bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of breast implant associated squamous cell carcinoma.
Authors: Niraula Sujan , Katel Anjan , Barua Amit , Weiss Anna , Strawderman Myla S. , Zhang Huina , Manrique Oscar , O'Connell Avice , Pandey Sirish Raj , Dhakal Ajay 
Published: June 2023

e12508 Background: Breast augmentation is a cosmetic procedure with low rates of complication like bleeding, infection, implant rupture, and capsular contracture. However, rare cases of breast implant-associated (BIA) malignancies, including anaplastic large cell lymphoma (ALCL) and squamous cell carcinoma (SCC), have been reported. BIA-SCC is rarer than ALCL and current literature is limited to case reports. In 2022, the American Society of Plastic Surgeons (ASPS) issued a BIA-SCC summary statement based on 16 reported cases in response to an FDA safety communication. The aim of this study is to review published cases of BIA-SCC and present clinical and outcome data systematically. Methods: We conducted a literature search in English to identify studies reporting BIA-SCC from inception to October 2022. Patient characteristics and relevant outcomes were gathered from the studies. The mortality rates at 6 and 12 months were calculated as the inverse of the Kaplan-Meier survival estimate and presented with a 95% confidence interval (CI). Results: 14 articles and 18 cases of BIA-SCC were identified through a literature search. A rising trend in case reporting was observed, with 4 cases in the 1990s and 14 cases since 2010. The mean patient age was 56 years (range 40-81), and the mean time from breast augmentation to symptom appearance was 21 years (range 10-35). Most patients (13/18, 72%) underwent the procedure for cosmetic reasons. Out of 17 cases with available implant information, 11 cases had silicone based implants and 6 cases saline implants. Implant surface information was available in 5 cases, 4 smooth and 1 textured. 16 patients had swelling of the breast and 15 patients had breast pain at presentation of BIA-SCC. All patients had their implants removed and 10 underwent mastectomy after a diagnosis of SCC. Of the 12 cases with available treatment information, 7 received adjuvant chemotherapy and/or radiotherapy, 2 received neoadjuvant chemotherapy, and 3 did not receive perioperative chemotherapy or radiotherapy. Follow-up data was available for 10 cases. The 6-month and 12-month mortality rates were 11.1% (95% CI: 0.5% to 40.6%) and 23.8% (95% CI: 2.8% to 56.1%). Conclusions: The estimated 6-month mortality rate of 11% (95% CI: 0.5%-40.6%) should be interpreted cautiously due to the small sample size. It is lower than the rate reported by ASPS (44%), but the reason for this difference cannot be accurately explained as the methodology for determining then mortality rate is not provided in the ASPS statement. This study provides a valuable systematic review of a rare and poorly understood condition with a poor prognosis. Monitoring and sharing information is crucial to improve detection and management of BIA-SCC. [Table: see text]
Accelerated partial breast irradiation (APBI) for ductal carcinoma in situ.
Authors: Roth O'Brien Diana A , Boe Lillian A , Mueller Boris , Cuaron John J , Xu Amy , Bernstein Michael B. , McCormick Beryl , Powell Simon N. , Khan Atif J. , Braunstein Lior Zvi 
Published: June 2023

e12516 Background: Landmark studies of accelerated partial breast irradiation (APBI) included patients with DCIS, but with limited guidance regarding subgroups of in situ disease. Suitability criteria defined by national guidelines for APBI are narrowly constrained among those with DCIS, and controversy persists regarding optimal patient selection. Here, we report disease outcomes for a heterogeneous cohort of patients with DCIS who received APBI. Methods: Using a prospectively maintained institutional database, we identified patients with DCIS who underwent lumpectomy and adjuvant APBI from 2000 to 2022. Clinicopathologic characteristics were collected, and patients were classified as suitable, cautionary, or unsuitable for APBI by the latest American Society for Radiation Oncology (ASTRO) criteria. Outcomes of interest included local recurrence (LR), overall survival (OS), and follow up time. Cumulative incidence functions were calculated to estimate the incidence of LR over time. All statistical analyses were performed in R version 4.2.2. Results: The cohort comprised 176 patients, median age 60 years (IQR 52, 66). Median DCIS size was 9 mm (IQR 4, 15 mm), and approximately 20% had multifocal disease. Most patients had negative final surgical margins (160, 91%), with 10 patients having ≤2 mm margins and 6 having ≤1 mm margins for DCIS. 18 (10%) patients had nuclear grade I disease, 111 (63%) had grade II disease, and 33 (19%) had grade III disease, with a small subset classified as grade I-II or II-III. Most patients (161, 91%) had ER+ DCIS, and 72 (41%) received endocrine therapy. By ASTRO criteria, 118 (67%) patients were suitable for APBI, 57 (32%) cautionary, and 1 (0.6%) was unsuitable. At a median 24 months of follow up (range 2 to 127 months) we observed only one LR, yielding a 2-year LR rate of 0.6%. The LR occurred in the cautionary group, yielding a 2-year LR rate of 1.8% for the cautionary subset. The patient with LR was 56 years old, with 24 mm of high grade DCIS, ER+, with lumpectomy to negative margins, and did not receive endocrine therapy. No breast cancer mortality events were observed. Conclusions: Our early-term results exhibit excellent local control for patients with DCIS who received lumpectomy and APBI, even among those classified as “cautionary” by national guidelines. Although our findings are limited by short follow up, these results suggest that broadening the application of APBI for patients with DCIS may warrant further investigation.
Nomograms for predicting survival in patients with HER2 negative breast cancer.
Authors: Xu Yiyue , Zou Bing , Fan Bingjie , Li Butuo , Wang Linlin 
Published: June 2023

e12528 Background: It is increasingly recognized that there is considerable heterogeneity in HER2-negative breast cancer. The clinicopathological characteristics differed between HER2-low and HER2-0 breast cancer evaluated by immunohistochemistry (IHC) or in situ hybridization (ISH). HER2-low breast cancer may benefit from novel antibody-drug conjugates. However, the immunohistochemical agreement of HER2-low is poor. We aimed to construct nomograms to predict the survival of HER2-negative breast cancer and to evaluate the effects of HER2 on survival at the RNA transcript level. Methods: A retrospective analysis was performed on breast cancer patients who were evaluated HER2-negative by IHC or ISH in the TCGA database. Univariate and multivariate cox regression analysis was used to evaluate whether the HER2 RNA transcript level and clinical parameters were independent predictors for overall survival (OS), progression-free survival (PFS), and Disease-Specific Survival (DSS), and nomograms were generated for the prediction of 1-, 2-, 3-, 5-year OS, PFS, and DSS based on significant parameters. Survival curves were drawn using the Kaplan-Meier methods to compare mortality outcomes according to HER2 RNA transcript level (75% vs. 25%). Results: A total of 769 HER2-negative patients were included in the analysis. The median age of patients was 56 years (range 26-30), and the majority were White (80.3%). Univariate and multivariate cox regression analysis showed that age, pN_stage, and pM_stage were independent predictors for OS, but HER2 was not. The C-index of a nomogram based on these three parameters was 0.723 (95%CI, 0.6555-1). HER2, pT_stage, pN_stage, and pM_stage were analyzed as independent predictors of PFS. HER2, pN_stage, and pM_stage were independent predictors of DSS. The C-indexes of established nomograms were 0.734 (95%CI, 0.672-1) and 0.775 (95%CI, 0.686-1) respectively. PFS and DSS were significantly better for patients with high HER2 RNA transcript levels (PFS, log-rank p = 0.00446, HR = 0.352; DSS, log-rank p = 0.0119, HR = 0.247). Conclusions: In the TCGA database, the HER2 RNA transcript level was an independent predictor for PFS and DSS in HER2-negative breast cancer. Stratification of patients at the RNA level can help clinicians optimize treatment for HER2-negative breast cancer.
Real world treatment patterns and survival by germline BRCA (gBRCA) mutation status in patients with HER2-negative early breast cancer (eBC) in the US community oncology setting: A retrospective observational study.
Authors: Andersen Jay C. , Earla Jagadeswara Rao , Fulcher Nicole , Ndukum Juliet , Robert Nicholas J. , Robson Mark E. , Li Weiyan , Mejia Jamie 
Published: June 2023

e12535 Background: Germline BRCA mutations (gBRCAm) are associated with a higher risk of breast cancer at a younger age. Generally, gBRCA gene testing is performed in patients perceived as high risk for gBRCAm. Olaparib, a targeted poly (ADP-ribose) polymerase inhibitor (PARPi), has significantly improved overall survival (OS) in the randomized, double-blind OlympiA trial of patients with HER2-negative gBRCAm and was subsequently approved for the adjuvant treatment of patients with gBRCAm HER2-negative high-risk early breast cancer (eBC) treated with neoadjuvant or adjuvant chemotherapy. This study examines the real-world patient characteristics, treatment patterns and OS by gBRCA status among patients with HER2-negative eBC in a US community oncology setting prior to olaparib US approval for treatment of eBC. Methods: This retrospective observational study used structured data from The US Oncology Network's iKnowMed database. Adult patients were included if diagnosed with HER2-negative eBC (stage I-III) and if they initiated systemic neoadjuvant or adjuvant therapy between January 1, 2012-December 31, 2018 (followed through December 31, 2021). Patients were excluded if they progressed to stage IV within 6 months after neoadjuvant treatment or were diagnosed with another primary cancer. Descriptive analyses assessed patient characteristics, early-stage systemic treatments and OS among patients by gBRCA status. Results: Among 19,258 patients with BC meeting initial criteria, 1436 (7.5%) had a documented gBRCA test result. Among them, 10% had gBRCAm (n = 141, 43% hormone receptor positive [HR+], 57% triple-negative BC [TNBC]), 90% BRCAwt (n = 1294, 70% HR+, 30% TNBC), and 1 had a variant of uncertain significance. Median age at surgery was numerically lower in gBRCAm (43 years) than gBRCAwt (48 years) patients. Treatments included neoadjuvant-only therapy (gBRCAm 58%; gBRCAwt 34%), adjuvant-only therapy (gBRCAm 42%; gBRCAwt 66%) and both neoadjuvant and adjuvant therapy (gBRCAwt 0.1%). Median OS in both study cohorts was not reached. Median follow-up from surgery was less than 4 years (gBRCAm 47 months; gBRCAwt 46 months). At 48 months, estimated survival was 95% in gBRCAm and 94% in gBRCAwt patients. Conclusions: In this cohort of patients with HER2-negative eBC, among the 7.5% with a documented gBRCA result, 10% were identified with gBRCAm, reinforcing the need for gBRCA testing. Using structured real-world data through 2021 (prior to PARPi approval for eBC) with limited follow-up of < 4 years, our study found that OS by gBRCA status was similar among patients with HER2-negative eBC. Our further research with chart review data containing granular clinical information looking at intermediate endpoints such as recurrence in eBC is under way.
Symptom burden of patients with breast cancer on adjuvant hormone therapy: A preliminary report.
Authors: Gomaa Sameh , Lopez Ana Maria , Smith Rita , Slamon Rachel , Wen Kuang-Yi 
Published: June 2023

e12536 Background: Breast cancer (BCa) is the most common cancer in women. Adjuvant hormone therapy (AHT) showed consistent improvements in recurrence and survival rates. AHT use is associated with multiple side effects that cause a lack of adherence. This report aims to describe the symptom burden of BCA patients at treatment initiation from our ongoing RCT, which is directed at improving adherence through the innovative use of smart pill bottles. Methods: Descriptive statistics included socio-demographic information and medication use. Symptom burden and distress are assessed using the breast cancer prevention trial (BCPT) symptom scales. Self-efficacy is assessed using a modified version of Lorig’s Chronic Disease Self-Efficacy Scale for managing symptoms. Results are summarized as means (M), standard deviation (SD), ranges (R), and percentages. The relationship between patients’ symptoms and self-efficacy was analyzed using a multivariable linear regression model controlling for age and race. Results: Of the 119 patients included, the majority were White 80.7 %, with ages ranging from 31-81 with a mean age of 59.74 (SD=11.057). The majority had a college education or higher (61.3 %), married (66.4%), full-time workers (42.9 %) and had incomes of 75,000 USD or higher (59.0 %). The patients were on either Tamoxifen (17.7%), Anastrozole (55.4%), Letrozole (12.3%) or Exemestane (4.6 %). The (BCPT) subscales were; vasomotor symptoms (R=0-12.5, M= 5.8, SD= 3.14), Gastrointestinal symptoms (R=0-7.5, M= 2.97, SD= 1.14), bladder control (R=0-10, M= 3.09, SD= 1.87), Dyspareunia subscale (R=0-10, M= 3.53, SD= 2.27), Musculoskeletal pain (R=0-15, M= 7.5, SD= 3.53), Weight concerns (R=0-10, M= 4.22, SD= 2.16), Cognitive symptoms (R=0-15, M= 6.02, SD= 2.81). For the LORIG scales (R=1- 8.83, M= 6.04, SD=1.61). Patient symptoms were inversely correlated with higher LORIG scores for vasomotor symptoms (β = -.18, t(3) = -2.00, p= .048), Gastrointestinal symptoms (β = -.27, t(3) = -2.92, p= 0.004), Musculoskeletal pain (β = -.378, t(3) = -4.31, p= .000), Weight concerns (β = -.286, t(3) = -3.26, p= .0002), Cognitive symptoms (β = -.34, t(3) = -3.841, p= .000). Conclusions: Our results explore symptom burden and distress for breast cancer patients on AET. Based on the BCPT instrument subscales, musculoskeletal symptoms tend to be the most intrusive, with the highest mean score. Symptom burden was inversely related to higher self-efficacy represented by LORIG scores. This needs to be validated with further analysis in comparison to a control group across time points in the study to determine what would be a minimally important difference or change in score. This will help understand the interrelationships between physical symptoms and adherence to AHT. Clinical trial information: NCT04086875 .
Factors associated with oncotype and recurrence among a diverse breast cancer population seeking care at an urban safety-net hospital.
Authors: Wang Judy Jiaqi , Beaulieu-Jones Brendin , Acevedo Jose , Oshry Lauren , Merrill Andrea , Hirsch Ariel , Cassidy Michael Ryan , Ko Naomi Yu 
Published: June 2023

e12537 Background: The landmark trials, TAILORx and RxPONDER have established Oncotype DX (ODX) as a prognostic and predictive tool in the management of estrogen receptor positive (ER+), early-stage breast cancer. However, recent studies have revealed existing racial disparities in the ODX test. These findings call into question whether ODX is generalizable to diverse populations. We evaluated the prognostic value of ODX RS at an urban, academic safety net hospital. Methods: We conducted a single-institution retrospective study of patients diagnosed with invasive breast cancer and had an ODX test performed between January 1, 2010 to December 31, 2021. Demographic, tumor and treatment characteristics were obtained. Chi-square and ANOVA were used to examine associated factors among recurrences and non-recurrences. Results: We identified 315 patients diagnosed with ER+ breast cancer with an ODX test obtained. Racial breakdown was 47% White, 35% Black and 18% Other. 69% of the patients had public or no insurance. 20% of the patients had a low RS (0-10), 62% had intermediate (11-25) and 18% were high (26-100). 264 patients had no evidence of recurrence, 15 patients had a local or distant recurrence and 36 were unknown. Recurrence was significantly associated with younger age (p = 0.04), higher histologic grade (P < 0.001, < 0.001), intermediate oncotype score (p = 0.002) and no receipt of chemotherapy (p = 0.014). Focused analysis of the recurrence cohort demonstrates a significant proportion with an Intermediate ODX RS classification (93.3%, P = 0.001). 53% had distant recurrence, 20% had received adjuvant chemotherapy and 93.3% were adherent to hormonal therapy. Conclusions: In a diverse patient population, recurrences were significantly more likely among younger patients with high grade tumors, intermediate RS and those who did not receive chemotherapy. Further investigation and understanding whether Oncotype DX is generalizable to diverse breast cancer patient populations is needed.
BMI and mortality in hormone-negative breast cancer: A PLCO trial subgroup analysis.
Authors: Chamseddine Reem , Major Stella , Rafii Arash , Elmalik Hind Doha 
Published: June 2023

e12544 Background: Body Mass Index (BMI) is a significant prognostic factor in the survival of patients with hormone receptor-positive breast cancer (BC).[1-2] However, the relationship between BMI and survival is not well-established in hormone receptor-negative (HR-) breast tumors. [3] Emerging data is mixed: some studies show that BMI does not impact outcomes in HR- tumors [4], while others reveal worse survival in patients with elevated BMI.[5] In this study, our objective was to corroborate recent evidence about the relationship between BMI and mortality in hormone-negative breast cancer. Methods: We used the PLCO cancer screening trial, a publicly available database containing information about 155,000 participants enrolled in the United States between 1993 and 2001. Data were collected on cancer mortality through 2018 (median follow-up of 19.2 years post enrollment). The methodology of the PLCO trial has been described previously.[6] All female patients with a diagnosis of HR- BC diagnoses were selected for data retrieval, including HR-/HER2+ and HR-/HER2- tumors. Patients with equivocal receptor status were excluded. We used multivariate Cox regression to analyze mortality by BMI category, after adjusting for all significant variables at the bivariate level ( p <0.25). Results: 348 women with confirmed HR- BC at the time of study participation were included. Mean age was 69 years old, and 62 patients (17.8%) passed away due to breast cancer during study enrollment or follow-up. Patients who were of normal weight (BMI 25-<30) at age of trial enrollment were not significantly more likely to survive compared to overweight or obese patients (Hazard Ratio 1.274, p= 0.623). Conclusions: Our results show no significant relationship between BMI and mortality in patients with HR- BC tumors. This finding adds to the growing literature about weight status in hormone receptor-negative tumors. Our data suggests that the mechanism of tumor progression in HR- breast tumors is unlikely to involve signaling mechanisms in adipocytes. Clinical trial information: NCT00002540 , NCT01696968 , NCT01696981 , NCT01696994 . [Table: see text]
Genomic and transcriptomic profiling of inflammatory breast cancers and non-inflammatory breast cancers in Asian women.
Authors: Zhou Kaiwen , Lin Ying , Zhang Mengmeng , Shao Nan , Shan Zhen 
Published: June 2023

e12546 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Despite its rare incidence, it accounts for 10% of breast cancer-caused mortality. Previous studies based on NGS have focused on western populations and found no common genomic and transcriptomic difference that could distinguish IBC from non-IBC. Methods: We performed WES on 15 IBC samples and their paired normal blood to identify somatic genomic alterations, copy number variants and large structural variants. RNA-seq was performed on 16 IBC samples to examine the RNA expression, pathway enrichment and gene fusions. WES and RNA-seq data were further investigated to discover genes that were dysregulated in both genomics and transcriptomics. For comparison, we performed WES and RNA-seq on 5 non-IBC samples and acquired additional 33 non-IBC samples of Asian women from the Cancer Genome Atlas Program (TCGA). Results: Apart from results similar to the previous reports in western IBC, ZNF74 and DYNC2H1 were identified as Asian-IBC-specific somatic mutations in our cohort. Elevated HRD mutational signature and scarHRD score indicated increased HRD events in Asian IBC patients. Structural variation analysis showed that deletions were found more frequent in IBC. RNA-seq indicated increased immune activation in IBC samples, but the immune cell infiltration within the tumor microenvironment were similar between IBC and non-IBC. Multiple gene fusions were more frequently found in IBC, including CTC-786C10.1—RP11-680G10.1, TULP4—RP11-732M18.3, RN7SL4P—RN7SL173P. Combined analysis of WES and RNA-seq showed more frequent mutation and increased pathway enrichment of RAS pathway in IBC, which may explain the aggressive biological behavior of IBC, inhibitors such as sorafenib, tipifarnib and trametinib targeting RAS signaling and its downstream pathways were predicted to possess promising effects in IBC treatment. Conclusions: Our study is the first to provide a complete genomic and transcriptomic landscape of IBC based on combined analysis of WES and RNA-seq and the first to focus on Asian women. We discovered intriguing differences unique in Asian women that could potentially explain IBC etiology and presented RAS signaling pathway as a potential therapeutic target in IBC treatment.
The race, staging and clinical correlations with genetic mutations detected in breast cancer patients.
Authors: Kyaw Nay Yee Wint , Durana Theresa , Natarajan Vijaya , Xu Yiqing 
Published: June 2023

e12547 Background: Genetic testing has been applied widely in oncology and guidelines and criteria have been established for selection of testing. We aimed to study the variants of genetic mutations detected in a cohort of breast cancer patients of multiple ethnicity background, and its pathoclinical correlations. Methods: Breast cancer patients who have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Results: Among 767 patients tested, 77 patients were found to have germline mutations, including BRCA 1 (n = 20), BRCA 2 (n = 19), PALB2 (n = 12), CHEK 2 (n = 6), ATM (n = 4), RAD50 (n = 4), and others (n = 12). The race and ethnic groups were White/Caucasian (n = 23), African American (AA) (n = 25), Asian (n = 13), Jewish (n = 12) and Hispanic (n = 4). Genetic testing were performed when the tumors were diagnosed of stage 1-2 in 77.8% in white + jewish, 100% in Asian, 75% in Hispanic patients, but only 64% in AA patients. Non metastatic tumors with BRCA 1/2 mutation had a distribution in stage 1, 2, and 3 to be 30%, 37.5%, 27.5% respectively, while that for PALB2 was 0%, 83.3%, 8.3% respectively. BRCA 1 cancers showed 61.9% triple negative, 23.8% ER+/Her-2 neg, 14.3% ER-/Her-2 + distribution, and BRCA 2 cancers showed 31.6% triple negative, 63.2% ER+/Her-2 neg, and 5.3% ER+/Her-2 + distribution. PALB2 cancers showed 16.7% triple negative, 58.3% ER+/Her-2 neg, and 25% ER+/Her-2 + distribution. 4 (5.2%) patients were male, who had BRCA 2 (n = 2), RAD 50 (n = 1), and APC (n = 1), 3 were ER+/Her-2 neg, and 1 was ER+/Her-2 +. If NCCN criteria is used for selection for genetic testing, 8 (10.4%) patients will not meet the test criteria. Conclusions: Performance of genetic testing was done in more than 77% of the patient in early stage 1-2 breast cancer, which is significantly lower in AA subgroup (64%). BRCA 1/2 cancers presented in all early stages, while PALB2 cancers were predominantly stage 2 at diagnosis. Triple negative cancers were most common in BRCA 1, but can present in BRCA 2 and PALB2 mutations . RAD 50 and APC mutations can cause male breast cancer. Applying NCCN guideline, 10% patients will be missed for testing.