bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma VEGF-a, angiopoietin-2 (ANG2) and soluble(s)TIE2 in patients (pts) with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X).
Authors: Lam Siu W. , de Groot Steffen M. , Honkoop Aafke H. , Nota Nienke M. , Jager A. , van der Velden Ankie M.T. , Bos Monique M.E.M. , Linn Sabine C. , Van Den Bosch J. , Kroep Judith R. , Braun J. J. , de Haas Richard R. , Smorenburg Carolien H. , de Graaf Hiltje , Portielje Johanna Elisabeth A. , Los Maartje , de Gooyer Domingo , van Tinteren Harm , Boven Epie ,   Dutch Breast Cancer Trialists' Group (BOOG)
Published: March 2020

1072 Background: In the randomized phase II ATX trial, pts with HER2-negative LR/MBC were treated with first-line AT or ATX. We determined the prognostic value for outcome of VEGF-A, ANG2 and sTIE2 measured at baseline on cycle 1 day 1 (C1D1) and after cycle 1 (C2D1). Methods: 312 pts were randomized in 1:1 ratio to AT (T 90 mg/m2 on d1, 8, 15 and A 10 mg/kg on d1, 15 q4w x 6 cycles, followed by A 15 mg/kg on d1 q3w for next cycles) or ATX (T 90 mg/m2 on d1, 8, A 15 mg/kg on d1 and X 825 mg/m2bid on d1–14 q3w x 8 cycles, followed by the same dose of A and X q3w for next cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), response duration (RD), overall survival (OS) and safety. Plasma proteins on C1D1 (N = 173) and on C2D1 (N = 142) were measured by ELISA. The association of protein levels (continuous variable) with PFS and OS was evaluated by Cox proportional hazards model and Martingale residual plot. Results: At a median follow-up of 39 months (mo), there were 292 PFS events and 242 deaths. ATX significantly improved PFS as compared to AT (median 11 vs. 8.4 mo, stratified HR = 0.52; 95% CI, 0.41 – 0.67; P < .001). The confirmed ORR in measurable disease (N = 268) was 67% in ATX vs. 50% in AT. Median RD was 6.4 mo (95% CI, 6.1 – 8.3) in ATX v 5.4 mo (95% CI, 5.1 – 6.0) in AT. Median OS was 24.1 mo in ATX vs. 23.1 mo in AT (P= .44). The aselected ‘biomarker’ cohort (N = 173) and overall trial cohort had similar baseline characteristics. ANG2 on C1D1 moderately correlated with sTIE2 on C1D1 (Pearson’s r = .44, P < .001). High ANG2 on C1D1 was significantly associated with poor OS (HR = 1.6; 95% CI, 1.1 – 2.3; P = .01), but not with poor PFS (HR = 1.3; 95% CI, 1.0 – 1.3; P = .07). ANG2 on C2D1 was not significantly associated with OS (HR = 1.55; 95% CI, 0.99 – 2.4; P = .057) or with PFS (P= .6). sTIE2 and VEGF-A were not associated with outcome. All pts had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions: In HER2-negative LR/MBC, ATX is more effective (PFS, ORR and RD) than AT. A very high plasma level of ANG2 at baseline indicates a high risk for poor survival. Clinical trial information: NTR1348.
Assessing the impact of CMF/FEC/FEC-DOC/ETC (dose-dense) adjuvant chemotherapy in dependency of positive axillary lymph nodes on survival: A retrospective multicenter cohort study of 4,526 breast cancer patients receiving adjuvant chemotherapy.
Authors: Schwentner Lukas , Van Ewijk Reyn , Hoffmann Isabell , Kreienberg Rolf , Blettner Maria , Wöckel Achim ,   BRENDA Study Group
Published: March 2020

1074 Background: Adjuvant chemotherapy has changed dramatically in the last decades. Anthracycline-/taxane-based and dose-dense chemotherapy regimens improved survival in node positive breast cancer. This study tries to answer the following questions: (1) Are there differences in survival dependent on chemotherapy regimens in 0/0-3/4-10/<10 positive lymph nodes? (2) Is it possible to define a cut-off of positive lymph nodes for the use of Taxane-based and dose dense chemotherapy? Methods: This German is a multi-center [17 participating hospitals all are certified as breast cancer centers] retrospective cohort study. We included CMF (1.385), FEC (1.170), FEC-DOC (1.723), and dose-dense ETC (248) into the analysis. Results: In case of 0 LN CMF/FEC/FEC-DOC did not show significant differences in DFS, but OAS was significantly impaired by the use of FEC-DOC in 0 LN [p=0.024; HR=2.02 (95% CI: 1.10-3.73)] (no ETC use in 0 LN). In case of 1-3 positive LN CMF/FEC/FEC-DOC/ETC did not differ significantly in survival parameters. But in 4-10 LN FEC-DOC [p=0.049; HR=0.67 (95% CI: 0.44-0.99)] and ETC [p=0.024; HR=0.56 (95% CI: 0.34-0.93)] demonstrated a significant benefit in DFS and a strong trend in OAS. Dose-dense ETC showed a significant improvement in DFS [p=0.003; HR=0.35 (95% CI: 0.17-0.69)] and OAS [p=0.009; HR=0.35 (95% CI: 0.16-0.77)] in patients with >10 positive LN. Conclusions: Our data confirms that Taxane-based chemotherapy does not improve DFS in LN negative breast cancer, but rather demonstrated an inferior OAS. But in LN positive breast cancer we can demonstrate a benefit by the use of Taxane-based chemotherapy regimens. Furthermore, dose-dense ETC demonstrated a significant benefit in survival in >10 positive LN.
Community use of anthracyclines in metastatic breast cancer (MBC).
Authors: Krook James Edward , Kumar Akhil , Fishman Marc L. , Shimp William S. , Bobolts Laura Rose , Fishman Val , Davis Sharon , Huff Dinah , Anthony Carol , Walton Robert , Hrushesky William J. 
Published: March 2020

1080 Background: For decades, anthracyclines have been among the most useful treatments for women with MBC. Though recent publications have confirmed an overall decline in the use of anthracyclines in BC, most of that decline was felt to be due to its diminished utilization in the adjuvant management of BC. Current community anthracycline usage pattern in MBC is not known. We investigate and report, herein, how community oncologists in the southeast USA are currently utilizing anthracyclines for MBC. Methods: All chemotherapy treatment requests for HER2+ and HER2- Stage 4 BC were examined, from 2009 through 2012. Chi-Square test was performed for interaction between age and anthracycline utilization, with p-value less than 0.05 considered significant. The proportion of women who had been treated previously in the adjuvant setting with low cumulative doses of anthracyclines, which would have some effect upon subsequent use, was not retrievable. Results: During this span, 420 unique chemotherapy requests were initiated for 247 patients. These included 54 anthracycline requests for 50 MBC patients. The use of anthracyclines for metastatic HER2+ BC was virtually absent (one in 63 requests among 42 patients). The remaining 357 chemotherapy requests were for treatment of 205 HER2- MBC patients. Anthracyclines were employed in 22% of women under 65 years of age and in 25% of those older than 65 (p = 0.77). Approximately 83% (45/54) of anthracycline-requests were for conventional doxorubicin, either alone or in combination with other agents. The rest were for liposomal doxorubicin (6/54) or epirubicin (3/54). Conclusions: Data from the southeast USA identifies that anthracyclines are virtually never used in HER2+ MBC. Even in HER2- MBC, anthracyclines are used in only one out of 4 patients suffering from this disease. The effect of this unheralded alteration in oncology practice must be carefully considered when trends in metastatic breast cancer control are examined. [Table: see text]
Effect of capping chemotherapy dose on chemotherapy effect in morbidly obese women with breast cancer.
Authors: Porter David James , Wilson Michelle 
Published: March 2020

1081 Background: Obesity adversely affects outcomes from adjuvant (adj) chemotherapy for breast cancer. Capping of chemotherapy dose has been implicated as one factor that may contribute to this. We postulated that if capping resulted in underdosing, this would be reflected in the incidence of dose dependent toxicities (DDT) such as mucositis and haematological toxicity. Methods: We retrospectively reviewed records of breast cancer patients (pts) commencing adj chemotherapy from 1 Jan 2010-31 Dec 2010 at the Auckland Regional Blood and Cancer Service identified using a prospective pharmacy database. Baseline characteristics, BSA, body mass index (BMI), neutrophil (ANC) nadir, relative dose intensity (RDI) and dose limiting complications (DLC) were recorded. Results: 174 pts were identified. Median age was 49 yrs (24-73). 17.8% had a BSA >2. 3.2% pts with BSA>2 had BMI <30. 42% had a BMI ≥30 (17.9-61.0), of whom 59% had a BSA ≤2. All patients with BSA >2 had dose capping. 71 pts had a DLC. Neutropenic fever/infection or treatment delays from neutropenia were more common if BSA ≤2 vs. >2 (p=0.08) but not with other DDT. Treatment deferrals (18.8 vs. 16.1%) dose reductions (25.2 vs. 32.3%) and mucositis were similar in both groups. Mean baseline ANC was 4.4 in pts with BSA ≤2 and >2. Mean ANC nadir was 0.8 and 1.3 respectively (p<0.01). r2BSA vs nadir ANC was 0.012. G3/4 neutropenia was seen 76.5% of pts with BSA ≤2 vs. 44.8% if BSA >2 (RR 1.3 p<0.01). No pt had > G1 thrombocytopenia. Mean RDI was 93.2 and 94.8 respectively (p=0.4) Conclusions: Previous studies show ANC nadirs correlate well with drug exposure (area under plasma concentration vs. time curve) but poorly with BSA. Therefore we used hematological and DDT as surrogate measures for drug exposure in pts with and without capped doses. There was more G3/4 neutropenia (p<0.01) in uncapped pts but rates of other DDT were similar. Since BSA based dosing has little impact on inter-pt variability in systemic drug exposure and trials where capping was not used still show a poorer outcome in obese pts, these results suggest dose capping is a minor contributor to the worse outcomes in morbidly obese breast cancer pts having adj chemotherapy. Addressing obesity itself may be more important.
Neoadjuvant versus adjuvant chemotherapy with taxanes and anthracycline-based regimen: Which leads to better outcome in patients with different subtype breast cancer?
Authors: Yang Houpu , Wang Shu , Zhou Lixin , Guo Jiajia , Cao Yingming , Zhou Bo , Cheng Lin , Xie Fei , Liu Hongjun , Tong Fuzhong , Liu Miao , Liu Peng , Wang Siyuan , Yang Deqi , Zhang Jiaqing 
Published: March 2020

1084 Background: Neoadjuvant chemotherapy was reported to lead to equal outcome with adjuvant therapy in operable breast cancer. However, different molecular subtypes show variant response to chemotherapy, which is associated with different long-term prognosis. This study was to clarify whether molecular subtypes lead to different outcome between neoadjuvant and adjuvant chemotherapy. Methods: We identified 406 patients with stage II-III breast cancer who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. To minimize the confounding bias, only patients received taxanes and anthracycline based regimen (TA) were included. Cases were divided according to receipt of neoadjuvant and adjuvant therapy. Data were compared using χ2test and analysis of variance. Kaplan-Meier Curves were generated. Results: Of the 406 patients, 201(49.5%) received neoadjuvant chemotherapy and 205(50.5%) received adjuvant TA regimen. The pCR rate was 12.9%(26/201) in total, and 7%, 14%, 33.3%, 19.4% for Luminal A, Luminal B, HER2+ and Triple negative breast cancer(TNBC), respectively. The HER2+ and TNBC have significantly higher rates of pCR than Luminal type (p<0.05). In general the two groups showed little survival variance (p=0.073 for DFS and p=0. 601 for OS). In Luminal B, neoadjuvant settings led to worse disease free survival (DFS) and overall survival (OS) than adjuvant settings after controlling for the covariates associated with survival in unadjusted tests (HR=0.41, p=0.028 for DFS; HR=0.32, p=0.020 for OS). In HER2+ subtype, neoadjuvant group corresponded to better DFS and OS (HR=5.65, p=0.024 for DFS; HR=10.52, p=0.010 for OS). On the contrary, patients with TNBC and Luminal A undergoing neoadjuvant chemotherapy had equal DFS and OS compared with patients receiving adjuvant therapy (p>0.05). Conclusions: The results demonstrate survival difference between patients receiving neoadjuvant and adjuvant cytotoxic therapy in variant subtypes. Prospective studies are necessary to determine if the finding is durable and optimize the timing of chemotherapy for breast cancer with different molecular background.
Circulating biomarkers in patients receiving neoadjuvant chemotherapy combined with sunitinib for locally advanced breast cancer.
Authors: Brown-Glaberman Ursa Abigail , Specht Jennifer M. , Iannone Maria , Kurland Brenda F. , Livingston Robert B. , Stopeck Alison 
Published: March 2020

1089 Background: Biomarkers to guide the use of antiangiogenic therapy are lacking. Circulating endothelial cells (CECs) and their progenitor cells (CEPs) are increased in cancer patients. VCAM is an endothelial protein increased in response to VEGF stimulation, while CAIX is elevated in states of hypoxia; both correlate with tumor aggressiveness. Methods: We examined these circulating biomarkers in a phase II neoadjuvant trial in 63 patients (pts) with locally advanced HER2 negative breast cancer treated with 12 weeks (wks) of paclitaxel (T) plus sunitinib (S) followed by 15 wks of daily oral cyclophosphamide and weekly doxorubicin plus daily G-CSF (AC+G-CSF). Toxicity and clinical outcomes are reported as a separate abstract. Blood was collected at baseline, wk 12 and pre-surgery. For this analysis, responders were defined as patients with a pathologic complete response (pCR) and/or MDACC CPS+EG score ≤ 2 (a validated score combining clinical and pathologic results for predicting survival in the neoadjuvant setting). Plasma VCAM and CAIX levels were measured by ELISA using commercially available validated kits and CEC/CEPs by flow cytometry in our laboratory as previously published. Results: 28 (44%) pts were responders. CECs decreased significantly in response to T+S (p = 0.04) but not further with AC+G-CSF. No significant changes were seen in CEPs. VCAM and CAIX levels increased in pts with baseline levels below the median in response to T+S (VCAM p = 0.0003, CAIX p = 0.009). ER negative tumors had higher levels of plasma VCAM and CAIX at baseline compared to ER positive tumors (VCAM p = 0.01, CAIX p = 0.1). Lower baseline levels of VCAM and CAIX were associated with both response and pCR. VCAM and CAIX levels were correlated at baseline (r = 0.4, p = 0.01). Conclusions: CEC, VCAM, and CAIX levels significantly changed after treatment with T + S. Higher baseline levels of VCAM and CAIX were associated with ER negative tumors and lower response rates. Our results suggest that elevated baseline VCAM and CAIX levels are associated with more aggressive biology, and may correspond to less (not more) favorable outcome with the addition of a targeted antiangiogenic agent. Clinical trial information: NCT00513695.
Phase Ib study of eribulin (ERB) and cyclophosphamide (CTX) in metastatic breast cancer (MBC).
Authors: Truong Thach-Giao , Pelayo Michael , Grabowsky Jennifer A. , Melisko Michelle E. , Magbanua Mark Jesus Mendoza , Moasser Mark M. , Reinert Anne , Hwang Jimmy , Park John W. , Munster Pamela N. , Rugo Hope S. 
Published: March 2020

1095 Background: ERB is a non-taxane microtubule inhibitor approved for the treatment (Tx) of taxane (TAX) and anthracycline-treated MBC based on improved OS compared to treatment of physician choice. In the adjuvant setting, docetaxel/CTX (TC) was superior to doxorubicin/CTX for DFS and OS. ERB is active in TAX-resistant disease with a low rate of peripheral neuropathy (PN); its primary dose-limiting toxicity (DLT) is bone marrow suppression. We hypothesized that the combination of ERB and CTX would be well tolerated and active in patients with TAX-resistant disease, with potential applicability to the adjuvant setting. Methods: We designed a 3+3 phase Ib study of ERB, administered in 2 escalating doses on day 1 and 8, with CTX 600 mg/m2day 1 every 21 days. Eligibility included PN ≤ grade 1. Correlative studies to identify predictors of response and toxicity included whole blood for SNPs, GWAS, circulating tumor cells (CTC), and archived tumor RNA/protein expression analysis. Toxicity assessment included QoL and evaluation of PN. Results: 6 patients (pts) with MBC, median age 50 (47-63), were enrolled. All pts had prior TAX exposure and 4 pts had baseline grade 1 PN. Tumor characteristics included hormone receptor + (5 pts), HER2+ (2 pts), and triple-negative (1 pt). Median number of prior Tx for MBC was 5 (1-8). No DLTs were observed; the RP2D is eribulin 1.4 mg/m2 on D1 and D8 with CTX D1 600mg/m2. Neutropenia was the only G3/G4 non-DLT observed at this dose, requiring GCSF support in cycle1 in 2 of 3 pts. All grade toxicities included neutropenia (50%), thrombocytopenia, fatigue, nausea, PN, rash, mucositis, alopecia (33% each), and elevated liver enzymes (17%). Pts received a median of 5.5 cycles (range 3-13), with 3 pts still on Tx. Responses included 2PRs (33%) and 4 SD (67%). 2 pts stopped study Tx for QoL and continued ERB alone. Only 2 pts met threshold of >5CTC/7.5ml at baseline; these had a mean decrease of 90.5% at the start of cycle 2. Conclusions: ERB and CTX is a well-tolerated regimen with promising activity in MBC, with the primary toxicity being neutropenia requiring growth factor support. A phase II study in MBC is underway. Additional correlative studies are ongoing including molecular analyses of CTC. Clinical trial information: NCT01554371.
Effect of very small tumor size on recurrence-free survival and breast cancer-specific mortality stratified by guideline adherence: An analysis of the BRENDA Study Group.
Authors: Wöckel Achim , Schwentner Lukas , Wischnewsky Manfred , Kreienberg Rolf , Wolters Regine ,   BRENDA Study Group
Published: March 2020

1096 Background: Small tumor size (<5mm, T1a) carry an excellent prognosis, despite a variety of treatment approaches. Controversy exists over the extent of treatment, as to whether less than conventional treatment can be done. We therefore sought to explore the effect of very small tumor size on RFS and BCSM stratified by guideline adherence. Methods: The multicenter study population included 8935 early breast cancer patients diagnosed between 1992-2008, where 614 patients (6.9%) were T1a. T1a-patients were categorized according to guideline adherence and the influence on survival was calculated by Cox proportional hazard analyses (adjusted for age, grading, nodal status, hormonal status and co-existing morbidity). Results: The median age was 61 years and the median follow-up was 55 months. 449 [73.1%] patients were postmenopausal. 13.1% had G1, 61.9% G2 and 25% G3. 81.9% were HR positive and 18.4% HER2/neu-positive. 77.1% were N0, 11.9% had 1-3 and 11% more than 3 affected lymph nodes. Only 262 (42.7%) pts. were guideline adherent. Compared to guideline adherent patients RFS and BCSM were significantly (p< 0.001) worse for guideline-non-adherent patients (RFS: HR=3.88; 95% C.I.: 1.91-7.87) and (BCSM: HR= 4.28; 95% C.I.:2.04-9.00). After adjusting for age, grading, nodal status, hormone receptor status and comorbidity guideline adherence was still the most important variable for RFS and BCSM (RFS: p<0.001; HR=3.71; 95%C.I.: 1.80-7.67) and (BCSM: p<0.001; HR=3.82; 95% C.I.:1.80-8.11).The most important impact on RFS and BCSM had guideline violations of radiation (RFS: p=0.001; HR=3.19;95%C.I.:1.66-6.13) and (BCSM: p=0.009;HR=2.42;95%C.I.:124-4.72) respectively of chemotherapy (RFS: p=0.001;HR=1.43; 95%C.I.:1.43-4.39) and (BCSM: p<0.001;HR=3.17;95%C.I.:1.84-5.46). Conclusions: There is a strong association between guideline adherence and improved recurrence free survival and reduced breast cancer-specific mortality for breast cancer patients with very small tumor size. Violation of treatment guidelines for postoperative irradiation or chemotherapy is clearly associated with a deterioration of prognosis.
Axillary lymph node ratio (LNR) versus pathologic nodal stage (pN) as a prognostic factor in breast cancer: Validation of Vinh-Hung's model in an Indian population.
Authors: Batra Swati , Ganguly Manomoy , Kannan Narayanan , Talwar Rajnish , Takkar Puneet , Soneji Dharmesh , Kulshreshtha Pranjal , Sanchety Naveen , Kalaivani Mani 
Published: March 2020

1099 Background: The axillary lymph node ratio (LNR), i.e., the ratio of positive over excised lymph nodes offers potentially improved prognostication, selection for adjuvant therapy and inter-institutional comparability compared to conventional pathological nodal staging (pN). A consensus on appropriate cut-offs however, remains to be achieved. Values of 0.20 and 0.65 to classify patients into low, intermediate and high-risk groups were proposed by Vinh-Hung et al, in the largest study on the subject till date. We perform a validation of the LNR concept for the first time in an independent patient population from the Indian subcontinent. Methods: 225 patients with a median follow-up of 42 months (range: 2 – 246 months) who underwent upfront surgery for breast cancer at a tertiary care hospital in Delhi, India, were retrospectively analysed, using Cox multivariate regression. Results: Using the above cut-off points, 10-year disease-free survival (DFS) rates of 83%, 74% and 28% and adjusted hazard ratios (HR) of 1.19 (95% CI 0.33 to 4.37), 2.21 (95% CI 0.75 to 6.51) and 6.88 (95% CI 1.58 – 29.92; P = 0.01) were obtained for the low-, intermediate- and high-risk groups respectively. The corresponding risks for the pN1, pN2 and pN3 categories were 1.74, 1.74, and 1.35, representing inadequate, even reversed prognostic separation. When both the LNR and pN were included as continuous variables, the nodal ratio remained prognostically significant with an adjusted HR of 12.33 (95% CI 1.1 – 142.5, P = 0.04) in contrast to the number of positive nodes which were not found to be significantly associated with DFS (HR = 0.97, 95% CI 0.9 – 1.1, P = 0.41). Conclusions: The LNR outperformed the pN staging in predicting DFS in our cohort of patients, irrespective of whether it was modeled as a categorical or a continuous variable. Simultaneous analysis with pN only increased its prognostic weight and resulted in exclusion of pN from the multivariate model. Our study thus provides independent external validation of Vinh-Hung’s proposed cut-offs and contributes to the growing body of literature supporting the incorporation of a ratio-based system into breast cancer staging.