The aim of this observational study was to observe completion of tumour ablation by intralesional laser ablation. Laser Ablation was performed as a single procedure in 10 women over a 7 year period. All women who consented to the procedure were in stage late stage 2 and 3 with multifocal and/or multilocational disease. As such they were not candidates for Breast Conservation surgery. Pre laser PET scans confirmed the absence of Metastatic disease outside breast and Axilla. Results: All Post Menopausal patients showed a complete necrosis of the tumour and axillary lymph nodes on a follow up of 2 to 7 years. The findings were confirmed on serial PET scans after 6 months and 2 years. Pre menopausal women showed recurrence in non laserised areas and were given follow up Laser Ablation procedure. Conclusions: Laser Ablation is a viable procedure for patients unwilling for mastectomy in stage 3 Breast cancer. The skill sets required for the procedure are new and surgeons will have to be trained for the procedure.
H&E-like histology of unstained fresh and formalin fixed breast tissue with Photo Acoustic Remote Sensing (PARS) microscopy.
Authors: Mackey John Robert , Ecclestone Benjamin , Dinakaran Deepak , Bigras Gilbert , Reza Parsin Haji 
Published: June 2021

e12590 Background: Approximately 30% of breast cancer patients undergoing breast-conserving surgery (BCS) require re-excision(s) to obtain clear margins, causing delays in adjuvant treatment, poor aesthetic results, and increased infection rates, costs, and patient anxiety. Frozen section pathology assessment (FSA) reduces re-excision rates from 27% to 6%, but FSA extends operative times and has a false negative rate of 17%. Photo-Acoustic Remote Sensing (PARS) is a new laser-based light microscope that permits non-contact cellular resolution imaging of unstained tissues. Methods: We used an ultraviolet reflection-mode PARS microscope to study i) formalin-fixed, paraffin embedded (FFPE) breast tissue blocks, ii) unstained thin sections of FFPE invasive ductal carcinoma and ductal carcinoma in situ, iii) formalin fixed bulk surgical specimens of benign and malignant human breast tissue, and iv) benign and malignant fresh rodent mammary tissue without fixation, processing, or staining. Fresh tissues were imaged after a range of warm ischemic times and across a range of cold ischemic times in neutral phosphate buffered saline at 4°C. For each condition, an ultraviolet laser was used to excite DNA and other cellular components in these samples, and signals were captured using a continuous-wave detection laser. The PARS signal was false-colored to closely replicate traditional hematoxylin and eosin staining. Results: In all fixed tissues, PARS virtual histology images were of diagnostic quality, permitted margin assessment, and analogous to transmission light microscopy of standard hematoxylin and eosin-stained FFPE slides, achieved without tissue sectioning or tissue staining. Furthermore, PARS microscopy also provided cellular level virtual histology images in fresh breast tissue with warm and cold ischemic times ranging from twenty minutes to two hours; these images have no available clinical comparators as non-contact cellular level imaging of unprocessed fresh tissue has not previously been reported. In aggregate, we demonstrate the feasibility of PARS to provide diagnostic and margin assessment images across a range of tissues including formalin fixed and freshly resected, unstained, unprocessed breast tissue. Conclusions: PARS is a new microscope technology addressing the practical needs of intraoperative margin assessment during BCS: i) no requirement for tissue staining, ii) rapid acquisition of hematoxylin and eosin-like images without the requirement for tissue freezing, embedding, or sectioning, iii) diagnostic quality cellular resolution, and iv) assessment of resected bulk tissue margins. In principle, this technology may also permit label-free non-contact intraoperative margin assessment of the surgical cavity. These data support the clinical development and evaluation of PARS microscopic intraoperative assessment of BCS margins.
Prior DCIS and overall mortality in women with stage I breast cancer.
Authors: Nelson Rebecca A. , Lai Lily L. , Mortimer Joanne E. , Soto Perez De Celis Enrique , Chlebowski Rowan T. , Kruper Laura 
Published: June 2021

e12593 Background: Whether a prior diagnosis of ductal carcinoma in situ (DCIS) impacts women later diagnosed with invasive breast cancer is unclear. If localized breast cancer following DCIS is more aggressive than localized breast cancer alone, this could inform therapy decisions. To our knowledge, no study has examined the impact of prior DCIS on overall mortality in women with stage I invasive breast cancer. The study objective was to determine if overall mortality for women with stage I breast cancer with prior DCIS is different from those with stage I disease without prior DCIS. Our hypothesis was that women with prior DCIS would have higher mortality compared to those without prior DCIS. Methods: 302,484 patients with stage I cancer diagnosed from 1998 to 2016 were ascertained from SEER. Of these, 5,011 (1.7%) had prior DCIS. Patients with DCIS were matched 1:2 to women with no prior DCIS based on age, year of diagnosis, race/ethnicity, marital status, and invasive breast cancer characteristics including histology, tumor grade, tumor size, T stage, N stage, ER/PR status, surgery type, radiation, and chemotherapy status. The primary study outcome was overall mortality. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: Cases and controls had similar demographics. Compared to women with stage I breast cancer without prior DCIS, overall mortality was statistically significantly lower in women with stage I breast cancer with prior DCIS (hazard ratio [HR] 0.89 95% confidence interval [CI]0.80-0.98). Other factors associated with overall mortality were bilateral mastectomy (adjusted HR: 0.62; 95% CI: 0.49-0.78), radiation therapy (adjusted HR: 0.64; 95% CI: 0.56-0.75) and chemotherapy (adjusted HR: 0.85; 95% CI: 0.72-0.99). Factors associated with higher overall mortality included age (trend p < 0.001), tumor grade (trend p = 0.003), and negative PR receptor status (adjusted HR: 1.29; 95% CI: 1.13-1.45). Breast cancer specific mortality, however, was statistically significantly higher in women with prior DCIS to their breast cancer diagnosis compared to women without prior DCIS to their breast cancer diagnosis (HR 1.24 95% CI 1.01-1.52). Conclusions: Contrary to our hypothesis, women with prior DCIS and subsequent stage I breast cancer have lower overall mortality compared to matched controls with stage I breast cancer without prior DCIS. In contrast, those with prior DCIS have higher breast cancer specific mortality than those without prior DCIS. Reasons for this discrepancy are unknown, but since DCIS is most commonly diagnosed on mammogram, differences may be related to sociodemographic characteristics that are associated with both higher screening adherence and higher overall survival, such as higher income, higher education achievement , and higher access to health care.
Does pathological complete remission after neoadjuvant chemotherapy translate to longer relapse-free survival in patients with triple-negative breast cancer in the Indian population?
Authors: Sharma Rakesh Kumar , Gogia Ajay , Deo SVS , Sharma Dayanand , Mathur Sandeep , Sagiraju Hari Krishna Raju 
Published: June 2021

e12618 Background: Attainment of pathological complete remission (pCR) with neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) is associated with improved survival outcomes. However, data corroborating this fact is lacking from the Indian subcontinent. Methods: We evaluated 179 cases of TNBC, registered at Dr. B.R.A., I.R.C.H., AIIMS, New Delhi, from a period of May 2013 to July 2020, who were treated with neo-adjuvant chemotherapy (NACT) followed by surgery. Patients with oligometastatic disease who were treated with NACT with curative intent were also included in the analysis. Multivariate logistic regression analysis was done to explore the factors associated with the achievement of pCR. Survival analysis was done to study the correlation of pCR with relapse-free survival (RFS) and overall survival (OS). Results: The median age of our cohort was 43 (18-67) years. Study population comprised 104 (58.1%) pre-menopausal, 67 (37.4%) post-menopausal and 8(4.5%) peri-menopausal patients respectively. Twenty-three patients (12.9%) presented with early breast cancer, 144 (80.5%) were locally advanced and 12 (6.7%) were oligo-metastatic. Forty (22.4%), 127 (71.0%) and 12 (6.7%) patients were at clinical stages-II, III, and IV respectively at the time of presentation as per AJCC 7th edition. The median duration of symptoms was 4 (0.25-36) months. Forty-seven (26.3%) patients underwent breast conservation surgery and 128 (71.5%) patients had modified radical mastectomy. Overall pCR was attained in 29.6%(n=53) of the patients, with rates of 55%(n=22) and 23.6%(n=30) in patients with stage-II and stage-III respectively. Stage-II patients were more likely to achieve pCR after NACT [OR (95% CI: 4.3 (2.0-8.9)] when adjusted for other clinical covariates. Three-year RFS in patients achieving pCR was 94.7%, whereas in patients not achieving pCR was 43.9%, with a hazard of relapse or death significantly less in patients attaining pCR [HR (95% CI): 0.14 (0.06-0.37), p <0.0001]. Similarly, three-year OS was 97.4 % vs 73.8% in patients attaining pCR vs not attaining pCR, with a hazard of death significantly less in patients with pCR [HR (95% CI): 0.06 (0.01-0.45) p<0.006]. Conclusions: Our results confirm that attainment of pCR following NACT leads to better survival outcomes in TNBC. Factors associated with improved pCR rates in the Indian population needs further evaluation.