Treatment in Certified Breast Cancer Centers Improves Chances of Survival of Patients with Breast Cancer: Evidence Based on Health Care Data from the WiZen Study.

Introduction: Certified breast cancer centers offer specific quality standards in terms of their structure, diagnostic and treatment approaches with regards to breast surgery, drug-based cancer therapy, radiotherapy, and psychosocial support. Such centers aim to improve treatment outcomes of breast cancer patients. The question investigated here was whether patients with primary breast cancer have a longer overall survival if they are treated in a certified breast cancer center compared to treatment outside these centers. Methods: We used patient-specific data (demographics, diagnoses, treatments) obtained from data held by mandatory health insurance companies ( gesetzliche Krankenversicherung , GKV) and clinical cancer registries (KKR) for the period 2009-2017 as well as hospital characteristics recorded in standardized quality reports. Using multivariable Cox regression analysis, we investigated differences in survival between patients treated in hospitals certified as breast cancers centers by the German Cancer Society (DKG) and patients treated in hospitals which had not been certified by the DKG. Results: The sample population consisted of 143720 (GKV data) and 59780 (KKR data) patients with breast cancer, who were treated in 1010 hospitals across Germany (280 DKG-certified, 730 not DKG-certified). 63.5% (GKV data) and 66.7% (KKR data) of patients, respectively, were treated in DKG-certified breast cancer centers. Cox regression analysis for overall survival which included patient and hospital characteristics found a significantly lower mortality risk for patients treated in DKG-certified breast cancer centers (GKV data: HR = 0.77, 95% CI = 0.74-0.81; KKR data: HR = 0.88, 95% CI = 0.85-0.92). This result remained stable even after several sensitivity analyses including stratified estimates for subgroups of patients and hospitals. The effect was even more pronounced for recurrence-free survival (KKR data: HR = 0.78, 95% CI = 0.74-0.82). Conclusions: Patients who are treated by an interdisciplinary team in a DKG-certified breast cancer had clear and statistically significantly better survival rates. Certification is therefore an effective means of improving the quality of care, and more patients should be treated in certified breast cancer centers.

Optimizing Medication Safety with Oral Antitumor Therapy: A Methodological Approach for the Real-World Implementation of the AMBORA Competence and Consultation Center.

Generating evidence for the efficacy of an intervention is not sufficient to guarantee its implementation in real-world settings. The randomized AMBORA trial (Medication Safety with Oral Antitumor Therapy) demonstrated that an intensified clinical pharmacological/pharmaceutical care program has substantial benefits for patients, treatment teams, and the healthcare system. Thus, we are now investigating its implementation into routine care within the AMBORA Competence and Consultation Center (AMBORA Center). We perform a multicenter type III hybrid trial following the RE-AIM framework to assess the clinical effectiveness of this care program under real-world conditions, while evaluating the implementation outcomes. Semi-structured stakeholder interviews based on the Consolidated Framework for Implementation Research (CFIR) have been conducted to identify barriers and facilitators. So far, 332 patients treated with oral antitumor drugs have been referred to the AMBORA Center by 66 physicians from 13 independent clinical units. In 20 stakeholder interviews (e.g., with clinic directors), 30% (6/20) of the interviewees anticipated possible barriers which may partly hinder sustainable implementation (e.g., unavailable consultation rooms). Furthermore, important facilitators (e.g., operational processes) were identified. This methodological description adds knowledge on how to structure a hybrid effectiveness-implementation trial and proposes multilevel implementation strategies to improve the medication safety of oral antitumor therapy.

Impact of the COVID-19 pandemic on reported cancer diagnoses in Bavaria, Germany.

PURPOSE: The aim of our study was to explore the impact of the COVID-19 pandemic on reported cancer cases in Bavaria, Germany, by comparing pre-pandemic (March 2019 to February 2020) and pandemic period (March 2020 to February 2021). METHODS: Data on incident cases were retrieved from the Bavarian Cancer Registry (until 22nd April 2022). We included patients with malignant and in situ neoplasms reported by pathology departments with consistent reporting. We calculated the number of incident cases during the COVID-19 pandemic and the pre-pandemic period with 95% confidence intervals (CI) with Bonferroni correction (α = 0.0018) based on a Poisson approach. We stratified for malignancy (malignant, in situ), tumor site, and month of year. RESULTS: Data was available for 30 out of 58 pathology departments (51.7%) from Bavaria. Incident malignant neoplasms dropped from 42,857 cases in the pre-pandemic period to 39,980 cases in the pandemic period (- 6.7%; 95% CI - 8.7%, - 4.7%). Reductions were higher for colon, rectum, skin/melanoma as well as liver (> 10.0% reduction) and less for breast cancer (4.9% reduction). No case reductions were observed for pancreas, esophagus, ovary, and cervix. Percent changes were largest for April 2020 (- 20.9%; 95% CI - 24.7%, - 16.8%) and January 2021 (- 25.2%; 95% CI - 28.8%, - 21.5%) compared to the previous year. Declines tended to be larger for in situ compared to malignant neoplasms. CONCLUSION: Detection and diagnosis of cancer were substantially reduced during the COVID-19 pandemic. Potential effects, e.g. a stage shift of tumors or an increase of cancer mortality, need to be monitored.

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

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

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

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

Trastuzumab treatment of patients with early, HER2-positive breast cancer in 17 certified German breast cancer centers.

PURPOSE: Since 2008, guidelines recommend that patients with HER2-positive early breast cancer (BC) should receive adjuvant chemotherapy in combination with trastuzumab in Germany. However, recent studies highlight that a substantial share of patients do not receive trastuzumab. We investigate which patient characteristics are associated with a tumor board recommendation for trastuzumab in Breast Cancer Centers (BCC) certified by the German Cancer Society (DKG) and the German Society for Senology, and if the recommendation differs between BCCs. MATERIALS AND METHODS: Multi-level modeling was performed using quality assurance data based on 3052 HER2-positive, operated patients with a first diagnosis of early BC treated between 2006 and 2019 in 17 BCCs in Germany to investigate whether trastuzumab recommendation varies with patient sex, age, and disease characteristics, as well as over time and across BCCs. RESULTS: Tumor board recommendations for trastuzumab differ substantially between BCCs (intraclass correlation coefficient [ICC] null model: 0.11). Our final model (ICC 0.17, Akaike Information Criterion [AIC], 1328.0, R2 0.69) shows that physicians in BCCs more often recommend trastuzumab to patients who are younger than 60 years and those with a recommendation for any additional therapy (chemotherapy, radiation or endocrine therapy) (all p < 0.05). Furthermore, there is a significant time-dependent increase of trastuzumab recommendations (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.31-1.46, p < 0.05). CONCLUSION: In certified BCCs in Germany, guideline concordant trastuzumab recommendation is increasing since 2006 (positive cohort effect). Recommendation of trastuzumab for HER2-positive BC patients in BCCs is significantly associated with patients' age and the recommendations for other additional therapy strategies, apart from surgery. The quality assurance data analyzed do not include potentially relevant confounders, such as socioeconomic status or comorbidities.

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

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

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

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

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

Is there a benefit for adjuvant radio(chemo)therapy in early cervical cancer? Results from a population-based study.

PURPOSE: Due to insufficient and conflicting prospective evidence, the recommendations on when to apply adjuvant radiochemotherapy in early-stage cervical cancer vary between international guidelines. In this population-based study, we evaluated the outcome of patients with early-stage cervical cancer based on risk factors and the adjuvant therapy they received. METHODS: The effect of primary therapy (surgery and radiochemotherapy RCT, surgery and radiotherapy RT, and surgery alone) on overall survival (OS) and recurrence-free survival (RFS) was evaluated in the complete cohort of 442 patients and in subgroups according to risk profile and nodal status. RESULTS: In low-risk patients, there was no difference in OS (p = 0.276) depending on whether patients received adjuvant therapy or not. Concerning RFS, patients with RT (including one patient with RCT) exhibited a significantly worse outcome compared to the group with surgery alone (p = 0.015). In intermediate-risk patients, the administration of adjuvant RT significantly benefited RFS when compared to surgery only in multivariate analysis (p = 0.031). Concerning OS, no significant influence for adjuvant treatment could be seen (p = 0.354). Though trends towards better OS and RFS could be observed in patients of the high-risk group-both in RCT and RT groups compared to surgery alone-the effects did not prove to be significant. CONCLUSION: Our study reaffirms the evidence against the use of adjuvant radio(chemo)therapy in low-risk early-stage cervical cancer. In intermediate-, and less pronounced in high-risk patients, however, it seems to be beneficial. The role of adjuvant radio(chemo)therapy in early cervical cancer should be further investigated in prospective randomized trials.

Sentinel lymph node detection by means of indocyanine green using the Karl Storz VITOM® fluorescence camera: a comparison between primary sentinel lymph node biopsy versus sentinel lymph node biopsy after neoadjuvant chemotherapy.

PURPOSE: The usage of radioactive Technetium99m (Tc99m) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium99m (Tc99m) like limited availability, high costs and radioactivity exposure for both patients and surgeons. METHODS: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium99m (Tc99m) in the identification of the SLN in early breast cancer. RESULTS: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc99m. The conventional Technetium99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone. CONCLUSIONS: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.

Peri- and postmenopause-diagnosis and interventions interdisciplinary S3 guideline of the association of the scientific medical societies in Germany (AWMF 015/062): short version.

This short version of the interdisciplinary S3 guideline "Peri- and Postmenopause-Diagnosis and Interventions" is intended as a decision-making instrument for physicians who counsel peri- and postmenopausal women. It is designed to assist daily practice. The present short version summarizes the full version of the guideline which contains detailed information on guideline methodology, particularly regarding the critical appraisal of the evidence and the assignment of evidence levels. The statements and recommendations of the full version of the guideline are quoted completely in the present short version including levels of evidence (LoE) and grades of recommendation. The classification system developed by the Centre for Evidence-based Medicine in Oxford was used in this guideline.

Guideline-concordant chemotherapy in patients with hormone receptor-positive and node-positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients.

PURPOSE: The German guideline for breast cancer recommends using chemotherapy (CHT) in patients with hormone receptor-positive and node-positive, invasive breast cancer. The aim of this study was to analyse the effects of CHT in this patient group on overall survival (OS) and distant metastases-free survival (DMFS), especially considering the 70-year threshold. METHODS: 1772 patients from the clinical cancer registry Regensburg (Germany) with hormone receptor-positive and node-positive, invasive breast cancer diagnosed between 2003 and 2013 were analysed in a retrospective cohort study. OS and DMFS were evaluated by means of Kaplan-Meier and multivariable Cox-regression method. Results were further examined according to age at diagnosis. RESULTS: The comparison of 1544 patients with CHT to 228 patients without CHT showed a significant benefit for CHT regarding 5-year OS (91.3% vs. 76.8%) and 5-year DMFS (86.7% vs. 74.4%, both p < 0.001). Likewise, better OS and DMFS were seen in patients aged < 70 years using CHT compared to patients without CHT of the same age. Patients aged ≥ 70 years with CHT had a minimal benefit regarding 5-year OS compared to patients without CHT, but no advantage considering DMFS. All results were confirmed in multivariable analyses except for patients being ≥ 70 years of age. CONCLUSION: Patients with hormone receptor-positive and node-positive, invasive breast cancer benefit from chemotherapy with regard to a significantly better overall and distant metastases-free survival, although chemotherapy use in patients aged ≥ 70 years results in a smaller benefit considering OS and no benefit considering DMFS.

Impact of nodal status and treatment strategy on overall survival in advanced stage cervical cancer.

PURPOSE: The lack of prognostic data impedes implementation of optimal therapy for cervical cancer. For instance, recommended therapy for FIGO IIB cervical cancer is radical hysterectomy or radiochemotherapy. To enlighten different therapeutic approaches, we investigated the benefit of individual therapies or combination thereof in patients with or without infested lymph nodes. METHODS: The German Tumor Centre Regensburg registered 389 patients with FIGO IIB, IIIA, IIIB, and IVA cervical cancer between 2002 and 2015. We estimated hazard ratios (HR) for overall survival against different therapies using univariable and multivariable cox regression. After risk adjustment with respect to clinicopathological parameters, we performed model selection using conditional stepwise reverse selection. RESULTS: We demonstrated the need for thorough assessment of the nodal status to obtain reliable data for treatment strategy. Our analysis showed significant differences for overall survival in FIGO IIB depending on therapy and nodal status. Outcome was inferior with radiochemotherapy without surgery for patients with N0 compared to surgery and radiochemotherapy combined (HR 3.012; 95% CI 1.075-8.441; p = 0.036); however, for N1, radiochemotherapy without surgery resulted in comparable outcome (HR 0.808; 95% CI 0.189-3.403; p = 0.765), whereas surgery alone yielded in poor outcome (HR 2.889; 95% CI 1.356-6.156; p = 0.006). Regardless of the nodal status, chemotherapy was superior in advanced stage cervical cancer FIGO III to IVA. CONCLUSIONS: Our study suggests that in terms of oncological outcome FIGO IIB cervical cancer patients benefit from a combination of surgery and radiochemotherapy. However, in the presence of lymph node infestation, surgery does not add substantial benefit to the patient.

Adherence to guidelines and benefit of adjuvant radiotherapy in patients with invasive breast cancer: results from a large population-based cohort study of a cancer registry.

PURPOSE: According to German S3 guidelines, radiotherapy (RT) is indicated in patients with invasive breast cancer after breast-conserving therapy (BCT). The aim of this analysis was to assess adherence to guidelines, long-term survival, recurrence rates, and recurrence-free survival after adjuvant RT in patients with BCT in daily clinical practice. METHODS: This retrospective cohort study comprised data from the population-based clinical cancer registry of the Tumor Centre Regensburg (Bavaria, Germany). 6370 patients with non-metastatic invasive breast cancer and UICC tumor stages I, II, and III who were treated in certified breast cancer centers by BCT and diagnosed between 2003 and 2013 were included in the study. RESULTS: 6184 (97.1%) breast cancer patients received guideline concordant RT and showed a 3-year overall survival (OAS) of 96.8% in contrast to 90.9% in patients without RT (5-year OAS of 93.1% vs. 79.0%, p < 0.001). In multivariable Cox regression models, better overall survival was confirmed for the RT group (HR 0.64, 95% CI 0.46-0.88, p = 0.007). The 5-year local recurrence-free survival rate (RFS) in the irradiated patients was 92.1% vs. 62.0% in the comparison group (p < 0.001). The 10-year RFS was 80.5% vs. 36.0% (p < 0.001). This difference persisted after adjusting in multivariable analysis (HR 0.20, 95% CI 0.16-0.26, p < 0.001). CONCLUSIONS: This population-based analysis showed that the implementation of German guidelines in clinical routine was successful and guideline concordant adjuvant radiotherapy after BCT leads to better overall and recurrence-free survival and lower local recurrence rates.

Phase 1-3 of the cross-cultural development of an EORTC questionnaire for the assessment of sexual health in cancer patients: the EORTC SHQ-22.

To develop and pretest an European Organization for the Research and Treatment of Cancer Sexual Health Questionnaire (EORTC SHQ-22) for the assessment of physical, psychological, and social aspects of sexual health (SH) in male and female cancer patients and survivors. Questionnaire construction started with creating a list of relevant SH issues based on a comprehensive literature review. Issues were subsequently evaluated for relevance and prioritization by 78 healthcare professionals (HCP) and 107 patients from 12 countries during in-depth interviews (phase 1). Extracted issues were operationalized into items (phase 2). Phase 3 focused on pretesting the preliminary questionnaire in a cross-cultural patient sample (n = 171) using debriefing interviews. Psychometric properties were preliminary determined using a principal component analysis and Cronbach's alpha. We derived 53 relevant SH issues from the literature. Based on HCP and patient interviews, 22 of these 53 issues were selected and operationalized into items. Testing the preliminary 22-item short questionnaire resulted in a change of wording in five items and two communication-related items; no items were removed. Preliminary psychometric analysis revealed a two-factor solution and 11 single items; both scales showed good reliability indicated by a Cronbach's alpha of 0.87 (sexual satisfaction) and 0.82 (sexual pain). Cross-cultural pretesting of the preliminary EORTC SH questionnaire has indicated excellent applicability, patient acceptance, and comprehensiveness as well as good psychometric properties. The final development phase, that is psychometric validation (phase four) including large-scale, cross-cultural field testing of the EORTC SHQ-22, has commenced.

HER2 FISH results in breast cancers with increased CEN17 signals using alternative chromosome 17 probes - reclassifying cases in the equivocal category.

AIMS: HER2 testing of invasive breast cancer by in-situ hybridization guides therapy decisions. Probing HER2 and centromere of chromosome 17 (cen17) simultaneously is supposed to reveal both a potential HER2 gene amplification and polysomy 17. However, a considerable number of breast cancer patients with quasi polysomy 17 are considered 'equivocal', which is diagnostically meaningless. Moreover, patients with equivocal/false polysomic tumours are prevented from a potentially beneficial anti-HER2 treatment. Here we evaluated the RAI1, D17S122 and TP53 hybridization markers to indicate true polysomy reliably and to reclassify equivocal samples accurately as HER2-positive. METHODS AND RESULTS: Samples with (n = 82) and without (n = 52) increased cen17 copy numbers and 78 evidently HER2-amplified specimens were analysed using dual and triple marker hybridization probes. Selected putative polysomic samples were subjected to array-based comparative genomic hybridization (aCGH). We found that 37.8% samples with putative polysomy 17 did not show any gain in RAI1, D17S122 or TP53. Accordingly, aCGH revealed evidence for the presence of HER2/cen17 co-amplification rather than for true polysomy in those cases. Reflex testing using alternate 17p markers reclassified up to 56.3% equivocal cases as HER2-positive and the combined assessment of a 17p and 17q locus allows the differentiation of true versus false polysomy. CONCLUSIONS: An increased cen17 copy number does not necessarily reflect polysomy, and reflex testing facilitates the reclassification of 'equivocals'. Nevertheless, the prognostic and predictive value of a HER2/cen17 co-amplification versus HER2 gene amplification alone must still be evaluated prospectively.