bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence rate according to Oncotype Dx recurrence score (RS) in women with estrogen receptor (ER) positive, Her2 negative and 1 to 3 positive nodes: Real-world data in a Mexican private institution.
Authors: Amador Geovani , Andrade Moreno Raul Alejandro , Martínez-Herrera José Fabián , Gerson Raquel , Serrano Juan Alberto 
Published: June 2021

e12536 Background: Oncotype Dx is a 21 gene assay that evaluates de expression of 21 genes associated with recurrence in early breast cancer (EBC). In women with ER positive, HER2 negative and no lymph node involvement, it has demonstrated it prognostic value and has shown to predict the benefit of adjuvant chemotherapy in high-risk patients, sparing toxicity to patients with low risk of recurrence. Nevertheless, in women with ER positive, HER2 negative and 1 to 3 nodes, the role of de 21 gene assay was not clear until recently. Methods: Retrospective review of medical records of patients with ER +, HER2 negative and 1 to 3 positive nodes breast cancer treated at our institution. Clinicopathological characteristics and 21 gene recurrence score (RS) were collected and a survival analysis by the Kaplan-Meier method was performed in patients with RS < 25 and according to menopausal status as in RxPONDER in SPSS v 25.0 IBM. Results: From January 2008 to December 2018, data from 136 patients with EBC clinical stage (IA-IIB), HR +/ HER2-, N0-1 with Oncotype Dx performed were collected, of which only 25 patients had 1-3 nodal involvement and were included in the statistical analysis. Mean age at diagnosis was 54 years (35-73), the most frequent histology in the general population was invasive ductal carcinoma (92.0%), followed by lobular carcinoma (8.0%), 72.0% of patients presented in stage IIA, followed by stage IB in 20.0%. RE were positive in all patients and progesterone receptors were positive in 72.0%, none of the patients had HER2 overexpression, mean Ki-67 expression was 17.4% (4.0-50.0%). Most tumors were modemoderately differentiated (72.0%). Lymphovascular and perineural invasion were present in 44.0% and 24.0% respectively. Follow up data was available for 17 patients of which 12 had a RS of 25 or less. Recurrence was present in only 3 patients in this group of patients representing 25%. During the first 5 years only 1 patient recurred, which represents a 5-year Recurrence rate (RR) of 8.3% with a 5-year RFS of 91.7%. 10-year Recurrence free survival (RFS) was 75.0% with a median RFS that has not been reached. RFS was 80.0% in postmenopausal women compared 71.4% for those premenopausal at 10 years follow-up (p=0.735). None of the patients in this group received adjuvant chemotherapy. Conclusions: We report our experience at a comprehensive cancer center in a time lapse of 10 years. RFS at 5 years was 91.7% and at 10 years of follow up was 75%. This in accordance with the results of RxPONDER trial that reported a 5-year progression free survival of 92.4% in patients with chemo-endocrine adjuvant therapy and 91.0% in patients in the endocrine therapy only arm. This supports the use of this trial for decision making outside of the controlled clinical trials setting.
Impact of updated 2013 human epidermal growth factor receptor-2 testing guidelines on HER2 positive invasive breast cancer diagnosis: A three year retrospective study.
Authors: Mhadgut Hemendra , Sharma Purva , Tawadros Fady , Brooks Bill , Yakubenko Anna , Jaishankar Devapiran 
Published: June 2021

e12554 Background: Breast cancer is a frequently diagnosed malignancy in the United States accounting for approximately 266,000 cases and 40,000 deaths annually. Human epidermal growth factor receptor 2 (HER2) is a surface protein shown to affect cell proliferation, migration and survival - the hallmarks of neoplastic cells. HER2 is overexpressed in 20-35% of breast cancer cases and has a strong prognostic and therapeutic significance. This discovery led to development of therapeutic agents targeting HER 2 receptor. In 2013, College of American Pathologists (CAP) updated their recommendations for HER2 testing by incorporating an algorithm with immunohistochemistry (IHC) and In situ hybridization (ISH). The primary objective of our study was to assess for variance in HER2 interpretation by applying the updated 2013 criteria to all diagnosed cases in our hospital for the immediate previous three years. Methods: We retrospectively reviewed charts of patients diagnosed with invasive breast carcinoma from January 1, 2010 to December 31, 2012 at our hospital. The new American college of pathology criteria assessing FISH HER2 copy number and HER2/CEP ratio for each patient was compared to the old criteria to assess for variance in HER2 interpretation. Categorical variables are presented as percentages and kappa statistic was used to assess for variance. Results: We reviewed 526 charts with an invasive breast cancer diagnosis over a 3-year period. 10.83% of patients were HER2 amplified, 86.12% were non-amplified and 3.04% were equivocal. Applying the updated 2013 CAP criteria, we found that 11.21% were amplified, 74.33% were non amplified, and 14.44% remained equivocal. Kappa statistic indicated substantial agreement (0.804) between the old and new criteria. A review of our cohort revealed an overall lower level of HER2 positive cases at 10.83% (old criteria) and 11.21% (updated criteria) when compared to historical studies. The increase in equivocal cases from 3.04% to 14.44% with the new criteria suggests under diagnosis of HER2 positive cases. Due to the lack of IHC performed (as per old standards), further classification of equivocal cases (based on new criteria) was not possible. While we saw some movement in our data from non-amplified to equivocal, our analysis indicated substantial statistical agreement between the old and the new diagnostic criteria Conclusions: Our study did not show a variance in HER2 interpretation between the 2007 and 2013 CAP criteria which is reassuring. An increase of 11.4% cases in the equivocal category was noted and may reveal a significant difference if further delineation is feasible. This variance could be important given the prognostic and therapeutic implications in HER2 positive breast cancer.[Table: see text]
Predominance of RAD21 and ERBB2 amplification and progesterone receptor positivity in tumors of the right breast support breast cancer lateralization.
Authors: Spigelman Zachary , Murphy Jo-Ellen 
Published: June 2021

e12557 Background: Biologic lateralization broadly impacts breast cancer. Malignancies originating in the left breast compared to the right breast tend to be more frequent, larger and of poorer prognosis. Left breast tumors respond differently to HER2-neu signaling and have lateralized Ki67 expression. In a prior study a right-left asymmetry in the neutrophil/lymphocyte ratio (NLR) of breast cancers was identified (ASCO 2018, e13094). As a follow-up, retrospective analysis of results from comprehensive genomic profiling (CGP) of right and left side breast cancer specimens was performed to determine a potential genomic etiology for the observed NLR lateralization. Methods: Tumors from 43 consecutive breast cancer patients underwent analysis for all classes of genomic alterations by hybrid capture-based CGP (Foundation Medicine). The CGP results from the 25 left- and 18 right-sided breast cancer samples were analyzed along with the histologic grade and status of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Results: In this cohort of advanced breast cancer patients (stage 3-4), no statistically significant differences in lateralization were identified based on patient age, tumor stage, or frequency of ER or Her2 expression (Table). A predominance of PR positivity (p=0.14 chi square analysis) and amplifications in the ERBB2 (p=0.37) and RAD21 (p=0.08) genes were detected in right side tumors. Conclusions: Together with the prior study, trends in asymmetry based on genomic, pathologic, and immunohistologic differences have been detected in breast cancers, including an increased incidence of ERBB2 and RAD21 amplification in right-side breast tumors in this cohort. The predominance of lower PR positivity in the left breast tumors may be due to preferential hypermethylation, consistent with reports that it mediates biologic lateralization changes, downregulates PR expression, and alters amplification rates. Epigenetic methylation, may contribute to asymmetric breast cancer biology and have implications for therapeutic strategy. Further study is warranted.[Table: see text]
Potential determinants of radiation-induced lymphocyte decrease and lymphopenia in breast cancer patients by machine learning approaches.
Authors: Yu Hao , Chen Fang , Yang Li , Jin Jian-Yue , Kong Feng-Ming Spring 
Published: June 2021

e12567 Background: Radiation-induced lymphopenia accompanied with radiation therapy is associated with inferior clinical outcomes in a wide variety of solid malignancies. This study aimed to examine the potential determines of radiation-induced lymphocyte decrease and radiation-induced lymphopenia in breast cancer patients who underwent radiotherapy. Methods: Patients with breast cancer treated who underwent radiotherapy were enrolled in University of Hong Kong-Shenzhen Hospital (our cohort). Circulating lymphocyte levels were evaluated within 7 days prior to and end of radiation therapy. Feature groups including clinical data, tumor characteristics, radiotherapy dosimetrics, treatment regiments were also collected. We applied machine learning algorithms (Extreme Gradient Boosting, XGboost) to predict the ratio of lymphocyte level after radiotherapy to baseline lymphocyte level and the event of lymphopenia and compared with Lasso regression approaches. Next, we used Shapley additive explanation (SHAP) to explore the directional contribution of each feature for lymphocyte decrease and lymphopenia. For the purpose of model validation and proof-of-concept validation, an independent cohort of patients enrolled in prospective trial was eligible (IP cohort). Results: A total of 589 patients were enrolled in our cohort and 203 patients in IP cohort. XGboost models which trained in our cohort with performances of a mean RMSE: 0.157 and R2: 53.9% for the ratio of lymphocyte levels; a mean accuracy: 0.757 and ROC-AUC: 0.733 for the lymphopenia events, separately. These models can predict the ratio of lymphocyte levels with a mean RMSE: 0.175 and R2: 47%; predict the lymphopenia events with a mean accuracy: 0.739 and ROC-AUC: 0.737 in the totally independent IP cohort. The feature group of dosimetrics had the largest predictive power with RMSE: 0.192, R2: 29.8%, accuracy: 0.678 and ROC-AUC: 0.667; followed by the group of baseline blood cells with predictive power as RMSE: 0.207, R2: 18.9%, accuracy: 0.669 and ROC-AUC: 0.645. Next, by SHAP value analysis, we investigated that integral dose of the total body, V5 dose, mean lung dose and V20 dose of ipsilateral lung/bilateral lungs were in consequence important promote factors for lymphocyte decrease and for the event of lymphopenia, while the features of baseline monocyte, mean heart dose and tumor size played a role of protection at some extend. Conclusions: In this study, we constructed robust XGboost models for predicting the lymphocyte decrease and the event of lymphopenia in breast cancer patients who underwent radiation therapy. We also applied SHAP analysis for revealing the directional contribution of features. These results are important either for the understanding the contributions of dosimetrics on immune response or for the refine of radiation dosimetrics before treatment in future clinical usages.
Family history of breast and/or ovarian cancer (FHBOC) as an independent prognostic factor in triple negative breast cancer overall survival.
Authors: Rioja Patricia , Ruiz Rossana , Morante Zaida , Mantilla Raul , De la Cruz Ku Gabriel Antonio , Lujan-Peche Maria , Cotrina Jose Manuel , Fuentes Hugo , Neciosup Silvia P. , Gomez Henry Leonidas 
Published: June 2021

e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.
Outcome of neoadjuvant treatment in triple-negative breast cancer in a rural underserved community.
Authors: Majer Martin , Little Elizabeth Fauchier , Jones Sarah , Dong Jasmine , Hutton David , Bezdickova Karolina , Tomanova Lucie , Promlap John , Promlap Tien , Schneringer Greg , DeMartini Steve , Russell Michael , Joyner April , Schmidt Susan , Nagubandi Ravi , Skau Randell , Swars Monica , Powell Megan , Ordorica Edward J. 
Published: June 2021

e12608 Background: Complete pathological response (pCR) is a surrogate of successful neoadjuvant treatment of triple-negative breast cancer (TNBC). We extended our study from 2016, where we discussed unusually high pCR employing taxane/platinum (T/P) without the use of adriamycin and cyclophosphamide (AC). Methods: This is a retrospective observational study of an underserved, low income, rural population in Oroville, California over 10 years (2011-2021). Neoadjuvant chemotherapy was offered to eighteen women with ages ranging from 36 to 77 years old (mean age is 56). Minimum requirements for evaluation was three cycles administered within 90 days of starting treatment. The primary end point of this study was pCR. We analyzed the relationship between pCR, chemotherapy regimen, proliferation rate of original tumor by Ki-67 and the ratio of neutrophil and lymphocyte (NLR). The two regimens of chemotherapy included both standard AC+T or the alternative treatment with T/P. We grouped Ki-67 to above and below 50% pre-treatment. NLR was grouped between those above and below 3.2. Results: Our study produced a respectable response rate with 12/18 (67%) achieving pCR. There was no difference with or without exposure to anthracyclines. Out of the twelve who achieved pCR, eight (67%) received T/P and four (33%) got AC+T. Ki-67 in all eighteen patients ranged from 2% to 97% with a median of 75%. Ki-67 was >50% in 10/12 (83%) patients who achieved pCR and 3/6 (50%) in those who did not have a response. NLR was a significant predictor for pCR. 8/12 (67%) of patients who experienced pCR had a NLR of <3.2 compared to the 1/6 ( 17%) with no response. The p-value is .0455. Conclusions: Treatment with the alternative regimen of T/P didn’t affect pCR in our population. We hypothesize that some of the beneficial effects of cytotoxics affected the patient’s immunological milieu on top of the direct effect of the malignant clone.
Clinical and pathological response to neoadjuvant chemotherapy (NCT) in patients with triple-negative breast cancer (TNBC).
Authors: Krivorotko Petr , Zhiltsova Elena , Gigolaeva Larisa , Emelyanov Alexander , Pesotskiy Roman , Yerechshenko Sergey , Nikolaev Kirill , Komyahov Alexander , Ivanova Olga , Tabagua Tengiz , Zernov Konstantin , Ivanov Vadim , Aseeva Zalina , Bessonov Alexander , Semiglazov Vladimir 
Published: June 2021

e12616 Background: Neoadjuvant chemotherapy (NCT), Triple-negative breast cancer (TNBC) including anthracyclines and taxanes for early stages of TNBC, allows to achieve pathological complete response (pCR) in 25-36% of patients. Pathological complete response (pCR) significantly correlates with an increase in disease-free survival (DFS) and overall survival (OS). Methods: Randomized, monocentric trial was conducted in NN Petrov National Medical Research Center of Oncology from 2016 to 2019. 99 patients aged from 28 to 68 years with confirmed TNBC were included in trial: 96 had invasive ductal carcinoma G3, 3 - metaplastic cancer, negative BRCA mutations (a test for Founder mutations was performed).Patients were randomized in 3 groups, depending on the NCT regimen:1st subgroup (24 patients) - Eribulin in combination with Carboplatin AUC 5 x 4 cycles 2nd subgroup (37 patients) - Paclitaxel in combination with Carboplatin AUC 5 x 4 cycles 3rd subgroup (38 patients) –Carboplatin AUC5 + Doxorubicin + Paclitaxel x 6 cycles. Patients 1 and 2 subgroups in an adjuvant mode received 4 cycles of AC. Results: Clinical complete response (cCR) by physical examination (palpation) was achieved in 44 out of 99 patients (44.4%). Clinical complete response (cCR) by ultrasound and MG - in 27 (27.2%) patients. Miller-Payne V regression stage was achieved in 55 out of 99 cases (55.6%). In clinical cT1-T2 stage (n = 70), ypCR was achieved in 49 cases (70%), cT3-T4 (n = 29) ypCR in 6 patients (20.68%). Before NCT, 71 patients had status cN0-N1. Conversion to ypN0 occurred in 57 patients (80.2%). In 28 patients with cN2-N3 status, conversion to ypN0 occurred in 7 patients (25%). The median follow-up was 58 months. Progression was observed in 15.1% of patients, mortality – 6%. Local recurrence - 6 patients (6%), all patients were with residual tumor after NCT. Distant recurrence – 8 patients (8.1 %). Local recurrence rate and distant recurrence rate did not correlate with type of surgery (BCS or ME), but correlated with ypCR. Conclusions: NCT for TNBC is advisable both for locally advanced breast cancer and early breast cancer BC. De-escalation of BC surgery is possible in the future, especially in cT1-T2 stage patients (n = 70) where ypCR rate reaches 70%. It is planned to continue the trial with the vacuum aspiration biopsy of the tumor bed and SLNB after NCT.SLNB after NCT is advisable only in cN0-N1 group of patients (n = 71), since conversion to ypN0 was achieved in 57 patients - 80.2%.
Survival outcomes of breast cancer patients with brain metastases: Single center experience from Northern India.
Authors: Sagiraju Hari Krishna Raju , Gogia Ajay , Sharma Dayanand , Deo S. V. S. , Mathur Sandeep 
Published: June 2021

e13003 Background: Brain metastasis (BM) is a poor prognostic factor for survival among breast cancer (BC) patients. Very few studies reported in the literature have challenged this premise, suggesting that time to the occurrence of brain metastasis and the survival times following brain metastasis differ significantly between BC subtypes. The purpose of this study was to evaluate the clinico-pathological characteristics associated with brain metastasis free survival (BMFS), survival after brain metastases (SABM) and overall survival among Indian women with BC and BM. Methods: Among 621 patients treated for metastatic BC from 2015 to 2018 at All India Institute of Medical Sciences-New Delhi, 79 (12.7%) patients were identified to have BM. Of these ten individuals have presented with BM at the time of presentation. Survival analysis and Cox proportional hazards models were fitted to explore clinco-pathological factors that are associated with survival outcomes in these individuals. Results: Median age of the sample is 42 years (range:22-64). Triple negative breast cancers (TNBC) accounted for 25.3% and HER2 positive were 49.4% in our sample. Median time for the occurrence of BM from cancer diagnosis was 20.5 months (95% CI:14.7-26.2) in the overall sample, while among TNBC and HER2 positive tumors was 14.1 and 20.6 months respectively. In Cox multivariable model, T4stage [Hazard Ratio (HR) (95%CI): 2.4(1.1-5.3)], having a metastatic disease other than to brain at the time of presentation [HR(95%CI): 2.8(1.5-5.4)] and TNBC [HR(95%CI): 2.7(1.1-6.7)], was observed to be significantly associated with BMFS. Median SABM was 7.9 months (95% CI 5.2–16.2) and the median overall survival from the cancer diagnosis was 32.4 months (95% CI 23.4–40.8). Adjusted for age, only the presence of multiple brain lesions (>2) was significantly associated with SABM [HR (95%CI): 2.4(1.1-5.2)]. However, TNBC [HR (95%CI): 2.9(1.2-7.4)]and baseline metastatic disease [HR (95%CI): 2.2(1.2-4.2)] were significantly associated with overall survival following cancer diagnosis in these individuals. HER2 positivity was not associated with BMFS or SABM in this cohort. Conclusions: In this single-institutional study, clinical T4 stage, TNBC subtype and baseline metastatic disease have shown to be significantly associated with BMFS and overall survival. These results suggest that women in Indian population with these baseline clinico-pathological characteristics at the diagnosis of breast of cancer should be frequently monitored for BM.