bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes after omission of surgery for ductal carcinoma in situ: A National Cancer Database (NCDB) analysis.
Authors: Poli Elizabeth C , Dong Wenli , Shaitelman Simona Flora , Tamirisa Nina , Babiera Gildy , Shen Yu , Bedrosian Isabelle 
Published: June 2022

e12574 Background: Clinical trials of active surveillance (AS) for Ductal Carcinoma in Situ (DCIS) are underway. We sought to understand the historical management of biologically favorable DCIS and to determine the long-term outcomes of patients who did not have surgery at time of diagnosis. We hypothesized that women who had biologically favorable DCIS and underwent AS would have excellent long-term outcomes. Methods: The NCDB was queried from 2004 to 2017 for women diagnosed with DCIS. This cohort was further refined to identify those with biologically favorable DCIS defined as grade 1 or 2 and hormone receptor (HR) positive. Women under age 40 were excluded. AS was defined as either no surgery or surgery >12 months from diagnosis. A Cochran-Armitage test was used to assess the trend of surgery omission over year of diagnosis. Multivariable logistic regression was used to assess association between baseline factors and AS. Kaplan-Meier curves were estimated to show overall survival (OS) in this biologically favorable DCIS group that underwent AS, stratified by age (<50, 50-65, >65). Univariate and multivariable Cox proportional hazard models were used to determine the effects of prognostic factors on survival distributions. Results: There were 74,868 women with grade 1 or 2, HR positive DCIS, of whom 2,384 (3.2%) were treated with AS. The proportion of patients with biologically favorable DCIS who underwent AS increased over time, peaking in 2017 with 4.2% of DCIS cases diagnosed that year treated with observation (p<0.001). Only 17% of the patients in the AS group received hormonal therapy. On multivariable analysis, increasing age (OR 1.02, p<0.001), black race (OR 1.7, p<0.001), and being uninsured (OR 2.2, p<0.001) were all associated with increased likelihood of AS. In an unadjusted analysis, receipt of surgery was associated with improved OS in the entire cohort. However, the OS benefit from surgery differed when stratified by age. In women <50 years of age, OS outcomes were similar, with 10-year OS of 97.4% in the immediate surgery cohort vs 99.1% in AS cohort (p=0.43). In contrast, in women >50 years of age, 10-year OS was higher for women undergoing surgery (85.3% vs 70.0% in AS group, p <0.001). This association with OS in this older cohort persisted even after adjusting for age, race and comorbidity as well as facility demographics. Conclusions: The proportion of patients with low or intermediate grade, hormone receptor positive DCIS not treated with surgery has remained small but is increasing over time. AS of biologically favorable DCIS in younger, healthier women is not associated with adverse survival. In older women, the finding of benefit of surgery over AS is very likely confounded by underlying health factors that are not fully captured with co-morbidity scores.
Second primary malignancy in stage I and II breast cancer survivor: A United States population-based study.
Authors: Abdulhaleem Mohammed 
Published: June 2022

e12579 Background: In United States, breast cancer accounts for over 260,000 cases each year and is responsible for over 40,000 deaths. Survival primarily depends on the stage at time of diagnosis. 5-year survival among early breast cancer is more than 50%. It is known that patients with cancer undergoing treatment have a significant risk of developing a second primary malignancy (SPM); we aimed to focus our study at the incidence of various SPM among patients surviving stage I and II breast cancer, which can help in their targeted surveillance. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to select adult patients (18 and above) diagnosed with stage I and II breast cancer as their first malignancy between January 2000 and December 2015. This is one of the largest cancer registries worldwide. SPM is metachronous cancer which develops six months after an index localized breast cancer diagnosis based on Warren and Gates criteria. Multiple primary standardized incidence ratios (MP-SIR) and absolute excess risk (AER) for an occurrence of SPM were obtained utilizing SEER. SIR is observed to expected incidence ratio (O/E) of SPM and AER, it is an actual number of excess SPMs in patients with early breast cancer per 10,000 person-years at risk. Statistical significance was defined as a p-value ≤ 0.05. Results: We localized 513,408 patients with a diagnosis of stage I and II breast cancer from 2000 - 2015. Patients were followed for a median duration of 8.92 years (range 0.5 to 15.92). Of these patients, 81.5% were white. About 8.6% (43938) of patients developed 47708 primary malignancies. These malignancies were significantly higher than the general population with O/E ratio of 1.15 and AER of 17.12. The median age of diagnosis of SPM was 69.8 years (range 22.8 – 105.08 years). The average latency to develop SPM was 5.28 years (range 0.5 – 15.92 years). Among solid tumors, a statistically significant increased risk was observed with salivary gland, tongue, gastric, colon, lung cancer, and genitourinary cancers. Among hematological malignancies, statistically significant risk was seen for ALL, AML and CML. The risk of hepatobiliary, CNS cancers and lymphoma were significantly lower among our cohort included in current study. The SPM was found significantly increased after the latency of 24 months, and the risk of SPM was greater across all age groups. Conclusions: Due to robust breast cancer screening strategies, a significantly higher proportion of the patients are diagnosed early in the course of the disease which tends to be curative and this group of patients has better survival rates. Our study recognizes that the risk of certain SPM is higher in stage I and II breast cancer survivals compared to general population; and they would benefit from guidelines that can identify cancer with increased risk in these patients population.
Axillary surgery after neoadjuvant chemotherapy in breast cancer patients downstaging from cN+ to ycN0.
Authors: Krivorotko Petr , Emelyanov Alexander , Komyahov Alexander , Zhiltsova Elena , Gigolaeva Larisa , Tabagua Tengiz , Nikolaev Kirill , Pesotskiy Roman , Gukova Viktoriia , Amirov Nikolay , Channov Valentin , Yerechshenko Sergey , Zernov Konstantin , Semiglazov Vladimir 
Published: June 2022

e12580 Background: Axillary lymph node dissection is a redundant method of surgical treatment and axillary staging for a large number of patients receiving neoadjuvant therapy with positive lymph nodes before NCT. Methods: The study included 212 patients with breast cancer (cT1-3N1M0) who received treatment at the breast tumors department of the N.N. Petrov NMRC of Oncology from 2019 to 2021 All patients included in the study had the cN1 initial status of the axillary lymph nodes. All patients underwent neoadjuvant systemic therapy and subsequent sentinel lymph node biopsy (SLNB). In patients with pathomorphologically proven metastatic lymph nodes (cN1) even at the initial diagnosis, lymph node marking was performed before the start of NCT and targeted axillary lymph node dissection after the completion of neoadjuvant systemic therapy. In the same patients, after SLNB and targeted axillary lymph node dissection, a complete (standard) axillary lymph node dissection was performed to determine the false-negative rate and the oncological safety of the procedure. Results: The identification rate of only one sentinel lymph node was 21% (40 out of 193 patients), two sentinel lymph nodes - 30% (58 out of 193 patients), more than 3 - 49% (95 out of 193 patients). When only 1 sentinel lymph node was found, the false-negative rate of SLNB was 20.0% (4 of 20) (95% CI, 5.7 to 43.7). When two sentinel lymph nodes were found, the false-negative rate of SLNB was 20.0% (6 of 30) (95% CI, 7.7 to 38.6). When three sentinel lymph nodes were found, the false negative rate of SLNB was 4.7% (2 of 43) (95% CI, 0 to 15.8). Among 45 patients who had a microseed with the iodine-125 radioisotope installed before the start of treatment, the frequency of identifying a marked node was 100%. In 19 patients, tumor cells were found in the lymph nodes. The false-negative rate of targeted axillary dissection in combination with SLNB was 5.3% (1 of 19) (95% CI, 0 to 26.0). Conclusions: Targeted axillary dissection and sentinel lymph nodes biopsy, provided that 3 SLNs are removed, are reliable methods for identifying patients in whom systemic therapy is guaranteed to achieve complete response of regional lymph nodes (ypN0), thereby relieving patients of the need to perform a crippling complete axillary lymph node dissection. Clinical trial information: 3/198.
Sentinel node biopsy and regional recurrence following neoadjuvant chemotherapy in patients with isolated tumor cells: A rare event.
Authors: Moody Alison , Jutla Jaswinder , Chung Alice P. , Basho Reva K , Giuliano Armando E. 
Published: June 2022

e12581 Background: Lack of consensus exists regarding the optimal surgical axillary management of breast cancer patients treated with neoadjuvant therapy followed by sentinel node biopsy (SNB) with only isolated tumor cells (ITCs) identified in the sentinel node (SN). Few studies with limited patients have addressed this. A prospectively maintained database was reviewed to identify residual nodal metastatic burden and outcomes for patients with SN ITCs. Methods: Operable breast cancer patients treated with neoadjuvant therapy followed by breast surgery with SNB were identified who had only ITCs in the SN. Patients were excluded who had recurrent breast cancer, metastatic disease at time of operation, or who had an operation performed at another institution. Residual burden of axillary metastatic disease in patients who underwent completion axillary dissection and locoregional recurrence were examined. All SNs were examined with both hematoxylin and eosin stains as well as well as immunohistochemical stains. Results: 875 patients underwent neoadjuvant therapy followed by breast surgery and SNB from July 2007 to November 2021. Seventeen patients (1.9%) had only ITCs in the SN. The mean patient age of these 17 patients was 55.6 years (range 31-83 years). The majority had invasive ductal carcinoma (n = 15, 88.2%). Fourteen patients (82.4%) had ER+ tumors, 11 (64.7%) PR+ tumors, 2 patients (11.7%) had HER2+, and 3 patients (17.6%) had triple negative cancers. All patients had clinical T1 to T3 tumors and clinical N0 (n = 11, 64.7%), N1 (n = 5, 29.4%), or N2 (n = 1, 5.9%) disease. Two patients had isolated tumor cells identified on frozen section. Both of these patients underwent axillary dissection during the index operation and had further nodal disease identified (1 patient with ITCs only and 1 patient with macrometastasis). Fourteen patients had SN tumor free frozen sections but ultimately had ITCs identified with H&E. Five of these patients underwent a completion axillary dissection. Three of the 5 patients (60%) had additional ITCs identified after completion ALND. Fourteen patients had nodal irradiation. The three patients who did not receive irradiation did not undergo ALND. All patients with ER+ tumors received adjuvant endocrine therapy, the 2 patients with HER2+ cancers received adjuvant targeted HER2 therapy, and 4 patients received adjuvant chemotherapy. At a mean follow-up of 21.8 months (range 2-63 months), no locoregional recurrences occurred in any patient. Conclusions: ITCs in the SN after neoadjuvant therapy is a rare finding and are unlikely to be associated with regional recurrence.
Axillary dissection 10 years after Z0011.
Authors: Palka-Kotlowska Magda , Custodio-Cabello Sara , Cabezon-Gutierrez Luis , Oliveros-Acebes Eduardo , Khosravi-Shahi Parham , Rabadan-Ruiz Lorenzo 
Published: June 2022

e12582 Background: Axillary involvement is one of the strongest prognostic factors in breast cancer. Axillary lymphadenectomy (AL) has been considered one of the milestones to reduce relapse risk of local breast carcinoma. Z0011 trial, demonstrated that axillary dissection was not necessary in cases with one or two nodes involved. The authors proposed 3 sentinel nodes to decide if AL should be done. Since in the trials that explored the omission of lymphadenectomy obtained between one and six nodes, there is no consensus about how many lymph nodes should be obtained in the axillary sampling. The objective of this study is to obtain real data about axillary staging in real practice after Z0011 trial. Methods: 197 patients were selected from clinical records of Hospital Universitario de Torrejon. All patients were diagnosed with localized infiltrating breast carcinoma between 2016 and 2021. All were candidates for sentinel node biopsy (SNB) analyzed by OSNA or histopathology analysis. Patients with in situ tumors, those who underwent neoadjuvant chemotherapy We retrospectively reviewed the number of axillary nodes obtained in SNB and if axillary dissection was performed or not. Results: From 197 patients, 150 were included in the study (47 were excluded because were diagnosed with in situ carcinoma, received neoadjuvant chemotherapy or followup was lost). All 150 women were patients with infiltrating breast cancer who underwent conservative surgery or mastectomy and SNB. After surgical treatment, all patients received subsequent therapies indicated in each case (chemotherapy, radiotherapy or hormone therapy). Medium age at diagnosis was 57 years (range 30-87). Median number of sentinel nodes obtained in SNB was 2 (range 1 to 5). 40 patients had tumor infiltration in SNB, but only 15 underwent axillary dissection,10 of them had one node involved, 4 had 2 nodes involved and one had 3 nodes involved, from up to four extracted. 5 patients had more node involved than those found on the sentinel node biopsy, and all had macrometastasis. Capsular rupture was identified in 7 cases. None of the patients had relapse until the time of follow up was closed. Conclusions: Rate of axillary dissection after Z0011 has decreased without increasing risk of loco-regional or distant relapse. During the time of surgery, not always is possible to obtain 3 sentinel nodes, which could involve more aggressive surgery and comorbidities. Techniques of sentinel node identification are needed and further investigation to resolve in which cases axillary dissection is unavoidable.
Low-dose apatinib combined with neoadjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer (LANCET): A single-center, single-arm, phase II trial.
Authors: Yang Ciqiu , Zhang Junsheng , Wang Kun 
Published: June 2022

e12613 Background: Anti-angiogenic therapy combined with chemotherapy could improve pathologic complete response for breast cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits VEGF receptor 2. We assessed the efficacy and safety of the combination therapy of apatinib and standard chemotherapy in patients with triple negative breast cancer (TNBC). Methods: This single-arm, phase II study enrolled patients aged 18-70 years with previously untreated stage IIA-IIIB TNBC. Patients received oral apatinib at a dose of 250 mg once daily and intravenously docetaxel every three weeks for four cycles, followed by epirubicin plus cyclophosphamide every three weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in the breast and lymph nodes. Secondary endpoints included objective response rate, event-free survival (EFS), overall survival (OS), and safety. Results: Between August 1, 2018 and March 10, 2021, we screened 34 patients and enrolled 31 patients. At the date of cut-off on December 31, 2021, the median follow-up time was 22.9 months (range: 10.1-41.6 months). The pCR in both breast and lymph nodes were achieved in 17 (54.8%; 95%CI: 36.0–72.7) of 31 patients. Objective responses were achieved in 29 patients (93.5%; 95%CI: 78.6-99.2), and disease control was achieved in 31 patients (100%; 95%CI: 88.8–100.0). The 2-year EFS and 2-year OS were 90.9% and 94.4%, respectively. The five most common treatment-related adverse events were fatigue (51%), hypertension (41%), anorexia (39%), hand-foot syndrome (35%), and diarrhea (32%). Few grade 3 or more adverse events were observed. Conclusions: The combination of apatinib with docetaxel followed by the epirubicin plus cyclophosphamide showed excellent efficacy and manageable toxicities; further randomized controlled phase III trials are warranted. Clinical trial information: NCT03243838.
A novel immune cell signature predicts pathological complete response to neoadjuvant chemotherapy in triple negative breast cancer patients in the Q-CROC3 trial.
Authors: Basik Mark , Zeng Yixiao , Aguilar Adriana , Milne Katy , Lafleur Josiane , Florianova Livia , Aleynikova Olga , Ferrario Cristiano , Boileau Jean-Francois , Marcus Elizabeth A. , Pilon Yohann , Ranjbari Dorsai , Discepola Federico , Greenwood Celia 
Published: June 2022

e12614 Background: Tumor infiltrating lymphocytes (TILs) have been associated with good prognosis and response to neoadjuvant chemotherapy. Several reports have shown that the heterogeneity of tumor infiltrating immune cells affects the response to chemotherapy, with for example low levels of FOXP3 expressing T cells associated with good prognosis and pathological complete response (pCR) to chemotherapy. Methods: We examined different immune cell markers on 52 pre-chemotherapy biopsy specimens obtained from triple negative breast cancer patients undergoing neo-adjuvant chemotherapy from the Q-CROC-03 trial. Slides were stained for CD8, CD3,PD-1, PDL-1, FOXP-3 and Granzyme B using multi-colour immunohistochemistry and automated cell counting of stroma and epithelial counts was conducted using the Vectra/inForm image analysis platform. We had total of 39 variables for analysis and we performed Penalized logistic regression for variable selection. Results: Nine variables were found statistically significant to predict response to chemotherapy, PD1+ stroma counts being the one with the highest probability of association with response. A tree algorithm was then used on all 9 variables to identify the best variable and threshold combination to identify patients who respond to chemotherapy. We separated our cohort in test (25% of samples n = 13) and training (75% of samples n = 39) sets for this analysis. Restricting the tree depth to 2 variables for clinical interpretability identified the combination of average counts of stromal PD1+ and average density of stromal FOXP3+ as predictors of chemo response (accuracy 0.82). Both stromal average PD1+ counts and average stromal FOXP3+ density positively correlated with the levels of TILS. Conclusions: Combining FOXP3 and PD1 protein expression in the stroma of pre-treatment biopsies of triple negative breast cancers receiving neoadjuvant chemotherapy is highly predictive of pCR.
Short-term preoperative endocrine therapy allows to estimate and revert patient prognosis with further treatment plan correction in HR+ HER2- early breast cancer patients.
Authors: Zhukova Lyudmila , Ganshina Inna , Ignatieva Maria , Ivanyuk Maria , Kolyadina Irina Vladimirovna , Kvetenadze Gurami , Valeeva Alexandra , Sorokina Irina 
Published: June 2022

e12628 Background: The anomaly function of ER/PR-dependent molecular cascade is a key driver of ER-positive HER2-negative breast cancer (HR+ HER2- BC) progression. Ki67>10% and/or grade 3 (G3) determine the initial poor patient (pts) prognosis in this group. The short-term pre-operative endocrine therapy (P-ET) simply allows to look ahead to properly the further adjuvant therapy (AT) and to estimate the endocrine therapy (ET) sensibility of each pts in the routine clinical practice. The existing diagnostic methods weaknesses for the baseline lymph nodes invasion, high BC heterogeneity do not allow to accurately estimate the disease stage and tumor phenotype, respectively, with 100% accuracy before surgery. In addition to pre-ET the post-operative IHC is a base method for further pts treatment plan especially for high heterogenicity breast tumors. Our study is focused on pts proportion estimation with P-ET benefit or tumor phenotype reversion in patients with early HR+ HER2- BC. Methods: HR+ HER2- BC pts stages I-II any level of Ki67 independent from grade have received P-ET (letrozole (L)/anastrozole (A)/tamoxifen (TAM)) no less than 2 weeks until surgery in MCSC named after A.S. Loginov. Enrollment period runs from Jun’21 and will end with 1,000 pts. The primary goal of the study was pts’s proportion evaluation with baseline Ki67>10% who experienced suppression of the proliferation marker to 10% or less and/or phenotype change during P-ET followed by AT strategy amendment. Results: At the data cut-off (Jan’22) 832 pts (5 pts were men) with HR+ HER2- BC were enrolled (IIT population) with median age 61 (range:26-85) and ECOG 0-2. 736 (89%) pts have baseline Ki67>10% of whom 100 (14%) pts - with G3, 291 (35%) pts - with baseline Ki67≥30%. Tumors of the 398 (54%) pts suppressed proliferation marker Ki67≤ 10% and 352 (88%) pts among them avoid planned adjuvant chemotherapy followed by ET prolongation independent of ET type (L/A/TAM). The median time of P-ET amounted to 39,5 days (range: 14-90) in focused group. Post-operative evaluation of specimens in 20 (2,4%) pts have resulted in the identification of phenotype change to HER2+ BC and TNBC with subsequent modification of AT decisions (including anti-HER2-based and/or dose dense regimens). Conclusions: In HR+ HER2- early BC pts short-term P-ET simply allows to estimate pts prognosis and further AT strategy proper planning: to identify the pts population of whom CT can be avoided while maintaining treatment efficacy with a better quality of life (42% pts of IIT) (1), to radically change the planned AT to achieve optimal treatment results (2,4% pts of IIT) (2).