Lukas Schwentner

Survival of patients with bilateral versus unilateral breast cancer and impact of guideline adherent adjuvant treatment: a multi-centre cohort study of 5292 patients.

UNLABELLED This retrospective multi-centre study is focussed on recurrence free and overall survival of bilateral breast cancer (BBC) versus unilateral breast cancer (UBC). The impact of BBC on survival is stratified to guideline adherence, according to the German national S3-guideline. Another aim of the study is to identify the influence of various guideline violations in adjuvant treatment on survival of BBC patients. 229 (4.3%) patients had BBC and 5063 (95.7%) had UBC. There is a significant association between BBC/UBC and recurrence free (RFS: p < 0.001) and overall survival (OAS: p = 0.003). Only 15.7% of patients with BBC are treated 100% guideline adherent (index- + contralateral tumour). 31.0% (30.5%) were guideline adherent with respect to the index (contralateral) tumour. The outcome decreases significantly with the number of guideline violations. There was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading and if guideline adherent treatment was applied. CONCLUSION 1. Patients with BBC have primarily a worse prognosis in terms of RFS and OAS than patients with primarily UBC. 2. There is a strong association between guideline adherence and RFS/OAS of patients with BBC or UBC. The outcome decreases with the number of guideline violations. 3. If guideline adherent treatment was applied (for both tumours in case of BBC) there was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading.

A comparison of international breast cancer guidelines – Do the national guidelines differ in treatment recommendations?

AIM OF THE STUDY Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.

Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9156 patients

BackgroundTriple-negative breast cancer (TNBC) remains a challenging topic for clinical oncologists. This study sought to evaluate TNBC versus other breast cancer subtypes with respect to survival parameters. We evaluated possible differences in survival in TNBC by age and by the extent to which evidence-based treatment guidelines were adhered.MethodsThis German retrospective multi-center cohort study included 9156 patients with primary breast cancer recruited from 1992 to 2008.ResultsThe rates of guideline adherence are significantly lower in TNBC compared to non-TNBC subtypes. These lower rates of guideline adherence can be observed in all age groups and are most pronounced in the >65 subgroup [<50 (20.9% vs. 42.0%), 50–64 (25.1% vs. 51.1%), and >65 (38.4% vs. 74.6%)]. In TNBC patients of all age groups, disease-free survival and overall survival were associated with an improvement by 100% guideline-adherent adjuvant treatment compared to non-adherence. Furthermore, TNBC patients of all ages had similar outcome parameters if 100% guideline-adherent adjuvant treatment was applied.ConclusionThe rates of guideline-adherent treatment were significantly lower in TNBC, even though guideline adherence was strongly associated with improved survival. In the case of 100% guideline-adherent treatment, no difference in survival was observed over all the age groups examined, even in the group of >65-year-old TNBC patients.

Participation in adjuvant clinical breast cancer trials: Does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9433 patients

UNLABELLED Adjuvant clinical trials (CTs) usually compare a standard treatment regime versus an innovative new substance or regimen. Participation in CT however, is available for only few patients and exclusion criteria are usually very strict. Therefore we used an unselected patient cohort to investigate the following questions: MATERIAL AND METHODS This German retrospective multi-centre cohort study included 9433 patients with primary breast cancer recruited from 1992 to 2008. RESULTS One thousand two hundred and fifty-five (13.3%) patients participated in adjuvant clinical trials (PA) and 8178 (86.7%) did not (NPA). RFS was higher among participants (PA) than among non-participants (NPA) [p=0.006], but differences in overall survival (OAS) were not significant [p=0.15]. When stratified for guideline adherence, the outcome was not different for guideline conform NPA [RFS: p=0.88] [OAS: p=0.37] compared to PA. Survival parameters however, were significantly poorer in non-guideline conform PA [RFS: p<0.001] [OAS: p<0.001] and non-guideline conform NPA [RFS: p<0.001] [OAS: p<0.001] as compared to guideline adherent PA. DISCUSSION There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials tended to higher survival rates, but only if guideline-adherent treatment was applied. Patients who do not have access to clinical trials may profit substantially from guideline-adherent adjuvant treatment.

Ovarian cancer: in search of better marker systems based on DNA repair defects.

Ovarian cancer is the fifth most common female cancer in the Western world, and the deadliest gynecological malignancy. The overall poor prognosis for ovarian cancer patients is a consequence of aggressive biological behavior and a lack of adequate diagnostic tools for early detection. In fact, approximately 70% of all patients with epithelial ovarian cancer are diagnosed at advanced tumor stages. These facts highlight a significant clinical need for reliable and accurate detection methods for ovarian cancer, especially for patients at high risk. Because CA125 has not achieved satisfactory sensitivity and specificity in detecting ovarian cancer, numerous efforts, including those based on single and combined molecule detection and “omics” approaches, have been made to identify new biomarkers. Intriguingly, more than 10% of all ovarian cancer cases are of familial origin. BRCA1 and BRCA2 germline mutations are the most common genetic defects underlying hereditary ovarian cancer, which is why ovarian cancer risk assessment in developed countries, aside from pedigree analysis, relies on genetic testing of BRCA1 and BRCA2. Because not only BRCA1 and BRCA2 but also other susceptibility genes are tightly linked with ovarian cancer-specific DNA repair defects, another possible approach for defining susceptibility might be patient cell-based functional testing, a concept for which support came from a recent case-control study. This principle would be applicable to risk assessment and the prediction of responsiveness to conventional regimens involving platinum-based drugs and targeted therapies involving poly (ADP-ribose) polymerase (PARP) inhibitors.

The role of preoperative ultrasound evaluation of inguinal lymph nodes in patients with vulvar malignancy

OBJECTIVES Inguinal lymphadenectomy in vulvar malignancies is associated with significant morbidity, especially in patients over 70 years old. Under certain conditions, surgical guidelines recommend biopsy and evaluation of the sentinel node in early vulvar cancer. The purpose of our study is to evaluate ultrasonography as a predictor of inguinal lymph node involvement. METHODS A retrospective study was performed with 60 patients who had vulvar malignancies (92% of which were squamous cell carcinomas) and who were treated at our hospital between 2002 and 2012. The patients ranged in age from 35 to 89 years, with a median age of 76 years. In total, 118 groin scans were retrospectively evaluated for sonographic evidence of lymph node involvement (i.e., absence of fatty hilum, irregular shape, cortical region diameter and vascularization pattern). The results were then compared with histopathologically confirmed lymph node status. RESULTS Histopathologically confirmed lymph node status was available for 107 of the inguinal nodes examined by ultrasound, and lymph node metastases were found in 38 (35.5%) cases. The presence or absence of inguinal lymph node metastases was correctly identified by sonography in 92 (86.0%) of the scanned areas. Sensitivity was 76.3%, specificity was 91.3%, and positive and negative predictive values were 82.9% and 87.5%, respectively. CONCLUSIONS Ultrasonography of the inguinal lymph nodes showed a relatively high sensitivity and specificity for predicting inguinal tumor metastases. However, our results indicate that surgical lymph node staging is still needed to precisely determine inguinal lymph node status in vulvar cancer, especially because a missed lymph node-metastasis is often fatal.

Sentinel Node Biopsy and Axillary Dissection in Breast Cancer: The Evidence and Its Limits

BACKGROUND Increasing evidence suggests that surgical removal of the axillary lymph nodes (axillary dissection, ALD) in early breast cancer yields no advantage in terms of either overall or disease-free survival, even in women with involvement of sentinel nodes. The optimal role of sentinel node biopsy (SNB) in neo-adjuvant therapy is currently under discussion. METHOD This review is based on a selective search in the Medline, EMBASE, Cochrane Library, and G.I.N. (Guidelines International Network) databases for relevant articles on the role of axillary dissection in node-positive breast cancer and the role of SNB in neo-adjuvant chemotherapy. RESULTS Although no single study provides adequate evidence, the available literature increasingly casts doubt on the putative therapeutic benefit of ALD as part of a multimodal treatment strategy for breast cancer. It is currently unclear what group of patients, if any, might benefit from ALD. Nor is any definitive judgment possible, from the available evidence, regarding the optimal role of SNB in neo-adjuvant therapy. The most recent evidence indicates that SNB after neo-adjuvant chemotherapy in ycN0 patients who had suspect lymph nodes before systemic treatment has a low rate of sensitivity. CONCLUSION Current evidence indicates that the radicality of lymph node surgery in the treatment of breast cancer can be reduced, even if the node status is positive.

Do Patients with Luminal A Breast Cancer Profit from Adjuvant Systemic Therapy? A Retrospective Multicenter Study.

Background Luminal A breast cancers respond well to anti-hormonal therapy (HT), are associated with a generally favorable prognosis and constitute the majority of breast cancer subtypes. HT is the mainstay of treatment of these patients, accompanied by an acceptable profile of side effects, whereas the added benefit of chemotherapy (CHT), including anthracycline and taxane-based programs, is less clear-cut and has undergone a process of critical revision. Methods In the framework of the BRENDA collective, we analyzed the benefits of CHT compared to HT in 4570 luminal A patients (pts) with primary diagnosis between 2001 and 2008. The results were adjusted by nodal status, age, tumor size and grading. Results There has been a progressive reduction in the use of CHT in luminal A patients during the last decade. Neither univariate nor multivariate analyses showed any statistically significant differences in relapse free survival (RFS) with the addition of CHT to adjuvant HT, independent of the nodal status, age, tumor size or grading. Even for patients with more than 3 affected lymph nodes, there was no significant difference (univariate: p = 0.865; HR 0.94; 95% CI: 0.46–1.93; multivariate: p = 0.812; HR 0.92; 95% CI: 0.45–1.88). Conclusions The addition of CHT to HT provides minimal or no clinical benefit at all to patients with luminal A breast cancer, independent of the RFS-risk. Consequently, risk estimation cannot be the initial step in the decisional process. These findings–that are in line with several publications–should encourage the critical evaluation of applying adjuvant CHT to patients with luminal A breast cancer.

The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients

BackgroundMammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study.MethodsWe retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup.ResultsOverall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p < 0.01). For invasive lobular cancers, the mammography showed better correlation with histology than ultrasound (p = 0.01), whereas there was no such advantage for invasive ductal cancers. Ultrasound was significantly superior for HR negative cancers (p < 0.001). HER2/neu positive cancers were also more precisely assessed by ultrasound (p < 0.001). The size of HER2/neu negative cancers could be more accurately predicted by mammography (p < 0.001).ConclusionThis multicentered health services research approach demonstrates that predicting tumor size by mammography and ultrasound provides accurate results. Biological tumor features do, however, affect the diagnostic precision.

Is there a role of the local tissue RAS in the regulation of physiologic and pathophysiologic conditions in the reproductive tract

The renin–angiotensin system is well known as a systemic endocrine pathway that regulates blood pressure and salt–water metabolism. In addition to the systemic renin–angiotensin system there is evidence in different species for the presence of a local tissue renin–angiotensin system, which allows local production of the bioactive peptides angiotensin II and angiotensin (1-7). The local renin–angiotensin system has been found in a variety of tissues including tissue of the human reproductive tract. Thus, it was suspected that it may have important functions in the local hormonal microenvironment. Here, a systematic literature search was undertaken to review whether there is evidence for regulatory functions of the local tissue renin–angiotensin system in the human reproductive tract under physiological and pathological conditions.