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Purpose Discordance in human epidermal growth factor receptor 2 (HER2) status between primary tumor and metastases might have important implications for treatment response and therapy decisions. Here, we evaluate both the frequency of circulating tumor cells (CTCs) and the factors predicting HER2 discordance between primary tumor and CTCs as a potential surrogate for tumor biology and tumor heterogeneity in patients with metastatic breast cancer. Patients and Methods The number of CTCs in 7.5 mL of peripheral blood and HER2 status were evaluated in 1,123 women with HER2-negative metastatic breast cancer. HER2 discordance was defined as the presence of at least one CTC with a strong immunocytochemical HER2 staining intensity. Factors predicting discordance in HER2 phenotype were assessed using multivariable logistic regression. Results Overall, 711 (63.3%) of 1,123 screened patients were positive for CTCs (≥ one CTC). Discordance in HER2 phenotype between primary tumor and CTCs was observed in 134 patients (18.8%) and was significantly associated with histologic type (lobular v ductal; odds ratio [OR], 2.67; 95% CI, 1.63 to 4.39; P < .001), hormone receptor status (positive v negative; OR, 2.84; 95% CI, 1.15 to 7.02; P = .024), and CTC number (≥ five v one to four; OR, 7.64; 95% CI, 3.97 to 14.72; P < .001). Conclusion HER2 discordance between primary tumor and CTCs was observed in 18.8% of patients and was associated with histologic type, hormone receptor status of the primary tumor, and CTC number. The clinical utility of CTCs as liquid biopsy to assess tumor heterogeneity of metastatic disease and guide treatment decisions must be evaluated in prospective randomized trials.

Background: The analysis of liquid biopsies, e.g., circulating tumor cells (CTCs) is an appealing diagnostic concept for targeted therapy selection. In this proof‐of‐concept study, we aimed to perform multiparametric analyses of CTCs to select targeted therapies for metastatic breast cancer patients. Methods: First, CTCs of five metastatic breast cancer patients were analyzed by whole exome sequencing (WES). Based on the results, one patient was selected and monitored by longitudinal and multiparametric liquid biopsy analyses over more than three years, including WES, RNA profiling, and in vitro drug testing of CTCs. Results: Mutations addressable by targeted therapies were detected in all patients, including mutations that were not detected in biopsies of the primary tumor. For the index patient, the clonal evolution of the tumor cells was retraced and resistance mechanisms were identified. The AKT1 E17K mutation was uncovered as the driver of the metastatic process. Drug testing on the patient’s CTCs confirmed the efficacy of drugs targeting the AKT1 pathway. During a targeted therapy chosen based on the CTC characterization and including the mTOR inhibitor everolimus, CTC numbers dropped by 97.3% and the disease remained stable as determined by computer tomography/magnetic resonance imaging. Conclusion: These results illustrate the strength of a multiparametric CTC analysis to choose and validate targeted therapies to optimize cancer treatment in the future. Furthermore, from a scientific point of view, such studies promote the understanding of the biology of CTCs during different treatment regimens., Cancers, 13 (23), ISSN:2072-6694

Introduction Invasive breast cancer with neuroendocrine differentiation is a rare subtype of breast malignancy. Due to frequent changes in the definition of these lesions, the correct diagnosis, estimation of exact prevalence, and clinical behaviour of this entity may be challenging. The aim of this study was to evaluate the prevalence, clinical features, and outcomes in a large cohort of patients with breast cancer with neuroendocrine differentiation. Patients Twenty-seven cases of breast cancer with neuroendocrine differentiation have been included in this analysis. Twenty-one cases were identified by systematic immunohistochemical re-evaluation of 465 breast cancer specimens using the neuroendocrine markers chromogranin A and synaptophysin, resulting in a prevalence of 4.5%. A further six cases were identified by a review of clinical records. Results Median age at the time of diagnosis was 61 years. 70% of patients had T2 – 4 tumors and 37% were node-positive. The most common immunohistochemical subtype was HR-positive/HER2-negative (85%). 93% were positive for synaptophysin and 48% for chromogranin A. Somatostatin receptor type 2A status was positive in 12 of 24 analyzed tumors (50%). Neuroendocrine-specific treatment with somatostatin analogues was administered in two patients. The 5-year survival rate was 70%. Conclusions Breast cancer with neuroendocrine differentiation is mostly HR-positive/HER2-negative and the diagnosis is made at a higher TNM stage than in patients with conventional invasive breast carcinoma. Moreover, breast cancer with neuroendocrine differentiation was found to be associated with impaired prognosis in several retrospective trials. Due to somatostatin receptor 2A expression, somatostatin receptor-based imaging can be used and somatostatin receptor-targeted therapy can be offered in selected cases.

Background Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. Methods The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). Results Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). Conclusions The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings.

Background HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. Methods The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. Results 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1–1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. Conclusion This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.

Chronic pain conditions are the top reason patients seek care, the most common reason for disability and addiction, and the biggest driver of healthcare costs; their treatment costs more than cancer, heart disease, dementia, and diabetes care. The personal impact in terms of suffering, disability, depression, suicide, and other problems is incalculable. There has been much effort to prevent many medical and dental conditions, but little effort has been directed toward preventing chronic pain. To address this deficit, a massive open online course (MOOC) was developed for students and healthcare professionals. "Preventing Chronic Pain: A Human Systems Approach" was offered by the University of Minnesota through the online platform Coursera. The first offering of this free open course was in the spring of 2014 and had 23 650 participants; 53% were patients or consumers interested in pain. This article describes the course concepts in preventing chronic pain, the analytic data from course participants, and postcourse evaluation forms.慢性疼痛疾病是寻求医疗护理的 第一大原因、残疾和成瘾的最常 见原因，以及推动医疗护理成本 升高的最大原因，且慢性疼痛疾 病 治 疗 的 费 用 多 于 癌 症 、 心 脏 病、老年痴呆症和糖尿病。但无 法 计 算 患 病 的 痛 苦 、 残 疾 、 抑 郁、自杀和其他问题对人产生的 影响。为预防许多医学和牙科疾 病，我们已作出了许多努力，但 直接针对预防慢性疼痛的努力仍 很少。为弥补此不足，我们为学 生和医疗保健专业人员开展了一 项大型网络公开课 (MOOC)。明尼 苏达大学通过 www.Coursera.org 提供了“预防慢性疼痛：一种人 类系统法”公开课。此免费公开 课于 2014 年春天首次开播，有 23650 人参加学习；其中 53% 的 参加者是患者或关注疼痛治疗的 消费者。本文描述了预防慢性疼 痛的课程理念、课程参与者的分 析数据和课后评价表。.Las afecciones de dolor crónico son el principal motivo de búsqueda de asistencia sanitaria, la causa más frecuente de discapacidad y toxicomanía, y el factor generador de costos sanitarios más importante, con un coste mayor al generado por el cáncer, la cardiopatía, la demencia y la diabetes. Las repercusiones en cuanto a sufrimiento, discapacidad, depresión, suicidio y otros problemas son incalculables. Se han consagrado grandes esfuerzos a la prevención de muchas enfermedades médicas y dentales, pero no se han dirigido los suficientes hacia la prevención del dolor crónico. Para hacer frente a este déficit, se ha desarrollado un curso en línea masivo y abierto (massive open online course, MOOC) para estudiantes y profesionales sanitarios. La Universidad de Minnesota ofreció el curso “Prevención del dolor crónico: enfoque de un sistema humanista” a través del sitio www.Coursera.org. La primera oferta de este curso abierto y gratuito se hizo en primavera de 2014 y acogió a 23 650 participantes; de los cuales un 53 % eran pacientes o clientes interesados en el dolor. En este artículo se describen los conceptos del curso en la prevención del dolor crónico, los datos analíticos de los participantes y los formularios de evaluación posteriores al curso.

Introduction: Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. Methods: This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI)

Decisions on the type of adjuvant treatment in older breast cancer patients are challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty on the basis of studies usually excluding patients over 69 years. To aid this decision, we analyzed a database of 6000 unselected patients and of those evaluated elderly primary breast cancer patients with hormone receptor-negative tumors from 1963 until 2003 in respect of survival data depending on adjuvant treatment. A total of 131 elderly (i.e., >65 years) patients were observed retrospectively for a median of 72 months. Patients received breast-conserving therapy or mastectomy and adjuvant radiotherapy, chemotherapy, and endocrine therapy. Data were collected from a hospital-intern database. Median age at diagnosis was 72 years. Mostly, tumors were small (81 % T1, 17 % T2) but of unfavorable grading (40 % G2, 35 % G3). Lymph nodes were positive in 42 %. Mastectomy was performed in 65 %. While 42 % of patients received radiotherapy, only 10 % were treated with chemotherapy. Patients with G2 and G3 tumors (p = 0.027), younger women (p = 0.012), and patients with positive lymph node status (p

Myofascial trigger point pain is an extremely prevalent cause of persistent pain disorders in all parts of the body, not just the head, neck, and face. Features include deep aching pain in any structure, referred from focally tender points in taut bands of skeletal muscle (the trigger points). Diagnosis depends on accurate palpation with 2-4 kg/cm2 of pressure for 10 to 20 seconds over the suspected trigger point to allow the referred pain pattern to develop. In the head and neck region, cervical muscle trigger points (key trigger points) often incite and perpetuate trigger points (satellite trigger points) and referred pain from masticatory muscles. Management requires identification and control of as many perpetuating factors as possible (posture, body mechanics, psychological stress or depression, poor sleep or nutrition). Trigger point therapies such as spray and stretch or trigger point injections are best used as adjunctive therapy.

Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare.Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC.Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P=0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P<0.001).Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.

Orofacial Pain Dentistry is concerned with the prevention, evaluation, diagnosis, treatment, and management of persistent and recurrent orofacial pain disorders. The American Dental Association, through the Commission on Dental Accreditation (CODA), now recognizes Orofacial Pain as an area of advanced education in Dentistry. It is mandated by CODA that postgraduate orofacial pain programs be designed to provide advanced knowledge and skills beyond those of the standard curriculum leading to the DDS or DMD degrees. Postgraduate programs in orofacial pain must include specific curricular content to comply with CODA standards. The intent of CODA standards is to assure that training programs develop specific educational goals and objectives that describe the student/resident’s expected knowledge and skills upon successful completion of the program. A standardized core curriculum, required for accreditation of dental orofacial pain training programs, has now been adopted.Among the various topics mandated in the curriculum are pharmacology and, specifically, pharmacotherapeutics. The American Academy of Orofacial Pain (AAOP) recommends, and the American Board of Orofacial Pain (ABOP) requires, that the minimally competent orofacial pain dentist* be knowledgeable in the management of orofacial pain conditions using medications when indicated. Basic knowledge of the appropriate use of pharmacotherapeutics is essential for the orofacial pain dentist and, therefore, constitutes part of the examination specifications of the ABOP. The minimally competent orofacial pain clinician must demonstrate knowledge, diagnostic skills, and treatment expertise in many areas, such as musculoskeletal, neurovascular, and neuropathic pain syndromes; sleep disorders related to orofacial pain; orofacial dystonias; and intraoral, intracranial, extracranial, and systemic disorders that cause orofacial pain or dysfunction. The orofacial pain dentist has the responsibility to diagnose and treat patients in pain that is often chronic, multifactorial, and complex. Failure to understand pain mechanisms can lead to inaccurate diagnoses and ineffective, delayed, or harmful treatment. It is the responsibility of the orofacial pain dentist to accurately diagnose the cause(s) of the pain and decide if treatment should be dentally, medically, or psychologically oriented, or if optimal management requires a combination of all three treatment approaches. Management may consist of a number of interdisciplinary modalities including, eg, physical medicine, behavioral medicine, and pharmacology or, in rare instances, surgical interventions. Among the essential armamentarium is the knowledge and proper use of pharmacologic agents.

e11615 Background: Recent data indicate that persisting CTCs after chemotherapy are associated with poor prognosis. (Rack et al. JNCI 2014) CTC profiling for establishing new treatment strategies, like targeted approaches against CTCs, are important. Accurate phenotypic assessment is crucial, so this study aims to test the suitability of the BioMarQ System (BMS)(Janssen Diagnostics, LLC), a research use only enhancement of the FDA-cleared CellSearch System (CSS)(Janssen Diagnostics, LLC) for simultaneous CTC enumeration and HER2 assessment based on automatically generated fluorescence and cell morphology data. Methods: Data on HER2 status of CTCs were obtained by visual assessment after immunocytochemical staining for HER2 with the CSS. Overall 290 CTCs were isolated from the blood of a metastatic breast cancer patient and classified either HER2 positive or HER2 negative by immunocytochemical staining combining visual inspection (CSS) and automatic assessment (BMS). A discriminant analysis was performed t...

1010 Background: Gemcitabine (G) has shown to have a relevant single agent efficacy and to improve chemotherapy response to taxanes in advanced BC patients. Aim of this study was to evaluate the ef...

TPS11132 Background: Although the prognostic value of CTC enumeration in metastatic breast cancer (MBC) is well understood, the value of taking into account the molecular characteristics of CTCs in...

11042 Background: Recent studies revealed that temporal changes in circulating tumor cells (CTC) prevalence assessed before and immediately after adjuvant chemotherapy (CT) might indicate treatment response in early breast cancer (EBC). However, there is limited knowledge on CTC status one or more years after chemotherapy treatment. Here we present descriptive data on CTC status prospectively evaluated 2 and 5 years after primary diagnosis in the German SUCCESS A study. Methods: The SUCCESS A trial is a large, randomized, open-label, 2x2 factorial design Phase III study comparing disease free survival (DFS) in patients with EBC treated with 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide (FEC) followed by either 3 cycles of Docetaxel (D) or 3 cycles of Gemcitabine-Docetaxel (DG), and comparing DFS in patients treated with 2 years or 5 years of Zoledronate. CTC status at various time points was assessed using the FDA-approved CellSearch System (Veridex, USA). Results: Data on CTC status both at 2 years and at 5 years after primary diagnosis were available for 983 (26.2%) out of 3754 randomized patients. After 2 and 5 years, CTCs were found in 132 (13.4%; median 1; range 1 – 99) and 88 (9.0%; median 1; range 1 – 60) patients, respectively. The majority of patients (n = 779; 79.2%) had no CTCs at any of the two time points. CTCs were found at 2 years but not at 5 years after primary diagnosis in 116 (11.8%) patients, at 5 years but not at 2 years of follow-up in 72 (7.3%) patients, and both at 2 and at 5 years of follow-up in 16 (1.6%) patients. Conclusions: CTCs in peripheral blood were detected in a subset of early breast cancer patients without relapse up to five years after primary diagnosis. These CTCs may indicate the presence of occult “dormant” micrometastases.

e22059 Background: The goal of this study was to evaluate both ER- and HER2-status on DTCs in the bone marrow of patients with early BC and to compare these with the corresponding PT. In case of discordant expression, DTCs might help in properly selecting targeted therapy according to their phenotype. Methods: Bone marrow (BM) samples were obtained from early BC patients at the time of first breast surgery (years 2006 to 2009). Two cytospins with 106 BM cells were prepared after Ficoll enrichment for mononuclear cells. We were able to determine the presence of DTCs (cytokeratin (CK)+cells) in a total of 58 patients. Simultaneously ER- and HER2-expressions were analyzed by immunocytochemistry using a triple fluorescence staining method. Briefly, antibodies (AB) directed against human ER (secondly labeled with Cy3, red), HER2 (DyLight488, blue) and CK (Coumarin-AMCA, green) were used. The manual analysis was conducted using a computerized fluorescence microscope (Axioskop, Zeiss, Germany). Criteria for CK-positivity and HER2-overexpression were the ring-like appearance of the respective membrane-staining and for ER-expression a nuclear staining. Data on ER- and HER2-status of the PT were available for all 58 and 54 of the patients respectively. Results: The median number of DTCs detected was 12 (range 1-95; total number of DTCs 1132). 41 (71%) of the patients had at least one ER+ DTC, 25 (43%) at least one HER2+ DTC, 15 (26%) at least one ER+/HER2+ DTC and 13 (22%) had DTCs neither expressing ER nor HER2. The concordance rate between ER-status on DTCs and PT was 74%. 6 (43%) patients with ER- PT had ER+ DTCs. The concordance rate between HER2-status on DTCs and PT was 52% and 22 (46%) patients with HER2- PT had HER2+DTCs. Seven out of 10 patients with a triple-negative PT had at least one DTC positive for ER, HER2, or both. Conclusions: Our study confirms that the ER- and/or HER2-status on DTCs might differ compared to the PT. This discordance, which we demonstrated at the protein level, could be especially important for patients with a triple-negative PT and ER+ or HER2+ DTCs, since they might respond favorably to an endocrine or HER2-targeted therapy.

11043 Background: The discordance between HER2-expression on circulating tumor cells (CTC) in peripheral blood and the primary tumor has already been shown by our study group for early breast cancer patients with HER2-positive tumors. Here, we compare the results to CTC prevalence and HER2-status of CTC after adjuvant chemotherapy. Methods: The SUCCESS B trial compares FEC-Docetaxel vs. FEC-Docetaxel-Gemcitabine and HER2-targeted therapy as adjuvant treatment for patients with early, HER2-positive, node positive or high risk node negative primary breast cancer. We prospectively analyzed 23ml peripheral blood before and after chemotherapy. CTC and HER2-status were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK 8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for HER2-phenotyping. Cutoff for CTC positivity was ≥ 1 CTC. HER-positivity of CTC was assigned if at least one CTC showed strong HER2 staining (3+). Results: CTCs and their HER2-status both before and after chemotherapy were available for 392 patients. In 179 (45.7%) patients no CTC were detected before and after chemotherapy. CTC status changed from positive before to negative after chemotherapy in 104 (26.5%) patients and from negative before to positive after chemotherapy in 69 (17.6%) patients, while 40 (10.2%) patients had a consistently positive CTC status. Patients were significantly more likely to change their CTC status from positive to negative than from negative to positive (p = 0.01). Of the 40 patients with CTC both before and after chemotherapy, 14 (35%) patients had HER2-positive CTC before and after therapy, and 9 (22%) patients had HER2-negative CTC at both time points. 7 (18%) patients had HER2-positive CTC before but not after chemotherapy, while 10 (25%) patients showed the reverse pattern (p = 0.63). Conclusions: Cytotoxic treatment does not seem to influence the HER2-status on CTC. Follow-up data within the Success B trial will analyze the relevance of the HER2-expression of CTC to predict the efficacy of targeted treatment.

e22075 Background: Prevalence of CTCs after adjuvant chemotherapy in patients with EBC might indicate both treatment response and prognosis. Here we present data on CTC prevalence and quantity assessed after chemotherapy in correlation with tumor characteristics and chemotherapeutic treatment in patients with Her2-negative EBC from the German SUCCESS C study. Methods: The SUCCESS C trial is a randomized, open-label, Phase III study comparing disease free survival (DFS) in patients with HER2-negative EBC treated with either 3 cycles of Epirubicin-Fluorouracil-Cyclophosphamide(FEC) followed by 3 cycles of Docetaxel(DOC), or 6 cycles of a anthracycline-free regimen with Docetaxel-Cyclophosphamide(DOC-C). The CTC status at chemotherapy cycle 6 was prospectively evaluated using the FDA-approved CellSearch System (Veridex, USA). Results: Valid data on CTC status after chemotherapy were available for 2,336 patients (78% estrogen receptor positive, 6% pT3 or pT4, 12% pN2 or pN3). CTCs were found in 278 (11.9%) patients (median 1, range 1 – 69 CTCs). One CTC was detected in 164 (59%), two CTCs in 57 (21%), three to five CTCs in 45 (16%), and more than five CTCs in 12 (4%) of these patients. CTC prevalence was not significantly associated with tumor size (pT1, pT2, pT3, pT4), nodal stage (pN0, pN+), grading (G1, G2, G3), histological type (invasive ductal, invasive lobular, other), estrogen receptor status, progesterone receptor status, or treatment arm (FEC-DOC, DOC-C), as revealed by both univariate analyses (Chi-square tests, all p > 0.1) and a logistic regression with CTC prevalence as dependent variable. Conclusions: In about 12% of patients with Her2-negative EBC, CTCs in the peripheral blood were detected at the end of adjuvant chemotherapy treatment. However, neither CTC prevalence nor quantity of CTCs were related to tumor characteristics or type of chemotherapeutic regimen. The low rate of CTC-positive patients might be attributed to the negative HER2 status and reflects therefore the relatively low risk of these patients to develop metastatic relaps. Clinical trial information: NCT00847444.

Three studies are presented demonstrating the reliability of the pressure algometer as an index of myofascial trigger point sensitivity. The first study showed high reliability between and within experimenters when measuring marked trigger point locations. In study 2, significant between experimenter reliability in locating and measuring the same unmarked trigger point locations was shown, while study 3 supported the idea that trigger points are discrete points of focal tenderness within the muscle. The ability to quantify and reliably measure trigger point sensitivity opens the door to a range of clinical and research possibilities for myofascial and related musculoskeletal pain problems.

SYNOPSIS The response of 25 chronic myofascial head and neck pain patients to a systematic musculoskeletal rehabilitation program was examined. The program emphasized the acquisition of self-management skills through a highly structured interdisciplinary format. Physical and cognitive behavioral therapies were aimed at reducing factors which perpetuate myofascial pain. Results immediately following treatment, and at three, six and twelvemonths post-treatment when compared to pretreatment scores, showed highly reliable reductions in self-reports of pain and medication intake.

In order to determine the relationship between trigger point sensitivity and the referred symptoms of myofascial pain, VAS ratings of referred pain intensity and pressure algometer measures of myofascial trigger point sensitivity were taken pre and post treatment of the muscle containing the trigger point with passive stretch. The results in 20 subjects, experiencing unilateral or bilateral myofascial head and neck pain, showed that myofascial trigger point sensitivity decreases in response to passive stretch as assessed by the pressure algometer, and that trigger point sensitivity and intensity of referred pain are related.

• Reflex sympathetic dystrophy of the face is an infrequently reported cause of chronic facial pain. We report the cases of two patients who were diagnosed and treated by sympathetic blockade of the stellate ganglion. Pathophysiologic mechanisms and rationale for treatment are discussed.

Memory for the intensity of past physical pain depends critically on the intensity of present pain. When their present pain intensity was high, patients with chronic headaches of myofascial origin rated their maximum, usual, and minimum levels of prior pain as being more severe than their hourly pain diaries indicated. When their present pain intensity was low, the same patients remembered all 3 levels of prior pain as being less severe than they actually had been. The results show that pain produces systematic distortions of memory similar to those associated with alterations of affect or mood, and suggest a resolution to a conspicuous conflict in the current pain literature.

Three case presentations illustrate that the clinical signs and symptoms of occipital neuralgia may be produced by myofascial pain. Assessment of myofascial trigger points is needed before making a diagnosis of occipital neuralgia. Myofascial trigger points can be effectively treated with minimally invasive procedures, thereby avoiding irreversible surgical interventions.

Background Women undergoing elective caesarean section experience anxiety. However, course, extent and duration of anxiety have not been investigated yet. This study aimed to explore anxiety levels during the course of the day of surgery by employing and comparing subjective as well as objective measures. By examining their correlation it is intended to give methodological support for interventional studies. Methods This is a monocentric, prospectively planned study in which 47 women with an indication for primary caesarean section took part. Anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI-trait and STAI-state), the visual analogue scale for anxiety (VASA) as well as saliva cortisol at three time points on the day of the caesarean section (at admission, at skin closure and 2 h post surgery). Results Peak anxiety levels for the STAI-state and VASA were highest at admission and showed significant decreases to skin closure (p