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Abstract Background The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies. Methods The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm. Results Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories. Conclusion Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.

Purpose: The West German Study Group (WSG) Breast Cancer Intrinsic Subtype (BCIST) study was designed to assess the influence of Prosigna gene signature assay results on physicians' adjuvant treatment recommendations by determining the extent of change in pre-test treatment recommendations following assay results. Secondary objectives were to assess the influence of Prosigna results on physicians' confidence in their therapeutic recommendations and on patients' decisional conflict status, anxiety levels, and functional status.Methods: This prospective, observational, decision impact study enrolled consecutive postmenopausal patients with estrogen-receptor (ER)-positive, HER2-negative, lymph-node-negative early-stage breast cancer in 11 centers in Germany. Physicians based their pre-test adjuvant treatment recommendations on standard clinico-pathological parameters. Tumor specimens were assayed using the Prosigna test in a WSG central pathology laboratory following manufacturer's guidelines. An independent pathology laboratory performed subsequent Prosigna assays on tumor sections to assess assay result concordance with the central laboratory. Physicians completed treatment confidence questionnaires prior to and after receiving Prosigna test results. Patients completed standardized questionnaires on decisional conflict, anxiety, and health status both before and after Prosigna testing.Results: The present study population consisted predominantly of low-to-intermediate risk patients (N = 198). Prosigna had 29.3% discordance in intrinsic subtyping with local immunohistochemistry test results. After Prosigna test results, a change in the adjuvant therapy recommendation occurred in 36 (18.2%) patients; 22 (11.1%) patients switched from no chemotherapy to chemotherapy. After Prosigna test results, physicians expressed increased confidence in their prognostic assessment in 87.9% of patients, and increased confidence in their treatment recommendation in 89.4%. Patients reported improved anxiety and emotional/functional well-being after receiving Prosigna test results.Conclusions: Use of the Prosigna assay led to a change in 18.2% of adjuvant treatment decisions. Prosigna testing was associated with increased patient and physician confidence in treatment decisions, and with decreased patient anxiety and improved well-being. Any comparison of the therapeutic decision-making impacts of different genomic assays must account for potential confounding factors. [ABSTRACT FROM AUTHOR]

The article presents a study on the Canadian trial of hypofractionated radiation therapy of breast cancer. An investigation was conducted to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as the 5-week schedule. The study noted 6.7% on the risk of local recurrence at 10 years among 612 women undergoing standard irradiation while 6.2% among 622 women under hypofractionated regimen. Both regimens have almost the same cancer treatment outcome.

Background: Routine use of multigene RT-PCR based assays as Recurrence Score (RS) vs. single markers (grade, uPA/PAI-1, HR, HER2, Ki-67) is controversially discussed in early BC. Several definitions of luminal A/B subtypes have been proposed by St. Gallen guidelines and individual researchers (grade 1/2 vs. 3, Ki-67 cut-offs 14 or 20%). Recently, integration of PR>20% was proposed as an immunhistochemical luminal A subtype definition (Ki-67<14%). Here, we present the final WSG-planB trial correlation analysis of risk assessment tools and the first prospective comparison of central and local pathology IHC/FISH assessment, RT-PCR for single markers, impact of central/local grade regarding allocation of patients to luminal A/B subtypes. Methods: planB trial (04/09 to 11/11: n=2,449 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2-BC; n=3197 registered; n=3072 available for central tumor bank). RS was used as selection criterion for chemotherapy (CTx) omission in HR+ BC (if RS<11 in pN0/pN1). Risk assessment by grade, HR, HER2 (IHC/FISH), Ki-67 was evaluated locally and centrally by an independent trial pathologist in all tumors. Clinical risk was estimated using AdjuvantOnline 8.0 (cut-off of 88% of breast cancer specific survival after 10 years without therapy in HR+ disease). Results: RS distribution in 2569 HR+ tumors: 0-11 (18%), 12-25 (60%), >25 (22%) (RS1853%/34%/13%). Luminal A subtype based on Ki-67 cut-off of <14%/<20%: 50.4%/68.8%. If PR>20% was included in the luminal A/Ki-67<14% definition: 37.6%. Luminal A/B based on local/central grade: 79%/21%; 67.9%/32.1%. In 354 pN0-1 patients, CTx was omitted based on low RS (88% compliance). In this group, 62% were high-risk by clinical-pathological criteria. Allocation to luminal A/B subtypes based on local/central grade varied substantially: overall concordance was 72%, but 40% of locally luminal B (HR+/G3) were luminal A (HR+/G1/2) by central and 60% of centrally luminal B were luminal A locally. Moderate correlations were found between RS and central grade (Spearman correlation rs=0.317; p < 0.001), local grade (0.321; p < 0.001) and Ki-67 (rs = 0.374; p < 0.001), particularly due to poor correlations in the RS group <26. Correlations between groups were: RS12 and luminal A/B Ki-6714 (rs = 0.26; p < 0.001). Inclusion of PR>20% moderately improved the correlation between luminal subtypes and RS to rs=0.34; p < 0.001. Data on allocation to luminal subtypes by local/central Ki-67 will be presented at the meeting. Conclusions: Our results represent the first prospective correlation of different luminal A/B definitions vs. a guideline mentioned gene signature (RS). High RS usually implies high grade and luminal B classification, the converse is not true. There is substantial heterogeneity in risk assessment by luminal A/B classification and grade in low/intermediate RS groups. Concordance for central/local assessment of grade and luminal A/B status was limited. There is strong need for standardization of molecular subtype's immunhistochemical/clinical definition prior to implementation into daily routine. Clinical significance of these findings will be addressed by further follow up of the WSG-planB trial. [ABSTRACT FROM AUTHOR]

Background: Appropriate indication for chemotherapy (CTx) in patients with hormone receptor (HR) positive breast cancer (BC), prediction of CTx response, and addition of novel targeted therapies are the most important questions in adjuvant therapy of early BC. Few well evaluated prognostic tests identify patients (pts) with a low-risk profile resulting in a low enough CTx benefit to justify omission of CTx. Several clinical trials with results still pending have already addressed this question such as TAILORx, MINDACT, NNBC-3, WSG-planB. However, proliferation seems to be a key part of all prognostic genomic signatures. Moreover, dynamic changes of proliferation (as a result of endocrine, cytotoxic and targeted therapy) during therapy have been shown to be most important for outcome prediction in patients with pathological complete response to neoadjuvant chemotherapy in distinct BC subtypes (luminal B, TNBC, HER2+). Trial design: ADAPT is one of the first new generation adjuvant trials dealing with individualization of adjuvant decision-making in early BC. The WSG-ADAPT trial combines static assessment of prognosis of patients by a genomic signature (Recurrence Score in HR+ disease) and conventional prognostic markers (nodal status) with dynamic measurement of proliferation/apoptosis changes during a short course of preoperative therapy. ADAPT will establish early predictive molecular surrogate markers for outcome by assessing response to a short 3-week induction treatment, using a baseline diagnostic core biopsy and a second biopsy after induction treatment. ADAPT consists of an umbrella trial and four different sub-protocols (HR+/HER2-, HR+/HER2+, HR-/HER2+ HR-/HER2-) and is set up as a prospective, multi-center, controlled, non-blinded, randomized phase II/III trial. Eligibility criteria: Pre-/postmenopausal women with histologically confirmed unilateral primary invasive early BC. Women identified to require chemo- or targeted (anti-HER2) therapy must have adequate laboratory values and organ function. Pts must have no contraindications for the planned treatment. Specific aims: Primary endpoints will include evaluation of the dynamic test for outcome prediction and prospective comparison of 5yr EFS in responders (intermediate risk (RS 12-25) and good response to short-term endocrine therapy in HR+/HER2- as well as pts with pCR in HER2+/triple negative (TN) disease) compared to low risk HR+/HER2- (RS ≤11, N0-1) pts (control group). Secondary endpoints will include overall survival. Statistical methods: Assumption across sub-protocols is that adjuvant CTx can be spared in HR+/HER2- BC or pCR be achieved in HER2+/TN in expected 1120 (HR+/HER2-) or 170 (HER2+/TN) pts respectively within the main phase. Their outcome will be compared to the control group (expected n=640 HR+/HER2- pts: low risk (by RS) and thus no CTx). Assuming 94% 5yr survival in control group, one-sided test of non-inferiority at 95% CI will have 80% power for a survival non-inferiority margin corresponding to 3.2% (i.e. 90.8% survival). Present and target accrual: By June 2012, 11 of 12 initial sites have been initiated, and 7 pts recruited. Target accrual for run-in phase is 400 pts (4000 for run-in and main phase). [ABSTRACT FROM AUTHOR]

The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations. Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy—General (FACT-G) score], using an Aalen–Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL. In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform). PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application. • PreCycle evaluated the impact of an autonomous symptom monitoring application on TTD of QoL. • Primary endpoint was TTD of QoL in HR+/HER2- MBC treated with endocrine therapy + palbociclib. • Deterioration of QoL was significantly delayed with interactive CANKADO PRO-React-based ePRO assessment. [ABSTRACT FROM AUTHOR]