Patient Participation in Multidisciplinary Tumor Conferences from the Providers' Perspective: Is It Feasible in Routine Cancer Care?

OBJECTIVE: Recent studies from Germany show that a small amount of breast and gynecological cancer patients participate in multidisciplinary tumor conferences (MTCs) at some cancer centers. One reason for the variation by center might be the providers' attitudes about and experiences with MTC patient participation (MTCpp), which has not been analyzed before. Therefore, it is the aim of this study to analyze the providers' expected or experienced feasibility concerning MTCpp at breast and gynecological cancer centers in Germany. METHODS: This paper presents cross-sectional qualitative interview data from the PINTU study. From April to December 2018, n=30 health-care providers from n=6 breast and gynecological cancer centers in North-Rhine-Westphalia, Germany, were interviewed. One-half of the providers had no experience and the other half had experience with MTCpp. Inductive and deductive coding was performed in order to capture the feasibility aspects of participation. RESULTS: MTCpp seems not to be feasible in routine cancer care following providers' expected barriers and negative experiences. However, MTCpp seems to be feasible for selected cancer patients following providers' expected opportunities and positive experiences. Our results show that both provider groups report positive and negative experiences or expectations. CONCLUSION: The mixed findings regarding expected or experienced feasibility of MTCpp provide first insights into differences concerning MTCpp between organizations. Our results suggest that the providers' perceptions (expectations and experiences) influence the possibility for patients to participate in an MTC in a cancer center.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Ovarian Cancer: Evaluation of Side Effects in a Single Institution Cohort.

BACKGROUND/AIM: Peritoneal carcinomatosis is a sign of advanced ovarian cancer. If cytoreductive surgery results in a tumor-free situation with the remaining tumor being less than 0.25 cm, Hyperthermic intraperitoneal chemotherapy (HIPEC) may further improve prognosis. PATIENTS AND METHODS: Patients with ovarian cancer and peritoneal carcinomatosis underwent cytoreductive surgery. In 43 patients with optimal tumor debulking, HIPEC was performed. The peri- and post-operative course was observed. Adverse events were recorded after the Clavien-Dindo classification. RESULTS: The median age of the patients was 56 years, the median peritoneal cancer index (PCI) was 13, and the median operation time was 356 min. There was no postoperative surgery associated death. No adverse events were recorded in 16 (37.2%) of 43 patients, no grade III or IV adverse events were reported for 33 (76.7%) patients, and no grade IV adverse events were reported for 41 (95.3%) patients. Grade III adverse events occured in 19 (44.2%) of the 43 patients. Grade IV adverse events occured in 3 (7.0%) of the 43 patients. CONCLUSION: In ovarian cancer, multiple surgical procedures may be necessary in order to have macroscopically eradicated tumor tissue. The combination with HIPEC, further improves survival of patients with peritoneal carcinomatosis.

A matched-pair analysis on survival and response rates between German and non-German cancer patients treated at a Comprehensive Cancer Center.

BACKGROUND: Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as 'foreign') cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. METHODS: During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. RESULTS: No significant differences regarding the patients' survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. CONCLUSIONS: In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.

Ultrasound screening of ovarian cancer.

Ovarian cancer has a high mortality rate. The most common serous type spreads rapidly throughout the peritoneal cavity when 5-year survival is 10%. If diagnosed in earlier stages where the cancer is still confined to the ovary, this survival rate is about 90%. This is the reason to be interested in screening at earlier stages in the average-risk general population. Thus, annual transvaginal ultrasound (TVS) alone or as a multimodal screening test following serum carbohydrate antigen 125 (CA125) has been investigated. Ultrasound lacks sensitivity and specificity; new contrast-enhanced approaches might improve these. When the serum marker is combined with ultrasound and interpreted by a rise in the level rather than by a fixed cut-off, improved sensitivity and specificity and a late but not significant reduction in mortality are observed. Further investigations could highlight the interest of a shorter than annual screening, of a long-term follow-up and new contrast-enhanced ultrasound techniques.

Impact of retroperitoneal lymph node dissection in ovarian cancer - time for paradigm shift?

Ovarian cancer is the second most common malignant neoplasm of the genital tract. Staging procedures for ovarian cancer include longitudinal laparotomy, hysterectomy, bilateral salpingo-oophorectomy and infragastric omentectomy as well as systematic pelvic and para-aortic lymphadenectomy. In general, the goal of this primary procedure is to achieve the maximum cytoreduction of all abdominal diseases; a residual disease <1 cm defines optimal cytoreduction, however, a maximal effort should be made to remove all gross disease as this offers superior survival outcomes. The role of lymphadenectomy in ovarian cancer has been the focus of gynecological oncologists during recent years. The core issue of the controversy is whether the removal of lymph nodes should be performed only to stage the disease or if the removal itself improves survival. To further comprehend the issue, one must take into account that several studies have shown that systematic lymphadenectomy is associated with a risk of vascular injury, lymph cyst formation, pulmonary embolism and increased post-operative mortality even when performed by surgeons with extensive experience. We present an extensive review of the available literature on the matter, hoping to provide some insight into the true need for such a procedure.

Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management.

In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the "golden standard" approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.

Vaginal dryness: individualised patient profiles, risks and mitigating measures.

Vaginal dryness (VD) affects both pre- and postmenopausal women at any age. Since the hormonal regulation changes during the climacteric period are considered as being the main course of the VD, affected women prefer not to talk about the problem. However, the problem does exist, and unfortunately if any, relatively minor group in the population possesses the health literacy at sufficient level to understand that VD is a suboptimal health condition which carries a multi-factorial character. Thereby, some of the contributing factors are clearly preventable and, therefore, if treated properly, have a potential to milden the VD. Current chapter demonstrates specific signs and symptoms of Flammer syndrome in women suffering from vaginal dryness, although individualised patient profiles clearly discriminate between pre- and postmenopausal women regarding the subgroup-specific symptoms. Noteworthy, about 20% of the VD patients involved in the study notify a delayed or even impaired wound healing observed for themselves over a couple of years. Optimising modifiable risk factors accompanying FS phenotype at the level of primary prevention is strongly recommended. Individualised patient profiles provide important information for VD mitigating measures tailored to the person. Further, future projects should essentially deal with the complexity of vulvar-vaginal dryness as part of the Sicca syndrome in individuals with FS phenotype, in order to prevent genital female cancers which may occur at any age. In contrast to the human papilloma virus as possible trigger of the disease, the role of the vulvar-vaginal dryness as an important risk factor is strongly underestimated in currently applied diagnostic and treatment approaches.

Oral etoposide for metastatic choriocarcinoma: a case report and review of guidelines.

BACKGROUND AND PURPOSE: Choriocarcinoma (CCA) is a rare form of malignant trophoblastic disease. Systemic polychemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) is the mainstay of treatment for metastatic disease. Due to the rarity of the condition, however, the evidence basis for this management is small and other chemotherapy regimens may also be effective. The reported case presents anecdotal evidence of an effective etoposide monotherapy treatment. METHOD: CASE PRESENTATION: We report the case of a patient with gestational choriocarcinoma and pulmonary metastases initially treated with methotrexate. Due to local disease progression, she underwent hysterectomy and continued treatment with methotrexate. After pulmonary progression, she was switched to oral etoposide. RESULTS: After four cycles of etoposide monotherapy at a oral dosage of 100 mg d1-7, q28, the patient had no evidence of disease according to human chorionic gonadotropin serum levels and imaging studies. The treatment was well tolerated with World Health Organization (WHO) grade 2 alopecia and hot flushes as the most prominent side effects. The patient has achieved a sustained complete remission with a follow-up of 6 years. CONCLUSION: Oral etoposide may be an effective treatment alternative to EMA/CO in selected patients with oligometastatic CCA.

Premenopausal breast cancer: potential clinical utility of a multi-omics based machine learning approach for patient stratification.

BACKGROUND: The breast cancer (BC) epidemic is a multifactorial disease attributed to the early twenty-first century: about two million of new cases and half a million deaths are registered annually worldwide. New trends are emerging now: on the one hand, with respect to the geographical BC prevalence and, on the other hand, with respect to the age distribution. Recent statistics demonstrate that young populations are getting more and more affected by BC in both Eastern and Western countries. Therefore, the old rule "the older the age, the higher the BC risk" is getting relativised now. Accumulated evidence shows that young premenopausal women deal with particularly unpredictable subtypes of BC such as triple-negative BC, have lower survival rates and respond less to conventional chemotherapy compared to the majority of postmenopausal BC. WORKING HYPOTHESIS: Here we hypothesised that a multi-level diagnostic approach may lead to the identification of a molecular signature highly specific for the premenopausal BC. A multi-omic approach using machine learning was considered as a potent tool for stratifying patients with benign breast alterations into well-defined risk groups, namely individuals at high versus low risk for breast cancer development. RESULTS AND CONCLUSIONS: The study resulted in identifying multi-omic signature specific for the premenopausal BC that can be used for stratifying patients with benign breast alterations. Our predictive model is capable of discriminating individually between high and low BC-risk with high confidence (>90%) and considered of potential clinical utility. Novel risk assessment approaches and advanced screening programmes-as the long-term target of this project-are of particular importance for predictive, preventive and personalised medicine as the medicine of the future, due to the expected health benefits for young subpopulations and the healthcare system as a whole.

Ribavirin in Acute Hepatitis E Infection in Patients with Gynecological Cancer: A Case Series.

Hepatitis E virus infection is usually a self-limited disease. However, during the last years there has been growing evidence for prolonged and chronic infection occurring in patients with immunosuppression. Also patients with malignant and rheumatic diseases have been identified to be at risk for chronic hepatitis E. However, their course and prognosis are not well characterized and there have been no reports of hepatitis E virus infection in patients with gynecological cancer. Here, we report three Caucasian females with breast and ovarian cancers presenting with elevation of aminotransferase levels during anticancer treatment. Although only few or no clinical hints suggested hepatitis E virus infection, the diagnosis of hepatitis E virus infection was confirmed by seroconversion, which might occur with some delay, and/or by polymerase chain reaction. While two patients had a self-limited course, the third patient with a high-risk oncological constellation required ribavirin in order to resume chemotherapy. These cases highlight the need for hepatitis E virus testing in patients with gynecological cancer and elevated aminotransferase levels. Further, these cases show that in selected high-risk patients, ribavirin treatment may be necessary based on the decision of a multidisciplinary team.

Improved sensitivity for detection of breast cancer by combination of miR-34a and tumor markers CA 15-3 or CEA.

BACKGROUND: MicroRNAs biomarkers have shown value for diagnosis and prognosis of various cancers. Combination with established tumor markers has rarely been done. RESULTS: Breast cancer patients had significantly higher serum RNA loads (AUC 0.665), lower miR-34a (AUC 0.772), higher CEA and CA 15-3 levels (AUCs 0.717 and 0.721) than healthy controls. miR-34a correlated with tumor stage and hormone receptor status. There was no significant difference between groups for all other miRNAs. Combination of miR-34a with CEA or CA 15-3 led to improved AUCs of 0.844 and 0.800, respectively. Sensitivity of miR-34a and CA 15-3 reached 56.1% at 95% specificity. When compared with benign breast diseases, combination of miR-34a (AUC 0.719) and CEA (0.623) or CA 15-3 (0.619) resulted in improved performances (0.794 and 0.741). Sensitivity of miR-34a and CA 15-3 reached 53.7% at 95% specificity. CONCLUSION: While miR-34a provides valuable information for diagnosis and staging, combination with tumor markers CA15-3 or CEA improves the sensitivity for breast cancer detection. PATIENTS AND METHODS: The diagnostic relevance of the miR-21, miR-34a, miR-92a, miR-155, miR-222 and miR-let-7c was tested in sera of 103 individuals (55 breast cancer, 20 benign breast diseases, 28 healthy controls). MiRNAs were detected by quantitative rt-PCR after extraction and reverse transcription. Cel-miR-39 and miR-16 were used for normalization. Established tumor markers CEA, CA 15-3, CA 19-9 and CA 125 were measured by automatized immunoassays. Diagnostic performance was tested by areas under the curve (AUC) of receiver operating characteristic (ROC) curves and sensitivities at 90% and 95% specificity.

Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation of expression and a case report of radionuclide therapy.

PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for positron emission tomography/computer tomography (PET/CT) imaging in patients with several cancer types, including breast cancer. So far, PSMA expression in breast cancer endothelia has not been sufficiently characterized. METHODS: This study comprised 315 cases of invasive carcinoma of no special type (NST) and lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor endothelia was detected by immunohistochemistry. Further, vascular mRNA expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with invasive breast cancer provided by The Cancer Genome Atlas (TCGA). RESULTS: Sixty percent of breast cancer cases exhibited PSMA-positive endothelia with higher expression rates in tumors of higher grade, NST subtype with Her2-positivity, and lack of hormone receptors. These findings were confirmed on mRNA expression levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 × higher than in other tumors). Further, a case of a patient with metastatic breast cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide therapy is discussed in detail. CONCLUSIONS: This study provides a rationale for the further development of PSMA-targeted imaging in breast cancer, especially in triple-negative tumors.

Multi-omic approach decodes paradoxes of the triple-negative breast cancer: lessons for predictive, preventive and personalised medicine.

Breast cancer epidemic in the early twenty-first century results in around two million new cases and half-a-million of the disease-related deaths registered annually worldwide. A particularly dramatic situation is attributed to some specific patient subgroups such as the triple-negative breast cancer (TNBC). TNBC is a particularly aggressive type of breast cancer lacking clear diagnostic approach and targeted therapies. Consequently, more than 50% of the TNBC patients die of the metastatic BC within the first 6 months of the diagnosis. In the current study we have hypothesised that multi-omic approach utilising blood samples may lead to discovery of a unique molecular signature of the TNBC subtype. The results achieved demonstrate, indeed, multi-omics as highly promising approach that could be of great clinical utility for development of predictive diagnosis, targeted prevention and treatments tailored to the person-overall advancing the management of the TNBC.

Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology.

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment.

Preoperative breast MRI-examination for all patients with histologically proven breast cancer? A concept for a prospective multicenter trial.

Background A published retrospective data of our study group demonstrated that premenopausal women, patients with lobular invasive breast cancer or patients with high breast density [American College of Radiology (ACR) classification 3+4] significantly benefit from magnetic resonance imaging (MRI) leading to additional detection of malignant foci of 20.2% in the index and 2.5% in the contralateral breast, which would otherwise not be detected by routine imaging. Critics of preoperative MRI focus on higher false-positive rates leading to unnecessary surgical procedures and mastectomies. Therefore, MRI in preoperative imaging remains controversial. Methods To validate our retrospective data we initiate a prospective one-armed multicenter trial for patients with histologically confirmed breast cancer performing routine imaging by ultrasound and mammography followed by MRI imaging based on menopause status, histologic subtype, ACR and Breast Imaging Reporting and Data System (BIRADS)-classification. Primary endpoint is the rate of additional findings and change of treatment strategy, secondary endpoints are local recurrence-free, distant recurrence-free and overall survival. Additional MRI findings are calculated to be above 10% with a number of 100 patients recruited and a power of 80%. Conclusion MRI is detecting more tumor foci than conventional imaging but remains controversial in primary breast cancer for preoperative imaging because of the fear of over-diagnosis and the increased morbidity of additional potentially unnecessary surgical procedures. This planned one-armed prospective multicenter trial is designed to confirm our retrospectively revealed data defining subgroups with significant benefit of preoperative MRI to come to a consensus avoiding over-diagnosis and false-positive results leading to clinically beneficial and cost-effective use of preoperative MRI.

Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of value in discriminating benign and malignant cervical diseases. Carcinoembryonic antigen and alpha-fetoprotein distinguished precancerous breast and vulva diseases from healthy controls. These findings show that luminescent oxygen channeling immunoassays-based tumor marker assays provide reliable results in routine diagnostics.

Lipofilling effects after breast cancer surgery in post-radiation patients: an analysis of results and algorithm proposal.

BACKGROUND: Lipofilling or autologous fat transfer is an established technique in plastic surgery. Herein, we describe the lipofilling effects after implant-based breast reconstruction in post-radiation patients and propose an algorithm for indication of lipofilling. METHODS: Forty patients with a history of breast cancer were included in this retrospective analysis. Patients had undergone either breast conserving therapy or mastectomy. Twenty-six patients underwent additional radiation therapy. Patients were assessed using a post-radiation skin scoring classification. RESULTS: In total, 68 lipofilling procedures were analyzed. Scar release, skin softening, improved quality of life, and improvement of post-radiation findings are results of lipofilling with a closed filtration system. In all patients with post-surgical radiation, an improvement of tissue quality was observed. Staging revealed that lipofilling improved mean post-radiation skin scores of 2.40 ± 0.89 to 1.21 ± 0.76 (p ≤ 0.000). There was no recurrence of breast cancer in our study patients. CONCLUSIONS: This study introduces an algorithm using lipofilling in reconstructive breast surgery and especially in post-radiation patients with low risks as well as very high acceptance in patients with various indications for this procedure. A regenerative aspect was also detectable in patients following radiation therapy and reconstruction. Lipofilling is a safe and effective procedure with a low incidence of minor complications. It is therefore a feasible method to resolve volume deficiencies and asymmetric results after oncologic breast surgery. Nevertheless, a prospective study has now been initiated focusing on the oncologic safety of lipofilling including ultrasound and radiological examinations to validate the findings of this initial study. Level of Evidence: Level IV, therapeutic study.

Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?

The breast cancer (BC) diagnosis currently experiences the epidemic evolution with more than half of million deaths each year. Despite screening programmes applied and treatments available, breast cancer patients frequently develop distant metastases. The brain is one of the predominant sites of the metastatic spread recorded for more than 20% of BC patients, in contrast to the general population, where brain tumours are rarely diagnosed. Although highly clinically relevant, the brain tumour mystery in the cohort of breast cancer patients has not been yet adequately explained. This review summarises currently available information on the risk factors predicting brain metastases in BC patients to motivate the relevant scientific areas to explore the data/facts available and elucidate disease-specific mechanisms that are of a great clinical utility.

Diagnostic relevance of a novel multiplex immunoassay panel in breast cancer.

Multiple factors contribute to the development and progression of breast cancer. Markers of tumor growth and invasion, cell death, immune activation, and angiogenesis can be assessed in parallel by a novel multiplex immunoassay panel. The diagnostic performance of a multiplex cancer biomarker magnetic bead panel comprising 24 tumor associated parameters was evaluated in sera of 154 women including 77 patients with breast cancer, 10 with precancerous lesions, 31 with benign breast diseases, and 36 healthy controls. Marker levels were log-transformed for variance stabilization. Significance testing was done using t-test or Wilcoxon rank-sum test with correction of p values for multiple testing. Furthermore, receiver operating characteristic analyses were performed. Serum levels of several biomarkers were significantly (p ≤ 0.001) higher in cancer patients than in healthy controls, particularly alpha-fetoprotein, cancer antigen 15-3, cancer antigen 19-9, migration inhibitory factor, carcinoembryonic antigen, cancer antigen 125, hepatocyte growth factor, soluble Fas, tumor necrosis factor-α, stem cell factor, and osteopontin. As most markers were also elevated in benign breast diseases, only cancer antigen 15-3 showed significant differences to cancer patients (p ≤ 0.001). The resulting areas under the curve in receiver operating characteristic curves for discrimination between benign and malignant breast diseases achieved 0.71 with a sensitivity of 33.8% at 95% specificity. Multiplexing enables parallel analysis of different biomarker classes for cancer detection. Established cancer antigen 15-3 proved to be most relevant for differential diagnosis.

Impact of Preoperative Breast MR Imaging and MR-guided Surgery on Diagnosis and Surgical Outcome of Women with Invasive Breast Cancer with and without DCIS Component.

Purpose To (a) compare the diagnostic accuracy of breast magnetic resonance (MR) imaging with that of conventional imaging (digital mammography and breast ultrasonography) in the identification of ductal carcinoma in situ (DCIS) components of biopsy-proven invasive breast cancer before surgery and (b) investigate the surgical outcome (positive margin rates and mastectomy rates) of women with breast cancer who underwent preoperative MR imaging combined with MR-guided needle biopsy and/or MR-guided lesion localization or bracketing where appropriate. Materials and Methods The authors performed a prospective two-center study of 593 consecutive patients with biopsy-proven invasive breast cancer who underwent breast MR imaging in addition to conventional imaging. MR-guided vacuum biopsy and MR-guided lesion bracketing were performed for DCIS components visible at MR imaging alone. The accuracy of breast MR imaging was compared with that of conventional imaging, and surgical outcomes (positive margin and mastectomy rates) were investigated. Results Surgical-pathologic assessment demonstrated DCIS components in 139 of the 593 women (23.4%). The sensitivity of MR imaging for the diagnosis of DCIS components pre-operatively (84.9%; 118 of 139) was significantly higher than that of conventional imaging (36.7%; 51 of 139) (P < .0001); more than half of DCIS components (51.1%; 71 of 139) were detected only with MR imaging. The sensitivity advantage of MR imaging over conventional imaging increased with increasing relative size of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for small, marginal DCIS components was 56.8% (21 of 37) versus 29.7% (11 of 37); the sensitivity for extensive DCIS components was 91.7% (55 of 60) versus 41.7% (25 of 60); the sensitivity for large, predominant DCIS components was 100.0% (42 of 42) versus 35.7% (15 of 42). Moreover, the sensitivity advantage of MR imaging over conventional imaging increased with increasing nuclear grade of DCIS components, as follows: The sensitivity of MR imaging versus conventional imaging for low-grade DCIS components was 74.0% (20 of 27) versus 40.7% (11 of 27); the sensitivity for intermediate-grade DCIS components was 84.1% (53 of 63) versus 34.9% (22 of 63); the sensitivity for high-grade DCIS components was 91.8% (45 of 49) versus 36.7% (18 of 49) (P < .05-.001 for all). Positive margin rates were low overall (3.7% [95% Clopper Pearson confidence interval [CI]: 2.3%, 5.6%]) and did not differ significantly between the 139 women with DCIS components (5.0% [95% CI: 2.0%, 10.1%]) compared with the 454 women without such components (3.3% [95% CI: 1.9%, 5.4%]). The same was true for mastectomy rates (10.8% [95% CI: 6.2%, 17.2%] vs 8.1% [95% CI: 5.8%, 11.1%]). Conclusion Breast MR imaging improves depiction of DCIS components of invasive breast cancers before surgery and is associated with positive margin and mastectomy rates that are low irrespective of the presence or absence of DCIS components. © RSNA, 2017.