bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplified lymphatic microsurgical preventing healing approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection.
Authors: Ozmen Tolga , Layton Christina , Friedman Eldar Orli , Melnikau Siarhei , Kesmodel Susan , Avisar Eli 
Published: June 2021

e12581 Background: Lymphedema (LE) is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 16%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of LE dramatically. Our initial study showed an 88% decrease in clinical LE rate. In the initial study, we used arm circumference measurement for the diagnosis of LE and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting LE. Methods: All patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (± 10 L-Dex unit) or >10 L-Dex unit increase above patient’s baseline was considered as LE. The incidence of LE was compared between patients with and without SLYMPHA. Results: 194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ±37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of LE (16% vs 32%; p=0.01; OR 0.4 [0.2-0.8]). Conclusions: SLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery. [Table: see text]
Developing and validating deep learning-based heterogeneous model to improve diagnostic performance of ultrasound elastography for axillary lymph node metastasis of early breast cancer.
Authors: Li Jian , Nian Cai , Ze-Ming Xie , Jingwen Zhou , Kemin Huang 
Published: June 2021

e12583 Background: To improve the performance of ultrasound (US) for diagnosing metastatic axillary lymph node (ALN), machine learning was used to reveal the inherently medical hints from ultrasonic images and assist pre-treatment evaluation of ALN for patients with early breast cancer. Methods: A total of 214 eligible patients with 220 breast lesions, from whom 220 target ALNs of ipsilateral axillae underwent ultrasound elastography (UE), were prospectively recruited. Based on feature extraction and fusion of B-mode and shear wave elastography (SWE) images of 140 target ALNs using radiomics and deep learning, with reference to the axillary pathological evaluation from training cohort, a proposed deep learning-based heterogeneous model (DLHM) was established and then validated by a collection of B-mode and SWE images of 80 target ALNs from testing cohort. Performance was compared between UE based on radiological criteria and DLHM in terms of areas under the receiver operating characteristics curve (AUC), sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for diagnosing ALN metastasis. Results: DLHM achieved an excellent performance for both training and validation cohorts. In the prospectively testing cohort, DLHM demonstrated the best diagnostic performance with AUC of 0.911(95% confidence interval [CI]: 0.826, 0.963) in identifying metastatic ALN, which significantly outperformed UE in terms of AUC (0.707, 95% CI: 0.595, 0.804, P<0.001). Conclusions: DLHM provides an effective, accurate and non-invasive preoperative method for assisting the diagnosis of ALN metastasis in patients with early breast cancer.[Table: see text]
Comorbidities at time of diagnosis as a predictor of more or less aggressive treatment modalities in early-invasive breast cancer.
Authors: Raychaudhuri Sreejata , Kyko Jaclyn M , Ruterbusch Julie J. , Beebe-Dimmer Jennifer Lynn , Schwartz Ann G. , Simon Michael S. 
Published: June 2021

e12591 Background: Comorbidities and advanced age have been shown to play important roles in breast cancer treatment and outcomes. Reduced doses of chemotherapy, worse treatment-related side-effects, poor performance status in patients with significant comorbidities, and the biological interplay between other diseases and cancer may also play roles. We evaluated the relationship between age and pre-existing comorbidities and receipt of local and systemic therapy in a cohort of African American (AA) women with early invasive breast cancer. Methods: The study population included 1,169 AJCC stage I-III invasive breast cancer survivors from the Detroit Research on Cancer Survivors (ROCS) study, a large cohort of AA cancer survivors. Comorbidities (both individual diseases and a combined count that was categorized as low/medium/high comorbidity burden), age at diagnosis, and other demographic variables were obtained from self-reported standardized questionnaires. Cancer-related variables including treatment were obtained from the Metropolitan Detroit Cancer Surveillance System registry. Recommended treatment was subdivided into localized (surgery ± radiation; N = 1,156), hormonal (N = 848) and chemotherapy (N = 680). Logistic regression estimated the associations between age and pre-existing comorbid conditions and the receipt of recommended treatments. Adjusted models included variables that were selected a priori and were significant predictors in univariate analysis. Results: Most women received recommended localized treatment (82.6%), hormone treatment (73.7%), and chemotherapy (79.9%). There were no differences in receipt of localized treatment based on age or comorbidity burden in adjusted analyses. However, arthritis and depression were significantly associated with not receiving recommended localized treatment (Odds ratio (OR): 0.66, 95% CI: 0.47, 0.93 and OR: 0.53, 95% CI: 0.36, 0.78, respectively). Women with a history of obesity (BMI ≥30) were more likely to receive recommended hormone therapy (OR: 1.64, 95% CI: 1.19, 2.26), while women with congestive heart failure were less likely (OR: 0.46, 95% CI: 0.23, 0.90). Receipt of recommended chemotherapy was less likely for those with increasing age (Ptrend< 0.01) and increasing comorbidity burden (Ptrend= 0.02). Those with a history of arthritis (OR: 0.66, 95% CI: 0.44, 0.99) and hypercholesterolemia (OR: 0.62, 95% CI: 0.41, 0.95) were also less likely to receive recommended chemotherapy. Conclusions: Advanced age and presence of pre-existing co-morbid medical conditions appears to influence the receipt of chemotherapy, while individual conditions were associated with receipt of local treatment or hormone therapy in a cohort of AA survivors, suggesting the importance of providing comprehensive medical care for all women with early invasive breast cancer.
Type of recurrence, cause of death and second neoplasms among 737 patients with ductal carcinoma in situ of the breast: 15-year follow-up.
Authors: Niwinska Anna , Kunkiel Michal , Wardzynska Katarzyna 
Published: June 2021

e12592 Background: The aim of the study is to assess the results of the treatment of 737 consecutive patients with DCIS with particular attention to the character of recurrences, other neoplasms and causes of deaths. Methods: A retrospective analysis was carried out of 737 consecutive DCIS patients treated in one institution in the years 1996-2011. The percentage of failures, causes of death, cumulated recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast conserving treatment BCT, breast conserving surgery BCS), was calculated. Results: 66 recurrences (42% DCIS, 58% invasive) were reported: 61 recurrences in the breast, 5 outside the breast. The comparison of mammography images before the initial treatment and after local recurrence revealed the true recurrence in the breast in 48/61 (79%) of cases. The cumulated recurrence risk after 15-year observation, after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2 %, respectively (p < 0.001). 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively, p = 0.329. In the course of the whole observation period 124 other neoplastic lesions in 121 patients (16%) were reported including 58 (8%) contralateral breast cancers. Deaths due to DCIS progression were reported in 4 (0.5%) of patients. An overwhelming majority (74/86) of deaths was linked to the age of the patients or other diseases, including other neoplasms. Conclusions: The highest recurrence risk reported in patients after BCS was unacceptable and, moreover, it kept growing over the fifteen years of observation. 79% of recurrences in the treated breast were true recurrences. Local recurrences were effectively treated without influence on OS. The percentage of deaths due to DCIS was low.
Association of cytoplasmic HMGB1 (cHMGB1) expression with local tumor recurrence in triple-negative breast cancer.
Authors: Oliveira Iandra Freire , Rocha Jhonata Lima , Pereira Anamaria Falcão , Lopes Marina Helena Silva , Cajado Aurilene Gomes , Sant'Ana Rosane Oliveira , Almeida Paulo Roberto Carvalho , Lima Roberto César Pereira , Wong Deysi Viviana Tenazoa 
Published: June 2021

e12595 Background: Breast cancer is one of the most frequent neoplasms worldwide, contributing to women's morbimortality. Triple-negative breast cancer (TNBC) is a highly aggressive subtype of cancer marked by negative estrogen receptors, progesterone receptors, and lack of the human epidermal growth factor 2 (C-erbB2, HER2/neu) gene overexpression. The high mobility group box-1 (HMGB1) is a factor that regulates malignant tumorigenesis, proliferation, and metastasis. Aim: Here, the HMGB1 expression was investigated as a prognostic factor for TNBC. Methods: Clinico-pathological data and surgical paraffin histopathology blocks were assessed from 85 patients treated at Haroldo Juaçaba Hospital (Ethics committee approval number 407.395). Samples were analyzed by immunofluorescence using the Tissue Microarray technique to determine the percentage of fluorescent cells with cytoplasmic HMGB1 (cHMGB1) expression. Results: The clinico-pathological data analysis indicated that patients were older than 50 years (68.2%) and diagnosed with grade 2–3 ductal carcinomas (91.8%). Tumor metastasis was observed in 9.9% of cases. TNBC patients that tumor cells presented high cHMGB1 fluorescence demonstrated increased local tumor recurrence compared with low expressing tumors (P=0.019). Five-year overall survival was simmilar between the patients with low (63%) versus high (66%) cHMGB1 expression (P=0.7441). Additionally, the risk of death was 0.8 (95% CI = 0.21–2.96). Conclusions: The cHMGB1 expression is associated with an increased tumor relapse in TNBC, not affecting patients' survival.
Geographical disparities of incidence and prevalence of triple-negative breast cancers: Multistate study data analysis.
Authors: Jeon Hyein , Lee Myeong , Jaloudi Mohammed 
Published: June 2021

e12599 Background: Higher prevalence of triple negative breast cancer (TNBC) in black women with associated poor outcomes due to various disparities is well documented within a single state. We examine multiple states to better understand the state effect on such differences in incidence and prevalence of TNBC in black women. Methods: Female patients of ages 19 years old and above with breast cancer from the Surveillance, Epidemiology and End Results (SEER) Program across 13 states (608 counties) from 2015 (n = 66,444) and 2016 (n = 66,122) were examined. The relationships between the proportion of black and white women and the rate of patients with different tumor subtypes (luminal A, luminal B, HR-HER2+, and triple negative) were examined at the county level using ordinary least-square regression models. In parallel, due to consideration of various state-specific healthcare policies, socio-cultural norms, and socio-economic disparities, multi-level regression models were applied to examine the nested, random effect of each state on TNBC prevalence in each county. Bonferroni correction was applied to reduce the Type I error caused by repeated use of the same variables in multiple tests. Results: The baseline breast cancer rates between black and white women were similar in the population (0.171% for black and 0.168% for white). Consistent to previous studies, we demonstrate a significant positive correlation (p < 0.001) in TNBC in black females in both years. Surprisingly, when accounted for the random effects on states, 38.2% (2015) and 34.3% (2016) increase in incidence of TNBC in black females were seen, suggestive of state-specific disparity affecting race-specific health. In 2015, other subtypes of breast cancer in both black and white females did not result in significant relationship. Interestingly, in 2016, there was a significant relationship seen between the TNBC rate in white females and the white female population rate only after adjusting for the state effect (p = 0.026). This indicates the impact of non-biological factors such as state-wide health policies. Additionally, HR-HER2+ black females had a significant relationship against respective population rate only after adjusting for the state effect as well (p = 0.0394). For luminal A white females, a 15% decrease in incidence was seen after adjusting for state effect (p = 0.0424). Conclusions: This is the first known across-state examination of breast cancer subtypes by race with random effects on state. This study shows the role of state-specific factors affecting incidence in black and white females and potentially indicates the importance of state-level management for breast cancer on health disparities in addition to race-driven effects. Further studies are needed to elucidate comparable differences between states affecting the rates of various subtypes of breast cancer and thus health outcomes.
The effects of vitamin D (Vit D) replacement on pathological complete response (PCR) in breast cancer (BC) patients receiving neoadjuvant systemic chemotherapy (NAC).
Authors: Ozmen Vahit , Ordu Cetin , Ilgun Ahmet Serkan , Unal Caglar , Soybir Gursel , Erdogan Zeynep , Aktepe Fatma , Tuzlali Sitki , Ozturk Alper , Alco Gul , Duymaz Tomris , Kayan Tapan Tuba , Ozmen Tolga 
Published: June 2021

e12604 Background: Studies show that Vit D increases apoptosis by inhibiting the proliferation of BC cells. The aims of this study were to prospectively investigate the effects of Vit D replacement on PCR rates in patients receiving NAC. Methods: Breast cancer patients qualified for NAC between June 2019 and September 2020 and consent for the study were given weekly oral 50,000 IU Vit D (study group). The Control group consisted of patients who were given NAC between 2015-2020 and who did not receive Vit D replacement. Tumor characteristics and PCR compared between the study and control groups. Results: A total of 117 patients included in the study (55% in the study group). Both groups had similar patient, tumor, and treatment characteristics. PCR (ypT0/is ypN0 and ypT0/is) rates were significantly higher in the study group (28.1% vs 11.3%, p=0.025 and 37.5% vs 13.2%, p=0.003, respectively). In multivariate logistic regression analysis, estrogen receptor (ER) and HER 2 positivity, and Vit D3 replacement were identified as independent variables affecting PCR. Conclusions: Adding Vit D to NAC in breast cancer patients significantly increases PCR. This effect is more prominent in ER negative and HER2 positive breast cancer patients. Clinical trial information: NCT03986268. [Table: see text]
Determination of endocrine sensitivity by response of the proliferative marker KI67 after short-term preoperative endocrine therapy and their correlation to oncotype score platform.
Authors: Murillo Serafin Morales , Gasol Cud"S Ariadna , Morera Morillo Ester , Canosa Morales Carles , Olivé Jordi Melé , Vilardell Villellas Felipe , Sánchez Guzmán Douglas René , Salud Salvia Antonieta 
Published: June 2021

e12609 Background: Endocrine sensitivity (ES) determined by response to the Ki67 index to short-term preoperative endocrine therapy (ET) is accepted but not included in adjuvant treatment decision. However, genomic platforms have been incorporated into decision guides. Therefore, it would be interesting to analyze the correlation between both tools to improve the determination of endocrine sensitivity. Methods: A prospective series of 129 patients with early N0/N1 ES breast cancer was analyzed and Oncotype Dx platform was performed. Clinicopathological variables, and changes in ki67 index less than 10% (ES) were correlated with Oncotype Dx Recurrence Score (RS). Results: Median age was of 58 (23-84), 32% were premenopausal, median tumor size was of 22mm (7-90), nodal involvement was of 31%, 20% were progesterone receptor negative and initial median ki67 index of 24% (5-70). RS distribution: 27% RS 0-11, 29% RS 11-18, 23% RS 18-25, 21% RS > 26. All premenopausal patients received Tamoxifeno as preoperative ET and letrozole for postmenopausal. Globally, 62% of patients had ES with a decrease < 10% of ki67 after preoperative ET: 24/41 in premenopausal and 56/87 in postmenopausal. In all series ES according to RS was distributed: 80% in RS < 11, 61% RS 11-18, 55% RS 18-25 and 50% RS > 26. In premenopausal patients, ES and RS distribution was: 75% RS < 11, 62% RS 11-18, 57% RS 18-25 and 33% RS > 26. In postmenopausal patients, ES and RS distribution was: 83% RS < 11, 61% RS 11-18, 55% RS 18-25 and 58% RS > 26. ES results were not conditioned by tumor size or nodal involvement. RS > 26 was strongly associated with less ES with an OD of 4 (p = 0.014) and RS 18-25 with an OD of 3.25 (p = 0.037). The sensitivity and specificity for ES and RS < 11, was of 80% and 44%, respectively. Conclusions: We have found an ES of 62% in the whole population with the following distribution according RS: 80% in RS < 11, 61% RS 11-18, 55% RS 18-25 and 50% RS > 26. Of note, in premenopausal patients, ES rate in RS > 26 is only of 33%. Determination of ES by response of ki67 is feasible and correlates with data of genomic platforms. Both tools could help to predict ES in this setting.
Tumor mutation burden and PIK3CA mutations are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment.
Authors: Shi Qiyun , Xuhong Juncheng , Ge Jia , Liu Feng , Lan Yang , Zhang Yi , Luo Tao , Bian Xiuwu , Qi Xiaowei , Jiang Jun 
Published: June 2021

e12610 Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods: To date, a total of 96 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results: Among the cohort of 96 cases, a total of 32 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 18 of them achieved total pCR. The most frequently mutated driver genes were TP53 (75%), PIK3CA (44%), NBN (9%), RUNX1 (9%), FANCD2 (9%), ATRX (9%), MAP3K1 (9%) and NF1 (9%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (63%), MYC (22%), CCND1 (19%), CDK12 (16%) and FGF19 (16%), respectively. The median tumor mutation burden (TMB) of the 36 patients was 4.23 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had significantly higher median TMB (5.29 vs 3.17 mut/Mb, P = 0.025). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (88.9% vs 14.3%, P < 0.001). Conclusions: Preliminary results suggested that HER2-positive breast cancer patients with higher TMB and activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. *Qiyun Shi and Juncheng Xuhong contributed equally. #Co-corresponding author (Dr. Jun Jiang, jcbd@medmail.com.cn; Dr. Xiaowei Qi, qxw9908@foxmail.com). Clinical trial information: ChiCTR1900022293.
Association between body mass index and pathologic complete response in different breast cancer molecular subtypes.
Authors: Vaca-Cartagena Bryan , Becerril Gaitan Andrea , Ferrigno Ana Sofia , Aranda-Gutierrez Alejandro , Gonzalez-Mondellini Fabio A. , Roman-Zamudio Mariana , Acosta-Sandoval Marcos A , Torres-Leal Ma. Inés , Díaz-Pérez Héctor Marcelino , Cardona-Huerta Servando , Villarreal-Garza Cynthia 
Published: June 2021

e12624 Background: Obesity (BMI ≥30 kg/m2) and breast cancer (BC) are two major public health concerns worldwide. Obesity has been linked with aggressive clinicopathological features and inferior survival rates in patients with BC, regardless of molecular subtype. In addition, obesity has been associated with decreased pathological complete response (pCR) rates in some BC cohorts. However, the impact of obesity on pCR rates in different BC molecular subtypes is still a subject of debate. This study aims to explore the impact of obesity on pCR rates in women with different BC subtypes in a public health-care center. Methods: Medical records of women diagnosed with primary BC between 2009 and 2020 in a center in Monterrey, Mexico were reviewed. Patients with stage II or III at diagnosis treated with neoadjuvant chemotherapy (NAC) were considered eligible. Associations between variables were examined using Fisher's exact test of independence, employing logistic regression to calculate odds ratios (OR) when appropriate. Results: A total of 559 patients with a median age at diagnosis of 48 years (range 25-85) were included. Patients were diagnosed with stages II (37%) and III (63%). The most common molecular subtype was HR+/HER2- (49%), followed by TNBC (25%), HR-/HER2+ (15%), and HR+/HER2+ (11%). Regarding BMI, a significant proportion of patients was either overweight (34%) or obese (47%). In this cohort, a total of 134 (24%) patients achieved pCR following NAC with anthracycline- and/or taxane-containing regimens. pCR rates by subtype were as follows: HR-/HER2+ (41%), TNBC (34%), HR+/HER2+ (31%), and HR+/HER2- (13%). A significant association between pCR rates and molecular subtype was found (p<0.001). Overall, obesity was not significantly associated with pCR rates. However, on a stratified analysis, obese patients with HR+/HER2+ tumors had significantly decreased pCR rates compared to their non-obese counterparts (OR=0.21; 95%CI 0.05-0.93; p=0.040). pCR rates according to molecular subtype and obesity status are shown in the table below. Conclusions: Obesity has an adverse influence on pCR rates in patients with HR+/HER2+ tumors. Given the endemic nature of obesity in several low- and middle-income countries, effective programs that focus on prevention, weight reduction strategies, and health promotion are warranted. Furthermore, women should be encouraged to improve their diet and engage in regular physical activity. Efforts to elucidate potential factors that underlie lower pCR rates in obese patients with certain BC subtypes are required. [Table: see text]