bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of the level of tumor markers and mutations in the BRCA1/2 genes in breast cancer patients with metachronous tumors.
Authors: Kamishov Sergey Viktorovich , Izrailbekova Kamila Shavkatovna , Balenkov Oleg Yurievich 
Published: June 2022

e12563 Background: Primary multiple malignant tumors are more common in women with breast cancer (BC). However, the difference in the frequency of mutations in the BRCA1/2 genes in metachronous BC tumors has not been fully studied, and there are also conflicting data on the increase in the level of specific tumor markers in this category of patients. Methods: The survey included 58 patients with BC with II-III clinical stages of the disease, of which metachronous tumors in terms of 6 months or more were found in 26 (44.8%) patients, among them metachronous cancer of the second breast - in 14 (53 .8%), cancer of the body of the uterus - in 7 (26.9%) and ovarian cancer - in 5 (19.2%) patients. In the control group of 32 (55.2%) patients with initially diagnosed BC, with the same stages of the disease. Tumor markers were determined in the peripheral venous blood of patients using reagent kits for ELISA analysis produced in Russia. The study of mutations in the BRCA1/2 genes was performed using sequencing on the Illumina MiSeq platform in tumor samples from waxed histological blocks. Library sequencing was performed using MiSeq Reagent Kit v2. Results: ELISA analysis of the level of tumor markers in patients with BC showed that with the development of metachronous cancer, the studied markers were more common than in the control group. In patients with metachronous tumors, elevated levels of CA-125 occurred in 10 (38.5%) patients, CA-15-3 - in 8 (30.8%), CA-19-9 - in 4 (15.4%), AFP - in 5 (19.2%), CEA - in 6 (23.1%). In the control group, CA-125 was found in 6 (18.8%) patients, CA-15-3 - in 5 (15.6%), CA-19-9 - in 2 (6.3%), AFP - in 1 (3.1%), CEA - in 2 (6.3%). Excess levels significant for diagnosis were observed for CA-125 and CA-15-3 in both groups of patients, but in the group of patients with BC with metachronous tumors, these figures were approximately 2 times higher. In the rest of the patients, the oncomarkers under consideration did not reach values significant for diagnosis. The total incidence of patients with clinically significant germline variants in the BRCA1/2 genes in the control group was 5 (15.6%), of which there were predominantly patients with an increased frequency in the population (5382insC, 4154del4, C61G). The total incidence of BC patients with metachronous tumors with germline and somatic variants in the BRCA1/2 genes was 16 (61.5%), with an increased frequency in the same population, mainly in patients with germline mutations. Conclusions: Dynamic study of the level of tumor markers CA-125 and CA-15-3 and CA-19-9 may be useful in the preventive examination of patients with a history of BC as an early diagnosis of the development of metachronous tumors in this category of patients. The most important diagnostic unfavorable factor in the development of metachronous tumors in the examined BC patients was germline mutations in the BRCA1/2 genes.
Gene expression profiling for breast cancer in the Philippines: Real-world data on feasibility, possible disparities, and clinical implications for LMICs.
Authors: Kho Markyn Jared Ngo , Kho Mark Richard 
Published: June 2022

e12569 Background: Racial, biological and socioeconomic disparities have most recently been shown to impact on specific molecular subtypes of breast tumorsand on its clinical implications including the decision to omit adjuvant chemotherapy. Despite considerable logistical and cost constraints, we provide the first-ever documented and tangible profile of gene expression of breast cancers in the Philippines for a better understanding of its role in facilitating future testing and health policy making in an LMIC setting. Methods: This is a case series review of the 70-gene (MammaPrint) and 80-gene (BluePrint) signature done among Filipino patients from Dec 2013 to Nov 2021. Data on demographics, tumor characteristics, adjuvant therapy received and clinical risk assessment in the MINDACT study to c-low or c-high were gathered and analyzed. Results: Thirty-six females aged 36-75 years with invasive breast carcinoma Stage I to IIB had the following profile: Low Risk Luminal A (19, 52.8%), High Risk Luminal B (7, 19.4%), High Risk Her-2 (3, 8.3%), High Risk Basal (7, 19.4%). All low-risk patients underwent adjuvant endocrine therapy alone thus foregoing otherwise clinically recommended chemotherapy. No significant trend (in age, laterality, tumor grade and stage) can be discerned within all stratification groups except in the following areas: Histology: low risk profile in lobular carcinoma (n=2) Tumor Size: high risk profile in all tumors measuring 4.1 – 5 cms (n=4) Nodal Status: low risk profile in 6 of 8 patients with node+ disease LVI among node- patients: low risk profile in all 6 LVI+ tumors HR status: high risk profile in all 7 tumors with HR- status Her-2 neu status: good IHC test correlation with genomic subtype HR and Her-2 neu status: HR+her2- status in all 19 low risk tumors while high risk basal subtype in all 5 HR-her2- or triple-negative (TNBC) tumors Clinical risk in MINDACT: low genomic risk in 11 of 25 (44%) c-high patients. Conclusions: Gene profiling of breast cancer in a resource-limited setting is feasible and imperative to avoid chemotherapy and/or overtreatment. Clinically relevant disparities may exist which in turn can affect outcomes, decisions and health policies in adjuvant therapy and overall cancer care.[Table: see text]
Analysis of non-sentinel lymph node status on 10-year overall survival among patients with breast cancer and sentinel lymph node metastasis.
Authors: Lei Huizi , Yuan Pei , Xu Binghe , Ying Jianming 
Published: June 2022

e12584 Background: To investigate retrospectively the effect of non-sentinel lymph node status (non-SLN) on 10-year overall survival (OS) and non-SLN metastasis risk factors in patients with breast cancer and sentinel lymph node (SLN) metastasis. Methods: A large population (n = 15510) underwent SLN dissection in Cancer Hospital, Chinese Academy of Medical Sciences from 2011 to 2022. In total, 3033 (19.6%) cases had at least one SLN metastasis, which underwent axillary lymph node (ALN) dissection. The clinicopathological characteristics and their relationship with non-SLN status were analyzed. Among patients from 2011-2012(n = 132), the effect of non-SLN status on 10-year OS and disease-free survival (DFS) with SLN metastasis were also analyzed. Results: In 3033 patients with SLN metastasis, the mean age was (50.42±10.59) years. The average number of SLN metastasis in each patient was 1.75±1.21, the average number of SLN detected was 4.89±2.03 and the average number of ALN removed was 22.36±8.88. The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis ( P< 0.05), but not the age, T stage and histological grade. In 132 patients from 2011-2012, a median follow-up of 9.1 years (interquartile range, 7.3-9.5 years), the non-SLN metastasis occurred in 60 cases (45.5%), DFS 70.8%, OS 85.9%; non-SLN non-metastasis occurred in 72 cases (54.5%), DFS 85.6%, OS 90.4%. There was no significant difference between two groups in DFS(χ² = 0.61, P = 0.43) and OS (χ² = 0.06, P = 0.81). Conclusions: The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis. There were no significant differences between non-SLN metastasis group and non-metastasis group in DFS and OS.
Survival trends of patients with Paget disease of the breast: A National Cancer Database (NCDB) study.
Authors: Truong Gia Thinh , Creech Zachary , Denny Regan , Hu Robert W. , Verplancke Kiana , Silberstein Peter T. , Tupper Connor 
Published: June 2022

e12585 Background: Paget disease of the breast is a malignant tumor that comprises only 1-3% of all breast carcinomas. It may coexist with an underlying ductal carcinoma in situ or present alone without additional carcinomas. Due to the rarity of this carcinoma and minimal literature available, we intend to identify potentially important prognostic factors, particularly those of socioeconomic origin. Methods: We performed a retrospective investigation of 5,918 patients diagnosed with Paget Disease of the breast from the NCDB between 2004-2018. Patient demographic and clinical characteristics such as household income, insurance status, treatment center type, and treatment center location were extracted from the database. Survival rates were compared using Kaplan-Meier curves, log-rank test, univariate and chi-square analysis. Data were analyzed using SPSS statistics 27. Results: African American patients had higher mortality rates than Caucasian patients (p < 0.005). Patients with underlying intraductal carcinoma of the breast had the highest survival rates (p < 0.001). Patients who received immunotherapy as part of the treatment plan had a significantly higher survival rate than those who did not (136.97 vs. 144.24 months respectively, p < 0.001). Patients coming from lower median household incomes had significantly lower survival rates. Specifically, patients with a household income of less than $38,000 had a lower mean survival rate compared to those with a household income of greater than $63,000 (122.74 months compared to 140.63, respectively, p < 0.001). Those with private insurance had a higher mean survival time than those with Medicaid and no insurance (170.60, 138.13, and 130.69 months respectively, p < 0.001). Patients from counties in metro areas with populations of 1 million or more had a significantly higher survival rate than those from counties in metro areas with less than 1 million (p < 0.003). In addition, patients treated at academic centers had a higher mean survival rate than those treated at non-academic centers (p < 0.001). Conclusions: Our results show significant variation in survival rates among patients based on their socioeconomic and treatment center characteristics. Additional research targeting patients with these characteristics can lead to improved clinical outcomes.
Patterns of care and survival outcomes for young women treated for early breast cancers in a community hospital system.
Authors: Thet Aye , Hadid Tarik H. , Boura Judith , Gohel Narendra , Falk Jeffrey , Vlachaki Maria T. , Jay Allison , Chuba Paul J. 
Published: June 2022

e12586 Background: Younger women with breast cancer have relatively poor prognosis and higher rates of locoregional recurrence. Epidemiologic data suggest equivalent survival with mastectomy or breast conserving surgery (BCS) in this population. We analyzed patterns of care and survival outcomes for women aged < 45 years with breast cancer treated at Ascension Macomb Oakland Hospital (AMOH), Ascension St John Hospital (ASJH), and Ascension Providence Hospital (APH). Methods: Between 2006 and 2015 there were 4703 patients treated for breast cancers at AMOH, ASJH, and APH. We identified a subset of 319 patients aged < 45 treated for breast cancers and investigated patients' tumor characteristics, type of surgery, and overall survival by using the Metric database and reviewing patient charts. Kaplan-Meier analysis and log-rank tests together with univariate analysis was done by using SAS for Windows 9.4. Results: With median follow-up of 53 months among living patients, 26 patients had died. African American race was associated with decreased overall survival (log-rank p=0.0031). Factors associated with improved overall survival included AJCC stage grouping (p=0.009), estrogen receptor (p=0.0004) or progesterone receptor positivity (p=0.005), or HER2 negativity (p=0.039). Similarly, survival was different according to grouping cases as luminal A (n=174), luminal B (n=39), basal (n=46), HER2 (n=23) and unknown phenotype (n=37) (P=0.008). Considering all cases 91 were treated with BCS (28.5%) and 228 with mastectomy (71.4%; 113 unilateral and 115 bilateral with or without reconstruction). Conclusions: In this group of young women, overall survival was influenced by stage and breast cancer phenotype as expected. African American race was associated with inferior overall survival. We found high rates of mastectomy with or without reconstruction. In the future comprehensive disease profiling will help to direct decision making.
Characteristics of cytokine profile of wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Przhedetskaya Viktoria Yu , Sagakyants Aleksandr B. , Przhedetskiy Yuriy V. , Zlatnik Elena Yu , Shulgina Oksana G. , Zolotareva Ekaterina I. , Ulianova Elena P. , Bondarenko Elena S. , Pozdnyakova Viktoria V. , Ulianova Yulia V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Pustovaya Irina V. , Chertova Natalia A. , Goncharova Elena G. , Maldonado Mary L. , Vladimirova Liubov Yu 
Published: June 2022

e12589 Background: Breast reconstruction after mastectomy for breast cancer (BC) is an important rehabilitation stage. Breast prosthesis implantation is sometimes accompanied by different complications which can be influenced by the immune system status. The aim of this study was to identify characteristics of the local cytokine profile in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Levels of cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and TNF-α were determined by ELISA in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery. Results: Levels of IL-6 in wound fluid of patients with TI statistically significantly decreased by 43% (p=0.036) and 41% (p=0.039) on days 3-4 and 7 after the surgery, and IL-2 decreased by 27% (p=0.045) with its further increase by 44% (p=0.037) compared to day 1. A pronounced increase of the IFN-γ levels by 118% (p=0.018) and 158% (p=0.012) was registered respectively on days 3-4 and 7 after surgery. Conclusions: Reconstructive surgery with TI is followed by a local increase in levels of IL-2 and IFN-γ which may indicate increasing antitumor potential of the microenvironment. The revealed decrease in IL-6 levels after TI implantation indicates certain features of the inflammatory reaction development in the intervention site.
Integrated tumor genomic and immune microenvironment analysis identifies predictive biomarkers associated with the efficacy of neoadjuvant therapy for triple-negative breast cancer.
Authors: Zhu Yanhui , Pan Chaohu , Zhang Hongfei , He Gao , Yu Xiafei , Cui Xiaoli , Yang Junzhe , Zhang Xiaoqiang , Gao Edmond , Liu Xiaoan 
Published: June 2022

e12592 Background: Although neoadjuvant chemotherapy (NAC) is currently the best therapy for triple-negative breast cancer (TNBC), resistance still occurs in a considerable proportion of TNBC patients, making it crucial to understand resistance mechanisms and identify predictive biomarkers for patient selection. Methods: Biopsy samples were collected from 21 patients with TNBC who underwent NAC. Whole-exome sequencing, targeted sequencing, and multiplex immunohistochemistry (mIHC) were carried out on the all clinical samples and used to identify and validate potential biomarkers associated with response to NAC. In addition, data on 190 TNBC patients who had undergone chemotherapy were obtained from The Cancer Genome Atlas (TCGA) and analyzed to further validate our findings. Results: Both the tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were significantly higher in responders than in non-responders. Higher response rates and longer survival rates were observed in patients with higher TMB. Patients with higher ratios of CD8 to M2 macrophages had higher response rates and improved survival rates. Finally, integrated analysis demonstrated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages could further distinguish responders from non-responders in both enrolled patients and from public data. Conclusions: The findings of this study indicated that the combination of TMB and the ratio of CD8 T cells to M2 macrophages may be a potential biomarker for improving the recognition of NAT responders, thereby providing a basis for developing precision NAT regimens.
Dose-dense neoadjuvant chemotherapy in triple-negative breast cancer: Real-world data from a developing country.
Authors: Sharma Rakesh Kumar , Gogia Ajay , Sagiraju Hari Krishna Raju , Deo S V Suryanarayana , Sharma Dayanand , Mathur Sandeep 
Published: June 2022

e12594 Background: Dose-dense adjuvant chemotherapy has been shown to be associated with improved long-term survival outcomes in triple-negative breast cancer (TNBC). However, there is a lacuna of data on the benefits of dose-dense neo-adjuvant chemotherapy (NACT) in TNBC particularly with respect to pathological complete response (pCR) rates and with the relapse or overall survival. To our knowledge no studies have been reported regarding the use or benefit of dose-dense NACT (ddNACT) over conventional NACT (cNACT) among Indian women with TNBC. Methods: This retrospective study included, 217 newly diagnosed cases of TNBC, treated with sequential anthracycline and taxane based NACT followed by definitive surgery. Study groups consisted of 137 patients who received 3-weekly conventional chemotherapy (cNACT group) and 80 patients with 2-weekly dose-dense NACT (ddNACT group) with granulocyte-colony-stimulating factor (GCSF) prophylaxis. Primary endpoint of the study was pathological complete response (pCR) rate and secondary endpoints were relapse-free survival (RFS), overall survival (OS) and grade-3/4 chemotoxicities. Fisher’s exact test was used to compare pCR rates. Kaplan-Meier and cox regression survival analysis were used to compare survival outcomes. Results: Median age (Interquartile range) in overall population, cNACT and ddNACT group were 43 (37-50), 44 (37-50) and 42 (36.5-48) years respectively. Baseline parameters were comparable between study groups, except that ddNACT group had higher proportion of premenopausal patients as compared to cNACT group (72.5% vs 55.5%). Majority of the patients presented at advanced stage, with stage-III being predominant, constituted by 97 (70.1%) and 55 (67.5%) patients in cNACT and ddNACT group respectively. No significant difference in pCR rate (32.8% vs 31.3%; p=0.808) was observed across the study groups. In multivariate analysis, dose-dense chemotherapy was no better than conventional chemotherapy for achieving pCR (Odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.45-1.63; p=0.639 and had no RFS advantage over conventional chemotherapy [Median RFS: Not reached in ddNACT vs 56.1 months in cNACT; Hazard Ratio: 0.83, 95% CI (0.48-1.44)]. OS was also comparable in both the groups with 3-year survival rate of 78.8% (95%CI: 60.9-89.2) in ddNACT group vs 84.3% (95% CI: 74.8-90.4) in cNACT group. Grade-3/4 toxicities were comparable in both groups. Conclusions: This observational study focusing on ddNACT among TNBC patients demonstrated similar pCR and toxicity rates with no significant survival benefits compared to cNACT regimen. Cost-benefits of frequent hospital visits for GCSF administration associated with dose dense therapy need further consideration before implementing such these regimens in lower-middle income countries.
Biomarker evolution after neoadjuvant systemic therapy in breast cancer.
Authors: Castillo Dan Ran , Pairawan Seyed Saeed , Denham Laura , Lum Sharon S. , Nagaraj Gayathri 
Published: June 2022

e12615 Background: Tumor heterogeneity is one of the hallmarks of breast cancer (BC) and has major implications for treatment response and resistance. Currently, there are no specific guidelines regarding biomarker reassessment on residual tumor post-neoadjuvant systemic therapy (NAST). In this study, we compared biomarker discordance between pre- and post-NAST tumors at our institution and determined if actionable changes were observed. We also report the impact of the detected biomarkers differences on the choice of adjuvant treatment. Methods: We conducted a retrospective review of BC patients who received NAST followed by definitive surgery from 2004 to 2020. The initial tissue biopsies were tested for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status per ASCO/CAP guidelines and repeated on the residual tumor tissue after NAST. Descriptive statistics was used to compare clinicopathologic characteristics. The biomarkers were compared using Wilcoxon’s t test and McNemar’s test. Concordance analysis of intrinsic subtypes was evaluated by Cohen’s kappa method. Results: Out of 434 patients who undergone surgical resection following NAST, 95 (22%) patients were identified to have repeat biomarker testing of residual invasive BC post NAST. 30 out of the 96 patients were found to discordant receptor status on repeat biomarker testing. In this cohort of thirty patients with discordant biomarkers, median age was 51.5 (29-70 years), 33.3% cases had stage II, and 56.7% had stage III BC. 66.75 patients were ER positive and/or PR positive, 20% patients were HER2 positive with one triple positive, and 13.3% patients were triple negative on pre-NAST tumors. Majority of the retesting was performed on breast tissue (90%, n = 27). The biomarker change was noted in 11 out of 30 (36.7%) for ER, 12 out of 30 (40%) for PR, and 13 out of 30 (43.3%) for HER2 marker. Concordance analysis demonstrated that HER2 was the most prone to change (Cohen K = -0.003) from pre-NAST to post-NAST specimen, whereas ER (Cohen k = 0.26) and PR (Cohen k = 0.18) were less subject to change. Kappa assumes theoretical maximum value of 1 when pre- and post-NAST are in agreement, a negative value indicates a poor concordance. One third of patients with discordant biomarkers had additional adjuvant treatment. 8 out of 30 patients (26.7%) were started on adjuvant anti-HER2 therapy due to HER2 positivity on post-NAST tumors. After ER positivity was detected on residual BC tumors, 2 initial triple negative patients (6.7%) were initiated on adjuvant endocrine therapy. Conclusions: Biomarker discordance due to tumor heterogeneity is an increasingly recognized phenomenon. Given the prognostic and therapeutic implications of biomarker driven BC management, retesting biomarkers routinely after NAST on residual invasive tumor would be beneficial in this patient population.