The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

High concordance of 70-gene recurrence risk signature and 80-gene molecular subtyping signature between core needle biopsy and surgical resection specimens in early-stage breast cancer.

BACKGROUND AND OBJECTIVES: With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. METHODS: Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. RESULTS: We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CONCLUSIONS: CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.

Correction to: Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations.

The article "Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations", written by Barbara Schwartzberg et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on July 9, 2018, without open access.

Phase 2 Open-Label Trial Investigating Percutaneous Laser Ablation for Treatment of Early-Stage Breast Cancer: MRI, Pathology, and Outcome Correlations.

BACKGROUND: An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ. METHODS: Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin-eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns. RESULTS: In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9-91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2-99.9%). CONCLUSIONS: Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.

Effects of stellate-ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot study.

BACKGROUND: Debilitating hot flushes and sleep dysfunction often affect survivors of breast cancer, most notably in those taking anti-oestrogen medications. Conventional treatments have been only partially effective in diminishing these issues, and some have serious risks. We did a pilot study to investigate our hypothesis that stellate-ganglion block can be a safe and effective treatment for hot flushes and sleep dysfunction in this patient population. METHODS: 13 survivors of breast cancer (in remission) with severe hot flushes and night awakenings were treated with stellate-ganglion block at the anterolateral aspect of the C6 vertebra on the right side under fluoroscopy. Patients recorded hot flushes in a daily diary by use of the Hot-Flash Score, devised by Sloan and colleagues, and night awakenings by use of the Pittsburgh Sleep Quality Index. Both instruments were used 1 week before the procedure [A40] and then weekly after the procedure for 12 weeks. We used the generalised-estimating-equations method to analyse the longitudinal measurements of the number of hot flushes and night awakenings over time. This method is a popular approach to analysing datasets that have repeated measures from the same person, and is robust because it does not need the complete distribution of the outcomes to be specified. This trial is registered on the International Standard Randomised Controlled Trial Number register (ISRCTN14318565). FINDINGS: There were no adverse events resulting from the stellate-ganglion block, although patients had temporary Horner's syndrome indicating the effectiveness of the block. Five patients had only one stellate-ganglion block and eight had two stellate-ganglion blocks. The total number of hot flushes decreased from a mean of 79.4 (SD 37.4) per week before the procedure to a mean of 49.9 (SD 39.9) per week during the first 2 weeks after the procedure (p=0.0002). The total number of hot flushes continued to decrease over the remaining follow-up period (weeks 3-12), and stabilised at a mean of 8.1 (SD 5.6) per week (p<0.0001). The number of very severe hot flushes was decreased to near zero by the end of the follow-up period (week 12; p<0.0001). Night awakenings decreased from a mean of 19.5 (SD 14.8) per week before the procedure to a mean of 7.3 (SD 7.1) per week during the first 2 weeks after the procedure (p<0.0001). The total number of night awakenings continued to decrease over the remaining follow-up period (weeks 3-12) and stabilised at a mean of 1.4 (SD 1.2) per week (p<0.0001). INTERPRETATION: The findings of this study suggest that stellate-ganglion block can provide survivors of breast cancer with relief from hot flushes and sleep dysfunction with few or no side-effects. Long-term relief of symptoms has the potential to improve overall quality of life and increase compliance with anti-oestrogen medications for breast cancer.