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Emissions of CO2 from soils make up one of the largest fluxes in the global C cycle, thus small changes in soil respiration may have large impacts on global C cycling. Anthropogenic additions of CO2 to the atmosphere are expected to alter soil carbon cycling, an important component of the global carbon budget. As part of the Duke Forest Free-Air CO2 Enrichment (FACE) experiment, we examined how forest growth at elevated (+200 ppmv) atmospheric CO2 concentration affects soil CO2 dynamics over 7 years of continuous enrichment. Soil respiration, soil CO2 concentrations, and the isotopic signature of soil CO2 were measured monthly throughout the 7 years of treatment. Estimated annual rates of soil CO2 efflux have been significantly higher in the elevated plots in every year of the study, but over the last 5 years the magnitude of the CO2 enrichment effect on soil CO2 efflux has declined. Gas well samples indicate that over 7 years fumigation has led to sustained increases in soil CO2 concentrations and depletion in the δ 13C of soil CO2 at all but the shallowest soil depths. [ABSTRACT FROM AUTHOR]

Reva Schneider1, Ayman Barakat1, John Pippen1,2,3, Cynthia Osborne1,2,3 1Medical Oncology, Baylor-Sammons Cancer Center, 2Texas Oncology PA, 3US Oncology, Dallas, TX, USA Abstract: Estrogen and its metabolites play a significant role in the proliferation of hormone receptor-positive breast cancer. In postmenopausal women, aromatase inhibitors can significantly reduce estrogen levels by blocking enzyme-mediated estrogen synthesis within tissues. Third-generation aromatase inhibitors have now surpassed tamoxifen as first-line therapy for postmenopausal women with metastatic, hormone receptor-positive, breast cancer, showing improved response rates and time to progression. Aromatase inhibitors have shown incremental improvements in disease-free survival, lower local recurrence rates, lower metastatic recurrence rates, and a lower incidence of contralateral breast cancer over tamoxifen when used in the adjuvant setting. Aromatase inhibitors are recommended to be used as adjuvant therapy within the first 5 years of hormonal therapy and may be used either upfront for 5 years or sequenced with tamoxifen. No superiority of one aromatase inhibitor over another has yet been shown. The side effect profiles of aromatase inhibitors have some key differences compared with tamoxifen. These differences may influence treatment choices as well as impact compliance. Keywords: aromatase inhibitor, breast cancer, postmenopausal, hormonal therapy

Objective: Antenatal and early neonatal nutritional environment may influence later metabolic health. Infants of mothers with gestational diabetes mellitus (GDM) have higher risk for childhood obesity and metabolic syndrome (MetS). Leptin and adiponectin are known biomarkers for MetS and may guide interventions to reduce later obesity. We sought to examine the relationship between birthweight, early infancy feeding practices, and biomarkers for MetS in offspring of women with mild GDM., Study Design: Secondary analysis of a prospective observational follow-up study on the offspring of women who participated in a multicenter randomized treatment trial on mild GDM. Children were evaluated by research coordinators and biospecimens collected at the age of 5 to 10. Plasma concentrations of leptin and adiponectin were compared between large for gestational age (LGA) and average birthweight (AGA) infants, and according to whether solid foods were introduced early (<6 months of age) or at the recommended age (≥6 months of age). Multivariable analysis adjusted for fetal sex, race/ethnicity, and maternal body mass index., Results: Leptin and adiponectin were measured in 336 plasma samples. In bivariate analysis, compared with AGA children, LGA children had lower leptin (5.0 ng/mL [3.6-6.0] vs. 5.8 ng/mL [4.5 = 6.6], p  = 0.01) and similar adiponectin (6.3 µg/mL [5.1-7.9] vs. 6.4 µg/mL [5.3-8.6], p  = 0.49) concentrations. Maternal/child characteristics were similar between the early/delayed solid feeding groups. Leptin and adiponectin concentrations were similar in the early fed and delayed feeding groups (5.8 ng/mL [4.6-6.7] vs. 5.6 ng/mL [4.2-6.6], p  = 0.50 and 6.4 µg/mL [5.4-8.1] vs. 6.4 µg/mL [5.1-8.8], p  = 0.85, respectively). After controlling for covariates, children who were LGA and AGA at birth had similar leptin concentrations., Conclusion: Birthweight and early infancy feeding practice are not associated with alterations in leptin and adiponectin in children of women with mild GDM., Key Points: · Adipocytokines are markers of metabolic status.. · Children of women with mild GDM may be at risk for MetS.. · Biomarkers similar in LGA and AGA groups.. · Biomarkers similar in early and delayed solid-fed groups.. · Nonhuman milk does not modify effect of feeding practice.., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T)., Experimental Design: Treatment comprised eight cycles of AC→T (T dose: 100 mg/m(2) on day 1) or AC→XT (X dose: 825 mg/m(2) twice daily, days 1-14; T dose: 75 mg/m(2) on day 1). The primary endpoint was 5-year disease-free survival (DFS)., Results: Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67-1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51-0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)-positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of <10% or <20%, respectively, and only 17 (2%) and 53 (6%) DFS events, respectively, occurred in these groups at 7 years., Conclusions: The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients., (©2015 American Association for Cancer Research.)

We analyzed the genomic and phosphoproteomic profiles of breast cancer tissue obtained from six patients with estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer who had highly durable (≥ 5 years) and, in some cases, ongoing clinical responses with capecitabine. Formalin-fixed, paraffin-embedded tissue samples from patients' primary (n = 4) or metastatic (n = 2) breast cancers were utilized for targeted next-generation sequencing and reversed phase protein microarray. Two patients received capecitabine monotherapy. Four patients received capecitabine in combination with paclitaxel; three of these continued single-agent capecitabine after stopping paclitaxel. Capecitabine was discontinued for progressive disease after a mean of 66 months in four patients (range 54-86 months), and two patients remain on therapy, having received capecitabine for >91 months and >122 months, respectively. Three patients' cancers (50%) had likely functional alterations in DNA repair and chromatin remodeling genes, while three other patients' cancers had variants of unknown significance in these pathways. Mutations in PIK3CA, amplifications of FGFR1 or ZNF703, or phosphorylation of HER family receptors and their downstream proteins did not preclude exceptional responses to capecitabine. None of the patients' tumors harbored TP53 or PTEN mutations. Four of the patients had breast cancer tissue available for PTEN immunohistochemistry, and all four patients' cancers were positive for PTEN. These surprising findings in a group of phenotypically similar patients with ER-positive, endocrine therapy-pretreated, HER2-negative metastases, are supported by preclinical data showing that sensitivity to 5-fluorouracil is enhanced by deficiencies in chromatin remodeling and homologous recombination genes. Our findings suggest that mutations that inactivate homologous recombination and/or chromatin remodeling genes within ER-positive, HER2-negative breast cancers may predict for highly durable responses to capecitabine., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To evaluate satisfaction with work-life balance (WLB) and career plans of US oncologists., Methods: The American Society of Clinical Oncology conducted a survey of US oncologists evaluating satisfaction with WLB and career plans between October 2012 and March 2013. The sample included equal numbers of men and women from all career stages., Results: Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys. From 1,117 oncologists (37.3% of overall sample) completing full-length surveys, we evaluated satisfaction with WLB and career plans among the 1,058 who were not yet retired. The proportion of oncologists satisfied with WLB (n = 345; 33.4%) ranked lower than that reported for all other medical specialties in a recent national study. Regarding career plans, 270 oncologists (26.5%) reported a moderate or higher likelihood of reducing their clinical work hours in the next 12 months, 351 (34.3%) indicated a moderate or higher likelihood of leaving their current position within 24 months, and 273 (28.5%) planned to retire before 65 years of age. Multivariable analyses found women oncologists (odds ratio [OR], 0.458; P < .001) and those who devoted greater time to patient care (OR for each additional hour, 0.977; P < .001) were less likely to be satisfied with WLB. Satisfaction with WLB and burnout were the strongest predictors of intent to reduce clinical work hours and leave current position on multivariable analysis., Conclusion: Satisfaction with WLB among US oncologists seems lower than for other medical specialties. Dissatisfaction with WLB shows a strong relationship with plans to reduce hours and leave current practice. Given the pending US oncologist shortage, additional studies exploring interactions among WLB, burnout, and career satisfaction and their impact on career and retirement plans are warranted.

Purpose: To evaluate the personal and professional characteristics associated with career satisfaction and burnout among US oncologists., Methods: Between October 2012 and March 2013, the American Society of Clinical Oncology conducted a survey of US oncologists evaluating burnout and career satisfaction. The survey sample included equal numbers of men and women and represented all career stages., Results: Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys (median age of respondents, 52 years; 49.6% women). Among the 1,117 oncologists (37.3% of overall sample) who completed full-length surveys, 377 (33.8%) were in academic practice (AP) and 482 (43.2%) in private practice (PP), with the remainder in other settings. Oncologists worked an average of 57.6 hours per week (AP, 58.6 hours per week; PP, 62.9 hours per week) and saw a mean of 52 outpatients per week. Overall, 484 oncologists (44.7%) were burned out on the emotional exhaustion and/or depersonalization domain of Maslach Burnout Inventory (AP, 45.9%; PP, 50.5%; P = .18). Hours per week devoted to direct patient care was the dominant professional predictor of burnout for both PP and AP oncologists on univariable and multivariable analyses. Although a majority of oncologists were satisfied with their career (82.5%) and specialty (80.4%) choices, both measures of career satisfaction were lower for those in PP relative to AP (all P < .006)., Conclusion: Overall career satisfaction is high among US oncologists, albeit lower for those in PP relative to AP. Burnout rates among oncologists seem similar to those described in recent studies of US physicians in general. Those oncologists who devote the greatest amount of their professional time to patient care seem to be at greatest risk for burnout.

Background: To define protein molecular characteristics of tumor cells prior to, and immediately following, preoperative human epidermal growth factor receptor 2 (HER2)-targeted therapy that correlate with pathologic complete response (pCR) or non response (no pCR) to preoperative HER2-directed therapy and chemotherapy., Methods: This open-label, phase II study randomized patients with HER2-positive stage II or III invasive breast cancer to trastuzumab, lapatinib, or both, 2 weeks prior to and during chemotherapy with FEC75 for 4 courses; then paclitaxel 80 mg/m2 weekly for 12 courses, then surgery. Core needle biopsies were collected at baseline and after 2 weeks of anti-HER2 therapy prior to chemotherapy. Data were correlated with pCR, defined as absence of invasive tumor in breast and lymph nodes., Results: Of 100 enrolled patients, the analysis population included those who had surgery and received ≥75% chemotherapy (78% [n=78]). pCRs by arm are: trastuzumab (n=26), 54% [n=14]; lapatinib (n=29), 45% [n=13]; trastuzumab plus lapatinib (n=23), 74% [n=17]). Paired biopsy specimens were available for 49 patients (63%). Tumor cells of patients with pCR in the trastuzumab or lapatinib treatment arms showed nonphosphorylated FOXO, phosphorylated Stat5, and sparse signal-transduction protein network crosstalk representing different patterns of connections with PI3K and autophagy proteins compared with no pCR., Conclusion: In this exploratory study, pCR with preoperative anti-HER2 therapy and chemotherapy correlated with the levels and phosphorylation status of specific baseline signal pathway proteins in tumor cells. These data may provide candidate biomarkers to stratify initial treatment and potential combination therapies for future study. Tissue preservation technology introduced here makes this procedure widely feasible., Trial Registration: ClinicalTrials.gov: NCT00524303.

The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations of 267 stage I-III breast cancers. These tumor specimens typically consisted of >80% neoplastic cells. We examined 28 genes for 163 known cancer-related nucleic acid variations by Sequenom technology. We observed at least one mutation in 38 alleles corresponding to 15 genes in 108 (40%) samples, including PIK3CA (16.1% of all samples), FBXW7 (8%), BRAF (3.0%), EGFR (2.6%), AKT1 and CTNNB1 (1.9% each), KIT and KRAS (1.5% each), and PDGFR-α (1.1%). We also checked for the polymorphism in PHLPP2 that is known to activate AKT and it was found at 13.5% of the patient samples. PIK3CA mutations were more frequent in estrogen receptor-positive cancers compared to triple negative breast cancer (TNBC) (19 vs. 8%, p=0.001). High frequency of PIK3CA mutations (28%) were also found in HER2+ breast tumors. In TNBC, FBXW7 mutations were significantly more frequent compared to ER+ tumors (13 vs. 5%, p=0.037). We performed validation for all mutated alleles with allele-specific PCR or direct sequencing; alleles analyzed by two different sequencing techniques showed 95-100% concordance for mutation status. In conclusion, different breast cancer subtypes harbor different type of mutations and approximately 40 % of tumors contained individually rare mutations in signaling pathways that can be potentially targeted with drugs. Simultaneous testing of many different mutations in a single needle biopsy is feasible and allows the design of prospective clinical trials that could test the functional importance of these mutations in the future.

Unlabelled: Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by cremophor-formulated paclitaxel (cf-P) was efficacious in metastatic breast cancer (BC). Albumin-bound paclitaxel (ab-P) was safe and more effective than cf-P, and the addition of bevacizumab to cf-P improved efficacy. This study compared the safety of dose-dense ab-P vs cf-P plus bevacizumab following dose-dense adjuvant AC for early-stage BC., Patients and Methods: Women with operable, histologically confirmed BC were randomized to 4 cycles of dose-dense A 60 mg/m(2) plus C 600 mg/m(2) IV with SC pegfilgrastim, followed by 4 cycles of either dose-dense IV ab-P 260 mg/m(2) or cf-P 175 mg/m(2). Bevacizumab was given during and following chemotherapy. 97 and 96% of patients completed 4 cycles of AC therapy, while 84 and 85% of patients completed 4 cycles of taxane therapy in the ab-P and cf-P arms, respectively (N = 197). Baseline patient characteristics were similar. The most common grade ≥3 taxane-related adverse events (AEs) were fatigue and neutropenia. Dose reductions were similar between the treatment arms. During AC therapy, the majority of dose reductions were due to febrile neutropenia; during taxane therapy, the majority of cases were due to neuropathy. No taxane-related dose interruption occurred in the ab-P arm, while 3 occurred in the cf-P arm due to hypersensitivity reactions. The mean cumulative paclitaxel dose was 950.5 and 660.8 mg/m(2) in the ab-P and cf-P arms, respectively. A 44% higher paclitaxel dose was delivered in the ab-P compared with the cf-P arm (P < 0.0001), while achieving a similar safety profile. ab-P plus bevacizumab following AC therapy without prophylactic premedications was tolerable in early-stage BC patients.

Estrogen and its metabolites play a significant role in the proliferation of hormone receptor-positive breast cancer. In postmenopausal women, aromatase inhibitors can significantly reduce estrogen levels by blocking enzyme-mediated estrogen synthesis within tissues. Third-generation aromatase inhibitors have now surpassed tamoxifen as first-line therapy for postmenopausal women with metastatic, hormone receptor-positive, breast cancer, showing improved response rates and time to progression. Aromatase inhibitors have shown incremental improvements in disease-free survival, lower local recurrence rates, lower metastatic recurrence rates, and a lower incidence of contralateral breast cancer over tamoxifen when used in the adjuvant setting. Aromatase inhibitors are recommended to be used as adjuvant therapy within the first 5 years of hormonal therapy and may be used either upfront for 5 years or sequenced with tamoxifen. No superiority of one aromatase inhibitor over another has yet been shown. The side effect profiles of aromatase inhibitors have some key differences compared with tamoxifen. These differences may influence treatment choices as well as impact compliance.

Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control. Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89 macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%. Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of percentages reported in the literature.

Background: We hypothesized that distinct biological processes might be associated with prognosis and chemotherapy sensitivity in the different types of breast cancers., Methods: We performed gene set analyses with BRB-ArrayTools statistical software including 2331 functionally annotated gene sets (ie, lists of genes that correspond to a particular biological pathway or biochemical function) assembled from Ingenuity Pathway Analysis and Gene Ontology databases corresponding to almost all known biological processes. Gene set analysis was performed on gene expression data from three cohorts of 234, 170, and 175 patients with HER2-normal lymph node-negative breast cancer who received no systemic adjuvant therapy to identify gene sets associated prognosis and three additional cohorts of 198, 85, and 62 patients with HER2-normal stage I-III breast cancer who received preoperative chemotherapy to identify gene sets associated with pathological complete response to therapy. These analyses were performed separately for estrogen receptor (ER)-positive and ER-negative breast cancers. Interaction between gene sets and survival and treatment response by breast cancer subtype was assessed in individual datasets and also in pooled datasets. Statistical significance was estimated with permutation test. All statistical tests were two-sided., Results: For ER-positive cancers, from 370 to 434 gene sets were associated with prognosis (P ≤ .05) and from 209 to 267 gene sets were associated with chemotherapy response in analysis by individual dataset. For ER-positive cancers, 131 gene sets were associated with prognosis and 69 were associated with pathological complete response (P ≤.001) in pooled analysis. Increased expression of cell cycle-related gene sets was associated with poor prognosis, and B-cell immunity-related gene sets were associated with good prognosis. For ER-negative cancers, from 175 to 288 gene sets were associated with prognosis and from 212 to 285 gene sets were associated with chemotherapy response. In pooled analyses of ER-negative cancers, 14 gene sets were associated with prognosis and 23 were associated with response. Gene sets involved in sphingolipid and glycolipid metabolism were associated with better prognosis and those involved in base excision repair, cell aging, and spindle microtubule regulation were associated with chemotherapy response., Conclusion: Different biological processes were associated with prognosis and chemotherapy response in ER-positive and ER-negative breast cancers.

Purpose: This study compared disease-free survival (DFS) obtained with two different regimens of adjuvant therapy in high-risk breast cancer., Methods: Women (who had performance status [PS] of 0 to 1) with operable, histologically confirmed, stage I to III adenocarcinoma of the breast were eligible. Patients had undergone primary surgery with no residual tumor. Treatments were as follows: arm 1 was doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (ie, AC-P); and arm 2 was doxorubicin 50 mg/m(2) plus paclitaxel 200 mg/m(2) every 3 weeks for four cycles followed by paclitaxel 80 mg/m(2) weekly for 12 weeks., Results: Overall, 1,830 patients were enrolled and 1,801 were treated: arm 1 (n = 906; AC-->P) and arm 2 (n = 895; AP-WP). Overall, patients had a PS of 0 (88%), had estrogen receptor and progesterone receptor-positive disease (52%), had one to three positive nodes (46%), and were postmenopausal (57%); the median age was 52 years. Currently, 1,640 patients (90%) are alive. The 6-year DFS was 79% to 80% in both groups. Disease relapse was the cause of death for 83 patients in arm 1 and in 66 patients of arm 2. Overall 6-year survival rates were 82% and 87% in arms 1 and 2, respectively. Reasons for patients being taken off study treatment included toxicity (13% in arm 1 v 20% in arm 2), progressive disease or recurrence (7% v 5%), and consent withdrawn (9% v 8%), respectively. The most frequent toxicities were hematologic, including neutropenia and leukopenia followed by neuropathy, myalgia, nausea, fatigue, headache, arthralgia, and vomiting., Conclusion: The results indicate that the AP-WP regimen is an equally effective and tolerable option for the adjuvant treatment of patients with high-risk breast cancer. The substitution of paclitaxel for cyclophosphamide results in comparable effectiveness of the regimen.

Purpose: This phase II trial assessed efficacy and safety of pemetrexed plus gemcitabine to treat metastatic or locally advanced breast cancer in patients previously treated with taxanes., Patients and Methods: Eligible women with advanced breast cancer treated with taxanes in the adjuvant or metastatic setting received pemetrexed 500 mg/m2 on day 1 followed by gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Hematologic toxicities limiting day 8 gemcitabine dosing were observed in the first 20 patients, prompting a protocol amendment to evaluate pemetrexed 500 mg/m2 followed by gemcitabine 1500 mg/m2 on day 1 of a 14-day cycle. Patients received folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate (ORR)., Results: Between July 2003 and September 2006, 73 evaluable women (median age, 52.1 years; range, 28-73 years) were enrolled (21-day schedule: 21 patients, 52% estrogen receptor-positive, 24% HER2-positive; 14-day schedule: 52 patients, 58% ER-positive, 15% HER2-positive). For patients on the 21-day and 14-day schedules, median number of cycles was 4 (range, 1-8 cycles) and 5 (range, 1-38 cycles), respectively. The ORRs were 23.8% and 19.2%, respectively; median survival times were 16.2 months and 13.4 months. The most common grade 3/4 hematologic toxicities were neutropenia (71% vs. 33%) and leukopenia (24% vs. 14%); febrile neutropenia occurred in 10% and 6%. The most common grade 3/4 nonhematologic toxicity was fatigue (29% vs. 10%)., Conclusion: Pemetrexed/gemcitabine given on a 21-day or 14-day schedule is active in patients with advanced breast cancer previously treated with taxanes. A 14-day schedule appears to result in fewer serious toxicities.

Background: Adjuvant therapy with aromatase inhibitors is associated with increased bone loss in postmenopausal women with breast cancer. We assessed changes in bone mineral density (BMD) from baseline to 24 months in patients receiving either tamoxifen (T) or exemestane (E)., Patients and Methods: A total of 578 women randomly assigned to T 20 mg per day orally or E 25 mg/day orally enrolled in this substudy; baseline, 12-month, and 24-month BMD measurements of the femur and lumbar spine by dual-energy x-ray absorptiometry were planned. Women receiving bone antiresorptive agents were excluded. Mean BMD changes from baseline to 12 and 24 months were tested between the treatment groups using 2-sample t tests and both g/cm2 (as percent changes) and T scores (as differences from baseline)., Results: A total of 167 women with all 3 imaging studies were evaluable and form the basis of this report (T=89, E=78). Using T scores, the mean difference from baseline was significant between the 2 groups at 12 months at both the spine (P=.0002) and the hip (P=.0004), and at 24 months only at the hip (P=.02)., Conclusion: More bone loss occurred during the first 12 months of treatment with E compared with T, but by 2 years the differences were less apparent and bone loss with E had slowed.

Background: For chemosensitivity and resistance assays to be clinically useful in predicting patient outcome, they should require small amounts of tissue and be highly reproducible and reliable., Patients and Methods: Expanded tumor cells from transcutaneous biopsies of breast lesions (n=62) were tested for chemoresponse using the cell-based ChemoFx assay. Pathologic complete response (pCR) was determined on a subset of patients (n=34). Assay score and pCR were determined independently in a blinded manner. Logistic regression models were used to select predictors for response., Results: Tumor cells were successfully isolated from 83.9% of patients. Chemoresponse profiles were robust and reproducible with coefficient of variance of <3%. In a limited initial patient outcome correlation, assay score of docetaxel/capecitabine significantly predicted pCR; the cross-validated model was 75% accurate., Conclusion: It is feasible to assess the chemoresponsiveness of small breast lesions using the ChemoFx assay to assist in choosing neoadjuvant chemotherapy for breast cancer patients.