Predictive value of neutrophil-to-lymphocyte-ratio in neoadjuvant-treated patients with breast cancer.

PURPOSE: Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC. METHODS: A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003-2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes. RESULTS: A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043). CONCLUSION: NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC.

HER2-targeted therapy influences CTC status in metastatic breast cancer.

PURPOSE: As an independent, negative-prognostic biomarker for progression-free survival (PFS) and overall survival (OS), circulating tumor cells (CTCs) constitute a promising component for developing a liquid biopsy for patients with metastatic breast cancer (MBC). The effects of HER2-targeted therapy such as trastuzumab, pertuzumab, T-DM1, and lapatinib on CTC status and longitudinal enumeration were assessed in this trial. METHODS: CTC status of 264 patients with MBC was analyzed prior to and after 4 weeks of a new line of palliative systemic therapy. CTCs were assessed using CellSearch®. Three groups were compared: patients with HER2-positive MBC receiving ongoing HER2-targeted therapy (n = 28), patients with de novo HER2-positive MBC and no HER2-targeted therapy in the last 12 months prior to enrollment and start of HER2-targeted therapy (n = 15), and patients with HER2-nonamplified disease and no HER2-targeted therapy (n = 212). RESULTS: Positive CTC status (≥ 5 CTC/7.5 ml blood) at enrollment was observed in the 3 groups for 17.9, 46.7, and 46.2% (p = 0.02) of patients, respectively. At least one CTC/7.5 ml was seen in 28.6, 53.3, and 67.0% (p < 0.001) of these patients. Furthermore, 3.6, 40.0, and 3.3% (p < 0.001) of the patients had at least one HER2-positive CTC. After 4 weeks of therapy 7.1, 0.0, and 31.1% (p = 0.001) of patients had still a positive CTC status (≥ 5 CTC/7.5 ml blood). At least one CTC/7.5 ml was still observed in 25.0, 20.0, and 50.5% (p = 0.004) of the patients. Furthermore, 7.1, 0.0, and 1.9% (p = 0.187) had at least one HER2-positive CTC. After 3 months of therapy, 35.7, 20.0, and 28.3% (p = 0.536) showed disease progression. CONCLUSIONS: HER2-targeted therapy seems to reduce the overall CTC count in patients with MBC. This should be taken into account when CTC status is used as an indicator for aggressive or indolent metastatic tumor disease.

Estrogen, progesterone, and human epidermal growth factor receptor 2 discordance between primary and metastatic breast cancer.

BACKGROUND: The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses are frequently discordant between the primary tumor and metastatic lesions in metastatic breast cancer. This can have important therapeutic implications. PATIENTS AND METHODS: In all, 541 patients with available receptor statuses from both primary tumor and metastatic lesion treated at Heidelberg and Tuebingen University Hospitals between 1982 and 2018 were included. RESULTS: Statistically significant discordance rates of 14% and 32% were found for ER and PR. HER2 status was statistically insignificantly discordant in 15% of patients. Gain in HER2 positivity was associated with an improved overall survival, whereas loss of HR positivity was associated with worse overall survival. Antiendocrine treatment differed in 20% of cases before and after biopsy and HER2-directed treatment in 14% of cases. CONCLUSIONS: Receptor statuses are discordant between primary tumor and metastasis in a considerable fraction of patients with metastatic breast cancer. Next to a highly presumed predictive value with respect to efficacy of endocrine and HER2-targeted therapy, discordance seems to provide prognostically relevant information. Where feasible, metastatic lesions should be biopsied in accordance with current guidelines.

Efficacy of intraoperative specimen radiography as margin assessment tool in breast conserving surgery.

PURPOSE: To explore the ability of intraoperative specimen radiography (SR) to correctly identify positive margins in patients receiving breast conserving surgery (BCS). To assess whether the reoperation rate can be reduced by using this method. METHODS: This retrospective study included 470 consecutive cases receiving BCS due to a primarily diagnosed breast cancer. SR was carried out in two planes, assessing the specimen regarding the presence of the lesion and its relation to all margins. If indicated, re-excision of selective orientations was advised. Under consideration of gross inspection and the SR-findings, it was up to the surgeon whether to perform re-resections. The recommendations for re-excision were, separately for each orientation, compared to the histopathological results, serving as gold standard. RESULTS: Intraoperative SR was performed in 470 cases, thus 2820 margins were assessed. Of those, 2510 (89.0%) were negative and 310 (11.0%) positive. SR identified 2179 (77.3%) margins correctly as negative, whereas 331 (11.7%) clear margins were misjudged as positive. Of 310 infiltrated margins, SR identified 114 (4.0%) correctly, whereas 196 (7.0%) infiltrated margins were missed. This resulted in a sensitivity/specificity of 36.8%/86.8% and PPV/NPV of 25.6%/91.8%. Through targeted re-resections positive margins could be reduced by 31.0% [310 to 214 (7.6%)]. On case level, the rate of secondary procedures could be reduced by 37.0% [from 162 to 102 (21.7%)]. CONCLUSIONS: SR is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of according orientations in order to obtain a final negative margin status.

Non-sentinel axillary tumor burden applying the ACOSOG Z0011 eligibility criteria to a large routine cohort.

PURPOSE: In the ACOSOG Z0011 trial, patients with primary breast cancer (BC) and 1-2 tumor-involved sentinel lymph nodes (SLN) undergoing breast-conserving surgery gained no benefit from completing axillary lymph node dissection (cALND). This paper reports cALND rates performed in clinical routine on patients who would meet the Z0011 criteria. Further, patients still received cALND were analyzed concerning the number of non-sentinel metastases (NSM) to estimate occult axillary tumor burden. METHODS: Data were retrospectively analyzed from patients treated in 179 German breast centers between 2008 and 2015. Time-trend rates were determined for cALND regarding the presence of axillary macrometastases or micrometastases. Descriptive statistics were used to report the number of NSM depending on the number of SLN removed, tumor-involved SLN, tumor stage (pT1-2), and immunohistochemical subtype. Factors associated with NSM were identified using multivariable logistic regression. RESULTS: Altogether, data for 188,909 patients were available, of whom 13,741 (7.3%) were identified eligible for the Z0011 criteria. For these patients, the cALND rate for macrometastases declined from 96.4% in 2008 to 49.7% in 2015, for micrometastases from 86.7 to 5.9%. In total 9773 patients still received cALND, 33.4% of whom had NSM. The NSM rates were: 38.8% for pN(1/1sn), 28.6% for pN(1/2sn), and 50.9% for pN(2/2sn). Hormone receptor (HR) positive/HER2+ showed the highest NSM rate (41.6%), HR-/HER2- the lowest rate (29.4%). CONCLUSIONS: The rate of cALND for ACOSOG Z0011 eligible patients has decreased substantially in routine care in our nationwide cohort. Our data reveal a relatively high prevalence of additional axillary NSM tumor burden.

Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer.

PURPOSE: Serial longitudinal enumeration of circulating tumor cells (CTCs) has shown its prognostic value on progression-free survival and overall survival (OS) in patients with stage IV breast cancer. This study prospectively evaluated the role of CTCs as a prognostic marker during further progression of metastatic breast cancer (MBC). METHODS: Among 476 MBC patients recruited between 2010 and 2015, the 103 patients with a known CTC status at baseline (CTCBL) and within 4 weeks of tumor progression (CTCPD) were included. Progressive disease (PD) was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Using the CellSearch method, < 5 and ≥ 5 CTCs per 7.5 ml blood were determined as negative and positive, respectively. A shift in CTC status from baseline to progression ([Formula: see text] to [Formula: see text] and vice versa) was considered as alternating KineticsBL-PD. RESULTS: Median follow-up was 29.9 [21.2, 40.0] months. CTCPD positivity (37%, n = 38) was associated with a significantly shorter OS than CTCPD negativity (8.0 [5.1, 10.9] vs 22.6 [15.3, 39.8] months; P < 0.001). Alternating KineticsBL-PD was observed in 24% of the patients. This significantly changed the OS prediction of [Formula: see text] patients ([Formula: see text] vs [Formula: see text], 11.4 [9.7, not available (NA)] vs. 7.6 [4.4, 11.5] months; P = 0.044) and [Formula: see text] patients ([Formula: see text] vs. [Formula: see text], 8.4 [4.0, NA] vs. 22.6 [18.9, NA] months, respectively; P < 0.001). Prediction of survival was significantly improved (P = 0.002) by adding CTCPD status to clinicopathological characteristics and CTCBL status. CONCLUSIONS: CTC status upon further disease progression is a prognostic factor that could significantly improve well-established models. Thus, it represents a potential additional instrument supporting treatment decision.

Locoregional risk assessment after neoadjuvant chemotherapy in patients with primary breast cancer: clinical utility of the CPS + EG score.

PURPOSE: Locoregional control is a prerequisite to cure primary breast cancer but the prediction of locoregional recurrence to guide further local therapy following neoadjuvant chemotherapy remains a challenge. The CPS + EG score was designed to predict distant recurrences. Here we examine its ability to predict both not only distant but also locoregional recurrences with respect to accuracy and clinical applicability. METHODS: Clinical data from 432 patients with primary breast cancer treated with neoadjuvant chemotherapy between 2003 and 2011 were prospectively collected. Using the Kaplan-Meier method we analyzed the risk of local and distant recurrences according to individual CPS + EG scores, stratified by type of surgery. Possible confounding of the relationship between recurrence risk and CPS + EG score by established risk factors was accounted for in multiple survival regression models. Additionally, we analyzed the performance of the CPS + EG score to predict isolated locoregional recurrence by censoring patients with prior or simultaneous distant metastases. RESULTS: 5-year locoregional recurrence-free survival was 90%, and 5-year distant metastases-free survival was 82%. The CPS + EG score stratified patients into six prognostic groups with distinct 5-year locoregional recurrence-free survival, ranging from 100 to 41% (p = 0.02) and 5-year distant metastases-free survival, ranging from 96 to 35% (p < 0.0001). 8 patients (17%) with CPS + EG scores ≥ 4 experienced locoregional recurrence-5 of them presented with simultaneous distant disease. CONCLUSION: The CPS + EG score, originally designed to predict distant relapse, is also valuable for assessing local recurrence risks. Our data demonstrate that distant and locoregional recurrence risks are closely related. As prognosis of patients with high risk of locoregional failure based on CPS + EG is dominated by distant recurrences, escalating local therapies may have limited impact on overall prognosis.

Clinical Validation of the BREAST-Q Breast-Conserving Therapy Module.

BACKGROUND: The BREAST-Q is a patient-reported outcome measure to evaluate satisfaction and health-related quality of life (HRQOL) after breast surgery. The aim of this study is to test the acceptability, reliability, and validity of the most recently developed BREAST-Q module for breast-conserving therapy (BCT) in a prospective clinical cohort. METHODS: The BREAST-Q BCT module was translated into German according to international guidelines. A total of 253 women with primary breast cancer undergoing BCT were recruited preoperatively. This study evaluated the BREAST-Q BCT subscales by using psychometric methods including acceptability, reliability, and validity. To examine construct validity, convergent and discriminant validity were determined by testing the instrument's scales against the EORTC C30 and BR23 as reference questionnaires. RESULTS: Acceptability was supported by a high follow-up rate (90%) and low frequency of missing data (< 10%) in all but three scales. Scale reliability was supported by high Cronbach's alpha coefficients (> 0.86) and item-total correlations (range of means, 0.33-0.89). Validity was shown by convergent and divergent correlations. The hypotheses of relationships between the scales of the BREAST-Q and the EORTC QLQ C30 BR23 revealed moderate to high correlations. CONCLUSIONS: The BREAST-Q BCT module proved to be an accepted, reliable, and valid questionnaire for the assessment of HRQOL and patient satisfaction after BCT in breast cancer patients. It can be recommended as a possible standard PROM for individual clinical analysis, quality assessment, and future trials.

[Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth]. / Prävention und Therapie der Frühgeburt. Leitlinie der DGGG, OEGGG und SGGG (S2k-Niveau, AWMF-Registernummer 015/025, Februar 2019) ­ Teil 1 mit Empfehlungen zur Epidemiologie, Ätiologie, Prädiktion, primären und sekundären Prävention der Frühgeburt.

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.

[Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and the Management of Preterm Premature Rupture of Membranes]. / Prävention und Therapie der Frühgeburt. Leitlinie der DGGG, OEGGG und SGGG (S2k-Niveau, AWMF-Registernummer 015/025, Februar 2019) ­ Teil 2 mit Empfehlungen zur tertiären Prävention der Frühgeburt und zum Management des frühen vorzeitigen Blasensprungs.

AIMS: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups. METHODS: The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus). RECOMMENDATIONS: Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Initial results of the FUSION-X-US prototype combining 3D automated breast ultrasound and digital breast tomosynthesis.

PURPOSE: To determine the feasibility of a prototype device combining 3D-automated breast ultrasound (ABVS) and digital breast tomosynthesis in a single device to detect and characterize breast lesions. METHODS: In this prospective feasibility study, the FUSION-X-US prototype was used to perform digital breast tomosynthesis and ABVS in 23 patients with an indication for tomosynthesis based on current guidelines after clinical examination and standard imaging. The ABVS and tomosynthesis images of the prototype were interpreted separately by two blinded experts. The study compares the detection and BI-RADS® scores of breast lesions using only the tomosynthesis and ABVS data from the FUSION-X-US prototype to the results of the complete diagnostic workup. RESULTS: Image acquisition and processing by the prototype was fast and accurate, with some limitations in ultrasound coverage and image quality. In the diagnostic workup, 29 solid lesions (23 benign, including three cases with microcalcifications, and six malignant lesions) were identified. Using the prototype, all malignant lesions were detected and classified as malignant or suspicious by both investigators. CONCLUSION: Solid breast lesions can be localized accurately and fast by the Fusion-X-US system. Technical improvements of the ultrasound image quality and ultrasound coverage are needed to further study this new device. KEY POINTS: The prototype combines tomosynthesis and automated 3D-ultrasound (ABVS) in one device. It allows accurate detection of malignant lesions, directly correlating tomosynthesis and ABVS data. The diagnostic evaluation of the prototype-acquired data was interpreter-independent. The prototype provides a time-efficient and technically reliable diagnostic procedure. The combination of tomosynthesis and ABVS is a promising diagnostic approach.

Stimulation of chemokines in human endometrial stromal cells by tumor necrosis factor-α and interferon-γ is similar under apoptotic and non-apoptotic conditions.

PURPOSE: Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are pro-inflammatory cytokines which have been shown to be involved in the pathophysiology of implantation disorders. Both cytokines in combination are able to sensitize primarily resistant human endometrial stromal cells (ESCs) to Fas-induced apoptosis. Since CCL (CC-chemokine ligand) 5 and CCL2 are important regulators of the endometrial immune cell population, we examined the impact of TNF-α and IFN-γ on these two chemokines under non-apoptotic and apoptotic conditions. METHODS: ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with TNF-α, IFN-γ, an activating anti-Fas antibody and a caspase-inhibitor. CCL5 and CCL2 were measured using ELISA and real-time RT-PCR. Apoptosis was determined by flow cytometry, and cellular viability and membrane integrity were measured by fluorescent assays. RESULTS: The secretion of CCL5 and CCL2 was stimulated in undifferentiated and decidualized ESCs by the combination of TNF-α and IFN-γ under non-apoptotic as well as apoptotic (with Fas-stimulation in parallel) conditions. TNF-α or IFN-γ alone did not have this effect. The stimulatory influence of TNF-α plus IFN-γ on CCL5 and CCL2 in ESCs was also seen on the transcriptional level. Inhibition of cell death by a caspase-inhibitor had no influence on the secretion of CCL5 and CCL2 in ESCs under apoptotic stimulation. CONCLUSION: TNF-α and IFN-γ modulate the secretion of chemokines in ESCs independently of Fas-induced apoptosis. These results suggest a constant response pattern on pro-inflammatory cytokines within the population of human ESCs.

Gynecologic oncologists' attitudes and practices relating to integrative medicine: results of a nationwide AGO survey.

PURPOSE: The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals' knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. METHODS: Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. RESULTS: Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. CONCLUSION: There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer.

PURPOSE: While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC. METHODS: Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch™ system. Different cutoffs were analyzed both for iCTC and aCTC (≥5, ≥10, ≥25 and ≥50 CTC/7.5 ml). CTCKIN were characterized by ≥25 % changes in CTC counts. RESULTS: Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients, additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL positive 10.3 vs. aCTCBL negative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with ≥50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTCKIN showed stronger discriminating power than iCTCKIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4). CONCLUSIONS: Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts ≥ 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at ≥ 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.

Change of Patient-Reported Aesthetic Outcome Over Time and Identification of Factors Characterizing Poor Aesthetic Outcome After Breast-Conserving Therapy: Long-Term Results of a Prospective Cohort Study.

BACKGROUND: We analyzed the change of aesthetic outcome (AO) over time and explored factors characterizing poor AO after breast-conserving surgery (BCS). METHODS: This prospective single-center cohort study included 849 patients preoperatively planned for BCS between September 2007 and December 2011. Long-term follow-up was made once in 2013. AO was measured by the Aesthetic Status (AS) of the Breast Cancer Treatment Outcome Scale questionnaire. Clinical, surgical, and pathologic variables were evaluated to identify predictors of poor AO. We applied single factor variance analyses and univariable logistic regression analyses for outcome analysis. RESULTS: The long-term follow-up rate in 2013 was 73 % (621 nonrecurrent with final BCS). A poor or fair AO was reported in 30 (4.8 %) and 98 (15.8 %) of these 621 patients, respectively. Single factor variance analysis showed a negative impact of higher specimen weight on AO (p < 0.001). Univariable logistic regression analysis revealed the following risk factors for poor AO: radial breast incision [odds ratio (OR) 1.97], periareolar incision (OR 1.85), fishmouth-shaped incision with resection of the nipple-areola complex (OR 8.12), impaired wound healing (OR 3.14), and seroma (OR 2.16). No patient rating her AO as fair or poor shortly after BCS improved in the long-term follow-up. CONCLUSIONS: The incidence of poor AO is relatively rare but increases in the long-term follow-up. Patients experiencing poor AO after BCS are likely to remain unsatisfied with the outcome over time. Factors predicting unfavorable AO can assist preoperative planning with regards to the choice between simple breast conserving techniques or more complex oncoplastic procedures.

Prognosis of breast cancer molecular subtypes in routine clinical care: A large prospective cohort study.

BACKGROUND: In Germany, most breast cancer patients are treated in specialized breast cancer units (BCU), which are certified, and routinely monitored. Herein, we evaluate up-to-date oncological outcome of breast cancer (BC) molecular subtypes in routine clinical care of a specialized BCU. METHODS: The study was a prospectively single-center cohort study of 4102 female cases with primary, unilateral, non-metastatic breast cancer treated between 01 January 2003 and 31 December 2012. The five routinely used molecular subtypes (Luminal A-like, Luminal B/HER2 negative-like, Luminal B/HER2 positive-like, HER2-type, Triple negative) were analyzed. The median follow-up time of the whole cohort was 55 months. We calculated estimates for local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and relative overall survival (ROS). RESULTS: Luminal A-like tumors were the most frequent (44.7 %) and showed the best outcome with LCR of 99.1 % (95 % CI 98.5; 99.7), OS of 95.1 % (95 % CI 93.7; 96.5), and ROS of 100.0 % (95 % CI 98.5; 101.5). Triple negative tumors (12.3 %) presented the poorest outcome with LCR of 89.6 % (95 % CI 85.8; 93.4), OS of 78.5 % (95 % CI 73.8; 83.3), and ROS of 80.1 % (95 % CI 73.8; 83.2). CONCLUSIONS: Patients with a favorable subtype can expect an OS above 95 % and an LCR of almost 100 % over 5 years. On the other hand the outcome of patients with HER2 and Triple negative subtypes remains poor, thus necessitating more intensified research and care.

The presence of heparins during decidualization modulates the response of human endometrial stromal cells to IL-1ß in vitro.

PURPOSE: The aim of this paper is to study the impact of heparin on the response of human endometrial stromal cells (ESCs) to interleukin (IL)-1ß during decidualization in vitro. METHODS: ESCs were isolated from hysterectomy specimens of premenopausal women undergoing hysterectomy for benign reasons; decidualized in vitro and incubated in parallel with unfractionated heparin or tinzaparin; and stimulated with IL-1ß at days 0, 3, 6, and 9 during decidualization. IL-6, IL-11, and leukemia inhibitory factor (LIF) were analyzed using ELISAs and real-time RT-PCR. Cell viability was determined by a fluorometric assay. RESULTS: IL-1ß dose-dependently stimulated IL-6, IL-11, and LIF in distinct patterns in ESCs during decidualization. Unfractionated heparin as well as tinzaparin attenuated the IL-1ß-mediated induction of IL-6, IL-11, and LIF on protein and messenger RNA (mRNA) levels. The relative effects of heparin and tinzaparin were getting more pronounced during the time course of decidualization. CONCLUSIONS: Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1ß-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation.

LECANDUS study (LEsion CANdidate Detection in UltraSound Data): evaluation of image analysis algorithms for breast lesion detection in volume ultrasound data.

PURPOSE: This study aims at developing and evaluating a prototype of a lesion candidate detection algorithm for a 3D-US computer-aided diagnosis (CAD) system. METHODS: Additionally, to routine imaging, automated breast volume scans (ABVS) were performed on 63 patients. All ABVS exams were analyzed and annotated before the evaluation with different algorithm blob detectors characterized by different blob-radiuses, voxel-sizes and the quantiles of blob filter responses to find lesion candidates. Lesions found in candidates were compared to the prior annotations. RESULTS: All histologically proven lesions were detected with at least one algorithm. The algorithm with optimal sensitivity detected all cancers (sensitivity = 100 %) with a very low positive predictive value due to a high false-positive rate. CONCLUSIONS: ABVS is a new technology which can be analyzed by a CAD software. Using different algorithms, lesions can be detected with a very high and accurate sensitivity. Further research for feature extraction and lesion classification is needed aiming at reducing the false-positive hits.

Long-term objective esthetic outcome after breast-conserving therapy.

The prediction of unfavorable long-term esthetic outcome (AO) is important for patient consultation. We aimed to analyze variables characterizing the improvement and impairment of AO over time after breast-conserving surgery. A subgroup of a prospective, monocenter cohort study was analyzed to evaluate the results of the BCCT.core software (Breast Cancer Conservative Treatment.cosmetic results) which was used to objectively assess the AO before (n = 356), shortly after (n = 294) and in median 3 years after surgery (n = 356). We analyzed potential influencing factors (such as body mass index, (y)pT-stage, weight of resected specimen, etc.) on the AO using logistic regression analyses (n = 256). Finally, we tried to characterize groups of patients with improving or impaired AO over time (n = 294). Predictors for an unfavorable AO were an axillary lymphadenectomy (OR = 4.05), a tumor in the 12 o'clock position (OR = 2.22), a tumor stage larger or equal to (y)pT2 stage (OR = 2.11), and a surgical specimen weight >75 g (OR = 2.71). Patients with lower specimen weight were more likely to improve in the long-term follow-up (p = 0.018), whereas patients with a higher (y)pT-stage tended to become impaired with time. Although overall AO decreased over time, nearly half of the patients with an unfavorable AO shortly after surgery improved in the long-term follow-up. Predictors of unfavorable AO can be used in patient consultation preoperatively to prepare them for the postsurgical period and/or to recommend surgical alternatives (e.g., more complex oncoplastic techniques). Knowledge of improvement and impairment may help patients and physicians in the postsurgical consultation setting.

Quality of life and anxiety of patients affected by the PIP/Rofil Medical breast implant recall: results from a prospective monocentre cohort study.

BACKGROUND: The PIP/Rofil Medical breast implant recall affected around 40,000 women worldwide. An impact on quality of life (QoL) has been suspected but not yet reported. OBJECTIVE: To quantify QoL and anxiety in affected women with respect to implant indication and their removal. PATIENTS AND METHODS: Women who attended consultation and opted for implant removal between December 2011 and 2012 were eligible for study. Quality of life and anxiety were measured using validated questionnaires pre- and postoperatively. RESULTS: Fifty-five patients completed at least one questionnaire, of which 32 had received implants for breast cancer, 15 for aesthetic augmentation, and 8 for primary breast malformations. Removal of the implants improved QoL in every group, especially those who had malformations. The QoL of breast cancer patients was generally better compared to the patients with implant for other reasons. CONCLUSION: The recall of PIP/Rofil Medical breast implants had a measurable impact on QoL in affected women and no pathological worry was measurable among those women.