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PURPOSE Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach. METHODS In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2– MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%. RESULTS Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo. CONCLUSION In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2– MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

A well-known question by Gromov asks whether the vanishing of the simplicial volume of oriented closed connected aspherical manifolds implies the vanishing of the Euler characteristic. We study various versions of Gromov's question and collect strategies towards affirmative answers and strategies towards negative answers to this problem. Moreover, we put Gromov's question into context with other open problems in low- and high-dimensional topology. A special emphasis is put on a comparative analysis of the additivity properties of the simplicial volume and the Euler characteristic for manifolds with boundary. We explain that the simplicial volume defines a symmetric monoidal functor (TQFT) on the amenable cobordism category, but not on the whole cobordism category. In addition, using known computations of simplicial volumes, we conclude that the fundamental group of the 4-dimensional amenable cobordism category is not finitely generated. We also consider new variations of Gromov's question. Specifically, we show that counterexamples exist among aspherical spaces that are only homology equivalent to oriented closed connected manifolds., Comment: 41 pages, minor changes, a few typos fixed. To appear in Res. Math. Sci

Background: Survival outcome after developing brain metastasis is poor and there is an unmet need to identify factors that can promote brain metastasis. Granulocyte-colony stimulating factor (G-CSF) is given to support neutrophil recovery after myelosuppressive chemotherapy to some patients. However, there is emerging evidence that neutrophils can promote metastasis, including through the formation of neutrophil extracellular traps (NETs), scaffolds of chromatin with enzymes expelled from neutrophils to the extracellular space. In animal models, G-CSFs can induce NETs to promote liver and lung metastasis. The primary objective of this study was to test the association between G-CSF use and the later incidence of brain metastasis. Methods: Patients with de novo Stage IV breast cancer, without known brain metastasis at the time of initial diagnosis, were identified from electronic medical records covering the period from 1/1/2013 to 12/31/2020 at Northwell Health. Univariate and multivariate logistic regression models were used to test the association between variables of interest, including G-CSF use, and brain metastasis. Results: A total of 78 patients were included in the final analysis. Among those 78 patients, 24 patients (30.8%) had received G-CSF along with chemotherapy at least once. In logistic regression models, G-CSF use was not a significant factor to predict brain metastasis (OR 1.89 [95%CI 1.89-5.33]; P=0.23). Interestingly, in multivariate logistic models, pulmonary embolism (PE)/deep venous thrombosis (DVT) was a significant predictive factor of brain metastasis (OR 6.74 [95%CI 1.82-25.01]; P=0.004) (38.5% vs 21.5%). Conclusions: The use of G-CSF was not associated with increased risk of brain metastasis in patients with de novo Stage IV breast cancer. Interestingly, PE/DVT, which can be associated with elevated NETs, was associated with brain metastasis. Further studies are warranted to determine whether DVT/PE with or without elevated NETs levels in the blood, is predictive of developing brain metastasis in patients with de novo Stage IV breast cancer.

We show that the Waldhausen trace map $\mathrm{Tr}_X \colon A(X) \to QX_+$, which defines a natural splitting map from the algebraic $K$-theory of spaces to stable homotopy, is natural up to \emph{weak} homotopy with respect to transfer maps in algebraic $K$-theory and Becker-Gottlieb transfer maps respectively., Comment: 16 pages. Final version; to appear in Math. Z

Ο όγκος των πληροφοριών που παρέχονται µέσω των ψηφιακών εφαρμογών πολιτισμικού περιεχόµενου είναι µεγάλος και συνεπώς η ανάγκη για παροχή εξατοµικευµένης εµπειρίας επίσκεψης είναι επιτακτική, ώστε οι παρεχόµενες πληροφορίες να παρουσιάζονται µε αποτελεσµατικό τρόπο προς κάθε επισκέπτη σύµφωνα µε τα ατοµικά του γνωστικά χαρακτηριστικά. Ωστόσο, οι προσπάθειες που έχουν πραγµατοποιηθεί ως σήµερα δεν δίνουν έµφαση στη διαφορετικότητα των ανθρώπων ως προς τα γνωστικά τους χαρακτηριστικά, τα οποία έχουν κυρίαρχο ρόλο στον τρόπο µε τον οποίο κάθε άτοµο αναζητά, συλλέγει, οργανώνει, επεξεργάζεται, και ανακτά πληροφορίες. Η διατριβή συνέβαλε στη διαπίστωση ότι οι επισκέπτες σε χώρους πολιτισµού που έχουν διαφορετικά γνωστικά χαρακτηριστικά διαφέρουν στον τρόπο µε τον οποίο αλληλεπιδρούν και επεξεργάζονται την πληροφορία όταν χρησιµοποιούν ψηφιακές εφαρµογές πολιτισµικού περιεχοµένου. Αυτές οι διαφορές αναδείχθηκαν µέσα από την ποσοτική και ποιοτική ανάλυση δεδοµένων και έχουν άµεση σχέση µε την εµπειρία επίσκεψης. Οι υπάρχουσες εφαρµογές, οι οποίες δεν λαµβάνουν υπόψη τους τη διαφορετικότητα των επισκεπτών ως προς τα γνωστικά χαρακτηριστικά, δηµιούργησαν ανισορροπίες σχετικά µε την εµπειρία επίσκεψης (κατανόηση πολιτισµικού περιεχοµένου, ποσοστό εµβύθισης). Προτάθηκε το πλαίσιο CogniCHef, το οποίο αφορά τη σχεδίαση εξατοµικευµένων εφαρµογών πολιτισµικού περιεχοµένου που λαµβάνει υπόψη τα ατοµικά γνωστικά χαρακτηριστικά του επισκέπτη µε στόχο να του προσφέρει µια βελτιωµένη εµπειρία επίσκεψης. Επίσης, η διατριβή έδειξε ότι η έγκυρη και έγκαιρη διάγνωση των γνωστικών χαρακτηριστικών είναι εφικτή σε πραγµατικό χρόνο κατά την αλληλεπίδραση του επισκέπτη µε εφαρµογές πολιτισµικού περιεχοµένου, µε τη χρήση αυτοµατοποιηµένων διαδικασιών, οι οποίες βασίζονται στη συλλογή και ανάλυση δεδοµένων οφθαλµικής ιχνηλάτησης (eye-tracking data). Επίσης, έδειξε ότι το πλαίσιο µπορεί να χρησιµοποιηθεί αποτελεσµατικά από σχεδιαστές ώστε να υλοποιήσουν εξατοµικευµένες εφαρµογές πολιτισµικού περιεχοµένου µε βάση τα γνωστικά χαρακτηριστικά των επισκεπτών. Τέλος, έδειξε ότι οι εξατοµικευµένες εφαρµογές πολιτισµικού περιεχοµένου βελτιώνουν τη συνολική εµπειρία του επισκέπτη.

Adjoint functor theorems give necessary and sufficient conditions for a functor to admit an adjoint. In this paper, we prove general adjoint functor theorems for functors between ∞‐categories. One of our main results is an ∞‐categorical generalization of Freyd's classical General Adjoint Functor Theorem. As an application of this result, we recover Lurie's adjoint functor theorems for presentable ∞‐categories. We also discuss the comparison between adjunctions of ∞‐categories and homotopy adjunctions, and give a treatment of Brown representability for ∞‐categories based on Heller's purely categorical formulation of the classical Brown representability theorem.

We discuss two categorical characterizations of the class of acyclic maps between (path-connected) spaces. The first one is in terms of the higher categorical notion of an epimorphism. The second one employs the notion of a balanced map, that is, a map whose homotopy pullbacks define also homotopy pushouts. We also identify the modality in the homotopy theory of spaces that is defined by the class of acyclic maps, and discuss the content of the generalized Blakers-Massey theorem for this modality., Comment: 11 pages

Background: Recently non‐statutory allergy management guidance for schools has been produced in the United Kingdom; however, there has been limited progress in implementing this. The aim of this study was to evaluate the effect of face‐to‐face training on self‐reported school staff preparedness in managing the severely allergic child and whether it would stimulate schools' allergy policy review. Methods: A preparedness survey was conducted prior and 2 months post‐intervention to assess the effect of training on self‐reported preparedness and perceived confidence to manage children with food allergies. Results: A sample of 18 primary schools that consented to participate were selected. Of the trained schools, 89% of the head teachers felt confident in dealing with an allergy emergency compared to 39% prior training (p = 0.016). Post‐intervention all but one had arranged/were considering introducing allergy awareness sessions to help pupils manage their allergies (45% pre‐training vs. post‐training 93%, p = 0.003). Preventative measures for accidental exposure to food allergens (i.e., no food sharing policy) were adopted by all (pre‐training 61% vs. post‐training 100%, p = 0.03). Conclusion: A face‐to‐face school allergy training programme enhances self‐reported staff preparedness and promotes internal allergy policy review in managing the needs of these children, hence addressing the current gap between recommendations and practice in schools.

We prove general adjoint functor theorems for weakly (co)complete $n$-categories. This class of $n$-categories includes the homotopy $n$-categories of (co)complete $\infty$-categories, so these $n$-categories do not admit all small (co)limits in general. We also introduce Brown representability for (homotopy) $n$-categories and prove a Brown representability theorem for localizations of compactly generated $n$-categories. This class of $n$-categories includes the homotopy $n$-categories of presentable $\infty$-categories if $n \geq 2$, and the homotopy $n$-categories of presentable stable $\infty$-categories for any $n \geq 1$., n-GAFT is shown also for n=2; corrected some errors around the proof of Lemma 3.2.9 (Criterion B) and the corresponding examples; other minor improvements in the exposition and some more details. To appear in Documenta Mathematica

Recently non-statutory allergy management guidance for schools has been produced in the United Kingdom however there has been limited progress in implementing this. The aim of this study was to evaluate the effect of face-to-face training on self-reported school staff preparedness in managing the severely allergic child and whether it would stimulate schools’ allergy policy review. A preparedness survey was conducted prior and 2 months post-intervention to assess the effect of training on self-reported preparedness and perceived confidence to manage children with food allergies. A sample of 18 (10%) primary schools that consented to participate were selected. Of the trained schools, 89% felt confident in dealing with an allergy emergency compared to 39% prior training (p=0.016). Post intervention all but one had arranged/were considering introducing allergy awareness sessions to help pupils manage their allergies (45% pre-training vs post-training 93%, p=003). Preventative measures for accidental exposure to food allergens (i.e. no food sharing policy) were adopted by all (pre-training 61% vs post- training 100%, p=0.03). A face-to-face school allergy training programme enhances self-reported staff preparedness and promotes internal allergy policy review in managing the needs of these children, hence addressing the current gap between recommendations and practice in schools.

We consider the topological category of $h$-cobordisms between manifolds with boundary and compare its homotopy type with the standard $h$-cobordism space of a compact smooth manifold., Comment: 23 pages; simplified argument in section 5 and other minor revisions. Final version, to appear in Int. Math. Res. Not

12107 Background: Chemotherapy-induced nausea and vomiting (CINV), a major adverse effect of cancer treatment, can attenuate life quality. Multiple international antiemetic guidelines have recommended a 4-drug regimen (corticosteroid, 5-HT3 receptor antagonist, NK-1 receptor antagonist, and the antipsychotic medication olanzapine) for decreasing highly emetogenic CINV. This raised a question regarding whether antiemetic therapy regimens for highly emetogenic chemotherapy could be de-intensified, decreasing cost and side effects from anti-emetogenic agents. Methods: Study A221602 was developed to compare two olanzapine-containing antiemetic regimens, one with the use of an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Patients (pts) received intravenous highly emetogenic chemotherapy as either 1) cisplatin, given on one day, at a dose of ≥ 70 mg/m2, with or without other chemotherapy agent(s) or 2) doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) on one day. Pts in both arms received 1) a 5-HT3 receptor antagonist (palonosetron 0.25 mg IV or ondansetron 8-16 mg IV or 16-24 mg PO,) on day one, 2) dexamethasone (12 mg PO, day one followed by 8 mg PO, days 2-4), and 3) olanzapine (10 mg/day PO, days 1 to 4). On Day 1, all agents were given prior to chemotherapy, with the exception that olanzapine could be taken prior to chemotherapy or at bedtime. Additionally, pts were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV; 346 pts) or a matching placebo (344 pts). The primary objective was to compare the proportion of patients with no nausea for 5 days following receipt of their chemotherapy between the two study arms. Results: While there was no suggestion of outcome differences on day 1 between the two study arms, fewer pts (7.4%; upper limit of the 95% confidence interval was 13.5%) without NK-1 receptor antagonists were without nausea for the complete 5-day study period. Conclusions: Per the study design, created to exclude a 10% benefit for NK-1 receptor antagonists, the results did not provide sufficient evidence to reject the hypothesis that the 4-drug regimen was superior to the protocol 3-drug regimen (p=0.24). Support: UG1CA189823; Clinical trial information: NCT03578081.

Allergic diseases are on the increase and can affect the child’s well-being. The aim of this survey was to assess regional schools’ preparedness in dealing with anaphylaxis following the publication of national and international guidelines for schools in 2014. The survey was developed in 2015 and distributed to schools in Cumbria, North West England, UK between 2015 and 2016. Only 47% of the respondents (95% CI, 39–57%) felt confident to manage anaphylaxis. Schools without allergic pupils were significantly less likely to have a standard management protocol in place for emergencies compared to those with allergic pupils (p Conclusion: At the time of the survey, schools’ preparedness in the region, did not meet safety standards recommended by national and international organisations. Although schools have shown eagerness in accessing training in the management of anaphylaxis, tailored training for schools is not yet widely available. There is now an urgent need to design feasible training strategies that create a safe environment for allergic pupils across all UK schools. What is Known:• One quarter of the severe allergic reactions take place for the first time while at school with some of them being fatal.• School staff is ill-prepared in the management of anaphylaxis. Access to formal training is not widely available. What is New:• School staff remains unconfident in managing the severe allergic child.Training in the management of anaphylaxis is scarce, and when available, it does not offer the required depth to cover the holistic needs of allergic pupils.• Schools would welcome generic adrenaline autoinjectors and a national policy with central funding which would describe step by step the necessary measures for the management of anaphylaxis.

We define parametrized cobordism categories and study their formal properties as bivariant theories. Bivariant transformations to a strongly excisive bivariant theory give rise to characteristic classes of smooth bundles with strong additivity properties. In the case of cobordisms between manifolds with boundary, we prove that such a bivariant transformation is uniquely determined by its value at the universal disk bundle. This description of bivariant transformations yields a short proof of the Dwyer–Weiss–Williams family index theorem for the parametrized A-theory Euler characteristic of a smooth bundle.

We study a categorical construction called the cobordism category, which associates to each Waldhausen category a simplicial category of cospans. We prove that this construction is homotopy equivalent to Waldhausen's $S_{\bullet}$-construction and therefore it defines a model for Waldhausen $K$-theory. As an example, we discuss this model for $A$-theory and show that the cobordism category of homotopy finite spaces has the homotopy type of Waldhausen's $A(*)$. We also review the canonical map from the cobordism category of manifolds to $A$-theory from this viewpoint., Comment: Final version, to appear in J. Lond. Math. Soc

We give a new proof of an index theorem for fiber bundles of compact topological manifolds due to Dwyer, Weiss, and Williams, which asserts that the parametrized $A$-theory characteristic of such a fiber bundle factors canonically through the assembly map of $A$-theory. Furthermore our main result shows a refinement of this statement by providing such a factorization for an extended $A$-theory characteristic, defined on the parametrized topological cobordism category. The proof uses a convenient framework for bivariant theories and recent results of Gomez-Lopez and Kupers on the homotopy type of the topological cobordism category. We conjecture that this lift of the extended $A$-theory characteristic becomes highly connected as the manifold dimension increases., Comment: 13 pages. Final version; to appear in the Proceedings of the AMS

A d\'evissage-type theorem in algebraic $K$-theory is a statement that identifies the $K$-theory of a Waldhausen category $\mathscr{C}$ in terms of the $K$-theories of a collection of Waldhausen subcategories of $\mathscr{C}$ when a d\'evissage condition about the existence of appropriate finite filtrations is satisfied. We distinguish between d\'evissage theorems of single type and of multiple type, depending on the number of Waldhausen subcategories and their properties. The main representative examples of such theorems are Quillen's original d\'evissage theorem for abelian categories (single type) and Waldhausen's theorem on spherical objects for more general Waldhausen categories (multiple type). In this paper, we study some general aspects of d\'evissage-type theorems and prove a general d\'evissage theorem of single type and a general d\'evissage theorem of multiple type., Comment: minor changes; to appear in Annals of K-theory

Background: Aromatase inhibitors (AIs) are standard treatment for Estrogen Receptor (ER)+ breast cancers in post-menopausal women where the main source of estradiol comes from adipose tissue when the aromatase enzyme converts androgens to estrogens. However, in premenopausal women, functioning ovaries flood the body with estrogens, and aromatase inhibitors used alone offer no therapeutic benefit. In addition to tamoxifen and aromatase inhibitors, estrogen receptor down-regulators, are a third type of anti-estrogen. The first of this class to be FDA approved is Fulvestrant, which acts by promoting the proteosomal degradation of the ER. Like tamoxifen, fulvestrant binds directly to the ER but while tamoxifen has both antagonist and agonist effects on the ER, fulvestrant is a pure antagonist. Other important advantages of fulvestrant over tamoxifen are that 1) fulvestrant prevents the ER from binding DNA, 2) fulvestrant is not linked to increased risk of endometrial cancer, 3) fulvestrant promotes permanent degradation of the ER. The molecular machinery leading to the degradation of the ER in the nucleus following fulvestrant treatment is well described and correlates with its ubiquitination in the nucleus. A less well-recognized mechanism, is fulvestrant’s ability to promote the aggregation of the newly synthesized ER in the cytoplasm. Understanding that protein aggregates are toxic when not eliminated by the proteasome, we took advantage of this effect of fulvestrant to ask whether combining fulvestrant with the proteasome inhibitor Bortezomib could enhance the efficacy of Fulvestrant. Results: We found that bortezomib enhances the aggregation of the ER in the cytoplasm following treatment with fulvestrant. Further, these aggregates were found to be insoluble and to activate the unfolded protein response (UPR), a stress response that leads to cell death. Further, bortezomib is able to prevent the activation of cytoprotective responses linked to the acquisition of fulvestrant resistance. Furthermore, in a breast cancer mouse model of tamoxifen resistance, the combination induced tumor regression. We currently are testing new generation proteasome inhibitors and the results will be presented at the meeting. Conclusion: We conclude that adding bortezomib to fulvestrant enhances its efficacy by taking advantage of a previously poorly recognized mechanism–fulvestrant’s induction of ER aggregation in the cytoplasm. Further, our data suggest that this strategy will block the ability of cells to acquired resistance to fulvestrant. Our group has developed a clinical trial that has tested this combination and the results of this trial presented at the meeting. Citation Format: Doris Germain, Kerin Adelson, George Raptis, Samuel Waxman. Bortezomib enhances the efficacy of fulvestrant by promoting the aggregation of the ER in the cytoplasm [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-08.

We show that every fibrewise map from a Serre microfibration to a Serre fibration is n-connected if it is fibrewise n-connected. This generalises a result of M. Weiss and related results by Bokstedt-Madsen and Galatius-Randal-Williams. We also discuss an application to configuration spaces., OA-Komponente aus Allianzlizenz

B\"okstedt and Madsen defined an infinite loop map from the embedded $d$-dimensional cobordism category of Galatius, Madsen, Tillmann and Weiss to the algebraic $K$-theory of $BO(d)$ in the sense of Waldhausen. The purpose of this paper is to establish two results in relation to this map. The first result is that it extends the universal parametrized $A$-theory Euler characteristic of smooth bundles with compact $d$-dimensional fibers, as defined by Dwyer, Weiss and Williams. The second result is that it actually factors through the canonical unit map $Q(BO(d)_+) \to A(BO(d))$., Comment: 36 pages. This new version contains additional material and various other changes

Tipifarnib (T) is a farnesyl transferase inhibitor (FTI) that enhances the antineoplastic effects of cytotoxic therapy in vitro, has activity in metastatic breast cancer, and enhances the pathologic complete response (pCR) rate to neoadjuvant doxorubicin-cyclophosphamide (AC) chemotherapy. We, therefore, performed a phase I-II trial of T plus neoadjuvant sequential weekly paclitaxel and 2-week AC chemotherapy in locally advanced breast cancer. Eligible patients with HER2-negative clinical stage IIB-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) followed by AC (60/600 mg/m(2) every 2 weeks and filgrastim), plus T (100 or 200 mg PO on days 1-3 of each P dose, and 200 mg PO on days 2-7 of each AC cycle). The trial was powered to detect an improvement in breast pCR rate from 15 to 35 % (α = 0.10, β = 0.10) in two strata, including ER and/or PR-positive, non-inflammatory (stratum A) and inflammatory carcinoma (stratum B). Of the 60 patients accrued, there were no dose-limiting toxicities among the first six patients treated at the first T dose level (100 mg BID; N = 3) or second T dose level (200 mg BID; N = 3) plus paclitaxel. Breast pCR occurred in 6/33 patients (18 %, 95 % confidence intervals (CI) 7-36 %) and 1/22 patients (4 %, 95 % CI 0-8 %) in stratum B. Combination of the FTI T with weekly paclitaxel-AC is unlikely to be associated with a breast pCR rate of 35 % or higher in patients with locally advanced HER2/neu-negative inflammatory or non-inflammatory ER- and/or PR-positive breast carcinoma.

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A—500 mg intramuscular (i.m.) day −14, 1, 15 in cycle 1, and day 1 of additional cycles) or in combination with bortezomib (Arm B—1.6 mg/m2 intravenous (i.v.) on days 1, 8, 15 of each cycle). The study was powered to show an improvement in median progression-free survival (PFS) from 5.4 to 9.0 months and compare PFS rates at 6 and 12 months (α=0.10, β=0.10). Patients with progression on fulvestrant could cross over to the combination (arm C). Although there was no difference in median PFS (2.7 months in both arms), the hazard ratio for PFS in Arm B versus Arm A (referent) was 0.73 (95% confidence interval (CI)=0.49, 1.09, P=0.06, 1-sided log-rank test, significant at the prespecified 1-sided 0.10 α level). At 12 months, the PFS proportion in Arm A and Arm B was 13.6% and 28.1% (P=0.03, 1-sided χ2-test; 95% CI for difference (14.5%)=−0.06, 29.1%). Of 27 patients on arm A who crossed over to the combination (arm C), 5 (18%) were progression-free for at least 24 weeks. Bortezomib likely enhances the effectiveness of fulvestrant in AI-resistant, ER-positive metastatic breast cancer by reducing acquired resistance, supporting additional evaluation of proteasome inhibitors in combination with SERDs. A proteasome inhibitor likely enhances the effectiveness of the breast cancer drug fulvestrant, according to a small, randomized trial. Kerin Adelson, formerly of Mount Sinai and currently of Yale University School of Medicine, led this New York Cancer Consortium, National Cancer Institute-funded randomized phase II trial testing fulvestrant (an estrogen receptor degrader) with or without the addition of bortezomib (a drug that blocks the cellular complexes that break down proteins) in 118 postmenopausal women with a form of hormone receptor-positive metastatic breast cancer that is often treated with fulvestrant. Although the median time before tumors started to grow was similar between the two treatment arms of the study, a significantly larger fraction of patients who received bortezomib were living without tumor growth at 12 months compared to those who received fulvestrant alone. The addition of bortezomib may help delay or reverse resistance to fulvestrant.

Business managers support that decisions based on data analysis are better decisions. Nowadays, in the era of digital information, the accessible information sources are increasing rapidly, especially on the Internet. Also, the most critical information for business decisions is hidden in a large amount of unstructured data. Thus, Big Data analytics has become the cornerstone of modern Business Analytics providing insights for accurate decision making. ERMIS (Extensible pRoduct Monitoring by Indexing Social sources) system is able to aggregate unstructured and semi-structured data from different sources, process them and extracting knowledge by semantically annotating only the useful information. ERMIS Knowledge Base that is created from this process is a tool for supporting business decision making about a product.

Tamoxifen (Tam), the major drug for estrogen receptor (ER)-positive breast cancer, is converted to its active metabolites, Z- and Z′-endoxifen and 4-OH-Tam isomers, primarily by cytochrome P450 CYP2D6. In 117 patients taking 20 mg/day of Tam, we determined CYP2D6 genotypes and measured the plasma levels of Tam metabolites. The Z-endoxifen levels increased while Z′-endoxifen levels decreased with increasing metabolizer phenotype activity (MPA) score (P ≤ 0.0004). The dosage in patients with endoxifen

Breast cancer is the most commonly diagnosed malignancy in women worldwide. It is estimated that 207,090 women were diagnosed with and 39,840 women died of breast cancer in 2010. Surveillance, Epidemiology and End Results data predict that 12% of women born today, or 1 in 8 women, will be diagnosed with breast cancer in their lifetime. Long-term survival rates are closely linked to breast cancer stage at presentation. Sixty percent of women are diagnosed when the cancer is confined to the breast (without lymph node involvement), and these women have an excellent 5-year relative survival of 98%. Thirty-three percent of women with breast cancer present with disease that has spread to local/regional lymph nodes and for this group, 5-year relative survival is 83.6 %. Only 5% of women with breast cancer present with initial metastatic disease, and for this population 5-year relative survival is only 23.4% and close to none are cured of the cancer. 1 Breast cancer can metastasize many years after the initial diagnosis and treatment. Thus, the 5-year relative survival statistics omit recurrences that occur after 5 years, which is more common in women treated with adjuvant chemotherapy, trastuzumab, or hormonal modulation than in most other cancers. Furthermore, most of these relapses are outside the breast, leading to incurable stage IV disease. Despite recent advances in breast cancer therapy and earlier diagnosis with screening, 24% to 30%

In this paper we show an example of two differential graded algebras that have the same derivator K-theory but non-isomorphic Waldhausen K-theory. We also prove that Maltsiniotis's comparison and localization conjectures for derivator K-theory cannot be simultaneously true., 17 pages, in this new version we extend our results to all primes (before we worked with primes greater than three)

This paper studies the category of posets Pos as a model for the homotopy theory of spaces. We prove that: (i) Pos admits a (cofibrantly generated and proper) model structure and the inclusion functor Pos → Cat into Thomason's model category is a right Quillen equivalence, and (ii) there is a proper class of different choices of cofibrations for a model structure on Pos or Cat where the weak equivalences are defined by the nerve functor. We also discuss the homotopy theory of posets from the viewpoint of Alexandroff T0-spaces, and we apply a result of McCord to give a new proof of the classification theorems of Moerdijk and Weiss in the case of posets.

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses.

Purpose Fatigue is one of the most frequently reported and adverse effects of cancer chemotherapy. The present study tested the hypothesis that women's levels of emotional distress at the time of their initial outpatient chemotherapy treatment would predict the severity of their postinfusion fatigue. Methods Sixty stage I (32.6%) and II (67.4%) patients with breast cancer (mean age, 44.5 years) who were receiving standard outpatient chemotherapy participated. The independent variable, emotional distress, was assessed for “last night,” “this morning,” and “right now” with a visual analog scale (0 to 100). The dependent variable, post-treatment fatigue (PTF), was assessed (0 to 100) over each of the subsequent 6 days using end-of-day diaries, which also included assessments of distress and nausea (0 to 100). For the statistical analyses, post-treatment fatigue was divided into three phases with means calculated for days 1 through 2 (phase 1), 3 to 4 (phase 2), and 5 to 6 (phase 3). Results Consistent with the study hypothesis, patients' pretreatment distress level in the clinic was a significant (P < .001) predictor of PTF. There was also a significant (P < .025) interaction with phase, with distress becoming a predictor of PTF after phase 1. Multivariate analysis indicated that prior levels of distress were not independent predictors of PTF. Conclusions This study is the first to demonstrate time-specific effects of pretreatment distress on PTF. Possible mechanisms of these effects now warrant investigation, as do possible benefits of brief interventions to reduce patient distress immediately before treatment.

Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias.Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha.Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported.In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated.Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.

Purpose Aromatase inhibitors (AIs) improve survival in postmenopausal women with hormone-sensitive breast cancer, but can cause joint pain and stiffness. The purpose of the current study was to evaluate the prevalence of and identify risk factors for AI-related joint symptoms. Patients and Methods We performed a cross-sectional survey of consecutive postmenopausal women receiving adjuvant AI therapy for early-stage hormone-sensitive breast cancer at an urban academic breast oncology clinic. Patients completed a 25-item self-administered questionnaire assessing the presence of joint symptoms that started or worsened after initiating AIs. Multivariate regression was used to compare those with AI-related arthralgia with those who did not report symptoms, adjusting for demographic and clinical factors. Results Of 200 patients who completed the survey, 94 (47%) reported having AI-related joint pain and 88 (44%) reported AI-related joint stiffness. In multiple logistic regression analysis, being overweight (body mass index of 25 to 30 kg/m2) and prior tamoxifen therapy were inversely associated with AI-related joint symptoms. Patients who received taxane chemotherapy were more than four times more likely than other patients to have AI-related joint pain and stiffness (odds ratio [OR] = 4.08, 95% CI, 1.58 to 10.57 and OR = 4.76; 95% CI, 1.84 to 12.28, respectively). Conclusion Our study suggests that AI-related joint symptoms are more prevalent than what has been described previously in clinical trials. The success of AI therapy depends on patients' ability to adhere to treatment recommendations; therefore, additional studies of interventions that may alleviate these symptoms are needed.

Fatigue is the most common side effect of chemotherapy for cancer. Not yet explored is the possibility that patients may develop conditioned fatigue responses to clinic cues as a result of the repeated pairing of the clinic environment (conditioned stimulus) with infusions of chemotherapy (unconditioned stimulus) that cause fatigue (unconditioned response). As a first critical test of this possibility, breast cancer patients (N = 82) were studied across their first four cycles of chemotherapy. Consistent with conditioning: (1) fatigue levels in the clinic environment significantly increased with repeated pairings of the clinic environment and chemotherapy administration; (2) fatigue responses in the clinic environment prior to the fourth infusion (CR) were predicted by patients' previous experiences of post-infusion fatigue (UR) above and beyond effects of concurrent emotional distress. These results provide the first evidence in the literature that fatigue can be conditioned. Additional research is warranted to determine the clinical importance of this source of fatigue in chemotherapy patients.

Neo-adjuvant, dose-dense docetaxel, 100 mg/m(2) every 2 weeks x 4 cycles, was administered to 12 patients with locally advance breast cancer (LABC) (10 stage IIIa and three stage IIIb). Eligibility requirements included a PS 0-2, normal hepatic and renal function, and radiologic absence of metastatic disease. Filgrastim [granulocyte colony stimulating factor (G-CSF)] was started 1 day after chemotherapy and was given for 6 days. Complete blood counts were determined weekly. Surgery was planned upon recovery from the last dose of docetaxel and followed by 4 cycles of adjuvant doxorubicin plus cyclophosphamide (AC) and radiotherapy. Patients with ER status received tamoxifen. The median age was 45 (range 34-73) and pre-treatment pathology revealed poorly differentiated infiltrating duct carcinoma in 11 and infiltrating lobular cancer in one, with positive ER/PR status in five. Twelve patients were treated, and all are evaluable for response and toxicity. Nine patients had a major clinical tumor response with five PR and four pathologic complete responses (pCR rate of 33%). Three patients (of whom two with stage IIIb) had progressive disease and went on to receive neo-adjuvant therapy with AC. There was one instance of grade 3 hematologic toxicity (neutropenic fever in one G-CSF non-compliant patient). There were two instances of grade 3 extra-hematologic toxicity: one patient had severe pain and one had treatment-related fatigue. After a median follow-up of 20 months (range 7-49 months) all patients are alive and eight of nine responders remain progression-free. Despite the small size of our study, we believe that dose-dense neo-adjuvant docetaxel is well tolerated and its activity warrants confirmation in a larger number of patients.

The XXVII Annual Chemotherapy Foundation Symposium sponsored by The Mount Sinai School of Medicine is one of the leading forums for communication of important discoveries and new developments in cancer therapeutics. Here, we summarize and review the emerging advances in the treatment of breast cancer, which includes therapeutics in HER signaling, poly(ADP-ribose) polymerase inhibition, PI3K inhibitors and novel epithilones.

A single-arm pilot study explored the feasibility of adapting in Interpersonal Psychotherapy (IPT) by telephone to reduce psychological distress and to enhance coping during cancer treatment. Therapy focuses on role transitions, interpersonal conflicts, and grief precipitated by cancer. Breast cancer patients receiving high-dose chemotherapy received weekly sessions with a psychologist throughout chemotherapy and for 1 month afterwards. Patients could invite one 'partner' to receive individual telephone IPT. Psychosocial functioning was assessed using standardized measures at study entry, after chemotherapy, and following telephone IPT. Accrual and participation supplied evidence of feasibility: 14 patients and 10 partners were recruited, 82.5% of those eligible. Patients had a mean of 16 sessions; partners had a mean of 11. Participants rated their satisfaction with the program between 'good' and 'excellent'. A test of the efficacy of telephone IPT requires a larger, randomized trial. In order to standardize the intervention, a treatment manual was developed. This study indicated the importance of outreach to family members as well as to cancer patients, intensive patient education about oncology treatment and the medical care setting, and psychosocial services that continue after cancer treatment has been completed.

The aim of this phase II study was to characterise the efficacy and toxicity of semisynthetic paclitaxel in patients with metastatic breast cancer. Eligible patients had measurable disease and had been treated with one prior chemotherapy regimen either as adjuvant or for metastatic disease. Semisynthetic paclitaxel was given at a dose of 175mg/m2 over 3 h every 21 days with dexamethasone, cimetidine and diphenhydramine premedications. 31 patients were entered. All were evaluable for toxicity. 30 patients were evaluable for response because 1 patient was lost to follow-up after receiving one cycle. One patient achieved a complete response and 10 patients achieved partial responses for an overall response rate (CR+PR) of 37% (95% confidence interval 20–56%). 17 patients (55%) experienced at least one episode of grade 3 or 4 neutropenia. There were two episodes of febrile neutropenia complicating 155 cycles of therapy. One of these resulted in a treatment-related death in a patient with pulmonary metastasis. 3 patients required dose reductions for grade 3 sensory neuropathy. Our study shows that the antitumour activity and toxic effects of semisynthetic paclitaxel appear to be identical to the naturally occurring product.

The category of simplicial R-coalgebras over a presheaf of commutative unital rings on a small Grothendieck site is endowed with a left proper, simplicial, cofibrantly generated model category structure where the weak equivalences are the local weak equivalences of the underlying simplicial presheaves. This model category is naturally linked to the R-local homotopy theory of simplicial presheaves and the homotopy theory of simplicial R-modules by Quillen adjunctions. We study the comparison with the R-local homotopy category of simplicial presheaves in the special case where R is a presheaf of algebraically closed (or perfect) fields. If R is a presheaf of algebraically closed fields, we show that the R-local homotopy category of simplicial presheaves embeds fully faithfully in the homotopy category of simplicial R-coalgebras., Comment: 24 pages

Objective. The aim of the present study was to explore the relationship between diabetes mellitus type 2, Obsessive-compulsive disorder (OCD) symptomatology and depressive symptomatology with the metabolic profile of diabetic patients. Methods. One hundred and thirty-one diabetic patients were randomly selected. In the first assessment all participants completed the Zung Self Rating Scale (ZUNG) and the Maudsley O-C Inventory Questionnaire (MOCI). After 1 year, diabetic patients that were initially uncontrolled (n = 31) (HbA1c > 7) were re-evaluated by the same psychometric tools. From those 31 patients, 10 had managed to control their metabolic profile. Results. In the first evaluation MOCI and the sub-scale of slowness were statistically related with the diabetic profile (controlled, HbA1c > 7; uncontrolled, HbA1c > 7), with uncontrolled patients scoring significantly higher on the overall MOCI score and the factor of slowness of MOCI scale (P = 0.028). The analysis revealed a positive association between depressive symptomatology (P = 0.004) and obsessive-compulsive disorder symptomatology (P < 0.001) and the metabolic profile of the patients. In the second evaluation the patients that managed to control their metabolic profile scored lower in both ZDRS and MOCI, although these differences in scores failed to reach significance levels were indicative of a tendency. Conclusions. The present results provide initial evidence that diabetes mellitus type 2 is associated with obsessive-compulsive disorder symptomatology and depressive symptomatology.

5-azacytidine (5-AZA) and carboplatin (CBDCA) are two agents which have demonstrated antileukemic activity in a number of phase I-II trials. Their mechanisms of action and pharmacology related to cell resistance suggested suitability for combination therapy. The aim of this pilot study was to evaluate the effects of this combination in the treatment of patients with relapsed/refractory acute leukemia. A total of 21 patients was enrolled. 5-azacytidine, at doses ranging from 50–150 mg/m2/day, was administered as a 2-hr infusion for 5 consecutive days. On day 3, patients began a 5-day course of CBDCA given as a 24-hr continuous intravenous infusion of 250 mg/m2/day. There were no complete remissions with this regimen. Although there were three partial responses, these were generally of short duration. Nonhematologic toxicities were mild. No correlation was seen between response and serum platinum levels. These results demonstrate that the 5-AZA/CBDCA combination is ineffective therapy for heavily pretreated patients with acute leukemia. © 1996 Wiley-Liss, Inc.

It is well known that breast pathology is one of the areas within surgical pathology that often yields differences of opinion. This may in part be a result of the numerous factors that now need to be routinely analyzed in patients with breast lesions. As other fields of medicine have become increasingly subspecialized, so too has surgical pathology, and there is an increasing trend toward subspecialty diagnosis of surgical pathology cases in academic settings; that is, breast cancer cases are often signed out only by pathologists with expertise in breast pathology. However, this arrangement is not feasible in all academic centers, let alone community hospitals. Because of the sheer volume of breast surgery and the prevalence of breast cancer, it is not feasible to relegate all breast pathology interpretation to subspecialists. Therefore, second opinions may become critical for a significant number of patients. In fact, many medical centers require (and, we believe, rightly so) pathology review of outside material before surgery. In the article that accompanies this editorial, Kennecke et al examine the impact of routine second-opinion breast pathology review in a group of patients with breast cancer for whom a change in diagnosis would likely impact treatment. Some changes in pathology were not surprising. For example, it is known that histologic grade is among the parameters most discrepant when viewed by multiple pathologists. Nodal and margin status changes are less expected, however, particularly the former. It is surprising that of the 15 upstages from node negative, six were to N1, not just N0 (i ); these upstages occurred, for the most part, without the use of immunohistochemical stains. These patients alone should serve as a wake-up call for treating physicians that certain diagnoses in breast pathology are intrinsically more difficult, occasionally subtle, and prone to differences of opinion. As the authors additionally point out, the use of molecular testing such as Oncotype DX (Genomic Health, Redwood City, CA) has been used adjunctively to complement accurate histologic interpretation; that is, as a way of leveling the playing field vis-a-vis grading and subtyping of invasive carcinoma. Clearly, however, as this study shows, use of such testing is not enough. Parameters such as node status, lymphatic invasion, and margins are not directly measured by such tests, and therefore these sorts of discrepancies would not be accounted for by different test values, yet they remain influential to treatment decisions. In most institutions, negative margins are a requisite for deciding when to proceed with the radiation therapy phase of breast cancer treatment. It is disturbing, but not surprising, that eleven of the twelve cases that involved margin changes were from negative to positive. Depending on individual circumstances, in some practices this might require the patient to be referred back to the surgeon for reexcision. Two patients in the study who were initially diagnosed with invasion were found, on review, to only have ductal carcinoma in situ. As these patients and some of the margin data begin to indicate, discrepancies can go in either direction. In fact, not all initially reported patients with node-positive disease are truly node positive. One of us (I.J.B.) previously reported in Journal of Clinical Oncology a series of patients whose sentinel lymph nodes contained benign epithelial cells that were physiologically transported as a result of biopsyinduced displacement. We subsequently received numerous cases for second opinion in which the nodal status was unexpected, given the pathologic features of the primary tumor. Some of the cases were truly node positive and some were not; however, the reasons for the discrepancies were variable. The study by Kennecke et al specifically selected patients who were initially node negative, not node positive, but such diagnostic issues exist for a certain number of patients with nodepositive disease, as well, with equally important clinical implications. The practice of surgical pathology of the breast is not limited to cancer risk, typing, and prognostication. Pathologists routinely evaluate benign entities that constitute risk factors, such as atypical duct hyperplasia, lobular neoplasia, intraductal papilloma, and radial scar, to name a few. Differences of diagnostic opinion abound for such lesions, perhaps even more so than when grading invasive ductal carcinoma. So, too, have medical oncologists branched out. Management of risk with antihormonal therapy is, for the most part, in the domain of the medical oncologist. Therefore, proper pathologic classification has clinical oncologic implications even in patients without carcinoma. Clearly this study by Kennecke et al has a direct implication for patient care. A correct diagnosis may determine the use of effective treatment (or show particular treatments to be unnecessary), whereas an incorrect diagnosis may lead to treatment-related adverse effects without known benefit. Yet the study by Kennecke et al does not go far enough. Central routine review of a targeted subset of patients with breast cancer in a relatively controlled, closed system of health care is a laudable effort, even if incomplete. Without specifically addressing the JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 18 JUNE 2

Multiple cycles of high-dose chemotherapy can be hematologically supported by repeated administration of peripheral blood progenitors obtained after mobilization using cytokine alone or in combination with chemotherapy. We have explored the quality of such cells and their potential to undergo ex vivo expansion. Twenty-five leukapheresis samples from 19 patients who had received extensive prior chemotherapy for stage IV breast cancer were subjected to CD34+ cell selection using immunoaffinity columns of immunomagnetic bead separation. Cells were cultured in suspension in the presence of c-kit ligand, interleukin-3, interleukin-6, erythropoietin, and granulocyte colony-stimulating factor. Ten experiments were performed using weekly exchange of media and cytokines (Delta assay). Median myeloid and erythroid progenitors expanded 15-fold at 7 days (range, 7 to 43), 40-fold at 14 days (range, 18 to 470), 46-fold at 21 days (range, 0 to 118), and 21-fold at 28 days (range, 0 to 61). In a system using gas-permeable bags without exchange of media or cytokine, median progenitors expanded 13-fold at 7 days (range, 7 to 36), 14-fold at 10 days (range, 4 to 61), 14-fold at 12 days (range, 3 to 46), and 10-fold at 14 days (range, 1 to 35). Progenitor expansion less than 10-fold occurred in 8% of experiments at day 7, in 17% at day 10, in 43% at day 12, and in 50% at day 14. When autologous plasma, autologous plasma processed (removal of cryoprecipitate, centrifugation, then filtration), or human serum were substituted for 20% fetal calf serum, the ratio of progenitor expansion at 7 days relative to 20% fetal calf serum for 10% human serum, 20% human serum, and 1% autologous plasma processed was 1.01 (range, 0.62 to 1.33), 0.88 (range, 0.61 to 1.20), and 0.96 (range, 0.55 to 1.64), respectively. These findings support the feasibility of ex vivo expansion in a system free of nonhuman proteins of CD34(+)-derived progenitors obtained from the peripheral blood of patients who have received prior chemotherapy.

Background: Adiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes. We aimed to determine adiponectin levels and expression of its receptors (AdipoR1 and AdipoR2) in peripheral monocytes from overweight and obese patients with coronary artery disease (CAD). Methods: Fifty-five overweight/obese patients, suspected for CAD, underwent coronary angiography: 31 were classified as CAD patients (stenosis >= 50% in at least one main vessel) and 24 as nonCAD. Quantitative RT-PCR and flow cytometry were used for determining mRNA and protein surface expression of adiponectin receptors in peripheral monocytes. A high sensitivity multiplex assay (xMAP technology) was used for the determination of plasma adiponectin and interleukin-10 (IL-10) secreted levels. Results: Plasma adiponectin levels were decreased in CAD compared to nonCAD patients (10.9 +/- 3.1 vs. 13.8 +/- 5.8 mu g/ml respectively, p = 0.033). In multivariable analysis, Matsuda index was the sole independent determinant of adiponectin levels. AdipoR1 and AdipoR2 protein levels were decreased in monocytes from CAD compared to nonCAD patients (59.5 +/- 24.9 vs. 80 +/- 46 and 70.7 +/- 39 vs. 95.6 +/- 47.8 Mean Fluorescence Intensity Arbitrary Units respectively, p < 0.05). No significant differences were observed concerning the mRNA levels of the adiponectin receptors between CAD and nonCAD patients. AdipoR2 protein levels were positively correlated with plasma adiponectin and Matsuda index (r = 0.36 and 0.31 respectively, p < 0.05 for both). Furthermore, basal as well as adiponectin-induced IL-10 release was reduced in monocyte-derived macrophages from CAD compared to nonCAD subjects. Conclusions: Overweight patients with CAD compared to those without CAD, had decreased plasma adiponectin levels, as well as decreased surface expression of adiponectin receptors in peripheral monocytes. This fact together with the reduced adiponectin-induced IL-10 secretion from CAD macrophages could explain to a certain extent, an impaired atheroprotective action of adiponectin.