bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient factors influencing choice for mastectomy.
Authors: Hart M. R. , Steely A. M. , James T. A. , McCahill L. E. 
Published: February 2017

264 Background: The process of shared decision-making in the surgical management of breast cancer is complex. Many women eligible for breast conservation therapy (BCT) still choose total mastectomy (TM), and little is known about the factors responsible for their decision. We conducted a pilot, qualitative study in order to determine factors influencing the selection of TM over BCT, and to improve our understanding of patient’s concerns and priorities in their decision-making process for breast cancer surgery. Methods: Data were collected from a four-year, prospective Breast Cancer Surgical Quality Database. Study participants included female patients with invasive carcinoma who, despite being eligible for BCT, elected to undergo TM. Eligibility criteria included women with no contraindications to BCT, tumor size <2cm, and no evidence of extensive microcalcifications. Patients with tumor recurrence, multicentric disease, scleroderma, and lupus were excluded. Patients were contacted by phone and administered a survey designed to elicit the specific factors affecting their decision to undergo TM. Results: Out of 670 patients treated for IDC/ILC between 2003 and 2007, 12 met eligibility criteria and were subsequently interviewed. 10 patients identified fear of recurrence as the prevailing factor in their decision to undergo TM, and 5 patients identified availability of breast reconstruction as a moderate to strong influence in their decision to undergo TM. Time away from work and transportation during radiation therapy had minimal or no influence. Conclusions: Our results indicate that patients with small, invasive breast cancers who chose TM for their surgical treatment, despite being eligible for BCT, were primarily influenced by fear of recurrence. These decision factors persisted despite treatment at a multidisciplinary center, where patients are informed of equivalent survival and minimal difference in recurrence with appropriate BCT. These results highlight the need for further assessment of patient education and comprehension, as well as greater awareness of emotional factors which may influence a patient’s decision regarding the surgical management of her breast cancer.
Results by treatment modalities in multifocal/multicentric breast cancer: Retrospective analysis of 162 patients.
Authors: Kadioglu H. , Kayahan M. , Ersoy Y. E. , Memmi N. , Bozkurt S. , Cipe G. , Muslumanoglu M. 
Published: February 2017

266 Background: The prognostic value of multifocal, multicentric breast cancer is still not well known. Although some studies have suggested that it is associated with a worst prognosis some have not suggest. We evaluated the effect of treatment modalities on overall survival and disease-free survival in breast cancer. Methods: One hundred and sixty two women with multifocal multicentric breast cancer diagnosed at our oncology center between January 2004 and December 2010 were retrospectively evaluated. Multifocality was defined as the presence of 2 or more foci of the tumor clearly separated in the same breast. Multicentricity was defined as the presence of 2 or more foci at different quadrants. Patients received neoadjuvant chemotherapy were excluded. Results: Median age of 162 women was 48 y ± 13,63 y. Eighty two of 162 patients were treated with breast-conserving surgery and 80 were treated with mastectomy. Radiotherapy was added to adjuvant therapy to patients with 4 or more positive axillary nodes and/or treated with breast conserving surgery. Three (1.8%) patients were excluded because of bilateral cancer and 1 (0.6%) was excluded because of Tx tumor. Eleven of 162 (6.7%) patients were not seen after surgery so data about adjuvant treatment was not known. Fifty of 147 patients were stage III, 68 were stage II and 30 were stage I. 27 (17.2%) patients received anthracycline based chemotherapy, 30 (20.3%) patients received hormonotherapy and 91 (56.1%) patients received taxane based chemotherapy. Trastuzumab added to the treatment at all patients, if HER2 neu-positive. Median follow up was 41 ± 4.1 (72-9 months) months. 30 systemic diseases at 24 patients were seen on follow up. 18 patients were in taxane group, 4 patients were in anthracycline group, 2 patients were in hormonotheraphy group. Nine patients were died in taxane group, 1 died in anthracycline group and 1 died in hormonotherapy group. Conclusions: Our retrospective analysis showed worst prognosis at taxane group but; patients with positive lymph nodes and perinodal invasion gets taxane based treatments. This retrospective analysis showed that systemic recurrence and survival in multifocal breast cancer are similar with unifocal disease.
Effect of oral cyclophosphamide use on pathologic complete response rate in the neoadjuvant treatment of breast cancer.
Authors: Luque M. , Garcia-Teijido P. , Fernandez Y. , Sampedro T. , Reguero V. 
Published: February 2017

276 Background: Continuous exposure to cyclophosphamide (C) can result in selective cytotoxicity for endothelial cells, followed by antiangiogenic effects on tumor cells. In this study we analyzed the pathological complete response (pCR) rate in a cohort of patients (p) diagnosed with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (CT) based on anthracyclines and taxanes, depending on the route of administration of C (intravenous (IV) and oral arms). Methods: We retrospectively studied a consecutive series of p. with LABC treated with neoadjuvant CT in 2 hospitals in Asturias. The regimens used were CE100F, AC (regimens with IV C) or oral CAF (C 100mg/m2/day orally x 14 days, doxorubicin 30 mg/m2 day 1 and 8 and 5-FU 500 mg/m2 days 1 and 8 every 28 days) x 4 cycles. The anthracycline regimen was followed by weekly paclitaxel or docetaxel every 3 weeks. If HER2 overexpression, trastuzumab was given in combination with the taxane. Results: We identified 105 p., 65 of them treated with oral C and 40 with IV C (CEF 3 patients and AC 37 patients). The median age was slightly higher in the p. treated with C IV (52.2 vs. 47.7, p = 0.022), which also received a higher number of cycles (7.1 vs. 6.7, p = 0.025), although there were no significant differences in the anthracycline dose intensity (93% vs 89%, p = 0.093). There were no significant differences in tumor size, lymph node involvement, grade, estrogen receptor (ER) or HER2. The rate of pCR was significantly higher in p. receiving oral C (33.8% vs 10%, p = 0.004). Grade 3, negative estrogen receptors and HER2 were also significantly associated with a higher rate of pCR. On multivariate analysis only oral C was an independent factor associated with pCR. With a median follow up of 27.3 months (95% CI 24 to 30.6), there have been 10 recurrences (15.4%) in the continuous arm and 9 (22.5%) in the standard arm, without significant differences in disease free survival. Conclusions: Our results suggest that the pCR rate can be higher using oral C in the neoadjuvant treatment of LABC based on anthracyclines and taxanes. This hypothesis should be confirmed in a randomized and prospective study.
Pathologic response rate (pCR) and near-pathologic response rate (near-pCR) with docetaxel-carboplatin (TCarb) in early triple-negative breast cancer.
Authors: Kern P. , Kolberg H. C. , Kalisch A. , Liedtke C. , Otterbach F. , Kimmig R. , Kurbacher C. M. 
Published: February 2017

277 Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis unless a pathological complete response is achieved (Liedtke C et al. 2008: J Clin Oncol 26:1275-1281) or almost achieved (Symmans WF. 2007: J Clin Oncol 25:4414-4422). Sensitivity to platin compounds has been demonstrated in BRCA1-positive settings (Byrski T et al. 2010: J Clin Oncol 20:28:375-9; Silver DP. 2010: J Clin Oncol 28:1145-1153) with only limited numbers of patients (Byrski T et al. 2010: J Clin Oncol 20:28:375-9) or in sporadic breast cancer with heterogeneous cohorts (Sikov WM et al 2009: J Clin Oncol 27:4693-4700; Chang HR et al. 2010: Cancer 15; 116:4227-4237). Methods: This pivotal trial was to assess the efficacy of platinum and taxane-based combination therapy without the use of anthracyclines. 27 patients with primary TNBC (majority of them cT2, two cT3 and one cT4a) had to be unsuitable for standard anthracycline-based chemotherapy. They received 6 cycles, respectively in two cases only 5 cycles, of carboplatin AUC 6 and docetaxel 75 mg/m2 q3w. The primary endpoint was the pCR-rate, secondary endpoint toxicity. Results: 20 out of 27 (74%) patients had pathological complete response (52%) or near-complete response (22%)—ypT1mic and ypT1a—both being associated with a good prognosis. Seven remaining patients had still good partial response, leaving only low residual cancer burden, which was defined as ypT1. Treatment was well-tolerated: grade III and IV toxicities were neutropenia, thrombopenia, oedema, nausea, joint pain, nail changes, fatigue, hypertension, and alopecia. Conclusions: These results show a high efficacy of carboplatin AUC6 and docetaxel 75 mg/m2 q3w and good feasibility as primary chemotherapy for TNBC with a pCR- and near-pCR-rate of 74% and total response rate of 100%. The incorporation of anthracyclines and parp-inhibitors into further trial designs could enhance the efficacy of these compounds. The omission of exposure to anthracyclines in patients with considerable heart disease risks seems to be feasible with a good pCR-rate, the latter being a surrogate-marker for long-term survival.
Chemotherapy-induced amennorrhea: Predictive markers of response to neoadjuvant chemotherapy in breast cancer.
Authors: Ahn S. K. , Moon H. , Ko E. , Kim J. s. , You J. M. , Shin H. , Han W. , Noh D. 
Published: February 2017

281 Background: There is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated significance of CIA after neoadjuvant chemotherapy for predicting response to neoadjuvant chemotherapy in breast cancer patients. Methods: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. Results: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 vs. 38.27± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 mIU/ml vs. 45.76±30.31 mIU/ml; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly predictive of tumor response. CIA was only significant predictive factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). Conclusions: CIA is independent predictive markers of response to neoadjuvant chemotherapy in locally advanced breast cancer.
Mortality reduction in the Swedish mammography screening program.
Authors: Zahl P. H. , Mæhlen J. 
Published: February 2017

29 Background: The introduction of a nationwide mammography screening program in Sweden in 1986 was associated with a 50% persistent increase of breast cancer incidence (including carcinoma in situ). Whether screening has been instrumental in a recent decline in the breast cancer mortality remains an open question. Methods: We compared the 18 years breast cancer mortality for two groups of women; those diagnosed in the first 6 years of the screening program and those diagnosed during a 6 year period that included the last 4 years before screening started and the first 2 years of the screening program. The test group (n + 328,927) included women aged 40 to 69 at the first invitation to screening. On average the women in the age-matched control group (n + 317,404) were born 4 years earlier then the women in the test group. The numbers of incident invasive breast cancers in each county were obtained from the Swedish Cancer Registry (in-situ cancers were excluded) and the corresponding breast cancer deaths were obtained from the Swedish Causes of Death Registry. Results: After 18 years follow up, the mortality reduction was 14% in the test group. However, most of this difference (10%) occurred in the first five years after diagnosis reflecting improved medical treatment of breast cancer. Most of the 14% difference also disappeared if we adjusting for period effects. Conclusions: About 83% of women in the test group were also included in the control group making the two groups almost identical with respect to risk variables. By screening the control group at the end of a 6-year period, the results are adjusted for differences due to lead-time bias and by studying mortality instead of survival overdiagnosis (length time bias) is also adjusted for. We conclude that organized mammography screening is not an important cause for the reduction in the breast cancer mortality in Sweden.
Anticancer efficacy of natural withanolides in triple-negative breast cancer through down regulation of BRCA1, cell-cycle arrest, and induction of apoptosis.
Authors: Zhang X. , Samadi A. K. , Mukerji R. , Timmermann B. N. , Cohen M. S. 
Published: February 2017

291 Background: Triple negative breast cancer is often chemoresistant creating the need for novel improved drugs for this disease. Naturally derived withanolides such as withaferin A (WA) have shown potent preclinical efficacy in breast cancers. The purpose of this study is to better define the anticancer activity of WA and novel analogs(X001 and X003) containing a 19-OH substitution, in triple negative MDA-MB-231cells where BRCA1 is important for cell survival. Methods: Cells were treated with increasing doses of WA, X001, or X003 for 24 h. MTS and trypan blue exclusion assays were used to examine cell proliferation and viability. Cell cycle was examined using propidium iodide (PI) staining on flow cytometry (FC). Annexin-V/PI co-staining on FC was used to detect apoptosis. Western analysis was used to evaluate BRCA1 protein levels as well as to confirm apoptosis by PARP cleavage and caspase-3 activation. Results: X003, WA, and X001 inhibited MDA-MB-231 cell viability (IC50=125, 500 and 1300nM respectively). IC50 level of WA induced G2/M phase cell cycle arrest while 2.5μM also induced apoptosis at 24 h as well as a significant decrease in both total and phospho-Akt protein levels. In addition, WA decreased BRCA1, heat shock factor 1, and mutant p53 protein levels in a dose-dependent manner. 2.5 μM of WA decreased BRCA1 protein levels by 75% compared to controls at 24 h (p<0.01) while its natural analogs X003 and X001 induced apoptosis associated with BRCA1 down-regulation at 200nM (1.5xIC50) and 6.5μM (5xIC50) and a G2/M cell cycle arrest at only 50nM (50%IC50) and 2μM (1.5xIC50) respectively after 24 hours. Conclusions: Natural withanolides such as WA and its potent analog X003 demonstrate anticancer effects on triple negative breast cancer cells through cell cycle arrest, apoptosis and down-regulation of BRCA1 protein expression. Targeting BRCA1 in triple negative breast cancer with natural withanolides represents a novel approach for future translational studies in this difficult disease.
Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer.
Authors: Singh J. C. , Stein S. , Volm M. , Smith J. A. , Novik Y. , Speyer J. L. , Adams S. , Meyers M. I. , Muggia F. , Schneider R. , Formenti S. , Davis S. , Choi H. , Tiersten A. 
Published: February 2017

293 Background: RAD001 is an oral mTOR inhibitor that has exhibited activity in breast cancer. Triple negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents that cause interstrand cross-links. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in at least two different breast cancer cell lines (including ER/PR negative cell lines). We propose that combination RAD001 and carboplatin may have activity in triple-negative breast cancer. Methods: The primary objective of the study is to determine clinical benefit (complete remission; CR, partial remission; PR and stable disease; SD) and the toxicity of this combination in women with triple negative metastatic breast cancer who had received 0-3 prior chemotherapy regimens for metastatic disease. Prior carboplatin was allowed. Women with treated brain metastasis were eligible. Secondary objectives were to determine progression free survival. According to the original study plan, carboplatin AUC 6, was to be given intravenously every three weeks. 5 mg of RAD001 was to be given daily with a 3 patient run-in and then 10 mg daily if there were no dose-limiting toxicities. Due to a surprising amount of thrombocytopenia with this combination the dose of carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001 (and no plan to escalate to 10 mg). Results: Eleven patients of a planned 25 have been recruited thus far. Median age is 62. Median number of prior regimens is 1. Of the 6 patients assessable for response at this time, four have SD and two have had a PR. 1 SD was achieved in a patient progressing on prior carboplatin at study entry. Five of 7 patients assessable for toxicity had grade 3 or 4 thrombocytopenia and 2 patients had grade 3 neutropenia. All patients have had treatment held and/or dose reductions secondary to hematological toxicity. There have been no non-hematological grade 3 or 4 toxicities. Conclusions: Clinical benefit was observed in all 6 evaluable patients. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. We continue to accrue study subjects at the amended dosing.
Cost-effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal-related events (SREs) in metastatic breast cancer (mBC).
Authors: Carter J. A. , Snedecor S. J. , Kaura S. , Botteman M. 
Published: February 2017

294 Background: Dmab has been approved in the US for prevention of SREs in mBC on the basis of the results of a phase III trial comparing Dmab vs. ZOL in mBC. In this trial, overall survival, disease progression, and serious adverse events (SAEs) were similar across treatments. The cost of a Dmab injection ($1650) is nearly 2x that of ZOLs ($887). This analysis assessed the cost effectiveness of Dmab vs. ZOL in mBC from a US managed care perspective. Methods: A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration (Dmab=$32.46; ZOL=$153.86) costs for patients (pts) receiving Dmab or ZOL. Inputs were selected to reproduce the phase III trial outcomes up to 28 months. QALYs were estimated by assigning utilities to health states (prior to SRE; SRE; post-SRE, and death). SRE-related costs and utilities were obtained from the literature. Per-event SRE costs ranged from $4,039 (vertebral fracture) to $20,734 (bone surgery). In sensitivity analysis, SAEs were included ($15,441/pt with a SAE). Future outcomes were discounted at 3%/year. Results: Dmab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs vs. ZOL, resulting in an incremental cost of $6,884/pt (TABLE). The cost per QALY gained was $644,000 when excluding SAEs ($613,000/QALY when including SAEs). Conclusions: Dmab is predicted to result in an incremental cost/QALY gained >$600,000. This high cost/QALY is due to the higher drug acquisition cost of Dmab, combined with the limited prevention of SREs and lack of overall survival/disease progression benefits vs. ZOL. The cost/QALY of Dmab is far higher than what is considered to be good value for a medical intervention ($50,000 to $100,000/QALY), thus raising questions regarding Dmab's value in mBC. [Table: see text]
A phase II open-label trial to evaluate the efficacy and toxicity of erlotinib in women with metastatic, hormone receptor-negative, and HER2-negative breast cancer.
Authors: Rao R. D. , Siziopikou K. P. , Cobleigh M. A. 
Published: February 2017

296 Background: There is limited success with current therapies for triple negative (TN) breast cancer. Epidermal growth factor receptor (EGFR) is a therapeutic target in solid tumors. Overexpression of EGFR has been linked to an aggressive breast tumor phenotype with a poor prognosis. Previous work at RUSH showed that 64% of 66 TN tumors were EGFR positive (Siziopikou SABCS 2004). To date, the use of EGFR tyrosine kinase inhibitors (TKIs) in metastatic breast cancer (MBC) has been disappointing. These trials enrolled refractory patients and did not select for EGFR expression. We hypothesized that if selected for EGFR expression, there may be a cohort of TN MBC patients who benefit from an EGFR TKI. This is a phase II study of erlotinib in TN-EGFR-positive MBC. Methods: Eligible patients had TN-EGFR-positive MBC. EGFR positivity was defined as staining in >10% of tumor cells by IHC (Dako). Patients required measurable disease, prior treatment with anthracycline and taxane (adjuvant or metastatic setting) and ≤1 prior chemotherapy for MBC. Patients received erlotinib 150mg daily. Primary endpoint was progression-free survival (PFS). Initially, 18 patients were to be accrued. If ≥ 3 patients were progression-free at 4 months, accrual would continue to 43. Results: The study was terminated prematurely due to poor accrual. In total, 11 patients enrolled, 10 were treated. Mean age 56.7y, 18% African-American. Four patients had prior chemotherapy for MBC. Most patients progressed rapidly, median PFS was 29 days (95% CI 25.90 – 32.10). However, 2 patients had stable disease for 225 and 476 days. Treatment was well-tolerated. Toxicities in the 2 patients with stable disease included grade 2 rash, grade 1 diarrhea, grade 1 nausea, grade 2 weight loss and grade 1 diarrhea. Conclusions: Although most patients progressed rapidly, 2/10 patients had prolonged stable disease. This suggests there may be a subset of TN, EGFR positive MBC for whom EGFR-directed therapy may be suitable or that the natural history of their disease was indolent. Future studies to determine molecular and clinical profiles of patients likely to benefit from EGFR-TKI therapy in this population are warranted.