bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCH-P) in HER2-positive breast cancer: An Indian experience.
Authors: Gogia Ajay , Arora Shalabh , Deo SVS , Mathur Sandeep , Sharma Dayanand 
Published: June 2021

e12619 Background: Dual targeted therapy with chemotherapy is one of the therapeutic approaches as neoadjuvant treatment in HER2/neu positive breast cancer (BC). However the safety and efficacy data of dual-targeted, chemotherapy regimen (docetaxel, carboplatin, trastuzumab, & pertuzumab [TCH-P] is limited from the Indian subcontinent. Methods: This retrospective study aims to evaluate the efficacy and toxicity of neoadjuvant TCH-P regimen in early, locally advanced, and oligometastatic (OM) HER2-positive BC, at All India Institute of Medical Sciences, New Delhi, India, in between the period 2015-2020. Total 6 cycles of 3-weekly neoadjuvant chemotherapy (NACT) protocol containing docetaxel (75 mg/m2), carboplatin (AUC = 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) and pertuzumab ( 840 mg loading followed by 420 mg) were planned. Subcutaneous peg-filgrastim was prophylactically administered on day 2 of each cycle. The primary outcome was the pathological complete response (pCR), which was defined as an absence of invasive and noninvasive cancer in breast or lymph node and secondary outcome were clinical overall response rate (ORR), rate of breast conservation surgery( BCS) for patients for whom modified radical mastectomy( MRM)was planned and toxicity. Results: Forty-five patients with a median age of 48 years (31-65) were included in this study. The TNM (AJCC-7th edition) stage distribution was stage II, 14 (31.1%); stage III, 29 (64.5%); and stage IV (OM), 2 (4.4%). Clinical node positivity disease was found in 26 (57.8%) cases. Nineteen (42.2%) patients had hormone-positive and 26(57.8%) cases were premenopausal. The clinically ORR and CR were seen in 100% and 60% respectively. Overall pCR rate was observed in 25 (55.6%) patients (70% in stage II). BCS was performed in 23(51.1%) cases. In 12(26.6%) cases, planned MRM was changed to BCS following NACT. Grade 3 and 4 toxicities were diarrhea 7 cases, thrombocytopenia in 6, neutropenia in 4, febrile neutropenia in 1, and anemia in 2 cases. Ten patients required dose modification and interruption. No patient had congestive heart failure or induction death. Conclusions: This is the first study of the non-anthracycline-based neoadjuvant protocol in HER2 positive BC from India. The TCH-P is an effective, safe, and well-tolerated, protocol with a path CR rate of 55.6% and 26.6% BCS conversion rate from planned MRM.
The predictive value of neutrophil-to-lymphocyte ratio on overall survival and pathological complete response in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Tang Wenjie , Wang Linlin , Yu Jinming , Yu Yishan 
Published: June 2021

e12625 Background: Neutrophil-to-lymphocyte ratio (NLR) has been found to offer clear predictive utility for the overall survival (OS) and pathologic complete response (pCR) in breast cancer (BC) patients receiving neoadjuvant chemotherapy(NAC). However, previous studies mainly focused on pre-NLR. The aim of this study was to explore the role of pre-/post-NLR towards OS and longitudinal NLR kineticsonpCR for BC patients undergoing NAC. And we also tried to build a nomogram for OS prediction based on these parameters. Methods: In this study, we retrospectively collected 501 female patients with locally advanced BC receiving 4-8 cycles of NAC from 2009 to 2018. Clinicopathological characteristics, NLR at pre-, mid-(every two cycles of NAC) and post-treatment were collected. The primary endpoint was OS. Among the patients, 421 patients with available pre- and post-NLR were included in the survival analysis. These patients were randomly divided into a training cohort (n = 224) and a validation cohort (n = 197). Multivariate survival model was built by including all the significant prognostic factors from the univariate analysis in the training cohort, and a nomogram model was established by “R” version 3.4.3. The performance of the model was further tested in the validation cohort by the concordance index. The second endpoint was pCR. Longitudinal analysis of NLR was performed using a mixed-effects regression model to predict pCR among 176 patients who finished 8 cycles of NAC. Results: The median follow-up time was 43.2 months for 421 patients. In the training cohort, multivariate analysis revealed that ER status, clinical node stage , pCR , pre-NLR, and post-NLR (all Ps＜0.05) were independent predictors of OS. Nomogram for OS prediction was established by combining all these significant factors. The C-indexes of the nomogram were 0.764 and 0.693, respectively in the training and validation cohort. In the longitudinal analysis, patients achieved pCR experienced a reduction of NLR every 2 cycles (Coef = -0.032, std error = 0.014, P = 0.024). Conclusions: This study demonstrated the prognostic value of pre-NLR and post-NLR towards BC patients received NAC. Based on that , a novel nomogram was established to predict the 3- and 5- year OS for BC patients. And we also found patients who experienced a decline of NLR during NAC seems to be more likely to achieve pCR from chemotherapy. Routine assessment of NLR may be an easy and affordable tool for defining prognosis.
Real-world starting dose and outcomes of palbociclib plus an aromatase inhibitor for metastatic breast cancer.
Authors: Patt Debra A. , Liu Xianchen , Li Benjamin , McRoy Lynn , Layman Rachel M. , Brufsky Adam 
Published: June 2021

e13021 Background: Palbociclib (PA) has been approved for HR+/HER2–advanced/metastatic breast cancer (mBC) in combination with an aromatase inhibitor (AI) or fulvestrant for more than 6 years. Regardless of the labeled recommended starting dose of 125mg/day, some patients initiate palbociclib at lower doses in routine practice. This study described real-world starting dose, patient characteristics, and effectiveness outcomes of first line PA+ AI for mBC in the US clinical setting. Methods: We conducted a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records, which came from over 280 cancer clinics representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and September 2018, 813 HR+/HER2– mBC women initiated PA+AI as first-line therapy and had ≥ 3 months of potential follow-up. Patients were followed from start of PA+AI to December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS) was defined as the time from the start of PA+AI to death or disease progression. Real-world tumor response (rwTR) was assessed based on the treating clinician’s assessment of radiologic evidence for change in burden of disease over the course of treatment. Multivariate analyses were performed to adjust for demographic and clinical characteristics. Results: Of 813 eligible patients, 68.3% were white, median age was 65.0 years, and 42.9% had visceral disease (lung and/or liver). Median duration of follow-up was 21.0 months. 805 patients had records of PA starting dose, with 125mg and 75/100mg/day being 86.5% and 13.5%, respectively. Patients who started at 75/100mg/day were more likely to be ≥75 years than those who started at 125mg/day (38.5% vs 17.1%). Other baseline and disease characteristics were generally evenly distributed. Patients who started at 125mg/day had longer median rwPFS (27.8 vs 18.6 months, adjusted HR=0.74, 95%CI=0.52-1.05) and higher rwTR (54.0% vs. 40.4%) than those patients who started 100/75mg/day (adjusted OR=1.76, 95%CI=1.13-2.74). Table presents results in detail. Conclusions: Most patients in this study initiated palbociclib at 125mg/day and dose adjustment was similar regardless of starting dose. These real-world findings may support initiation of palbociclib at a dose of 125mg/day in combination with AI for the first-line treatment of HR+/HER2- mBC. [Table: see text]
Development of orally bioavailable prodrugs of fulvestrant for the treatment of metastatic/advanced breast cancer.
Authors: Purohit Parva , Brahmkshatriya Pathik , Goswami Vishalgiri 
Published: June 2021

e13027 Background: Fulvestrant, a potent, selective estrogen receptor degrader, is a primary drug of choice for treating advanced metastatic hormone receptor-positive breast cancer in postmenopausal women following anti-estrogen therapy. However, the existing therapy limits to inconvenient intramuscular injections due to low solubility, weak permeation, high metabolism, and poor pharmacokinetics profile. Additionally, it takes 30 days to reach maximal steady-state plasma concentration, limiting clinical efficacy. To overcome these issues, we modulated physicochemical properties of fulvestrant, enabling its oral delivery to improve bioavailability. Methods: Structurally diverse pro-moieties were appended on fulvestrant to improve solubility and ADME profile. Thermodynamic solubility, plasma/liver microsomal stability, and Caco-2 permeability studies were performed to identify lead molecules. Pharmacokinetic studies were performed for selected molecules in mice. Antitumor activity of once-daily oral dose of three molecules was evaluated in female nude mice using the MCF-7 xenograft model. The efficacy of lead molecules was compared with subcutaneously administered faslodex in terms of percentage tumor growth inhibition. Results: Several prodrugs of fulvestrant were synthesized and evaluated for their intrinsic properties suitable for increasing bioavailability of fulvestrant. Remarkable improvements (̃500 to 2000-fold increase) were achieved in solubility and permeability. The PoC established an increase in systemic plasma exposure of fulvestrant upon oral administration of prodrugs in mice with enhanced bioavailability (1.5-8.7-fold) as compared to fulvestrant given subcutaneously (Table). Herewith, we report the identification of KSHN001022, KSHN001075, and KSHN001126, the prodrugs of fulvestrant, which showed enhanced efficacy with better tumor volume reduction (̃48-88% regression in tumor volume) as compared to that of fulvestrant (78%) in the estrogen-dependent MCF-7 xenograft model. Conclusions: KSHN001 lead candidates demonstrated significantly higher bioavailability, hence, provides a novel strategy to deliver fulvestrant orally to pursue the potential benefits in patients with advanced metastatic disease.[Table: see text]
The effectiveness and safety of eribulin therapy in HR-positive HER2-negative metastatic breast cancer post-CDK4/6 inhibitor therapy in Russian clinical practice.
Authors: Kolyadina Irina Vladimirovna , Bolotina Larisa , Zhukova Lyudmila , Vladimirova Liubov Yu , Sultanbaev Alexander , Karabina Elena , Ganshina Inna , Ovchinnikova Elena , Kolyadina Irina Vladimirovna , Antonova Galina , Volkonsky Mikhail , Kolokolov James , Zueva Elena , Akopyan I , Fadeeva Natalia , Evstigneeva Irina , Orlova Svetlana , Vasilevskaya Anna , Shalaeva Oxana , Shirokova Oxana 
Published: June 2021

e13035 Background: EMPOWER trial demonstrated the benefit of eribulin administrated post CD4/6i in patients (pts) with HR+ HER2-negative (HR+HER2-) metastatic breast cancer (MBC). There are several important limitations to this trial: > 60% of pts were stage IV at the time of treatment initiation, eribulin used in late lines (2L only in 30% pts) and follow-up data were immature. Current study aimed to provide additional data on the real-world effectiveness and safety of eribulin monotherapy in this setting. Methods: Observation study of eribulin monotherapy in standard regimen enrolled 54 pts (median age 56; range 29-79 years) with HR+ HER2- MBC received at least one dose of eribulin post CDK 4/6i in metastatic settings; 24% pts had de novo metastatic BC, 76% - recurrent BC; 77% received palbociclib, 21% ribociclib, 2% both drugs; 49% pts received CDK4/6i with fulvestrant and 51% with AI. CDK4/6i was used: 49% pts in 1L, 36% in 2L, 16% in 3L. Median DOR of CDK4/6i treatment was 9.07 months (range 2-38). 94% pts received anthracyclines and taxanes, eribulin was used in 2L in 60%, 30% in 3L, 8% in 4L, 2% in 5L. The most common sites of metastases (Mts) were bones (78%), liver (73%), lung (56%) and brain (8%); visceral Mts were seen in 90% pts. Median follow-up – 11,5 months (range 3-36). Results: Median cycles of eribulin therapy was 10,5 (range 1-44); objective response rate was seen in 24%, stabilization - 67%, progression - in 9%. Median PFS was 10.0 months, there were no significant differences in the different subgroups (visceral/no visceral; recurrent/de novo BC; age; CDK4/6i as 1L vs 2L, fulvestrant vs AI), p > 0,05. Median PFS was higher in pts with lung Mts vs non-lung (24 vs 9,1 months, p = 0.056). Most common AEs all grades were neutropenia (26%), anemia (9%), asthenia (9%), polyneuropathy (11.1%). AE did not affect the effectiveness of eribulin (p = 0.648). Dose reduction was in 19% pts and did not affect the effectiveness of eribulin (p = 0.612). At median follow-up of 11.5 months, 92.5% of patients still alive. Conclusions: As post-CDK4/6i therapy, eribulin in HR+HER2- MBC pts was effective and well tolerated, regardless of age, line of CDK4/6, CDK 4/6i combination partner. Patients with metastasis to the lung have better mPFS. Results in this real-world population of pts with HR+HER2- MBC were consistent with the EMPOWER study, and support administration of eribulin in 2-3 lines as an effective option for post-CD4/6i pts.
Impact of race on the utilization and efficacy of CDK4/6i: Result from a real world database.
Authors: Dawood Shaheenah S. , Brzozowski Kaylen 
Published: June 2021

e13036 Background: The combination of the CDK4/6 inhibitors(CDK4/6i) and endocrine therapy has improved overall survival(OS) in patients(pts) with endocrine sensitive or resistant disease. Only 43 pts of black race were included in the first line trials making interpretation of results in this group difficult. The goal of this retrospective analysis of a real world database was to look at the clinical utilization and prognostic impact of CDK4/6i among pts of white and black race who have hormone receptor positive (HR+ve)/HER2-ve metastatic breast cancer(MBC). Methods: For this analysis, we utilized a federated network of de-identified health data representing approximately 64 million pt lives available through the TriNetX Platform. We identified 5400pts with information on race who had HR+ve/HER2-ve MBC diagnosed between 2015 and 2020. OS was computed using the Kaplan Meier product limit method. Propensity score matching was performed on all comparisons of survival, matching patients from two cohorts on secondary malignancy location (as noted in ICD-10 diagnosis coding)and age group. Results: 4182 white pts and 1199 black pts were identified, and 1,194 pts in each group remained after matching. Mean age at diagnosis was 57.2 and 58.3 yrs among white and black pts respectively. OS among pts of white and black race was significantly different (HR 1.4, 95%CI 1.12-1.70, p < 0.0001), and 2-yr OS was 87.8% and 82.6% respectively. 599(20%) pts of white race and 148(18%) pts of black race received CDK4/6i therapy. The rate of uptake of use CDK4/6i was initially similar in 2015 however by 2020 some differences were observed with rate of uptake being 190 per 1000 and 264 per 1000 among pts of black and white race respectively. Pts of each race appeared to have a similar prevalence of CDK4/6i per line of treatment. OS among pts who received CDK4/6i and were of white and black race was not significantly different(HR 0.94, 95% CI 0.65- 1.38, p = 0.80), and 2-year OS was 69.9% and 69.5% respectively. Conclusions: Overall the proportional use of CDK4/6i was similar among pts of black and white and race. Although initial uptake appears to have been consistent between Black and White pts, further attention is necessary to assess potential disparities in use as time progresses. The use of CDK4/6i in the setting of HR+ve/HER2-ve MBC diminishes the differences in outcome between the two races.
CTNND1 to mediate bone metastasis of triple-negative breast cancer via regulating CXCR4.
Authors: Gong Chang , Lin Qun , Fang Xiaolin , Jiang Wenguo , Li Jun , Li Juanmei , Shi Yu , Luo Qing , Liu Zihao , Cen Yinghuan 
Published: June 2021

e13045 Background: Compared to lumial breast cancer, the proporation of triple-negative breast cancer (TNBC) with bone metastases (BMs) is relatively low and few data focusing on the mechanism of the BMs in TNBC are available, Here, we screened that CTNND1 was associated with BMs of TNBC by integrating high-throughput sequencing, and further investigated the role of CTNND1 in BMs of TNBC in vitro. Methods: TNBC tissue samples with only BMs (n = 6) and without any metastasis (n = 10) were tested using high-throughput sequencing and 11 differentially expressed relative genes were identified. We then quantified these 11 genes in normal breast tissue samples (n = 26), TNBC tissue samples with only BMs (n = 10), TNBC tissue samples without any metastasis (n = 88) as well as luminal tissue samples with BMs（n = 10）through qPCR and immunohistochemical staining (IHC). The effects of knocking down CTNND1 on the interaction between TNBC cells and osteoblasts were examined by cell adhesion, transwell migration and matrigel invasion assays. To explorethe role of CTNND1 in mediating bone metastasis in TNBC, we used RNA-sequencing to find out the relative downstream gene CXCR4 and PI3K-AKT-mTOR pathway and verified it in vitro by Western Blotting. Results: Combining our high-throughput sequencing data, qPCR and IHC in clinical tissue samples, we verified that CTNND1 was decreased in TNBC patients with bone metastasis compared to normal tissue and luminal tissue with BMs. Knocking down of CTNND1 in TNBC cells including MDA-MB-231, MDA-MB-468 and BT549 weakened cells adhesion, but facilitated cells migration and invasion. Mechanically, knocking down of CTNND1 upregulated CXCR4 via activating PI3K-AKT-mTOR pathway in TNBC but not luminal and HER2- positive breast cancer cells lines. Conclusions: CTNND1 mediates bone metastasis in triple-negative breast cancer via regulating CXCR4.CTNND1 may serve as a potential predictor of bone metastasis for TNBC patients.
Association of pathological clinical characteristics, PD L 1 receptor expression (sp 142), with tumor lymphocytic infiltration cells (TILs) in patients (pts) with triple negative breast cancer (TNBC) in Tucumán, Argentina.
Authors: Zarba Juan Jose , Vinuales Ana , Holgado Silvia Victoria , Stagmeyer Erika 
Published: June 2021

e13049 Background: Breast cancer (BC) is the most prevalent tumor in women and the leading cause of cancer death in women. TNBC has the worst prognosis among BC subtypes and limited treatment options, mainly including chemotherapy. The efficacy of immunotherapy is clear for immunogenic tumors, such as melanoma, kidney cancer, non-lung cancer small cell, among others. BC seems to be less immunogenic. Basal-type TNBC present a prominent infiltration of inflammatory cells, suggesting that an immune pathway plays a role in tumorogenesis. The development of immunotherapy (IO)has reached an important turning point in the history of cancer treatment based on the use of the immune system itself to fight tumor cells. PD-L1 overexpression is the only predictive response biomarker for anti-PD-1 / PD-L1 therapy that is accepted in TNBM. Methods: Retrospectively, 68 cases of TNBC from the Pathological Anatomy Service of the Ntra. Sra. De las Mercedes Maternity Institute, of Tucumán, between 2010 and 2016 were analyzed. VENTANA anti PDL1 sp142 assay platform was used. Tumor-infiltrating immune cells (IC) are scored as the proportion of tumor area that is occupied by PD-L1 staining IC of any intensity. A specimen should be considered to have PD-L1 expression if the specimen exhibits ≥ 1% IC. In addition, carcinomas with a proportion greater than 50% of lymphocytic infiltration and its association with the expression of PD L1 were studied according to the recommendations of the International TILs Working group. Results: The median age of the patients was 56 years (21-80). The predominant histological type was non-specific type ductal carcinoma, reported in 45/68 cases (66%), following the medullar 9 / 68 (13%) lobular in 8/68 (11%), metaplastic 3/68 (4%) and other 4%. The tumor grade (G), half of the cases were G 3 with 34/68 (50%), G 2 with 42%. The largest proportion of pts, 42%, had no lymph node (LN) involvement, 33% had between 1 to 3 positive LN and 25% showed 4 or more LN. Stage II 39/68 patients (58%) in stage III 20/68 (30%), I (9%, 6) and IV (3%, 2). 16% (11/68) of the patients were PD-L1 positive. Tumors with lymphocytic infiltration between 0% and 10% expressed 24% (2/37), no expression was observed in tumors with TIls between 10 and 50% and in cases with lymphocytic infiltration greater than 50% expression of PD L was observed 1 in 9/18 cases (50%) (Fisher's exact test, p < 0.0001). Conclusions: It was demonstrated that there is an association between the stromal lymphocytic infiltrate (TILs) and the expression of PD-L1 in tumor cells, in this population of women from Tucumán, which would help to select patients as candidates for anti PD L1 therapies.
Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.
Authors: Grimm Michael , Ramaswamy Bhuvaneswari , Lustberg Maryam B. , Wesolowski Robert , Sardesai Sagar D. , VanDeusen Jeffrey Bryan , Cherian Mathew Amprayil , Stover Daniel G. , Gatti-Mays Margaret Elena , Pariser Ashley , Kassem Mahmoud , Stephens Julie , Palettas Marilly , Williams Nicole Olivia 
Published: June 2021

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]