Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes: Risk Pattern and Outcomes on a Community Level.

Introduction: The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX®) in patients with 0-3 lymph nodes in a high-volume community hospital. Methods: Patients with non-metastatic HR*/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX® testing were included in this retrospective study. The distribution of clinicopathologic characteristics, recurrence score (RS) risk, and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease-free survival (DFS) and overall survival (OS) were estimated. Results: From 2012 to 2017 ODX® was consecutively performed in 575 (16.4%) of 3,492 women with HR*/HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had an RS of 0 to 25 and 112 (20.3%) had an RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5-year DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p = 0.101) or OS (97.2% vs. 96.0%; p = 0.737) for patients with an RS of 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions: The results of the study confirm the observations from randomized studies on the use of the ODX® in a real-world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR*/HER2- breast cancer with 0-3 positive lymph nodes and RS <25.

Therapy response and prognosis of patients with early breast cancer with low positivity for hormone receptors - An analysis of 2765 patients from neoadjuvant clinical trials.

AIM: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. METHODS: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1-9%) and strong-positive (ER or PR 10-100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). RESULTS: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87-1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78-1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23-0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33-0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33-0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). CONCLUSION: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.

Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases.

BACKGROUND: The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice. METHODS: Data were provided by the population-based Munich Cancer Registry. Between 1998 and 2014, 1048 female patients with diagnosis of DCIS and treated at two Breast Care Centres were included in this observational study. The effectiveness of postoperative radiotherapy and variables predicting the use of radiotherapy were retrospectively analysed. RESULTS: After adjusting for age, tumour characteristics and therapies, Cox regression analysis for local recurrence-free survival identified RT as an independent predictor for improved local control (HR: 0.579; 95%CI: 0.384-0.872, p = 0.008). Ten-year cumulative incidence of in-breast recurrences was 20.0% following BCS, compared to 13.6% in patients receiving postoperative radiotherapy (p = 0.012). As an estimate for disease-specific survival, 10-year relative survival was 105.4% for patients receiving postoperative radiotherapy and 101.6% without radiotherapy. On multivariate analysis, postoperative radiotherapy was not associated with improved overall survival (HR 0.526; 95%CI: 0.263-1.052, p = 0.069). Over time, a significant increase of RT was registered: while 1998 only 42.9% of patients received postoperative radiotherapy, the proportion rose to 91.2% in 2014. Women aged < 50 years (OR: 2.559, 95%CI: 1.416-4.625, p < 0.001) or with negative hormone receptor status (OR: 2.625, 95%CI: 1.458-4.728, p = 0.001) or receiving endocrine therapy (OR: 1.762, 95%CI: 1.060-2.927, p = 0.029) were more likely to receive postoperative radiotherapy after BCS. CONCLUSIONS: In conclusion, this study provides insights regarding the adoption and treatment pattern of postoperative RT following BCS for DCIS in a large cohort reflecting "real-life" clinical practice in this setting. Postoperative RT was found to be associated with a reduced risk of ipsilateral recurrence and no survival benefit compared to observation alone.

A European, Observational Study of Endocrine Therapy Administration in Patients With an Initial Diagnosis of Hormone Receptor-Positive Advanced Breast Cancer.

BACKGROUND: Despite guideline recommendations, reports suggest that a proportion of patients with hormone receptor (HR)-positive locally advanced or metastatic breast cancer (LA/MBC) might not receive endocrine therapy. The aims of this study were to estimate the proportion of postmenopausal patients with an initial (primary) diagnosis of HR-positive LA/MBC in Europe, and to assess the administration of endocrine treatment in these patients. MATERIALS AND METHODS: Fourteen national and regional cancer registries across Europe were invited to participate in this observational study. Six registries each provided anonymized clinical information on > 5000 postmenopausal women with breast cancer diagnosed between January 2000 and December 2014, including age at diagnosis, estrogen and/or progesterone receptor status, disease stage, and receipt of endocrine therapy. The proportion of patients with an initial diagnosis of HR-positive LA/MBC and, of these, the proportion who received endocrine therapy, was calculated. RESULTS: Registries from Belgium, England, Ireland, Norway, The Netherlands, and Munich, Germany provided data. In total, 316,680 postmenopausal women were diagnosed with breast cancer, including 244,268 with known HR status and disease stage. Of these patients, 19,002 (7.8%) had a primary diagnosis of HR-positive LA/MBC. This proportion ranged from 5.4% (N = 4484) in England to 12.7% (N = 4085) in Germany. Most of these patients (n = 14,157; 74.5%) received endocrine treatment, ranging from 55.5% (n = 445) in Norway to 88.1% (n = 443) in Belgium. CONCLUSION: These results indicate that a sizeable proportion of postmenopausal patients in Europe received a primary diagnosis of HR-positive LA/MBC, and that almost three-quarters received subsequent endocrine therapy as per guideline recommendations.

No Survival Benefit for Patients with Treatment in Certified Breast Centers-A Population-based Evaluation of German Cancer Registry Data.

Much time and money has been spent on the establishment and preservation of certified breast centers (CBCs), but up to now there is almost no evidence for whether certification results in an improved outcome for breast cancer patients. The aim of this evaluation was to assess, whether the certification of specialized units had any influence on their patients' outcomes and if a survival difference between CBC patients and non-CBC patients can be shown. This population-based analysis included cancer registry data from 32,789 operated breast cancer patients with no prior cancer diagnosis and with active follow-up. They were diagnosed between 2004 and 2010 in four different regions in Germany. Survival was investigated using the Kaplan-Meier method and multivariate Cox regression analysis. A survival difference was found neither between patients with treatment before and after certification of specialized units nor between CBC patients and non-CBC patients aged up to 75 years. Only for patients older than 75 years, an improved survival could be seen for CBC patients (adjusted hazard ratio 0.77; 95% confidence interval 0.68-0.87). The improved survival of elderly CBC patients is most likely caused by selection effects concerning health status differences and not by processes attributable to certification. Thus, this study found that as of yet, certification has not influenced survival of breast cancer patients.