bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-drug resistance and breast cancer: A meta-analysis of MDR1 and its functional significance
Authors: Trock B. , Leonessa F. , Clarke R. 
Published: March 2020

11010 Background: The clinical significance of MDR1 as a mechanism of multidrug resistance in breast cancer has not been established. We conducted a meta-analysis examining MDR1/gp170 in breast cancer, significantly updating a meta-analysis we performed in 1997. Methods: Published papers on MDR1/gp170 and breast cancer were identified by searching literature databases and bibliographies of published papers. Pooled relative risks (RR) for association between MDR1/gp170 expression and clinical outcomes were estimated with the Mantel-Haenszel method. Results: 84 studies were included in analysis: 63 measured MDR1/gp170 expression, 21 measured response to chemotherapy, 11 used sestamibi imaging, and 11 evaluated multidrug resistance reversing agents. MDR1 expression was detected in 45.9% of breast tumors prior to treatment and 66.8% of tumors after treatment (p<0.0001). There were no significant differences in gp170 expression by antibody type (p=0.567). In 11 studies, MDR1/gp170 expression after chemotherapy was associated with a significant risk of non-response, RR=1.79 (95% CI=1.35, 2.35), p<0.0001. This effect was lower in 13 studies with MDR1/gp170 assessed prior to chemotherapy, RR=1.28 (1.06, 1.55), p=0.009. Only 7 of 16 studies showed significant associations with decreased progression-free or overall survival. Of 11 sestamibi imaging studies, 10 showed a significant association between shorter retention and higher levels of MDR1/gp170, suggesting active protein pumping of contrast agent. None of 11 studies of multidrug reversing agents found >25% of refractory patients improving to partial clinical response, but most studies did not confine treatment to patients with MDR1/gp170 expression. Conclusions: This meta-analysis includes nearly 3 times as many studies as our 1997 analysis. MDR1 is expressed in approximately half of breast cancer patients, and is induced by chemotherapy. MDR1 after chemotherapy is associated with RR=1.8 for failure to achieve a clinical response, and RR=1.3 without induction by chemotherapy. Sestamibi gives the strongest support for active efflux of agent by gp170, but studies with MDR reversing agents have shown little success, which may partly reflect poor study design. [Table: see text]
Surgeon specialization and patient satisfaction with breast cancer treatment
Authors: Waljee J. F. , Hawley S. T. , Alderman A. K. , Morrow M. , Katz S. J. 
Published: March 2020

11012 Background: Experience and practice setting vary greatly among surgeons who treat patients with breast cancer. Yet, little is known about how these factors influence patient outcomes such as patient satisfaction with aspects of care. Methods: All women with DCIS and a 20% random sample of women with invasive breast cancer diagnosed in 2002 and reported to the Detroit and Los Angeles metropolitan SEER registries were identified and surveyed shortly after receipt of surgical treatment. Attending surgeons were identified primarily using pathology reports and mailed a survey. The final sample contained complete dyad information for 64.6% of patients (n=1,539) and 69.7% of surgeons (n=318). Logistic regression was used to examine the associations between surgeon specialization (% of practice devoted to breast disease) and treating hospital cancer program status (no program, American College of Surgeons approved cancer program, or NCI cancer center) with four domains of patient satisfaction: 1) the surgical decision, 2) decision-making process, 3) surgeon-patient relationship, and 4) surgeon-patient communication, adjusting for patient and surgeon demographics and disease stage. Results: 34.5%, 32.5% and 33.0% of patients were treated by surgeons who devoted <30% (low volume), 30%-60% (medium volume), and >60% (high volume) of their practice to breast disease. Compared to patients who were treated by low volume surgeons, patients treated by medium or high volume surgeons were more satisfied with the decision making process (medium volume: OR=1.2, 95%CI 0.8–1.7, high volume: OR=1.8, 95% CI 1.1- 2.8, p=0.036) and more satisfied with the surgeon-patient relationship (medium volume: OR=1.1, 95% CI 0.7 - 1.7, high volume: OR=2.1, 95% CI 1.1–3.7, p=0.053). Similar trends were observed for the other domains of satisfaction. Treatment setting was not associated with patient satisfaction after controlling for other factors. Conclusions: Surgeon specialization, but not treatment setting, was associated with patient satisfaction. Examining the processes underlying these associations could inform strategies to improve the quality of breast cancer care. No significant financial relationships to disclose.
Validation of the 2005 St. Gallen risk categories for operated breast cancers using a database from a regional cancer center in Hong Kong
Authors: YAU T. , Soong I. , Chan K. , Chang A. , Sze H. , Yeung R. , Tung R. , Lau S. , Lee A. 
Published: March 2020

11019 Background: Breast cancer risk categories were revised by the St Gallen international expert consensus meeting in 2005. This study was to validate their application in Hong Kong. Methods: The clinical outcomes of female breast cancer patients presented from 1994 to 2002 were retrospectively analyzed. Patients with non-invasive cancers, unknown HER-2 status, unclear primary (T) or nodal (N) stage, distant metastases at presentation, induction chemotherapy or no definitive surgery were excluded. Results: 902 breast cancers were eligible for further analysis. Adjuvant radiotherapy, hormonal therapy and chemotherapy were given in 74%, 68% and 56% of patients respectively. The median follow-up was 5.4 years (range 0.3- 12.5 years). The risk categories were highly predictive of all survival outcome parameters (p<0.00005; Table). In the intermediate risk category, node-negative patients with endocrine responsive/ responsiveness uncertain tumors had better 5-year distant failure-free survival (DFFS) than the rest with either 1–3 positive nodes or endocrine non-responsive tumors (95% vs 89%, p=0.005). Patients with 1–3 positive nodes and HER-2 overexpressed tumors were classified as high risk but their 5-year DFFS was similar to that in the worse subgroup of intermediate risk and significantly better than those with ≥4 positive nodes (89% vs 65%, p=0.0001). Further analysis showed that HER-2 overexpression had adverse impact on DFFS of patients with ≥4 positive nodes (hazard ratios (HR) 1.78; 95% CI, 1.12 - 2.84; p=0.015) but not on those with ≤ 3 positive nodes (HR 1.15; 95% CI, 0.67 - 1.97; p= 0.61). Conclusions: The 2005 St Gallen risk category is a useful clinical tool but we cannot confirm the adverse impact of HER-2 overexpression in our patients with ≤ 3 positive nodes. [Table: see text] No significant financial relationships to disclose.
High-dose sequential chemotherapy (HDSC) with peripheral blood progenitor cells (PBPC) support for high-risk breast cancer (BC)
Authors: Sabbatini R. , Da Prada G. A. , Frassineti G. L. , Aietta M. , Pedrazzoli P. , Maur M. , Zambelli A. , Giovannini N. , Siena S. , Ponchio L. , Conte P. F. 
Published: March 2020

11026 Background: Recent reports suggest that intensified adjuvant chemotherapy with stem cell support improve disease free (DFS) and overall survival (OS) in subgroups of patients with high risk BC. We retrospectively analyzed the efficacy, safety and feasibility of a program of HDSC with PBPC support (according to the Milan protocol, ASCO 2001) in patients with BC at high risk of recurrence Methods: Between February 1995 and January 2001, 201 non-consecutive patients with more than 3 positive axillary nodes at surgery, median age 46 (range 27–62), has been evaluated. Median number of involved nodes was 15 (range 3–48), 38% and 49% pts had ER and PgR negative tumors, respectively. Fourty-sevent percent of pts had tumors with a high proliferative activity. HDSC consisted of sequential administration of cyclosphosphamide 7 g/m2 (day 0) plus filgrastim 5 μg/kg s.c. daily and stem cell collection, methotrexate 8 g/m2 plus vincristine 2 mg/m2 (day +16), and two consecutive courses of epidoxorubicin 120 mg/m2 (days +23 and + 38) plus filgrastim 5 μg/kg s.c. daily. Myeloablative therapy (day +58) consisted of thiotepa 600 mg/m2 and melphalan 160 mg/m2 plus PBPCs and filgrastim 5 μg/kg s.c. daily. Results: Three pts discontinued the program permanently because of toxicity. A median of 9,35x106/kg (range 3.35–35.62) CD34+ cells was infused. Engraftment for neutrophils (> 500/μl) and platelets (> 20.000/μl) was observed a median of 9 days (range 7–17) and 10 days (range 7–18) after PBPC infusion, respectively. No treatment-related deaths were recorded. After a median follow-up of 79 months, 108 (54%) pts are disease- free. Ninety-three patients experienced disease recurrence [9/93 (10%) pts had loco regional disease recurrence and 84/93 (90%) pts distant recurrence], of whom 58/93 (63%) have died. Five-year DFS and OS from the start of treatment are 55% and 71%, respectively. No poor marrow function, myelodysplastic syndrome or secondary tumors were observed. In 2-sided log-rank tests, hormone-receptor status and the number of tumor-positive axillary lymph nodes were significant prognostic factors for DFS. Conclusions: Our results confirm that HDSC is a safe procedure and is associated with favorable outcome in patients with high-risk BC. No significant financial relationships to disclose.
Retrospective analysis of clinico-pathological features and outcomes of 2,686 hormone receptors-positive breast cancer (HR+) patients in a consecutive mono-institutional series
Authors: Ferro A. , Triolo R. , Caffo O. , Barbareschi M. , Leonardi E. , Frisinghelli M. , Caldara A. , Ambrosini G. , Lucenti A. , Galligioni E. 
Published: March 2020

11036 Background: Clinico-pathological patterns, management and outcomes of HR+ vs HR- have been evaluated in a retrospective study. Methods: A series of 2686 BC patients (pts), treated at our institution from 1988 to 2000 with known immunohistochemical receptor status was investigated. Correlation between HR status and tumour size (T), nodal status (N), grading (G), mib-1, HER-2 and p53 and was evaluated by χ square test. Statistical analysis was performed to test the interaction between HR status and Disease Free Survival (DFS) and with specific and overall survival, using the log-rank test. Results: Among 2686 patients, 467 HR- (17%) and 2219 (83%) HR+ (364 pre and 1855 postmenopausal) were observed, with 1586 ER+PgR+, 555 ER+PgR-, 78 ER-PgR+. Pts with positive HR status showed a statistically significant correlation with lower T, G, mib-1, HER-2 and p53 expression.Chemotherapy was administered to 681 HR+BC (31% ) and to 301 HR-BC (65%), according to stage, age, and G. Tamoxifen based endocrine therapy was administered to 1167 HR+BC (53%) (associated to chemotherapy in 428 and alone in 739 pts). At a median follow up of 108 months, 499 relapses occurred in HR+ (22%) , and 141 in HR- pts (30%), with a 5,10, 15y DFS of 83%,72%, 62% in HR+ and 72%,66%, 57% respectively in HR- pts. More frequent sites of relapse were soft tissue (46%) and bone (35%) in HR+ and soft tissue (50%) and visceral (30%) in HR- pts. Seven hundred sixty pts have died: 576 HR+ (26%) and 184 HR- (39%), with a 5, 10, 15y specific survival of 90%, 84%, 75% which was significantly superior to the 78%, 73%, 69% respectively of HR-. However, considering that 230 HR+ and 44 HR- pts died without relapse, the 5,10,15y overall survival was 90%, 75% 61% for HR+ and 78%, 67%, 60% respectively for HR-. It appears therefore that the specific survival advantage in early years in favour of HR+ is progressively reduced by non specific mortality in late years which results in similar 15 y OS rates among HR+ and HR- pts. Conclusions: Our series appear to confirm the relationship between HR+ status and other more favourable clinical-pathological features, although long term OS is not apparently affected. No significant financial relationships to disclose.
Randomized phase II trial of three dosing schedules of nanoparticle albumin-bound paclitaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer: An initial interim safety report
Authors: Conlin A. K. , Seidman A. D. , Moynahan M. E. , Traina T. , Mace J. R. , Meiri E. , Bach A. , Edwards C. , Hudis C. A. 
Published: March 2020

1104 Background: Nanoparticle paclitaxel (NP) at 260mg/m2 every 3 weeks (q3wk) is more effective than standard paclitaxel (P) (Gradishar et al, JCO 2005). Weekly, uninterrupted administration of P is superior to q3wk P in MBC (Seidman et al, Proc ASCO 2004). When added to weekly P as 1st-line therapy for MBC, bevacizumab (B) improves response rate and progression-free survival (Miller et al, Proc ASCO 2005). We initiated a randomized phase II trial of NP given at 260mg/m2 q3wk (arm A) vs. 260mg/m2 q2wk with filgrastim (arm B) vs. 130mg/m2 weekly, all with B, as 1st-line therapy for patients (pts) with HER2- MBC. Methods: 66 of planned 225 pts have enrolled. After 31 pts had been randomized and treated, investigators concerned about possible differential neurotoxicity requested this early interim safety analysis. Median age is 54 (range 40–78). 83% are post-menopausal and 100% have visceral dominant disease. 68% had prior adjuvant or neo-adjuvant chemotherapy; 35% with taxanes. Results: With 170 cycles delivered (median: 4, range 1–15) 10 dose reductions have been necessary for NP (1 in A, 5 in B, 4 in C). No hypersensitivity reactions or dose interruptions have occurred for NP; 3 doses of B have been held due to hypertension. Significant preliminary antitumor activity has been noted in all arms. One grade 4 toxicity occurred in arm C, hyperglycemia. 15 grade 3 toxicities have been reported across all arms. Pts on arm A have experienced 3 grade 3 toxicities (30%): fatigue, neutropenia, and arthralgia with no grade 3 neurotoxicity. Pts on arm B have had 7 grade 3 toxicities (58%) with 3 pts experiencing grade 3 sensory neuropathy (25%) and others experiencing fatigue, neutropenia, anemia, esophagitis, dyspnea, and ataxia. 5 arm C pts experienced grade 3 toxicities (56%) including diarrhea, dehydration, mucositis, neutropenia, hypokalemia; 2 pts have had grade 3 sensory neuropathy (22%). Conclusions: This early safety analysis does not detect any statistically or clinically significant differences in grade 3 toxicity and all arms continue to accrue. The next protocol-specified safety analysis is expected in early 2007, with mature safety data for 60 pts. Updated results will be presented. [Table: see text]
Overnight fasting serum cholesterol, HDL, LDL and triglycerides levels and bone mineral density (BMD) values during adjuvant letrozole in daily practice.
Authors: Fontaine C. , Huizing M. , Dewaele A. , Vandenbossche K. , Vermey J. , Schallier D. , Geurs F. , Neyns B. , Degreve J. 
Published: March 2020

11040 Background: Background: Randomized clinical trials (RCT’s) have demonstrated a superiority of adjuvant aromatase inhibitors (AI’s) over tamoxifen (TAM) in disease free survival and overall survival, immediately postoperatively, in cross-over or extended setting in hormone receptor positive BC. In these studies AI’s were associated with increased bone demineralization and a rise in non- fasting serum cholesterol. Patients and methods: The tolerance for adjuvant letrozole was reviewed in 185 postmenopausal women with hormone receptor-positive early BC including fasting cholesterol levels and bone mineral density (BMD) values. Results: 121 patients (pts) received first-line adjuvant letrozole and 64 pts were crossed over from TAM. Median follow-up was 26 months (15–63 mths). Median age was 56 yrs (37–85y). Median time on letrozole was 23 months. Forty three of the 185 (24 %) of the pts discontinued the adjuvant therapy with letrozole (after a median duration of treatment of 5 months (1wk-30mths)), because of intolerance (83.7%)and PD in 16.3%. Median overnight fasting serum cholesterol levels did not change significantly (p=0.4) over a 2 year observation period from (203.5 mg/dl (131–342)) baseline to (205.5 mg/dl (151–330)) follow-up in 32 evaluable (14/32 pts prior TAM) pts. Median HDL levels rose from 65.5 mg/dl (38–107) to 70 mg/dl (38–103) (p=0.03) after 2 years, but LDL levels did not rise significantly. In the contrary triglycerides levels decreased from 122.5 mg/dl (48–238) to 105 mg/dl (47–285) (p=0.01). Despite the use of upfront biphosphonates in 1/3 of the pts, loss of BMD was significant for the lumbar spine after 2 years in 22 evaluable (8/22 prior TAM) pts (median T-score decreased from minus 0.3 to -0. 45, p=0.02), but not for the hip. Conclusion: Adjuvant letrozole did not significantly increase overnight fasting serum cholesterol levels in daily practice. Adjuvant letrozole was associated with a significant rise in HDL levels and a significant decrease in triglycerides levels after 2 years of therapy. Loss of BMD was observed in concordance with results from RCT’s. Adjuvant letrozole had to be discontinued prematurely because of tolerance issues in 20 % of the pts. No significant financial relationships to disclose.
How important is the axillary nodal status for adjuvant treatment decisions at a breast cancer multidisciplinary tumor board? A survival analysis
Authors: Reimer T. , Fietkau R. , Markmann S. , Stachs A. , Gerber B. 
Published: March 2020

11041 Background: Postoperative tumor board recommendations for breast cancer are mainly based on patient characteristics and tumor parameters such as size, histologic grade, lymphovascular invasion (LVI), hormone receptor and HER2/neu status. In the era of potential avoidance of axillary surgery in clinically node-negative patients we evaluate the impact of pathologic nodal status for adjuvant treatment decisions. Methods: The postoperative tumor board records of 207 consecutive breast cancer patients over a 1-year period were rediscussed without knowledge of pathologic nodal status. Differences between the two board recommendations for each patient were classified as major (chemo- and/or radiotherapy: present/absent) or minor (different chemotherapeutic protocols) discrepancies. The disease-free and overall survival rates among subgroups with different recommendations were calculated using Adjuvant! Online tool. The binary logistic regression was performed to analyze the impact of factors for prediction the major discrepancy subgroup. Results: The tumor board without information of pathologic nodal status resulted in treatment changes in 72 of the 207 patients studied (34.8%). Major discrepancies were observed in 37 patients (17.9%) leading to a complete shift of postoperative management. Disease-free and overall survival rates were not significantly different due to a balanced over- and undertreatment in this subgroup (21 cases with under-, 16 cases with overtreatment). The major discrepancies were related to LVI (P=0.001), postmenopausal status (P=0.047), and positive hormone receptor status (P=0.17) in the univariate setting. LVI was an independent parameter to predict the subgroup with major discrepancies performing a multivariate analysis (P=0.006; RR=4.5 [95%CI: 1.5–13.4]). Conclusions: The knowledge of pathologic nodal status is important for postoperative chemotherapy and postmastectomy radiotherapy indications. There is a risk for one third of all patients when avoiding axillary surgery to get an adjuvant therapy which differ from the current treatment guidelines. It is mandatory to know the nodal status for breast tumors with LVI. No significant financial relationships to disclose.
To analyze the efficacy, tolerability, toxicity profile, quality of life and pharmaco-economics of adjuvant TAC compared to FAC regimen in hormone receptor-positive breast cancer with more than four involved lymph nodes
Authors: Batra U. , Bapsy P. P. , Saini K. V. , Jain A. K. , Atilli A. V. , Lokanatha D. , Babu K. S. , Sanjeevan K. S. , Devaraju C. J. , Anupama G. 
Published: March 2020

11043 Aim: To analyze the efficacy, tolerability, toxicity profile, quality of life, survival rates and pharmaco-economics of TAC vs. FAC in women with ER/PR positive breast cancer and >4 involved lymph nodes. Methods: 100 patients with >4 node-positive breast cancer were randomly assigned to receive either 6 cycles of taxane-based (TAC) or anthracycline-based (FAC) adjuvant chemotherapy. All the patients received adjuvant radiotherapy and hormonal therapy after completion of chemotherapy. The primary end point was to assess disease-free survival (2 years), toxicity profile, QOL and to analyze the pharmaco-economics of both therapies. All patients completed EORTC QLQ 30, BR 23 questionnaire before randomization and before every cycle of chemotherapy. Pharmaco-economic feasibility was determined using cost of drugs, duration of hospital stay, laboratory investigations, management of complications and loss of wages. Treatment: The treatment (dose in mg/m2) was as follows: TAC: docetaxel 75, doxorubicin 50, cyclophosphamide 500; CAF: 5 flourouracil 500, doxorubicin 50, cyclophosphamide 500. Results: The patient demographics and primary tumor characteristics were comparable in both the arms. Taxane- based regimen was associated with decreased global QOL and physical function. The cost of TAC regimen was 25 times more than FAC regimen. Conclusion: Although TAC regimen had longer DFS as compared to FAC, it was associated with a higher incidence of side effects and increased duration of hospital stay. Further, high cost precludes its wide-spread use, and FAC regimen still continues to be the first choice treatment of high-risk node and receptor-positive breast cancer in a third world country like India. [Table: see text] No significant financial relationships to disclose.
Hormone replacement therapy (HRT) in women with previously treated primary breast cancer: Update XIII
Authors: Bluming A. Z. 
Published: March 2020

11044 Background: To assess the incidence of contralateral or recurrent breast cancer among women prospectively treated with HRT after initial breast cancer diagnosis. Methods: A community-based, prospective, single-arm, pilot study of HRT among 246 women with previously treated primary breast cancer. Results: Median duration of HRT is 89+ months (range 12+ -173+). Median interval from initial surgery to initiation of HRT is 52 months (range 2–361 months). Follow-up to date is 100%. Actuarial disease-free survival (DFS), disease-specific survival (DSS), & median duration of HRT by stage are listed in the table : *T0N0: 2 LCIS recurred locally after lumpectomy alone. 2 DCIS recurred locally after lumpectomy/RT 5 contralateral tumors (3 DCIS, 2 T1N0) 1 distant recurrence - liver. (alive 4 years later). **T1N0: 9 local recurrences after lumpectomy/RT 7 contralateral tumors. 8 distant recurrences - 3 lung, 2 liver, 3 bone - 4 died ***T2N0: 2 local recurrences after lumpectomy/RT 2 distant recurrences - lung - 1 died ****T1N1: 3 local recurrence after lumpectomy/RT 2 contralateral tumors 2 distant recurrences - 1 bone, 1 supraclav node - 2 died ***** T2–3N1: 1 contralateral tumor 3 distant recurrences - 1 cerv node-2 bone mets - 2 died One hundred and sixteen patients have stopped HRT (47%), 57 because of anxiety about taking HRT (23%), 50 because of breast cancer development (20%), 3 because of the development of non-breast cancers, 2 died of nonmalignant disease, 3 because of HRT-associated symptoms, and 1 because of pulmonary emboli without clinical phlebitis. CHRT, as opposed to ERT, was administered to 50% of all patients and 58% of the 50 who subsequently developed breast cancer on study. Actuarial DFS to 25 years for T1N0 patients was 67% versus 37% (DSS=86%) for comparable T1N0 patients who did not receive HRT. Conclusions: No evidence to date of increased development, recurrence or of breast cancer-related death associated with post diagnosis HRT. [Table: see text] No significant financial relationships to disclose.