Patient perception of meander-like versus radial breast ultrasound.

Background Radial breast ultrasound scanning (r-US) and commonly used meander-like ultrasound scanning (m-US) have recently been shown to be equally sensitive and specific with regard to the detection of breast malignancies. As patient satisfaction has a strong influence on patient compliance and thus on the quality of health care, we compare here the two US scanning techniques with regard to patient comfort during breast ultrasound (BUS) and analyze whether the patient has a preference for either scanning technique. Materials and Methods Symptomatic and asymptomatic women underwent both m-US and r-US scanning by two different examiners. Patient comfort and preference were assessed using a visual analog scale-based (VAS) questionnaire and were compared using a Mann-Whitney U test. Results Analysis of 422 VAS-based questionnaires showed that perceived comfort with r-US (r-VAS 8 cm, IQR [5.3, 9.1]) was significantly higher compared to m-US (m-VAS 5.6 cm, IQR [5.2, 7.4]) (p < 0.001). 53.8% of patients had no preference, 44.3% of patients clearly preferred r-US, whereas only 1.9% of patients preferred m-US. Conclusion: Patients experience a higher level of comfort with r-US and favor r-US over m-US. As the diagnostic accuracy of r-US has been shown to be comparable to that of m-US and the time required for examination is shorter, a switch from m-US to r-US in routine clinical practice might be beneficial. R-US offers considerable potential to positively affect patient compliance but also to save examination time and thus costs.

Impact of a brochure and empathetic physician communication on patients' perception of breast biopsies.

PURPOSE: This study investigated the effect of an intervention designed to reduce patients' emotional distress associated with breast biopsy. METHODS: 125 breast biopsy patients receiving standard of care (control group, CG) were compared to 125 patients (intervention group, IG) who received a brochure with information prior to the biopsy and were biopsied by physicians trained in empathic communication. Anxiety was assessed by the State-Anxiety Inventory (STAI-S) at four time points (pre- and post-procedural, pre- and post-histology). All participants completed pre- and post-procedural questionnaires addressing worries, pain and comprehension. We evaluated the impact of the intervention on STAI-S levels using a log-transformed linear mixed effects model and explored patients' and physicians' perceptions of the procedure descriptively. RESULTS: Post-procedural and post-histology timepoints were associated with 13% and17% lower with STAI-S levels than at the pre-procedural timepoint on average. The histologic result had the strongest association with STAI-S: malignancy was associated with 28% higher STAI-S scores than a benign finding on average. Across all time points, the intervention did not affect patient anxiety. Nevertheless, IG participants perceived less pain during the biopsy. Nearly all patients agreed that the brochure should be handed out prior to breast biopsy. CONCLUSION: While the distribution of an informative brochure and a physician trained in empathic communication did not reduce patient anxiety overall, we observed lower levels of worry and perceived pain regarding breast biopsy in the intervention group. The intervention seemed to improve patient's understanding of the procedure. Moreover, professional training could increase physicians' empathic communication skills. TRIAL REGISTRATION NUMBER: NCT02796612 (March 19, 2014).

Agreement in breast lesion assessment and final BI-RADS classification between radial and meander-like breast ultrasound.

BACKGROUND: This study prospectively investigates the agreement between radial (r-US) and meander-like (m-US) breast ultrasound with regard to lesion location, lesion size, morphological characteristics and final BI-RADS classification of individual breast lesions. METHODS: Each patient of a consecutive, unselected, mixed collective received a dual ultrasound examination. RESULTS: The agreement between r-US and m-US for lesion location ranged from good (lesion to mammilla distance ICC 0.64; lesion to skin distance ICC 0.72) to substantial (clock-face localization κ 0.70). For lesion size the agreement was good (diameter ICC 0.72; volume ICC 0.69), for lesion margin and architectural distortion it was substantial (κ 0.68 and 0.70, respectively). Most importantly, there was a substantial agreement (κ 0.76) in the final BI-RADS classification between r-US and m-US. CONCLUSIONS: Our recent comparison of radial and meander-like breast US revealed that the diagnostic accuracy of the two scanning methods was comparable. In this study, we observe a high degree of agreement between m-US and r-US for the lesion description (location, size, morphology) and final BI-RADS classification. These findings corroborate that r-US is a suitable alternative to m-US in daily clinical practice. Trial registration NCT02358837. Registered January 2015, retrospectively registered https://clinicaltrials.gov/ct2/results?cond=&term=NCT02358837&cntry=&state=&city=&dist =.

Comparison of radial and meander-like breast ultrasound with respect to diagnostic accuracy and examination time.

PURPOSE: To prospectively compare the diagnostic accuracy of radial breast ultrasound (r-US) to that of conventional meander-like breast ultrasound (m-US), patients of a consecutive, unselected, mixed collective were examined by both scanning methods. METHODS: Out of 1948 dual examinations, 150 revealed suspicious lesions resulting in 168 biopsies taken from 148 patients. Histology confirmed breast cancers in 36 cases. Sensitivity, specificity, accuracy, PPV, and NPV were calculated for r-US and m-US. The examination times were recorded. RESULTS: For m-US and r-US, sensitivity (both 88.9%), specificity (86.4% versus 89.4%), accuracy (86.9% versus 89.3%), PPV (64.0% versus 69.6%), NPV (both 98.3%), false-negative rate (both 5.6%), and rate of cancer missed by one method (both 5.6%) were similar. The mean examination time for r-US (14.8 min) was significantly (p < 0.01) shorter than for m-US (22.6 min). CONCLUSION: Because the diagnostic accuracy of r-US and m-US are comparable, r-US can be considered an alternative to m-US in routine breast US with the added benefit of a significantly shorter examination time.

Randomized controlled trial on the effect of an online decision aid for young female cancer patients regarding fertility preservation.

STUDY QUESTION: Does the use of an online decision aid (DA) about fertility preservation (FP), in addition to standard counselling by a specialist in reproductive medicine, reduce decisional conflict compared to standard counselling alone? SUMMARY ANSWER: Female cancer patients who could make use of the online DA had a significantly lower short-term decisional conflict score. WHAT IS KNOWN ALREADY: Nowadays, female cancer patients have several options for preserving fertility, but having to decide whether to opt for FP within a short time frame after cancer diagnosis and before the start of treatment is challenging. According to previous studies focussing mainly on breast cancer patients, decisional conflict among these women is high, and they have expressed the need for additional support. STUDY DESIGN, SIZE, DURATION: The study was a randomized controlled trial including female cancer patients who were referred by their treating oncologist to a specialist in reproductive medicine for fertility counselling. Participants were randomly assigned to the control group (counselling only) or to the intervention group (counselling and additional use of the online DA immediately after counselling). Recruitment was ongoing from July 2016 to December 2017 at eight fertility centres in Switzerland and Germany. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online DA was developed by an interdisciplinary team of specialists in reproductive medicine, gynaecologists, oncologists and psychologists. Of 79 recruited participants, 59 completed the first assessment and could therefore be enrolled in the study. They were asked to complete an online questionnaire at three time points: at T1, after counselling (control group, n = 27) or after counselling and the additional use of the DA (intervention group, n = 24); at T2, 1 month later (N = 41: control group, n = 23; intervention group, n = 18); and at T3, 12 months later (N = 37: control group, n = 20; intervention group, n = 17). The survey comprised questions about fertility-related knowledge, attitude towards FP, willingness to undergo FP and socio-demographic data, as well as the decisional conflict and decisional regret scales. MAIN RESULTS AND THE ROLE OF CHANCE: All participants showed low decisional conflict scores. Women who used the online DA in addition to counselling (intervention group) showed a significantly lower total score on the Decisional Conflict Scale (DCS) compared to the control group at T1 (P = 0.008; M = 12.15, SD = 4.38; 95% CI, 3.35-20.95) and at T2 (P = 0.043; M = 9.35, SD = 4.48; 95% CI, 0.31-18.38). At T3, the mean total score of the DCS was still lower in the intervention group compared to the control group; however, this group difference was no longer significant (P = 0.199, M = 6.86, SD = 5.24; 95% CI, -3.78 to 17.51). The majority of participants had already made a decision regarding FP (yes or no) at T1 (72.5%): 91.7% in the intervention group compared to 55.6% in the control group (P = 0.014). Those who had decided already at T1 showed significantly lower decisional conflict (P = 0.007; M = 13.69, SD = 4.89; 95% CI, 3.86-23.52). The average number of DA sessions per user was 2.23, and 80.8% of the participants completed the DA's value clarification exercises. Participants in the intervention group were satisfied with the DA and would recommend it to other patients. LIMITATIONS, REASONS FOR CAUTION: The recruitment of participants was challenging because of the emotionally difficult situation patients were in. This led to the limited sample size for final analysis. Education levels were high in two-thirds of the participants. It is difficult to say whether the DA would be equally effective in women with a lower educational background. WIDER IMPLICATIONS OF THE FINDINGS: There is evidence that the DA served as a helpful complement to the decision-making process for young female cancer patients qualifying for FP. This is, to our knowledge, the first randomized controlled trial evaluating a DA targeted at patients with several cancer types and in a language other than English (i.e. German). This study contributes to extending the range of the still limited number of DAs in the context of FP. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a research grant of the Swiss Cancer Research. The authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, trial no. NCT02404883. TRIAL REGISTRATION DATE: 19 March 2015. DATE OF FIRST PATIENT'S ENROLMENT: 4 July 2016.

Length Scale Matters: Real-Time Elastography versus Nanomechanical Profiling by Atomic Force Microscopy for the Diagnosis of Breast Lesions.

Real-time elastography (RTE) is a noninvasive imaging modality where tumor-associated changes in tissue architecture are recognized as increased stiffness of the lesion compared to surrounding normal tissue. In contrast to this macroscopic appraisal, quantifying stiffness properties at the subcellular level by atomic force microscopy (AFM) reveals aggressive cancer cells to be soft. We compared RTE and AFM profiling of the same breast lesion to explore the diagnostic potential of tissue elasticity at different length scales. Patients were recruited from women who were scheduled for a biopsy in the outpatient breast clinic of the University Hospital Basel, Switzerland. RTE was performed as part of a standard breast work-up. Individual elastograms were characterized based on the Tsukuba elasticity score. Additionally, lesion elasticity was semiquantitatively assessed by the strain ratio. Core biopsies were obtained for histologic diagnosis and nanomechanical profiling by AFM under near-physiological conditions. Bulk stiffness evaluation by RTE does not always allow for a clear distinction between benign and malignant lesions and may result in the false assessment of breast lesions. AFM on the other hand enables quantitative stiffness measurements at higher spatial, i.e., subcellular, and force resolution. Consequently, lesions that were false positive or false negative by RTE were correctly identified by their nanomechanical AFM profiles as confirmed by histological diagnosis. Nanomechanical measurements can be used as unique markers of benign and cancerous breast lesions by providing relevant information at the molecular level. This is of particular significance considering the heterogeneity of tumors and may improve diagnostic accuracy compared to RTE.

Diaphragmatic smears are not of additional benefit in the detection of peritoneal spread in gynecological cancers.

Peritoneal biopsies (PB) and peritoneal washing (PW) are routine measures in abdominal staging of gynecological malignancies and are used particularly for the assessment of occult microscopic tumor spread to the peritoneal surface including the diaphragm. Cytological diaphragmatic smears (DS) have been suggested as a supplemental tool; however, they are not routinely taken and their usefulness is still unclear. The present study retrospectively evaluated whether DS provide an additional benefit over PB and PW for the detection of peritoneal malignancies in patients with gynecological cancer. The data from patients who underwent laparotomy for suspected gynecological cancer and had DS and either PB, PW or ascites were reviewed. Sensitivity and specificity, and the number upstaged patients were determined. A total of 43 patients were excluded due to benign diagnosis (those with negative DS or PW) and 2 out of the remaining had 2 carcinomas simultaneously. Among these 41 malignancies, DS were positive in 12, PW in 18 and PB in 19 cases. No case was DS-positive while negative for both PB and PW. Four cases were missed when only PB and 5 when only PW was performed. Notably, no case of peritoneal disease was identified solely on positive DS, indicating that all 23 positive cases (presence of occult peritoneal disease in 56.1%) were identified by PB and PW together (100% sensitivity; 62% specificity). In addition, none of the cases was upstaged solely on positive DS results. Taken together, these data demonstrated that DS do not present an additional benefit to PW and PB in the detection of peritoneal gynecological disease.

Knowledge about and attitude towards fertility preservation in young female cancer patients: a cross-sectional online survey.

Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. However, because of their treatment, women might be confronted with impaired fertility. The options of fertility preservation (FP) techniques are increasing. The goal of this study was to assess knowledge about, and attitudes towards, fertility preservation in young female cancer patients. A cross-sectional online survey was conducted including 155 former female cancer patients from English and German speaking countries. The survey consists of questions about attitude towards, and knowledge about, fertility preservation. Results show that knowledge about fertility preservation was limited among participants. Positive attitudes towards fertility preservation significantly outweighed negative attitudes. Knowledge and attitude did not differ according to language or different healthcare systems. Confidence of knowledge was significantly higher in women who underwent any FP procedure compared to those who did not. Greater emphasis should be placed on counselling opportunities, the provision of adequate information and supporting material. A better understanding of these issues will hopefully enhance patients' decision-making about FP options and assist the development of strategies to improve quality of care.

Efficacy of adjuvant chemotherapy with carboplatin for early triple negative breast cancer: a single center experience.

BACKGROUND: Anthracycline- and taxane-based adjuvant chemotherapies are the most frequently used systemic treatments for women with triple negative breast cancer (TNBC). Adding platinum derivatives in the neo-adjuvant setting has been shown to not only improve the pCR rates, but also the 3 year DFS for TNBC patients; however, data on platinum derivatives in the adjuvant setting are limited. METHODS: We conducted a retrospective, single-center study in a Swiss breast cancer cohort to evaluate the role of carboplatin in addition to standard adjuvant therapy (anthracyclines and/ or taxanes) in early TNBC patients. All patients with stage I-III TNBC who underwent primary breast surgery between 2004 and 2014 were included. RESULTS: Eighty-three patients were included in the analysis. Stage and grade were well balanced between patients treated with standard chemotherapy (N=54; cohort A) or standard chemotherapy plus carboplatin (N=29; cohort B). The median time to local relapse (LRFS) was 15.0 months in cohort A versus 16.0 months in cohort B (p=0.655). The median time to distant relapse (DRFS) was 29.5 months in cohort A versus 25.0 months in cohort B (p=0.606) There was also no difference in overall survival between the two cohorts (mean overall survival 98 and 91 months, respectively; p=0.208). DISCUSSION: Our data suggest that in an unselected cohort of early TNBC patients, the addition of carboplatin in the adjuvant setting may not be beneficial with respect to relapse-free and overall survival. Further prospective trials to evaluate the addition of platinum in the adjuvant setting are warranted, especially to define subgroups of TNBC patients, which might benefit from carboplatin therapy.

Elastography Complements Ultrasound as Principle Modality in Breast Lesion Assessment.

BACKGROUND: The study aimed to improve breast cancer diagnosis with new ultrasound (US) modalities. We examined whether real-time elastography (RTE) complements the diagnostic performance of US. METHODS: The Ethical Committee approved the study. Patients provided written informed consent and received a whole breast workup. Breast lesions were evaluated by US and RTE. Lesions were assessed by BI-RADS, Tsukuba score (TS) and strain ratio (SR). RESULTS: The study included 164 breast lesions of which 101 were benign and 63 malignant. Women with benign lesions were predominantly premenopausal with sonographic dense breast tissue. Women with breast cancer were mostly postmenopausal, with a low sonographic density. Benign lesions had a mean TS of 2.05, which was significantly lower than the mean TS of 3.25 for malignant lesions. The SR for benign lesions (SR 1.83) was significantly smaller than for breast cancer (SR 4.83). Sensitivity and specificity was 95 and 81% for BI-RADS, 39 and 94% for TS, and 57 and 83% for SR, with a cutoff at 2.5. The combination of BI-RADS, TS and SR yielded a sensitivity of 95% and a specificity of 85%. CONCLUSION: Besides morphologic features revealed by US, elastic properties of breast lesions obtained by RTE can be exploited for diagnostic breast imaging.

Inter- and Intra-Observer Agreement in Ultrasound BI-RADS Classification and Real-Time Elastography Tsukuba Score Assessment of Breast Lesions.

Our aim was to prospectively evaluate inter- and intra-observer agreement between Breast Imaging Reporting and Data System (BI-RADS) classifications and Tsukuba elasticity scores (TSs) of breast lesions. The study included 164 breast lesions (63 malignant, 101 benign). The BI-RADS classification and TS of each breast lesion was assessed by the examiner and twice by three reviewers at an interval of 2 months. Weighted κ values for inter-observer agreement ranged from moderate to substantial for BI-RADS classification (κ = 0.585-0.738) and was substantial for TS (κ = 0.608-0.779). Intra-observer agreement was almost perfect for ultrasound (US) BI-RADS (κ = 0.847-0.872) and TS (κ = 0.879-0.914). Overall, individual reviewers are highly self-consistent (almost perfect intra-observer agreement) with respect to BI-RADS classification and TS, whereas inter-observer agreement was moderate to substantial. Comprehensive training is essential for achieving high agreement and minimizing the impact of subjectivity. Our results indicate that breast US and real-time elastography can achieve high diagnostic performance.

Decision-making about fertility preservation-qualitative data on young cancer patients' attitudes and needs.

The aim of the study was to get deeper insight into the significance of fertility in cancer patients, their attitude towards fertility preservation (FP), decisional conflicts, and patient's needs in the decision-making process. Focus groups with 12 female cancer survivors were held and revealed that the significance of fertility was high and attitude towards FP positive. Religious and ethical reservations were not negligible. Standardized decision aids were considered helpful. More support is highly in demand and specific tools would be beneficial.

The nanomechanical signature of breast cancer.

Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

[Fertility preservation and pregnancy in gynecological cancers]. / Fertilitätserhalt und Schwangerschaft bei gynäkologischen Malignomen.

Fertility preservation and pregnancy in gynecologic cancers are becoming more important since women delay childbearing and progress in medicine has a positive impact on survival of patients. The standard therapy in case of cancers of the endometrium, cervix and ovaries is a hysterectomy and a bilateral adnexectomy. If patients want to preserve fertility the standard procedure can be changed in well selected cases. In early stages of endometrial cancer progesterone therapy, in cervical cancer conisation or trachelectomy, and in ovarian cancer a fertility sparing operation can be offered. Nowadays a therapy option can be offered to all pregnant patients diagnosed with cancer - depending on the gestational age, the tumor type, tumor stage and the expectation of the future mother.

Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients.

The prognostic value of sentinel lymph node (SLN) micro-metastases and the question whether patients with SLN micro-metastases should undergo axillary lymph node dissection remain a matter of great debate. Based on the current literature and on our own data, we provide suggestive evidence that SLN micro-metastases in early stage breast cancer patients appear to have prognostic value and should impact the decision-making regarding adjuvant therapy, however, do not necessarily require further surgical treatment.

IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients.

BACKGROUND: Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately. METHODS: We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies. RESULTS: Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset). CONCLUSION: Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies. See the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741-7015/8/2.

Potential markers of preeclampsia--a review.

Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today.