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Identification of geriatric syndromes is important for determining functional age and optimizing care for people with cancer. Based on administration of a geriatric screening tool, we aimed to describe needed resources for geriatric syndromes, including lack of social support, depressed mood, deficits in instrumental and activities of daily living (IADL/ADL), falls, nutritional issues, polypharmacy, ability to pay for medications, and memory deficits, in a population of patients with breast cancer. Consecutive medical oncology patients with breast cancer age 65 years and older, seen at a tertiary care center, completed a screening tool, adapted from Overcash 2006, consisting of a nurse-administered memory assessment and a one-page, self-administered questionnaire. Responses identified geriatric syndromes. Demographics and clinical information were retrospectively gathered. Frequencies and means were used to describe data. From January 2012 through July 2014, patients (n = 429) completed the screening tool as part of routine care. Study group had mean age 76 years (range 65–89), mean time since diagnosis 6.5 years, 91% non-metastatic disease, mean Charlson Comorbidity score 1.8 (range 0–10). Treatment included partial mastectomy (49%), adjuvant radiation (43%), chemotherapy (25%), and endocrine therapy (61%). The screening tool identified need for social support (8%); depression (31%); mobility issues (20%); falls (28%); nutritional needs (33%); polypharmacy (83%); and memory deficit (19%). This screening tool identified geriatric syndromes requiring attention in many patients with breast cancer presenting for medical oncology appointments. In oncology practice, need for referral networks to address geriatric syndromes should be assessed. [ABSTRACT FROM AUTHOR]

Abstract Objective To explore the impact of symptoms on physical function in women on adjuvant endocrine therapy for breast cancer. Methods Eligible women were postmenopausal, had hormone receptor positive, stage I-IIIA breast cancer, completed surgery, chemotherapy, radiation, and on adjuvant endocrine therapy. At a routine follow-up visit, women (N = 107) completed standardized symptom measures: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy Neurotoxicity scales. Two performance measures assessed function: grip strength (Jamar dynamometer; n = 71) and timed get-up-and-go (TUG; n = 103). Analyses were performed with an overall symptom composite score. Correlations and multiple linear regression analyses were performed to test adverse effects on physical function. Results The mean age was 64 years (range 45–84), 81% white, 84% on an aromatase inhibitor, and on endocrine therapy for mean 35 months (range 1–130 months). Dominant hand grip strength was inversely correlated with symptom composite scores (r = −0.29, p =.02). Slower TUG was positively correlated with higher Charlson comorbidity level (r = 0.36, p <.001) and higher symptom composite scores (r = 0.24, p =.01). In multivariate analyses, weaker dominant and non-dominant hand grip strength were significantly associated with greater symptom composite scores (β = −0.27, t = 2.43, p =.02 and β = −0.36, t = 3.15, p =.003, respectively) and slower TUG was associated with higher symptom composite scores (β = 0.18, t = 1.97, p =.05). Conclusions Higher symptom burden is associated with worse physical function, as measured by hand grip strength and TUG. Further study to determine the impact of endocrine therapy and its side effects on function is warranted. [ABSTRACT FROM AUTHOR]

For [is greater than] 20 y, weight gain has been a commonly reported side effect of adjuvant chemotherapy (CT) for breast cancer. To determine causes for this energy imbalance, we undertook a study that assessed body weight and composition (via dual energy X-ray absorptiometry [DXA]), resting metabolic rate (RMR; via indirect calorimetry), energy intake (via 2-d 24-h dietary recalls) and physical activity (Stanford 5-City Physical Activity Questionnaires) throughout the year after the diagnosis of Stage I or II breast cancer in premenopausal patients who received CT compared with patients who received localized treatment (LT; surgery with or without radiation). Body weight and RMRs were measured at baseline and at 2, 6 and 12 mo; DXA was performed at baseline and at 6 and 12 mo; energy intake was assessed semimonthly and physical activity was assessed weekly. Analyses to determine differences in linear trends over time were performed (two-tailed tests; [Alpha] = 0.05). Preliminary analyses on complete data from 53 participants (n = 36 in the CT group, n = 17 in the LT group) suggest that there are significant gains in body weight by patients who receive CT compared with patients who receive LT (2.7 [+ or -] 4.5 vs. 1.0 [+ or -] 1.4 kg/y; P = 0.04). Furthermore, percent body fat increased from 33.6% [+ or -] 8.6% at baseline to 35.8% [+ or -] 9.0% at 1 y in the CT group whereas no change was noted in the LT group (i.e., 28.6% [+ or -] 6.7% to 28.5% [+ or -] 7.0%) (age- and race-controlled P-value = 0.001). Significant differences between groups also were seen with regard to lean body mass (P = 0.002), especially in the leg region (P = 0.01), where the CT group experienced losses and the LT group experienced slight gains. Decreases in physical activity were observed from baseline to follow-up in the AC group (506 [+ or -] 101 vs. 458 [+ or -] 114 kcal/d; P = 0.017), however, were not seen in the LT group. No differences over time or between groups were noted with regard to RMR or energy intake. These data support the need for early interventions focused on increased physical activity in order to reduce gains in weight and percent body fat by young women with breast cancer.

Purpose To explore how symptoms and psychosocial factors are related to intentional and unintentional non-adherent medication taking behaviors. Methods Included were postmenopausal women with hormone receptor positive, stage I-IIIA breast cancer, who had completed surgery, chemotherapy, and radiation, and were taking endocrine therapy. Self-administered, standardized measures were completed during a routine clinic visit: Brief Fatigue Inventory, Brief Pain Inventory, Menopause Specific Quality of Life Questionnaire, Functional Assessment of Cancer Therapy General and Neurotoxicity scales, and Self-Efficacy for Appropriate Medication Use Scale. Regression analyses were performed to determine the degree to which demographic, medical, symptom, and psychosocial variables, explain intentional, such as changing one's doses or stopping medication, and unintentional, such as forgetting to take one's medication, non-adherent behaviors. Results Participants were 112 women: mean age 64 (SD = 9) years; 81% white; mean time from surgery 40 (SD = 28) months; 49% received chemotherapy (39% including a taxane); mean time on endocrine therapy, 35 (SD = 29.6) months; 82% taking an aromatase inhibitor. Intentional and unintentional non-adherent behaviors were described in 33.9% and 58.9% of participants, respectively. Multivariate analysis showed that higher self-efficacy for taking medication was associated with lower levels of unintentional (p = 0.002) and intentional (p = 0.004) non-adherent behaviors. The presence of symptoms (p = 0.03) and lower self-efficacy for physician communication (p = 0.009) were associated with higher levels of intentional non-adherent behaviors. Conclusions These results suggest that women who report greater symptoms, lower self-efficacy for communicating with their physician, and lower self-efficacy for taking their medication are more likely to engage in both intentional and unintentional non-adherent behaviors. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the role of hypermethylation of the breast cancer-associated gene 1 (BRCA1) promoter in breast cancer risk. In the study, BRCA1 promoter hypermethylation was tested in breast cancer biopsies and initial random periareolar fine-needle aspiration (RPFNA) cytologic samples. It revealed the BRCA1 is not associated with the disease and at the same time does not predict mammary atypia in RPFNA cytologic samples.

Background: Numerous gene-expression signatures have been developed for breast cancer. However, assessments of their validity continue to largely ignore the impact of intratumor heterogeneity and technical variation on clinical utility. Here, the collection of replicate specimen in Barry et al (2010) is used to evaluate a broad collection of gene-expression signatures of prognosis and tumor biology. Methods: Eighteen patients with multiple frozen cores (one patient with quadruplicate, twelve with triplicate, and five with doublet samples) were previously identified in the Duke Breast SPORE tissue repository. Cores were assessed for percent invasive cancer cellularity, and tumor size, grade, and ER/PR status. RNA was extracted and hybridized to AffymetrixH133Plus2.0 microarrays. Expression signatures of prognosis and tumor biology were developed or translated to the Affymetrix platform using routines by Prat et al. (2012) and Haibe-Keins et al. (2012). Association between signatures, and precision among replicates are evaluated using Pearson and intraclass correlation. Coefficients are reported with 95% confidence intervals. Results: Among prognostic signatures, an imputed 70-gene signature of MammaPrint had the highest level of precision (ICC = 0.96, 0.91-0.98); strong concordance is seen with Affymetrix-based PAM50 risk-of-relapse (ICC = 0.82, 0.65--0.92); 16 of 18 patients had constant subtype calls. Substantially lower concordance was seen in the GENIUS prognostic model (ICC = 0.62, 0.35--0.82). In ER+ patients (n = 13), two algorithms to impute the 21-gene model of OncotypeDX recurrence score were concordant (r = 0.98, ICC= 0.90 and 0.83) and distinct from the GENIUS ER+ score (average r = 0.74, ICC=0.78). Imputed models for the Rotterdam 76-gene model (+ER status), GGI (+grade), and ROR-T (+tumor size) showed lower levels of correlation (0.47

Discusses a study on the contribution of thermochemoradiotherapy to the improvement of oxygenation in locally advanced breast cancer. Evaluation of the toxicity and efficacy of the treatment that consisted of concurrent taxane, radiotherapy and hyperthermia; Impact of the therapy on tumor hypoxia; Criticisms of the benefits of the actual treatment regimen.

Background Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. Patients and methods The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. Results Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. Conclusion Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. Clinical trial registration clinicaltrials.gov identifier: NCT00542451. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemical (IHC) assessment of the proportion of cells staining for the KI67 nuclear antigen is being increasing utilized in the management of patients with early-stage breast cancer (ESBC). A comprehensive systematic review and evidence synthesis of biomarkers potentially predictive of response to systemic therapy was initiated as a part of an NCI-funded comparative effectiveness research program. Methods: Studies of chemotherapy response prediction based on baseline IHC assessment of Ki67 in patients with ESBC receiving neoadjuvant systemic therapy were identified. Response was specified as pathologic complete response (pCR) or clinical response (ClinR). Assay predictive performance for response was assessed on the basis of sensitivity, specificity, predictive value and predictive odds ratio (POR±95%CLs) utilizing mixed effects models. Study results were fitted in an ROC analysis based on the method of DerSimonian and Laird. Publication bias was evaluated on the basis of funnel plot asymmetry assessed by Egger's regression intercept and Begg and Mazumdar's rank correlation. Results: Of 469 potentially eligible studies, dual blind full text review identified 42 eligible studies reporting 44 independent cohorts with 6,716 patients ( 21-979). While Ki67 cutpoints varied considerably, they were most commonly between 10%-30% (median 20%, range 1-50%). The analysis prsented here is limited to the 30 studies of ESBC patients (N = 3,343) receiving neoadjuvant therapy of which 14 reported fewer than 100 patients. The proportion of patients with elevated Ki67 across studies ranged from 0.20-0.92 (median = 0.54). Sensitivity and specificity for treatment response in patients with high vs. low baseline Ki67 was 0.65 [0.61, 0.68] and 0.52 [0.50, 0.54], respectively. Estimated response rates across studies in patients with high vs. low Ki67 were 31% [29%, 34%] and 19% [17%, 21%], respectively. The estimated POR for response across studies was 2.82 [2.14, 3.72; P < .001]. anthracycline regimens [0.92](Pinteraction = .043) and of cyclophosphamide-based [3.41] compared to non-cyclophosphamide regimens [2.00](P interaction=.039) but was not associated with treatment based on other drug classes. Although Ki67 predictive performance was not significantly associated with the cutpoint utilized or the proportion of patients with ER or PR+, Her2+, or high grade tumors across studies, analysis based on individual patient data is needed to assess performance in specific clinical subgroups. No significant publication bias was found. Conclusions: A compelling need exists for larger studies with greater methodologic rigor and standardization to assess the clinical validity of Ki67 in ESBC as well its clinical utility in guiding neoadjuvant treatment decisions compared to the use of conventional predictive markers. [ABSTRACT FROM AUTHOR]

Background: Microarray assessment of breast cancer demonstrates disease subsets among the major breast cancer biologic categories (ER, PR, HER-2) with likely additional prognostic and treatment (predictive) implications. Additional prognostic and predictive biomarkers and optimization of existing genomic platforms are needed to improve personalized breast cancer care. Methods: 76 early-stage ER+ patients with adequate RNA from fresh frozen tumor specimens and a concurrent 21-gene OncotypeDX recurrence score (RS) were identified across independent Duke studies linked to routine prospective breast biospecimen collection. Expression estimates for Affymetrix H133 Plus 2.0 microarrays were reviewed for quality control (Owzar 2008) and normalized across 4 batches with ComBat. Correlations of genomic prognostic signatures to true RS were assessed using Spearman coefficients. Discovery of new gene-level and pathway-level associations to breast cancer prognosis and prediction, based on RS, were corrected for multiple comparisons using the Bonferonni for the family-wise error rate (FWER) or Benjamini-Hochberg methods for the false discovery rate (FDR). Results: A total of 73 samples passed Affymetrix quality control: 32 "low risk", 32 "intermediate risk", and 9 "high risk" using standard recurrence score thresholds of <18 and >30. Median patient age is 55 (range 35-86). Two published algorithms to impute the RS from the Affymetrix model by Fan and Haibe-Keins were highly concordant (94%) with each other and showed strong correlation to actual RS (rho = 0.62, p = 5e-9). However, when the RS thresholds were applied to the microarray-based scores, lower agreement was observed (misclassification rate of 57%). Strong correlation was also observed with other breast signatures and RS, including an imputed 70-gene signature of MammaPrint (rho = 0.59, p = 3e-8) and the 50-gene PAM50 risk-of-relapse score (rho = 0.54, p = 8e-7), while poor correlation was seen for the GENIUS prognostic model (rho = 0.06, p = 0.6). Discovery of gene-level associations to RS identified 28 genes, including known cancer-associated genes such as BRCA2 (FWER adj p = 0.002), Cyclin E1 (FWER adj p = 0.015), and CDCA5 (FWER adj p = 0.048). Pathway-level association in KEGG and GO Biologic Processes, identified 24 and 104 categories respectively, including Cell Cycle pathways KEGG:04110 (FDR adj p = 0.002) and GO:0000085 (FDR adj p = 0.0007). Among 22 in-vitro derived oncogenic pathway signatures, significant negative correlation is seen with p53 (rho = -0.56, adj p = 4e-6) and positive correlation with beta-catenin (rho = 0.38, adj p = 0.015). A multi-gene model of association to OncotypeDX RS classification is being developed using Prediction Analysis of Microarrays (PAM). Conclusions: Microarray-based prognostic breast cancer signatures are generally concordant. However, their application across platforms is currently sub-optimal. In the context of OncotypeDX RS, additional key cancer-associated genes and pathways are found to be associated with breast cancer prognosis, potentially providing insight into treatment opportunities for ER+ breast cancer. Validation efforts of these findings in an independent patient cohort are underway. [ABSTRACT FROM AUTHOR]

Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX <=120 days after DX for patients with stage II/III ER/PR negative disease. We sought to examine the impact of delayed CTX on survival overall and stratified by disease-specific prognostic factors. Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04-2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89-1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74-1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99-1.76, p = 0.06). Patients who received CTX >135d(n = 231, HR1.25, 95% CI: 0.87-1.81, p = 0.22)or>150d(n = 128, HR1.15, 95% CI: 0.59-2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16-2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to -CTX interval was observed that warrants further examination. [ABSTRACT FROM AUTHOR]

Background: Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response [residual cancer burden (RCB)-0/1] to single-agent cisplatin or paclitaxel., Patients and Methods: This prospective phase II study enrolled patients with germline BRCA1/2 wild-type/unknown stage I-III TNBC in a 12-week randomized study of preoperative cisplatin or paclitaxel. The HRD assay was carried out on baseline tissue; positive HRD was defined as a score ≥33. Crossover to an alternative chemotherapy was offered if there was inadequate response., Results: One hundred and thirty-nine patients were evaluable for response, including 88 (63.3%) who had surgery at 12 weeks and 51 (36.7%) who crossed over to an alternative provider-selected preoperative chemotherapy regimen due to inadequate clinical response. HRD results were available for 104 tumors (74.8%) and 74 (71.1%) were HRD positive. The RCB-0/1 rate was 26.4% with cisplatin and 22.3% with paclitaxel. No significant association was observed between HRD score and RCB response to either cisplatin [odds ratio (OR) for RCB-0/1 if HRD positive 2.22 (95% CI: 0.39-23.68)] or paclitaxel [OR for RCB-0/1 if HRD positive 0.90 (95% CI: 0.19-4.95)]. There was no evidence of an interaction between HRD and pathologic response to chemotherapy., Conclusions: In this prospective preoperative trial in TNBC, HRD was not predictive of pathologic response. Tumors were similarly responsive to preoperative paclitaxel or cisplatin chemotherapy., Competing Interests: Disclosures The authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics., Patients and Methods: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out., Results: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them., Conclusion: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome., Clinical Trial Registration: clinicaltrials.gov identifier: NCT00542451., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance., Patients and Methods: Factors related to energy balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma. Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records)., Results: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P =.02). No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P =.01). Several differences between groups in 1-year change scores were detected. The mean change (+/- SE) in LT versus CT groups and P values for uncontrolled/controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P =.001/0.04); fat mass (+0.1 +/- 0.3 v +2.3 +/- 0.7 kg; P =.002/0.04); lean body mass (+0.8 +/- 0.2 v -0.4 +/- 0.3 kg; P =.02/0.30); and leg lean mass (+0.5 +/- 0.1 v -0.2 +/- 0.1 kg; P =.01/0.11)., Conclusion: These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weight gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain.

Background: Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy., Patients and Methods: Thirty women with metastatic breast cancer were enrolled. Dose-limiting toxicity was determined through a dose escalation scheme, and defined for the first treatment cycle, only. Pharmacokinetic studies were performed during the first cycle of treatment., Results: In the first cohort of Doxil 30 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8, patients experienced severe neutropenia. Vinorelbine administration was changed thereafter to days 1 and 15 of each cycle. Dose limiting toxicity was observed at Doxil 50 mg/m2 and vinorelbine 25 mg/m2. Doxil 40 mg/m2 and vinorelbine 30 mg/m2 was defined as the maximally tolerated dose. Few toxicities (principally neutro penia) were seen at this dose level, with the notable absence of significant nausea, vomiting, or alopecia. Though 63% of patients had received prior anthracycline-based chemotherapy, only one patient developed grade 2 cardiac toxicity. Pharmacokinetic studies revealed prolonged exposure to high doxorubicin concentrations for several days following Doxil administration., Conclusions: Combination chemotherapy with Doxil and vinorelbine affords treatment with two active drugs in women with metastatic breast cancer, and appears to have a favorable toxicity profile. A schedule of Doxil 40 mg/m2 day 1 and vinorelbine 30 mg/m2 days 1 and 15 given every 28 days is recommended for phase II studies.

Topical bovine thrombin preparations are used extensively in cardiovascular, neurosurgical, and otolaryngologic procedures. Patients who are treated with these topical thrombin preparations may develop antibodies to bovine coagulation factors that may cross-react with the endogenous human clotting proteins. We have identified four patients with acquired factor inhibitors following exposure to topical thrombin at Duke University Medical Center and summarize these cases in addition to 13 patients previously reported in the literature. In most cases, the inhibitor developed following a second (or subsequent) exposure to topical thrombin. The clinical course was extremely variable, ranging from totally asymptomatic to life-threatening hemorrhage. The most consistent laboratory abnormality was a prolonged bovine thrombin clotting time, which corrected, at least partially, when human thrombin was substituted for bovine thrombin. Some of these patients also developed factor V inhibitors with prolonged prothrombin and activated partial thromboplastin times. Although these patients have prolonged clotting times, they should not be considered "autoanticoagulated," since thromboembolic complications can still occur. Therapeutic intervention is largely empirical and depends on the clinical manifestations of the individual patient.