How to break bad news and how to learn this skill: results from an international North-Eastern German Society for Gynecological Oncology (NOGGO) survey among physicians and medical students with 1089 participants

BACKGROUND: Delivering bad news to patients is one of the most challenging tasks in medical practice. Despite its great relevance to patients, relatives, and medical staff, there is a paucity of data pertaining to training, experience, expectations, and preferences of physicians and medical students on breaking bad news. METHODS: We conducted an international survey in Germany, Switzerland, and Austria using an online questionnaire among physicians and medical students. RESULTS: A total of 786 physicians and 303 medical students completed the survey. Physicians stated that 32.7% deliver bad news several times a week and 45.2% several times a month. Difficulties controlling their emotions (35.1%) and remaining professional (43.4%) were the greatest challenges for physicians. Delivering bad news is associated with feelings of anxiety, both among experienced physicians (median of 3.8 out of 10.0) and medical students (median of 5.3). Conveying bad news is a burden to physicians and consequently has a substantial impact on their job satisfaction. All participants reported the need for more communication training concerning this subject. Only 49.5% of medical students and 67.3% of physicians mentioned having learned adequate communication skills. Our data demonstrate that communication training decreases the level of anxiety and increases the feeling of self-confidence towards breaking bad news. Preferred educational tools were seminars with simulation (students: 71.4%, physicians: 49.5%), observing more senior faculty (students: 57.4%, physicians: 55.1%), and supervision and feedback sessions (students: 36.3%, physicians: 45.7%). The largest barriers regarding education on communication were limited time (students: 77.0%, physicians: 74.9%) and missing awareness of supervisors (students: 60.6%, physicians: 41.1%). CONCLUSIONS: Our study showed a great need for systematic training and education in breaking bad news among physicians and medical students. Hospitals, medical schools, and postgraduate training programs are strongly encouraged to fill this gap, and improve sustainable doctor-patient communication to overcome the psychological burden for physicians.

Correlation of Ductoscopic and Histopathological Findings and Their Relevance as Predictors for Malignancy: A German Multicenter Study.

BACKGROUND/AIM: The study aimed at investigating the correlation between ductoscopic and histopathological findings and clarify whether the former allow for accurate prediction of malignancy. PATIENTS AND METHODS: The prospective national multi-center study covered a sample of 224 patients with pathologic nipple discharge. A total of 214 patients underwent ductoscopy with subsequent extirpation of the mammary duct. The ductoscopic findings were categorized according to shape, number, color and surface structure of lesions and vascularity and compared to the histological results and analyses. RESULTS: Ductoscopy revealed lesions in 134 of 214 patients (62.2%). The criteria "multiple versus solitary lesion" differed significantly between malignant and benign lesions. All other criteria were not statistically significant. Malignant tumors were more frequently presented as multiple lesions, benign lesions or masses as solitary lesions (80% vs. 24.8%; p=0.018). CONCLUSION: The ductoscopic criterion "solitary vs. multiple lesion" appears to have a low diagnostic prediction of malignancy or benignity.

High depletion of breast cancer cells from the peripheral blood with the method of non-specific separation.

Circulating epithelial tumour cells (CETCs) play an important role in the formation of metastases in breast cancer patients. The depletion of such CETCs from peripheral blood of breast cancer patients using non-specific separation (without antibodies) of tumour cells from normal blood leucocytes might contribute to reduce the load of the patient's blood with tumour cells and subsequently reduce the probability of metastasis formation. This method is based on cell type-specific interaction of living cells with Carboxymethyl Dextrane (CMD) coated magnetic nanoparticles. We have developed a mild flow separation method using CMD-coated magnetic nanoparticles (core size ca. 25 nm) along with a low-field gradient magnetic separator and an external separation column (blood bag). The ability of tumour cells to preferentially bind such particles and to separate tumour cells from the white blood cells from blood samples of 25 breast cancer patients (fresh and 24-hour stored blood samples) were tested. The circulating tumour cells were quantified before and after separation by maintrac analysis. We achieved a very high depletion rate of tumour cells to < 3% remaining in the investigated 24 hours stored blood samples and ≤14% in all fresh blood samples concurrent with maintaining 56% ± 4% of vital leukocytes in all fresh blood samples.

New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments.

Clear cell Renal Cell (RCC) and Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a pro-angiogenic/pro-inflammatory context. Despite conventional or targeted therapies, metastatic RCC and HNSCC remain incurable. Alternative treatments to reference therapies (sunitinib, a multi tyrosine kinase inhibitor for RCC or cisplatin for HNSCC) are urgently needed on relapse. Here, we described the relevance of targeting the ELR+CXCL cytokines receptors, CXCR1/2, for the treatment of these two cancer types. Methods: The relevance to patient treatment was evaluated by correlating the ELR+CXCL/CXCR1/2 levels to survival using online available data. We report herein the synthesis of new pharmacological inhibitors of CXCR1/2 with anti-proliferation/survival activity. The latter was evaluated with the XTT assay with leukemic, breast, RCC and HNSCC cell lines. Their relevance as an alternative treatment was tested on sunitinib- and cisplatin- resistant cells. The most efficient compound was then tested in a mouse model of RCC and HNSCC. Results: RCC and HNSCC expressed the highest amounts of CXCR1/2 of all cancers. High levels of ELR+CXCL cytokines (CXCL1, 2, 3, 5, 6, 7, 8) correlated to shorter survival. Among the 33 synthesized and tested molecules, compound C29 reduced ELR+CXCL/CXCR1/2-dependent proliferation and migration of endothelial cells. C29 exerted an anti-proliferation/survival activity on a panel of cancer cells including naive and resistant RCC and HNSCC cells. C29 reduced the growth of experimental RCC and HNSCC tumors by decreasing tumor cell proliferation, angiogenesis and ELR+/CXCL-mediated inflammation. Conclusion: Our study highlights the relevance of new CXCR1/2 inhibitors for the treatment of RCC or HNSCC as first-line treatment or at relapse on reference therapies.

Prognostic Value of "Prepectoral Edema" in MR-mammography.

BACKGROUND/AIM: Previous studies have indicated a highly significant correlation between invasive tumors and accompanying prepectoral edema (PE) in MR-mammography (MRM). The aim of the present study was to identify prognostic factors associated with PE as a diagnostic sign. MATERIALS AND METHODS: A total of 1,109 consecutive MRM exams were included in this study. Exclusion criteria were previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy (HRT) or previous mastitis. One hundred and sixty-two patients with 180 lesions were evaluated and histologically correlated. Diagnostic evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred and eighty lesions included 104 malignant lesions (93 invasive and 11 non-invasive) and 76 benign lesions. PE was detected significantly more frequently in presence of lymphangiosis carcinomatosa ((53.8%; 14/26) vs. (9.8%; 4/41)) (p<0,000). PE significantly correlates with positive axillary nodal status ((19.4% (12/62) vs. 44.4% (12/27)) (p=0.020), as well as pathologic enhancement of the pectoral muscle (5.4% (5/93) vs. 22.7% (20/88)) (p=0,015). PE significantly correlates with higher tumor grading (G3) (33.9% vs. 13.9%) (p<0.05). There was no significant difference in a positive vs. negative estrogen (p=0.681) and progesterone (p=0.751) and/or human epidermal growth factor receptor-2 (HER-2) (p=0.726) receptor status accompanied by PE. CONCLUSION: The presence of PE may be a strong prognostic indicator for lymphatic spread and the cancerous infiltration of lymph nodes. It is also associated with the infiltration of the pectoral muscle, as well as high tumor grading. There is no correlation between prepectoral edema and positive tumor receptor status.

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer.

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

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).

OBJECTIVE: In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. METHODS: Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. RESULTS: 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. CONCLUSIONS: Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Is "prepectoral edema" a morphologic sign for malignant breast tumors?

RATIONALE AND OBJECTIVES: A variety of morphologic and kinetic signs of benign or malignant breast lesions contribute to a final diagnosis and differential diagnosis in magnetic resonance (MR) mammography (MRM). As a new sign, prepectoral edema (PE) in patients without any history of previous biopsy, operation, radiation, or chemotherapy was detected during routine breast MR examinations. The purpose of this study was to retrospectively evaluate the role of this morphologic sign in the differential diagnosis of breast lesions. MATERIALS AND METHODS: Between January 2005 and October 2006, a total of 1109 consecutive MRM examinations have been performed in our institution. In this study, only patients who would later be biopsied or operated in our own hospital were included. They had no previous operation, biopsy, intervention, chemotherapy, hormone replacement therapy, or previous mastitis. In total, 162 patients with 180 lesions were included, histologically correlated later-on by open biopsy (124 patients and 136 lesions) or core biopsy (38 patients and 44 lesions). The evaluations were performed by four experienced radiologists in consensus. RESULTS: One hundred eighty evaluated lesions included 104 malignant lesions (93 invasive and 11 noninvasive cancers) and 76 benign lesions. PE was detected in 2.6% of benign lesions (2 of 76), in none of the Ductal cacinoma in situ (DCIS) cases (0 of 11), and in 25.8% of malignant lesions (24 of 93; P < .000). PE was found significantly more frequently in presence of malignant tumors >2 cm in diameter (48.5%, 17 of 35 vs. 13.8%, 8 of 58; P < .001). PE was not statistically associated to malignant tumor type, presence or absence of additional DCIS, and number of lesions. This resulted in the following diagnostic parameters for PE as an indicator for malignancy: sensitivity of 19.3%, specificity of 97.3%, positive predictive value (PPV) of 92.3%, negative predictive value of 48%, and accuracy of 57.7%. CONCLUSIONS: In case of occurrence, the "PE sign" seems to be a specific indicator for malignant tumors with a high PPV, independent from its entity.

Ductoscopic detection of intraductal lesions in cases of pathologic nipple discharge in comparison with standard diagnostics: the German multicenter study.

BACKGROUND: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. PATIENTS AND METHODS: Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. RESULTS: Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). CONCLUSION: Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium.

Breast pathology after cryotherapy. Histological regression of breast cancer after cryotherapy.

A breast saving treatment is contemporary the preferred method of treatment with comparable results in comparing with mastectomy. In this study were evaluated the effects of cryotherapy by histological verification of changes in post treatment resection specimens. Fifty-three patients in age of 38-81 year with histologically confirmed breast cancer in needle biopsies were managed by cryotherapy between 1999 and 2007. The patients were operated between day 1 and 35 after cryotherapy. The histologic examination of operation materials showed in all cases at least partial tumor destruction. In general in 54.7% of all handled cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1 and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor-free cases after cryotherapy were those with cT1 stage. The experience of operator and the correct selection of appropriate patients (primarily taking the tumor size into account) play the most important role for achieving the best results.

[The influence of medical informed consent discussion on postoperative satisfaction and quality of life of patients with uterine fibroids after myomectomy or hysterectomy]. / Der Einfluss des ärztlichen Aufklärungsgespräches auf die postoperative Zufriedenheit und Lebensqualität von Patientinnen mit Uterus myomatosus nach Myomenukleation oder Hysterektomie.

The surgical treatment of uterine fibroids represents an important column in the therapy of this disease. Aim of this study was to find out preoperative factors that influence the treatment success of a minimal-invasive surgical -therapy.In a retrospective study 228 patients were assessed. Measures comprised questions on the decision for surgery, satisfaction with the treatment, and the EQ-5D as a measure of QoL.The sample revealed an overall satisfaction with treatment and high QoL. A better postoperative contentment and QoL in patients who felt well informed about the surgical methods and who felt secure with their decision for a specific surgery was found.Regardless of the surgical method, the preoperative consultation and the certainty of the decision turned out to be determinants of the patients' postoperative contentment and QoL. The counseling gynecologist has an essential part in the patients' decision for the treatment.

Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the Arbeitsgemeinschaft Gynäkologische Onkologie.

OBJECTIVES: The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). METHODS: Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250 mg by IM injection every 4 weeks for at least 12 weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. RESULTS: Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3 months (ITT). Overall survival was 13.2 months (ITT). Treatment was well tolerated. CONCLUSIONS: Fulvestrant at a dose of 250 mg IM every 4 weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500 mg/4 weeks might improve the efficacy of this treatment.

Reduction mammaplasty for symptomatic macromastia: which factors influence the post-operative outcome?

PURPOSE: We evaluated the long-term results and patient's satisfaction in reduction mammaplasties for symptomatic mammary hypertrophy. METHODS: From 2002 to 2008 a total of 92 women underwent bilateral mammaplasty for a symptomatic macromastia at our department. Three different surgical techniques for reduction mammaplasty were used (Bostwick, Stroembeck, Ribeiro). Patients were re-contacted in 2009 and asked to complete a self-assessment survey in order to asses their satisfaction with the post-operative symptom-relief and the overall outcome. RESULTS: 90.5 % of all patients stated, that they would retrospectively re-opt for a reduction mammaplasty. Preoperative patients' age, BMI and severity of macromasty-related symptoms were found to be factors positively correlated with a high post-interventional satisfaction with the achieved symptom-relief and the overall outcome. No correlation was found between the amount of intra-operatively resected breast tissue and the post-operative patients' assessment. Patients' assessment regarding the achieved post-operative symptom relief was comparable for all three surgical techniques, however the overall outcome rating for both bi-pedicled approaches (Stroembeck and Ribeiro) was higher compared to the mono-pedicled Bostwick technique. CONCLUSIONS: Reduction mammaplasty for patients with a mammary hypertrophy and somatic symptoms could offer a causal and effective treatment. The predictive factors for a high patients' satisfaction identified in this study could become a valuable tool in the pre-operative patients counceling and their role should be further evaluated prospectively. The use of bi-pedicled surgical techniques seems to favor a high post-operative patients' assessment.

Health-related quality of life during sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: a multicenter phase ii study of the North Eastern German Society of Gynecological Oncology.

AIM: We describe the impact of a sequential dose-dense schedule of carboplatin and paclitaxel on the quality of life (QoL) of patients with ovarian cancer. PATIENTS AND METHODS: In this multicenter phase II trial, four cycles of carboplatin followed by 12 cycles of weekly paclitaxel were applied after cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ-C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months. RESULTS: Out of 104 eligible patients 87 (84%) participated in at least one QoL assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse than age-adjusted values for the general population. Subsequently QoL improved in general. During chemotherapy with paclitaxel, most functioning scales and symptoms worsened slightly (not significantly). However, peripheral neuropathy and chemotherapy-related side-effects increased to clinically important levels. At the end of treatment, most QoL scores were similar to those of the general population, but physical functioning and fatigue were worse. Sexual functioning and peripheral neuropathy remained problematic. CONCLUSION: QoL was affected mainly by the weekly paclitaxel schedule, but effects were in most cases only temporary. A dose-dense regimen using a sequential protocol may be favourable in terms of QoL.

Computer assisted analysis of MR-mammography reveals association between contrast enhancement and occurrence of distant metastasis.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is able to detect breast cancer with high sensitivity. Furthermore, this method provides functional information on tissue composition and vascularization. This study aims to identify the potential of DCE-MRI to predict distant metastasis in breast cancer patients using computer assisted interpretation of dynamic enhancement data. For this purpose, 59 consecutive patients with newly diagnosed invasive breast cancer received pretherapeutic DCE-MRI at 1.5 Tesla according to international recommendations. In all patients, follow up interval and occurrence of distant metastasis was documented. For DCE-MRI analysis dedicated software was used (Brevis, Siemens Healthcare, Erlangen, Germany). It allows semiautomatic identification of the most suspect curve in a lesion analyzed. Enhancement parameters assessed were "Initial Enhancement", "Washout", "Peak-Enhancement", and "Time to Peak Enhancement". Cox proportional hazards regression (CPHR) was used to analyze the effect of these parameters on the probability of metachronous distant metastasis. Median follow up period was 52.0 months. 6 patients developed distant metastases between 11 and 35 months after breast cancer diagnosis. In CPHR, Washout could be identified as significant and independent predictor for occurrence of distant metastasis (P = 0.0134). Our initial data demonstrate an association between computer measured enhancement parameters in DCE-MRI and occurrence of distant metastasis by quantification of Washout.

Laparoscopic myomectomy in peri- and post-menopausal women is safe, efficacious and associated with long-term patient satisfaction.

OBJECTIVE: Women in the peri- and post-menopause may ask for uterus-preserving therapy options when presenting with benign uterine disorders such as symptomatic fibroids. Laparoscopic myomectomy (LM) for patients in the peri- and post-menopause as a surgical alternative to hysterectomy is widely considered to be non-standard treatment. The aim of this study was to analyze safety and outcome of LM beyond the reproductive period. STUDY DESIGN: We evaluated the surgical outcome and patient satisfaction for a total of 451 patients: 85 peri- or post-menopausal women as group A and, for reference, 366 premenopausal women in group B, who received LM from 1998 to 2008 in our department. We analyzed data from our medical records and applied a patient questionnaire in September 2009. RESULTS: The average number of fibroids removed and size of the leading fibroid were similar in both groups. Time of surgery was different in group A, at 102.8 min, compared to group B, 128.6 min (p<0.01). Rates of intra- (2.21% overall) and post-operative complications (6.22% overall) were comparable for both groups. Post-surgical hospitalization was shorter in group B (4.4 days) compared to group A (5.0 days) (p<0.01). Evaluation of the questionnaire showed high satisfaction with the results of LM in both subgroups with a significantly lower number of relapses in group A (3.5%) compared to group B (11.2%). CONCLUSION: Laparoscopic myomectomy as a surgical treatment option in the peri- and post-menopause was characterized by a low rate of complications and relapses as well as a high degree of patient satisfaction in our analysis.

Effect of contrast agent on the results of in vivo ¹H MRS of breast tumors - is it clinically significant?

Choline (Cho) signal identification and quantification in (1)H MRS are used in breast cancer diagnosis. However, an influence of the gadolinium-based contrast agent on the Cho amplitude has been reported experimentally. This study aims to identify the impact of gadolinium-based contrast agents on Cho detection and quantification in postcontrast breast MRS. Consecutive patients were recruited prospectively and randomly allocated to two groups. Group A received a neutral (gadolinium diethylenetriaminepentaacetic acid bis-methylamide) and group B an ionic (gadolinium diethylenetriaminepentaacetic acid) contrast agent, each at a dosage of 0.1 mmol/kg. First, the presence of Cho was identified visually. Then, the normalized Cho intensity in malignant lesions was quantified. Multivariate analysis was applied to identify independent influencing factors on Cho. Sixty-three lesions were investigated [A, n = 34; B, n = 29; 43 malignant (one bilaterally malignant), 20 benign]. Cho was identified visually in 14 of 20 malignant tumors in group A and 12 of 22 malignant tumors in group B (p = 0.477). Normalized Cho differed significantly (p = 0.001) between groups A (mean, 26.8 ± 6.0 AU) and B (mean, 18.2 ± 12.5 AU). No linewidth differences were identified (p > 0.05). Multivariate analysis revealed only group membership (A versus B) as an independent predictor of Cho (p = 0.017). The results suggest stronger negative effects of an ionic relative to a neutral gadolinium-based contrast agent on breast tumor MRS in vivo. These results should be considered when conducting and comparing quantitative Cho measurements in the breast.

Loss of BRCA1 protein expression as indicator of the BRCAness phenotype is associated with favorable overall survival after complete resection of sporadic ovarian cancer.

OBJECTIVE: Hereditary epithelial ovarian cancers (EOCs) not expressing functional BRCA1 protein are characterized by defects in homologous recombination DNA repair, rendering such tumors more sensitive to DNA damaging agents and synthetic lethality, that is, poly-ADP-ribose-polymerase inhibitor treatment. The aim of this study was to evaluate the use of BRCA1 immunohistochemistry (IHC) for EOC prognosis and identification of features of the BRCAness phenotype. METHODS: Twenty-seven patients who were treated for advanced EOC by macroscopic complete surgical tumor resection and first-line carboplatin/paclitaxel treatment were included. Time to recurrence and overall survival time after initial surgery were determined, and patients' samples were evaluated for BRCA1 expression by IHC. BRCA1 messenger RNA expression and promoter methylation was analyzed to elucidate regulatory mechanisms involved in BRCA1 protein loss. RESULTS: BRCA1 IHC-negative patients had a significantly longer overall survival (crude rate, 1537 days) compared to the BRCA1 IHC-positive group (crude rate, 827 days; P = 0.01). The patients in the BRCA1 IHC-negative group were significantly younger (51 years) compared to BRCA1 IHC-positive patients (61 years; P < 0.01). Importantly, both transcriptional and posttranscriptional mechanisms regulate BRCA1 protein expression. Only protein but not messenger RNA level were associated with longer overall survival. CONCLUSION: Epithelial ovarian cancers with negative BRCA1 protein expression were identified in younger patients, showed a significantly better overall survival, prolonged treatment intervals and a tendency for an extended progression free time interval. BRCA1 IHC negativity of sporadic EOC may be predictive of sensitivity to platinum-based chemotherapy and the poly-ADP-ribose-polymerase inhibitor-sensitive BRCAness phenotype.

Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups.

PURPOSE: To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. PATIENTS AND METHODS: Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m(2)) followed by four 3-week cycles paclitaxel (175 mg/m(2)) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue. RESULTS: Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure. CONCLUSION: Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.