Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer.

PURPOSE: The optimal time to initiation of adjuvant chemotherapy (TTAC) for triple negative breast cancer (TNBC) patients is unclear. This study evaluates the association between TTAC and survival in TNBC patients. METHODS: We conducted a retrospective study using data from a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018, registered in the Tumor Centre Regensburg was conducted. Data included demographics, pathology, treatment, recurrence and survival. TTAC was defined as days from primary surgery to first dose of adjuvant chemotherapy. The Kaplan-Meier method was used to evaluate impact of TTAC on overall survival (OS) and 5-year OS. RESULTS: A total of 245 TNBC patients treated with adjuvant chemotherapy and valid TTAC data were included. Median TTAC was 29 days. The group receiving systemic therapy within 22 to 28 days after surgery had the most favorable outcome, with median OS of 10.2 years. Groups receiving systemic therapy between 29-35 days, 36-42 days, and more than 6 weeks after surgery had significantly decreased median survival, with median OS of 8.3 years, 7.8 years, and 6.9 years, respectively. Patients receiving therapy between 22-28 days had significantly better survival compared to those receiving therapy between 29-35 days (p = 0.043), and patients receiving therapy after 22-28 days also demonstrated significantly better survival compared to those receiving therapy after more than 43 days (p = 0.033). CONCLUSION: Timing of adjuvant systemic therapy can influence OS in TNBC patients. Efforts should be made to avoid unnecessary delays in administering chemotherapy to ensure timely initiation of systemic therapy and optimize patient outcomes.

Effects of Endocrine Interventions Targeting ERα or PR on Breast Cancer Risk in the General Population and Carriers of BRCA1/2 Pathogenic Variants.

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers.

HER4 Affects Sensitivity to Tamoxifen and Abemaciclib in Luminal Breast Cancer Cells and Restricts Tumor Growth in MCF-7-Based Humanized Tumor Mice.

The impact of the HER4 receptor on the growth and treatment of estrogen receptor-positive breast cancer is widely uncertain. Using CRISPR/Cas9 technology, we generated stable HER4 knockout variants derived from the HER4-positive MCF-7, T-47D, and ZR-75-1 breast cancer cell lines. We investigated tumor cell proliferation as well as the cellular and molecular mechanisms of tamoxifen, abemaciclib, AMG232, and NRG1 treatments as a function of HER4 in vitro. HER4 differentially affects the cellular response to tamoxifen and abemaciclib treatment. Most conspicuous is the increased sensitivity of MCF-7 in vitro upon HER4 knockout and the inhibition of cell proliferation by NRG1. Additionally, we assessed tumor growth and immunological effects as responses to tamoxifen and abemaciclib therapy in humanized tumor mice (HTM) based on MCF-7 HER4-wildtype and the corresponding HER4-knockout cells. Without any treatment, the enhanced MCF-7 tumor growth in HTM upon HER4 knockout suggests a tumor-suppressive effect of HER4 under preclinical but human-like conditions. This phenomenon is associated with an increased HER2 expression in MCF-7 in vivo. Independent of HER4, abemaciclib and tamoxifen treatment considerably inhibited tumor growth in these mice. However, abemaciclib-treated hormone receptor-positive breast cancer patients with tumor-associated mdm2 gene copy gains or pronounced HER4 expression showed a reduced event-free survival. Evidently, the presence of HER4 affects the efficacy of tamoxifen and abemaciclib treatment in different estrogen receptor-positive breast cancer cells, even to different extents, and is associated with unfavorable outcomes in abemaciclib-treated patients.

Automated breast ultrasound (ABUS) for intraoperative margin control on surgical specimens in breast conserving surgery.

PURPOSE: As breast-conserving surgery (BCS) has become the standard for treatment of early breast cancer, the need for new technologies to improve intraoperative margin assessment has become clear. Close or positive margins during BCS lead to additional surgeries, treatment delay, additional stress for patients and increasing healthcare cost. Automated three-dimensional breast ultrasound (ABUS) systems are meant to overcome the shortcomings of hand-held ultrasound (HHUS). In this study, we investigate the feasibility of ABUS to conduct ultrasound on surgical specimens in breast conserving therapy. METHODS: In this monocentric, non-interventional study, specimens of 40 women were examined via ABUS. A construction with isotonic saline solution, gel pads and ABUS membranes was invented by our team to produce images of breast cancer specimens using ABUS. Evaluation of the ABUS images was carried out by two independent physicians trained on ABUS evaluation. RESULTS: ABUS was conducted on 40 specimens. 90% of the generated images were of high quality. Measured tumor sizes with ABUS were bigger than measured tumor size with HHUS (mean tumor size 22.9 vs. 18.1 mm, CI 2.38-7.35, p < 0.05). The mean difference between the ABUS tumor size and the pathological tumor size was 1.8 mm (CI - 0.84-4.53, p = 0.17). The mean difference between the HHUS tumor size and the pathological tumor size was 3.2 mm (CI - 5.35 to - 1.03, p = 0.005). CONCLUSION: ABUS seems to be a suitable method to conduct specimen ultrasound. Further studies are required to evaluate the accuracy of ABUS for intraoperative margin assessment and possible implementation in clinical work routine.

Impact of cavity shaving on residual tumor rates in patients with primary invasive carcinoma and carcinoma in situ in breast conserving surgery.

BACKGROUND: Several international studies reported relatively high re-excision rates due to residual tumor in breast conserving surgery (BCS). Cavity shaving (CS) is a surgical strategy to reduce re-excision rates. This study aimed to investigate the effect of circumferential cavity shaving during BCS to reduce residual tumor. MATERIAL AND METHODS: A total of 591 patients with early invasive carcinoma or carcinoma in situ of the breast (ICD-10, C50 or D05) who were diagnosed between 01/01/2017 and 31/12/2019 and underwent BCS in a certified breast cancer center of the University Regensburg were analyzed regarding surgical excision methods. Patients with CS during BCS and patients with targeted re-excision in a specific direction depending on the result of intraoperative mammography or sonography during BCS were compared. The risk of pathologic residual tumor (R1) was compared between both groups by means of a multivariable binary logistic regression model to determine if there is a benefit of a certain surgical method to avoid a second intervention for re-excision. We adjusted for age, tumor size, nodal status, histologic type, surgeon, breast side, and neoadjuvant chemotherapy. RESULTS: 80 (n = 13.54%) patients had CS and 511 (n = 86.46%) had a targeted re-excision in a specific direction during BCS according to intraoperative mammography or sonography. After comparing both techniques in a multivariable regression model, there was no significant difference regarding risk of residual tumor (p = 0.738) in the total cohort. However, CS showed a tendency to be favorable regarding rates of residual tumor in patients with invasive breast cancer between 60 and 70 years (p = 0.072) and smaller T1-tumors (p = 0.057) compared to targeted intraoperative re-excision following mammographic or sonographic assessment. CONCLUSION: CS showed a tendency to reduce residual tumor compared to the standard technique of intraoperative re-excision in specific subgroups, although no statistical significance was reached. Further studies are needed to overcome potential limitations like surgeon-based bias and missing standardized definitions of CS to reduce residual tumor rates.

[Routine Practice Data for Health Care Analyses: Part 3 of the Manual]. / Versorgungsnahe Daten für Versorgungsanalysen ­ Teil 3 des Manuals.

Analyses of health and health care (hereafter referred to as "health care analyses") usually aim to make transparent the structures, processes, results and interrelationships of health care and to record the degree to which health care systems and their actors have achieved their goals. Health care-related data are an indispensable source of data for many health care analyses. A prerequisite for the examination of a degree of goal achievement is first of all an agreement on those goals that are to be achieved by the system and its substructures, as well as the identification of the determinants of the achievement of the objectives. Primarily it must be examined how safely, effectively and patient-centred systems, facilities and service providers are operating. It also addresses issues of need, accessibility, utilisation, timeliness, appropriateness, patient safety, coordination, continuity, and health economic efficiency and equity of health care. The results of health care include system services (outputs), on the one hand, and results (outcomes), on the other, whereby the results (patient-reported outcomes) and experiences (patient-reported experiences) reported are of particular importance. Health care analyses answer basic questions of health care research: who does what, when, how, why and with which resources and effects in routine health care. Health care analyses thus provide the necessary findings and key figures to further develop health care in order to improve the quality of health care. The applications range from capacity analyses to following innovations up to the concept of regional and supra-regional monitoring of the quality of care given to the population. Given the progress of digitalisation in Health Care, direct data from the care processes will be increasingly available for health care research. This can support care givers significantly if the findings of the studies are applied precisely and correctly within an adequate methodological frame. This can lead to measurable improved health care quality for patients. Data from the process of health care provision have a high potential. Their use needs the same scientific scrutiny as in all other scientific studies.

[Further Development and Interoperability in Oncological Care Structures, Quality Control and Research]. / Weiterentwicklung und Vernetzung der onkologischen Versorgungsstrukturen, der Qualitätssicherung und der Forschung.

How can we improve the interoperability of medical guidelines and the implementation and measurement of outcomes in medical health care for cancer patients as well as for care providers? This is the aim of the working group "Quality and Cross-linking". The following publication gives an overview of the targets reached in the development of guidelines together with quality indicators and documentation in cancer registries.

mdm2 gene amplification is associated with luminal breast cancer progression in humanized PDX mice and a worse outcome of estrogen receptor positive disease.

Estrogen receptor-positive breast cancer is a highly prevalent but heterogeneous disease among women. Advanced molecular stratification is required to enable individually most efficient treatments based on relevant prognostic and predictive biomarkers. First objective of our study was the hypothesis-driven discovery of biomarkers involved in tumor progression upon xenotransplantation of Luminal breast cancer into humanized mice. The second objective was the marker validation and correlation with the clinical outcome of Luminal breast cancer disease within the GeparTrio trial. An elevated mdm2 gene copy number was associated with enhanced tumor growth and lung metastasis in humanized tumor mice. The viability, proliferation and migration capacity of inherently mdm2 positive breast cancer cells in vitro were significantly reduced upon mdm2 knockdown or anti-mdm2 targeting. An mdm2 gain significantly correlated with a worse DFS and OS of Luminal breast cancer patients, albeit it was also associated with an enhanced preoperative pathological response rate. We provide evidence for an enhanced Luminal breast cancer stratification based on mdm2. Moreover, mdm2 can potentially be utilized as a therapeutic target in the Luminal subtype.

Protective effect of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to investigate the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. METHODS: In this population-based cohort study we analysed from clinical cancer registries to determine DFS of women with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IB1 cervical cancer with respect to conization preceding radical hysterectomy performed between January 2010 and December 2015. RESULTS: Out of 993 datasets available for the analysis, 235 patients met the inclusion criteria of the current study. The median follow-up was 5.4 years. During the study period, 28 (11.9%) recurrences were observed. All of these occurred in patients with FIGO stage IB1. For further evaluation, patients with FIGO IB1 tumors <2 cm were further analysed and divided into two groups, based on pre-operative conization. Pre-operative conization was associated with a reduced rate of recurrence (p = 0.007), with only three (5.2%) recurrences in this group (CO) compared to 25 recurrences (21.0%) in the group without conization (NCO) preceding radical hysterectomy. DFS was estimated at 79.0% and 94.8% in NCO and CO, respectively (p = 0.008). After adjustment for other prognostic covariates, conization remained a favourable prognostic factor for DFS (HR 0.27; 95% CI 0.08-0.93, p = 0.037). Lymph node involvement was the only unfavourable factor (HR 4.38; 95% CI 1.36-14.14, p = 0.014) in the multivariable analysis. CONCLUSIONS: Pre-operative conization is associated with improved DFS in early-stage cervical cancer independently of the surgical approach.

Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects.

PURPOSE: Protein kinase C (PKC) plays a pivotal role in malignant cell proliferation, apoptosis, invasiveness and migration. However, its exploitation as therapeutic target in breast cancer has been merely explored. Here were evaluated the AEB071 (Sotrastaurin™) treatment efficiency of breast cancer cell lines derived from estrogen receptor positive (T-47D), estrogen/HER2 receptor positive (BT474), and triple negative (HCC1806) breast cancer cells under 2D (monolayer) and 3D (multicellular tumor spheroids) culture conditions. Additionally, spheroid cocultures of BC and N1 fibroblasts were analyzed. METHODS: We quantitatively assessed the proliferation capacity of breast cancer cells and fibroblasts as a function of AEB071 treatment using flow cytometry. The activities of PKC isoforms, substrates, and key molecules of the PKC signaling known to be involved in the regulation of tumor cell proliferation and cellular survival were additionally evaluated. Moreover, a multigene expression analysis (PanCancer Pathways assay) using the nanoString™ technology was applied. RESULTS: All breast cancer cell lines subjected to this study were sensitive to AEB071 treatment, whereby cell proliferation in 2D culture was considerably (BT474) or moderately (HCC1806) retarded in G0/G1 or in G2/M phase (T-47D) of the cell cycle. Regardless of the breast cancer subtype the efficiency of AEB071 treatment was significantly lower in the presence of N1 fibroblast cells. Subtype specific driver molecules, namely IL19, c-myb, and NGFR were mostly affected by the AEB071 treatment. CONCLUSION: A combined targeting of PKC and a subtype specific driver molecule might complement specified breast cancer treatment.

Factors influencing treatment decision and guideline conformity in high-grade endometrial cancer patients: a population-based study.

PURPOSE: Treatment according to guidelines has been demonstrated to improve survival in a number of different cancer entities. Deviations from guidelines depend on several factors, including the patient's preferences, age and comorbidities. The aim of this study was to assess the adherence to guideline recommendations concerning surgical and adjuvant treatment in endometrial cancer. Furthermore, we sought to evaluate the reasons for non-adherence to guidelines by further examining the influence of comorbidities and age. METHODS: The influence of age, comorbidities, tumor stage and histological subtype on guideline adherence was evaluated by multivariable logistic regression in a cohort of 353 high-grade endometrial cancer patients. High-grade endometrial cancer was defined as carcinosarcoma, Type II (serous, clear cell, mixed cell carcinoma) and Type I G3 histology. RESULTS: Extensive surgical procedures, particularly systematic LNE, were less frequently applied in patients with comorbidities (p = 0.015) or higher age (p < 0.01). Guideline adherence was not affected by comorbidities (p = 0.563), but was significantly reduced with higher age (p < 0.01). In a multivariable model, higher age (p < 0.01), obesity (p = 0.011), higher FIGO Stage (p < 0.01) and histologic subtype (p < 0.01) significantly decreased OS. Surgery (p < 0.001), chemotherapy (p < 0.01) and systematic LNE (p = 0.011) were associated with higher OS. CONCLUSION: Age seems to be the strongest independent factor leading to guideline deviation. Comorbidities were associated with less aggressive treatment, but not with deviations from guidelines.

Symptom Burden and Palliative Care Needs of Patients with Incurable Cancer at Diagnosis and During the Disease Course.

BACKGROUND: Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied. MATERIAL AND METHODS: We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self-report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL-Q], Patients Health Questionnaire-4 [PHQ-4], modified Supportive Care Needs Survey [SCNS-SF-34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow-up. RESULTS: From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%). CONCLUSION: Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care. IMPLICATIONS FOR PRACTICE: A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients' needs.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

BACKGROUND: The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. PATIENTS AND METHODS: We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. RESULTS: The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1-7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. CONCLUSION: Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

Use of social service counseling by cancer patients: an analysis of quality assurance data of 6339 breast cancer patients from 13 certified centers in Germany treated between 2015 and 2017.

BACKGROUND: Integrated social care may help to mitigate social risk factors in order to achieve more equitable health outcomes. In cancer centers certified according to the criteria set out by the German Cancer Society, every patient must be given low-threshold access to qualified social workers at the center for in-house social service counseling (SSC). Previous analyses have demonstrated large variation in the utilization of these services across individual centers. Therefore, this research aims at investigating whether SSC utilization varies regarding breast cancer patient characteristics and center characteristics presenting a unique approach of using routine data. METHODS: Multilevel modeling was performed using quality assurance data based on 6339 patients treated in 13 certified breast cancer centers in Germany in order to investigate whether SSC utilization varies with patient sex, age, and disease characteristics as well as over time and across centers. RESULTS: In the sample, 80.3% of the patients used SSC. SSC use varies substantially between centers for the unadjusted model (ICC = 0.24). Use was statistically significantly (P < .001) more likely in women, patients with invasive (in comparison to tumor in situ/ductal carcinoma in situ) diseases (P < .001), patients with both breasts affected (P = .03), patients who received a surgery (P < .001), patients who were diagnosed in 2015 or 2017 compared to 2016 (P < .001) and patients older than 84 years as compared to patients between 55 and 64 years old (P = .002). CONCLUSION: The analysis approach allows a unique insight into the reality of cancer care. Sociodemographic and disease-related patient characteristics were identified to explain SSC use to some extent.

Comparison of survival outcomes and effects of therapy between subtypes of high-grade endometrial cancer - a population-based study.

BACKGROUND: Similarities in outcome between grade 3 endometrioid cancer and non-endometrioid histologies have been reported by a number of studies. Other reports, however, stated a significantly better prognosis for G3 endometrioid compared to type II histology. In this population-based study, we compared the outcome and treatment approaches of high-grade endometrial cancer patients with FIGO stages I-III depending on their histology. MATERIAL AND METHODS: 284 high-grade endometrial cancer patients diagnosed between 1998 and 2015 were retrospectively analyzed. Overall survival (OS), recurrence-free survival (RFS), and recurrence rates were compared depending on histology. RESULTS: Type I G3 patients had a statistically significant OS advantage over women suffering from type II carcinoma (HR 1.527, 95%-CI 1.024-2.276; p = 0.038) and carcinosarcoma (HR 2.106, 95%-CI 1.270-3.493; p = 0.004) in univariable and multivariable Cox-regression analysis. RFS in Type I G3 was significantly superior compared to patients with carcinosarcoma (HR 1.719, 95%-CI 1.018-2.901; p = 0.043) and not significantly superior to type II patients (HR 1.368, 95%-CI 0.920-2.036; p = 0.122). Cumulative recurrence rates were significantly higher in carcinosarcoma compared to type I G3 (HR 2.217, 95%-CI 1.096-4.485; p = 0.027) in univariable analysis, but not after risk adjustment (HR of 1.472, 95%-CI 0.654-3.311; p = 0.350). CONCLUSION: The prognosis of patients with type I G3 endometrial cancer patients seems to be significantly superior to patients with type II cancer and particularly carcinosarcoma. Systematic LND seemed to be beneficial in all of the three subtypes. The benefit of adjuvant treatment methods may differ between histologies.

Sedentary behaviour in relation to ovarian cancer risk: a systematic review and meta-analysis.

Sedentary behaviour is an emerging risk factor for several site-specific cancers. Ovarian cancers are often detected at late disease stages and the role of sedentary behaviour as a modifiable risk factor potentially contributing to ovarian cancer risk has not been extensively examined. We systematically searched relevant databases from inception to February 2020 for eligible publications dealing with sedentary behaviour in relation to ovarian cancer risk. We conducted a systematic review and meta-analysis, calculating summary relative risks (RR) and 95% confidence intervals (CI) using a random-effects model. We calculated the E-Value, a sensitivity analysis for unmeasured confounding. We tested for publication bias and heterogeneity. Seven studies (three prospective cohort studies and four case-control studies) including 2060 ovarian cancer cases were analysed. Comparing highest versus lowest levels of sedentary behaviour, the data indicated a statistically significant increase in the risk of ovarian cancer in relation to prolonged sitting time (RR = 1.29, 95% CI = 1.07-1.57). Sub-analyses of prospective cohort studies (RR = 1.33, 95% CI = 0.92-1.93) and case-control studies (RR = 1.28, 95% CI = 0.98-1.68) showed statistically non-significant results. Sensitivity analysis showed that an unmeasured confounder would need to be related to sedentary behaviour and ovarian cancer with a RR of 1.90 to fully explain away the observed RR of 1.29. Our analyses showed a statistically significant positive association between sedentary behaviour and ovarian cancer risk.

Long-term improvement of quality of life in patients with breast cancer: supporting patient-physician communication by an electronic tool for inpatient and outpatient care.

PURPOSE: The effectiveness of a pathway with quality of life (QoL) diagnosis and therapy has been already demonstrated in an earlier randomized trial (RCT) in patients with breast cancer. We refined the pathway by developing and evaluating an electronic tool for QoL assessment in routine inpatient and outpatient care. METHODS: In a single-arm study, patients with breast cancer with surgical treatment in two German hospitals were enrolled. QoL (EORTC QLQ-C30, QLQ-BR23) was measured with an electronic tool after surgery and during aftercare in outpatient medical practices (3, 6, 9, 12, 18, and 24 months) so that results (QoL-profile) were available immediately. Feedback by patients and physicians was analyzed to evaluate feasibility and impact on patient-physician communication. RESULTS: Between May 2016 and July 2018, 56 patients were enrolled. Physicians evaluated the QoL pathway as feasible. Patients whose physician regularly discussed QoL-profiles with them reported significantly more often that their specific needs were cared for (p < .001) and that their physician had found the right treatment strategy for these needs (p < .001) compared with patients whose doctor never/rarely discussed QoL-profiles. The latter significantly more often had no benefit from QoL assessments (p < .001). CONCLUSION: The QoL pathway with electronic QoL assessments is feasible for inpatient and outpatient care. QoL results should be discussed directly with the patient. CLINICAL TRIAL INFORMATION: NCT04334096, date of registration 06.04.2020.

Contralateral lymph node metastases in patients with vulvar cancer and unilateral sentinel lymph node metastases.

INTRODUCTION: The risk of contralateral lymph node metastases following unilateral sentinel lymph node (SLN) metastases in patients with vulvar cancer(s) remains to be systematically assessed. MATERIAL AND METHODS: We performed a multicenter, retrospective registry-based study of 476 patients with vulvar cancer. The primary outcome measure was the rate of contralateral non-SLN metastases in the case of positive unilateral SLN. RESULTS: Out of 476 patients with primary vulvar cancer, 202 received SLN biopsy: 58 unilateral and 144 bilateral. Out of 66 patients with unilateral metastatic SLN, 62 (93.9%) received contralateral lymphadenectomy-18 after unilateral and 44 after bilateral SLN biopsy. In the study group, 132 SLN were assessed with a median number of 2 (range 1-4) per patient and 76 of these were positive. Lymph node-positivity was associated with advanced tumor stage, as well as lymph and vascular space invasion. In the group of patients with bilateral inguino-femoral lymphadenectomy, 1004 lymph nodes were resected with a median number of 15 (range 10-29) per patient. After full dissection of the inguino-femoral lymph nodes, no contralateral non-SLN metastases were found. CONCLUSIONS: The risk of contralateral non-SLN metastases in patients with unilateral SLN metastases was low. Therefore, the impact of contralateral lymphadenectomy on patient survival should be investigated in further studies.

Icb-1 expression inhibits growth and fulvestrant response of breast cancer cells and affects survival of breast cancer patients.

PURPOSE: Human gene icb-1 recently has been reported to be part of a gene expression score predicting response to antiestrogen fulvestrant in breast cancer patients. In the present study, we examined to what extent icb-1 expression would affect the response of breast cancer cells to this antiestrogen in vitro and investigated underlying molecular mechanisms. Using open access mRNA data, we elucidated the significance of icb-1 expression for survival of breast cancer patients. METHODS: Icb-1 gene expression was knocked down by RNAi. Breast cancer cell growth after treatment with fulvestrant was assessed using the Cell Titer Blue assay. Gene expression was analyzed by Western blot analysis or RT-qPCR. Survival analyses were performed using bioinformatical online tools and data. RESULTS: Knockdown of icb-1 in T-47D breast cancer cells significantly increased growth of this cell line and also elevated the growth-stimulatory effect of E2 (p < 0.001). After treatment with different concentrations of fulvestrant, icb-1 knockdown cells exhibited a significantly enhanced response to this drug (p < 0.01). On the molecular level, icb-1 knockdown led to elevated expression of ESR1 and its target gene TFF1 (pS2) and enhanced E2-triggered up-regulation of proliferation genes. Finally, bioinformatical meta-analysis of gene expression data of 3951 breast cancer patients revealed that high icb-1 expression increases their relapse-free survival (HR = 0.87, p < 0.05). CONCLUSION: The presented data further support a tumor-suppressive role of icb-1 in breast cancer and suggest an inhibitory effect of this gene on fulvestrant action, which both are suggested to be mediated by suppression of cellular E2 response.

Minimal-invasive or open approach for surgery of early cervical cancer: the treatment center matters.

PURPOSE: The aim of the study was to compare recurrence-free survival (RFS) and overall survival (OS) of patients with early stage cervical cancer in dependence of surgical approach and treatment center. PATIENTS AND METHODS: A population-based cohort study including women with early stage IA1-IIB2 cervical cancer treated by radical hysterectomy between January 2010 and December 2015 was performed. RESULTS: The median follow-up time was 5.6 years. After exclusions, 413 patients were eligible for analysis: 111 (26.9%) underwent minimal-invasive surgery (MIS) and 302 (73.1%) open surgery. Both treatment groups were well balanced regarding the clinical and pathological characteristics. The mean age of the patients was 51.0 years. MIS was associated with improved RFS and OS compared with the open surgery. The 5-year RFS rates were 89.2% in the MIS group and 73.4% in the open surgery group (p = 0.004). The 5-year OS rates were 93.7% in the MIS group and 81.8% in the open surgery group (p = 0.016). After adjustment for other prognostic covariates, the MIS was further associated with improved RFS (HR = 0.45, 95% CI 0.24-0.86; p = 0.015) but not with OS. Nevertheless, after adjustment for treatment center, the surgical approach was not associated with significant difference in RFS (HR = 0.61, 95% CI 0.31-1.19; p = 0.143). Overall survival of patients treated in university cancer centers was significantly increased compared to patients treated in non-university cancer centers. The treatment center remains a strong prognostic factor regarding RFS (HR = 0.49, 95% CI 0.28-0.83; p = 0.009) and OS (HR = 0.50, 95% CI 0.26-0.94; p = 0.031). CONCLUSIONS: The treatment center but not the surgical approach was associated with the survival of patients treated with radical hysterectomy for early stage cervical cancer.