bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simulation model-based clinical decision tool to guide personalized treatment based on individual characteristics: Does 21-gene recurrence score assay testing change decisions?
Authors: Jayasekera Jinani , Sparano Joseph A. , Chandler Young , Isaacs Claudine , Kurian Allison W. , Kushi Lawrence H. , O'Neill Suzanne C. , Schechter Clyde B. , Mandelblatt Jeanne S. 
Published: June 2021

e12507 Background: There is a need for web-based decision tools that integrate clinicopathologic features and genomic information to guide breast cancer therapy for women with node-negative, hormone receptor positive, HER2 negative (“early-stage”) breast cancer. We developed a novel simulation model-based clinical decision tool that provides prognostic estimates of treatment outcomes based on age, tumor size, grade, and comorbidities with and without 21-gene recurrence scores (RS). Methods: We adapted an extant breast cancer simulation model developed within the NCI-funded Cancer Intervention and Surveillance Modeling Network (CISNET) to derive estimates for the 10-year risks of distant recurrence, breast cancer-specific mortality, other cause mortality and life-years gained with endocrine vs. chemo-endocrine therapy for individual women based on their age, tumor size, grade, and comorbidity-level with and without RS test results. The model used an empiric Bayesian analytical approach to combine information from clinical trials, registry and claims data to provide individual estimates. External validation of the model was performed by comparing model-based breast cancer mortality rates and observed rates in the Surveillance Epidemiology and End Results (SEER) registry. Results: Several exemplar profiles were selected to illustrate the clinical utility of the decision tool. For example, the absolute chemotherapy benefit for 10-year distant recurrence risk and life-years gained, without RS testing, and the outcomes if a woman got tested and had a RS 16-20 are provided below for a 40-44-year-old woman and a 65–69-year-old woman diagnosed with a small (≤2cm), intermediate grade tumor and mild comorbidities. Conclusions: Simulation modeling is useful for creating clinical decision tools to support shared decision making for early-stage breast cancer treatment.[Table: see text]
Projected long-term impact of adjuvant trastuzumab emtansine (T-DM1) on metastatic breast cancer occurrence in Turkey.
Authors: Press David J. , Özcan Gözde , Teksoy Ezgi , Tomar Akanksha , Revil Cedric , Napalkov Pavel , Williamson Mellissa 
Published: June 2021

e12523 Background: Progression from early stage breast cancer (eBC) to metastatic breast cancer (mBC) constitutes a substantial disease burden in Turkey. At a population-level, investment in treatment with curative intent may contribute to long-term reductions or delays in mBC. Women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive eBC who do not achieve pathologic complete response (pCR) after neoadjuvant taxane and trastuzumab-based treatment may be indicated for adjuvant trastuzumab emtansine (T-DM1) monotherapy. For this clinical population, the KATHERINE trial (NCT01772472) demonstrated significantly higher invasive disease-free survival among women who received adjuvant T-DM1 relative to trastuzumab (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; p<0.001). Methods: We developed epidemiology models based on data from cancer registries, observational studies, clinical trials, estimated population-level T-DM1 uptake, and extrapolations, by calendar year to predict the population-level number of women who will avoid mBC in Turkey over the next 10 years (i.e., 2022 to 2031). Weighted transitional probability averages were based on invasive disease-free and overall survival curves from the KATHERINE trial. Results: Over the next 10 years in Turkey, we projected that 22,597 women will be diagnosed with HER2-positive eBC and will not achieve pCR after neoadjuvant therapy. We projected that the total number of women who will experience mBC occurrence following adjuvant T-DM1 use from 2022-2031 will decrease annually from 0 to 249 relative to projections without introduction of T-DM1, with a cumulative total of 1,219 women not experiencing mBC occurrence, corresponding to 17% of total projected mBC occurrence over the next decade. At year 10 (2031), we projected that 29% fewer women would experience mBC occurrence in Turkey (604 with TDM-1 vs. 853 with trastuzumab). Conclusions: Population-level improvements in HER2-positive eBC to mBC disease progression are expected over the next 10 years in Turkey following adjuvant T-DM1 monotherapy. Further research will elucidate treatment-related improvements in costs to society as a result of population-level improvements in disease outcomes for women diagnosed with eBC.[Table: see text]
Breast cancer after IVF: Can ovary stimulation and follicular response affect prognostic factors?
Authors: Izquierdo Maxim , Baulies Sonia , Devesa Marta , Tresserra Fransec , Ara Carmen , Rodriguez Ignacio , Fabregas Rafael , Coroleu Buenaventura , Barri Pedro S , Barri Pere 
Published: June 2021

e12538 Background: The ovary stimulation and the follicular response is related with estradiol level. Study in breast cancer patients after IVF if ovarian response or number of IVF cycles affects the prognostic factors. Methods: Patients with breast cancer who underwent IVF are studied the prognostic factors (Ki67, HER2, estrogen receptor (ER), progesterone receptor (PR), oncogene p53, histologic grade) in relation to the ovary response and number of IVF cycles. Results: 73 patients with breast cancer after IVF are studied. They performed 135 cycles of IVF, 36 (49’3%) with 1 IVF and 37 (50’7%) with more than one IVF. Hyper response was present in at least one IVF in 24 (32.9%) patients and there was no hyper response in any IVF in 49 (67.1%) patients. The prognostic factors were: Ki 67> 20 in 31'91% (15/47) Ki 67 <20 in 68'08% (32/47), HER2 + 31'94% (23/72) HER2- 68'05% (49/72), p53 + 45'09% (23/51), p53-54'90% (28/51), HG II-III 56'36% (31/55), HG I 43'63% ( 24/55), RE + 87'5% (63/72), RE- 12'5% (9/72), RP + 76'38% (55/72), RP- 23'61% (17/72). None of prognostic factors varied with the ovary response (hyper response in at least one IVF cycle, normal response, normal or low response) (p=ns). The only prognostic factor that varied with the IVF number was p53 +. Patients with p53 + (23/51), 7 (30’43%) has one IVF, and 16 (69’53%) have more one IVF (p<0’05). Conclusions: In breast cancer after IVF, the ovary stimulation and the follicular response not affect Ki67, HER2, estrogen receptor, progesterone receptor, p53, and histologic grade. p53 positive is more frequent in patients with more than one IVF.
Gender disparity in breast cancer: A population-based study in the U.S. Department of Veterans Affairs.
Authors: Ajmal Zainub , Khan Abdul Moiz , Tuz Zahra Fatima , Gemoets Darren , Mehdi Syed Arzoo 
Published: June 2021

e12549 Background: Over the last several decades, the mortality for breast cancer has improved, however, there remains a large gender disparity with male patients having worse overall survival. Recent studies have identified increased mortality in male breast cancer (MBC) despite adjusting for age and other clinical factors necessitating a need to evaluate both screening and treatment patterns for MBC. The survival trends in MBC have not been studied across the VA population. Methods: Male and female breast cancer cases between 2000-2018 were identified in National VA Cancer Cube Registry. A total of 1511 cases of MBC and 8081 cases of female breast cancer (FBC) were identified. IRB approval was obtained. Statistical significance was set to 0.05, with significant results noted with an asterisk (*). Results: Our data showed that the number of new MBC cases per year remained stable over the study period while the FBC cases rose by 13.6* per year. The racial distribution of Caucasian and African American (AA) patients was comparable among the two groups. For FBC, the peak incidence was between ages 50-60, while for MBC, the peak incidence was at age greater than 70 years. Males were more likely to present at a later disease stage (stage III and IV) compared to females, (26.94% vs 13.8%) *. They also had a worse performance status (ECOG 3 or higher) at presentation compared to female patients, (3.72% vs 1.32%) *. The survival characteristics and first course of treatment received are summarized in the table below. Our findings show that males have a worse 5-year survival both in early and late-stage disease and across both Caucasian and AA races. This poor survival difference remains when comparing MBC patients older than 50 years but not when comparing the younger subset in both groups. These findings suggest that the overall poor survival of MBC may be related to late detection, advanced age at presentation and subsequent increased comorbidities and poor performance status. Conclusions: Patients with MBC present at a later disease stage and have a worse overall survival when compared to FBC. This difference in survival remained when stratified by age, race and stage at presentation. These results imply the possible underutilization of screening in males as well as differences in the clinical and pathological behavior of male and female breast cancer.[Table: see text]
Impact of pre-treatment derived neutrophil-lymphocyte-ratio on outcomes in patients with triple-negative breast cancer.
Authors: Sharma Rakesh Kumar , Gogia Ajay , Gupta Ritu , Deo SVS , Sharma Dayanand , Mathur Sandeep , Sagiraju Hari Krishna Raju 
Published: June 2021

e12556 Background: There is an ambiguity of data regarding the predictive and prognostic significance of pre-treatment-derived neutrophil-lymphocyte-ratio (DNLR) to attain pathologic complete response (pCR) after neo-adjuvant chemotherapy (NACT) and survival in patients with triple-negative breast cancer (TNBC). Methods: In this ambispective study, conducted at Dr. B.R.A., I.R.C.H., AIIMS, New Delhi, 328 patients of TNBC registered from a period of May 2013 to June 2020, who received treatment with curative intent were included. Patients with oligometastatic TNBC who received NACT with curative intent were also included in the analysis. Survival analysis to evaluate the correlation of pre-treatment DNLR with relapse-free survival (RFS) and overall survival (OS) was done. Logistic regression analysis was done to evaluate the association of DNLR with pCR among the subset of the sample who completed NACT and underwent surgery. Results: The median age of our cohort was 45 (18-74) years. Study cohort comprised of 165 (50.3%) pre-menopausal, 150 (45.7%) post-menopausal and 12 (3.7%) peri-menopausal patients respectively. Stage distribution as per AJCC 7th edition was stage-I 8 (2.4%), stage-II 127 (38.7%), stage-III 171(52.1%), and stage-IV 22 (6.7%) patients respectively. The median duration of symptoms was 3 (0.25-36) months. One seventy-three (52.7%) patients received NACT and underwent surgery, out of which 52 (30.1%) patients achieved pCR. Median DNLR in the overall population was 1.7 (0.4-10.1) and the median derived lymphocyte count of 2290 (370-11700) with < 5%(n = 14) having baseline lymphopenia( < 1000). Based on the maximum sensitivity and specificity, a DNLR cut-off point of 1.77 in the overall population and 1.88 among those patients who underwent surgery following NACT were used to categorize low and high DNLR. Median RFS was 73.5 months in our sample, whereas median OS was not reached. The 3-year RFS and OS rates were 65.8% (59.0-71.8) and 85.1% (79.5-89.2%) respectively. High DNLR( > 1.77) was not associated with RFS [HR (95%CI): 1.36 (0.90-2.06)] and OS [HR (95% CI): 0.97 (0.52-1.81)]. In a subset analysis of patients (173) undergoing surgery following NACT, high DNLR ( > 1.88) was not found to be associated with pCR [OR (95% CI): 0.81 (0.42-1.57)]. Conclusions: Pre-treatment DNLR is an easily available inflammatory marker. Indian patients of TNBC usually have raised baseline lymphocyte count, hence, pre-treatment DNLR may not be a reliable predictor of pCR and survival outcomes in these patients. Association of DNLR at various treatment and post-treatment time points with survival outcomes needs further exploration.
Spatiotemporal loco-regional recurrence patterns after breast-conserving surgery.
Authors: Qu Feilin , Mao Rui , Liu Zhebin , Lin Caijin , Li Junjie , Shao Zhiming 
Published: June 2021

e12580 Background: Loco-regional recurrence (LRR) following breast-conserving surgery (BCS) represents a heterogeneous class of disease that has significant variation in its biological behavior and prognosis. Herein we report for the first time the spatiotemporal patterns of LRR post-lumpectomy in a Chinese population-based cohort. Methods: This retrospective study analyzed the single institutional patient-level data of breast cancer patients who underwent BCS between January 2006 and December 2016 at Shanghai Cancer Hospital of Fudan University. The enrolled patients were followed up regularly after initial surgery. Multivariate Cox regression models were performed to identify independent risk factors for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype. Results: 4,325 patients were included, with a median follow-up of 66 months. A total of 120 (2.8%) LRRs were recorded as the first site of failure. Age at onset, pathologic stage, and molecular subtype were identified as predictors of loco-regional relapse. The major type of LRR was ipsilateral breast tumour recurrence (IBTR), which mainly (83.6%) occurred ≤5y post surgery. ARR curves showed that relapse peaked in the first 2.5 years in the overall population. Patients with regional nodal recurrence (RNR), shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2+ positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery. Conclusions: Currently, the LRR rate is generally low. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.
Anlotinib plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study.
Authors: Chen Xi , Zhang Shuqun , Li Xuexin , Zhang Yinbin , Li Youhuai , Kang Huafeng , Haitao Guan , She Qing , Ma Xiaobin , Diao Yan , Liu Di , Min Weili , Liu Mengjie , Wu Fei , Feng Cong 
Published: June 2021

e12585 Background: Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage triple-negative breast cancer (TNBC). This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary TNBC. Methods: Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented TNBC were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 8 cycles). Chemotherapy comprised of epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2, (21 days per cycle; both total 4 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Stratification was based on the clinical breast cancer stage. This study is registered on Chinese Clinical Trials.gov (ChiCTR2000038174), and still ongoing. Results: Between July 2019 to June 2020, 18 patients (female) with pathological stage ⅡB (83.3%), and IIIA (16.7%) were enrolled with a median age of 46 years (range: 32-72). Overall pCR rate was 44.4% (8/18, CI 95%: 24.6%-66.3%). The pCR rate of pathological stage IIB patients was 46.7%(CI 95%: 26.7%-69.9%), which is tend to be better than the pCR rate of 33.3%(CI 95%: 6.2%-79.2%) for patients with pathological stage IIIA. There are 21 kind of AEs were observed, all including 56 times grade 1 AEs and 34 times grade 2 AEs, no grade 3 or higher AE was observed. The most common AEs included hand-foot syndrome(55.6% in total with 33.3% grade 2 and 22.2% grade 1), oral mucositis(50.00% in total with 33.3% grade 2 and 16.67% grade 1), fatigue(61.1%, all grade 1), hoarse voice(33.3%, all grade 1), nasal bleeding(27.8%, all grade 1), hypertension(22.2% with 5.6% grade 2) and diarrhea(22.2% with 5.6% grade 2). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with high-risk, early-stage TNBC. Clinical trial information: ChiCTR2000038174.
Targeted breast surgery: Non-direct approach.
Authors: Kern Peter , Kessel Alina , Hoffmann Oliver , Bittner Ann-Kathrin , Kimmig Rainer 
Published: June 2021

e12602 Background: Breast conserving surgery is the standard in T1-T3 primary breast cancer. The cosmetic result is very much depending upon the surgeon ́s experience, the tumor-size/breast ratio and the technique applied. We have proposed a nomogram earlier (1) which has been cited earlier by the American Society of Breast Surgeons Consensus Conference as a concept for avoidance of re-excisions and achievement of a favorable aesthetic result. Our nomogram proposed 5 simple oncoplastic techniques to handle the vast majority of breast cancer cases, with high rates of free margins. However, these techniques all used direct access to the mammary gland through the skin above the tumor, leaving permanent scars in the visible skin of the breast. To avoid this, we now have chosen a more natural access to the mammary gland along natural transitions and Langerhans´s skin lines in this prospective open-label study. Methods: We conducted a prospective open-arm study including all primary invasive and non-invasive breast cancer cases of tumor stages AJCC 0-III A (Version 8.0). Non-palbable tumors and those undergoing neoadjuvant chemotherapy had to be marked by a wire and clipped before. Intraoperative ultrasound was applied before skin incision and after removal of the tumor including ultrasound of the specimen to confirm clear margins). Resection was performed as a segmentectomy and SLN biopsy and axillary clearance was done according to national guidelines. Access to the tumor was chosen in a non-direct approach according to the proximity of the tumor to one of the following natural transitions: 1. areola 2. axillary line 3. inframammary fold. Results: 84 patients with breast conserving targeted breast surgery with a "non-direct to the tumor approach" have been enrolled so far. 76 patients had primary surgery with stage distribution as follows: Tis (1), T1a (3), T1b (8), T1c (30), T2 (30), T3 (4) and T4b(1). 8 patients had neoadjuvant chemotherapy with stage distribution as follows: ypT0 (3), ypT1a (2), ypT1c (1) and ypT2 (2). Histopathology was predominantly invasive-ductal breast cancer (70), followed by invasive-lobular (6), ductulo-lobular (5), invasive- ductal and pure DCIS (1), invasive-ductal and mucinous (1) and mucinous only (1). After first surgery according to our nomogram 77 patients had a tumor resection with free margins and 7 with involved margins, thus 91,6 % tumors were resected with free margins at first surgery. The remaining 8,4 % of cases were margin-free after second surgery. Conclusions: Scars were not visible on the surface of the breast outside of natural transitions and rate of free margins was high with targeted breast surgery at a rate of 91,6 % without any cosmetic impairment due to the remote natural access to the mammary gland. Patient-reported outcome in detail has been evaluated by validated questionnaires and demonstrated a high satisfaction with scar pattern, volume and symmetry.
Similar decrease of proliferation employing Ki-67 after brief neoadjuvant hormonal treatment on invasive ductal carcinoma versus invasive lobular carcinoma.
Authors: Majer Martin , Little Elizabeth Fauchier , Jones Sarah , Dong Jasmine , Bezdickova Karolina , Hutton David , 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

e12606 Background: Invasive lobular carcinoma (ILC) differs from the more prevalent invasive ductal carcinoma (IDC) in histology, molecular underpinning, and biological responsiveness to cytotoxics. Patients diagnosed with IDC or ILC were evaluated in the clinical setting to determine if they differ in responsiveness to neoadjuvant hormone treatment. Methods: This is a retrospective observational study of an underserved, low income, rural population in Oroville, California. The data for this study was collected over ten years (2011-2021) from 58 estrogen receptor positive (ER+) breast cancer patients. The majority of these patients (48/58) were diagnosed with IDC with ages ranging from 35 to 91 (mean age is 66) and the remaining 10 were diagnosed with ILC with ages ranging from 58 to 85 (mean age is 64). Patients were given neoadjuvant hormone treatment starting after their initial biopsy confirming ER+ status until scheduled surgical removal by lumpectomy or mastectomy. Ki-67 was measured prior to treatment and then measured again after a minimum of 14 days on hormone therapy. The initial Ki-67 range for patients with IDC was 2%-75% (median of 15%). Ki-67 initial range for patients with ILC was 2%-30% (median of 11%). Positive response to treatment was set at > 50% reduction in Ki-67, with no response set at < 50% reduction in Ki-67. We compared the response rates of ILC and IDC patients using a chi-square test. Results: Chi-square analysis found no statistically significant difference between IDC and ILC response to hormone therapy. 34/48 (71%) patients with IDC responded to treatment, and 8/10 (80%) of ILC patients showed response. Incidentally, we noticed a higher prevalence of ILC in our community compared to expected numbers. Conclusions: When evaluating hormone therapy responsiveness in the neoadjuvant setting, there is no observable statistical difference in response rates between IDC and ILC. Neoadjuvant hormone testing employing Ki-67 response identifies subgroups of patients who benefit from the addition of new biologics (-ciclibs, mTOR inhibitors) in addition to hormone treatment. Our experience supports testing in this way to further individualize the care of patients unable to participate in clinical trials.