Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Blended online learning for oncologists to improve skills in shared decision making about palliative chemotherapy: a pre-posttest evaluation.

PURPOSE: To improve shared decision making (SDM) with advanced cancer patients, communication skills training for oncologists is needed. The purpose was to examine the effects of a blended online learning (i.e. e-learning and online training session) for oncologists about SDM in palliative oncological care and to compare this blended format with a more extensive, fully in-person face-to-face training format. METHODS: A one-group pre-posttest design was adopted. Before (T0) and after (T2) training, participants conducted simulated consultations (SPAs) and surveys; after the e-learning (T1), an additional survey was filled out. The primary outcome was observed SDM (OPTION12 and 4SDM). Secondary outcomes included observed SDM per stage, SPA duration and decision made as well as oncologists' self-reported knowledge, clinical behavioural intentions, satisfaction with the communication and evaluation of the training. Additionally, outcomes of the blended learning were compared with those of the face-to-face training cohort. Analyses were conducted in SPSS by linear mixed models. RESULTS: Oncologists (n = 17) showed significantly higher SDM scores after the blended online learning. The individual stages of SDM and the number of times the decision was postponed as well as oncologists' beliefs about capabilities, knowledge and satisfaction increased after the blended learning. Consultation duration was unchanged. The training was evaluated as satisfactory. When compared with the face-to-face training, the blended learning effects were smaller. CONCLUSION: Blended online SDM training for oncologists was effective. However, the effects were smaller compared to face-to-face training. The availability of different training formats provides opportunities for tailoring training to the wishes and needs of learners.

Limiting systemic endocrine overtreatment in postmenopausal breast cancer patients with an ultralow classification of the 70-gene signature.

PURPOSE: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making. METHODS: In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2- patients with 0-3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan-Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups. RESULTS: A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively. CONCLUSION: These survival analyses indicate that the postmenopausal node-negative ER+HER2- patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.

Feasibility and outcomes of a goal-directed physical therapy program for patients with metastatic breast cancer.

PURPOSE: To evaluate the feasibility and outcomes of a tailored, goal-directed, and exercise-based physical therapy program for patients with metastatic breast cancer (MBC). METHODS: This was an observational, uncontrolled feasibility study. The physical therapy intervention was highly tailored to the individual patient's goals, abilities, and preferences and could include functional, strength, aerobic, and relaxation exercises. Feasibility outcomes were participation rate (expected: 25%), safety, and adherence (percentage of attended sessions relative to scheduled sessions). Additional outcomes were goal attainment, self-reported physical functioning, fatigue, health-related quality of life, and patient and physical therapist satisfaction with the program. RESULTS: Fifty-five patients (estimated participation rate: 34%) were enrolled. Three patients did not start the intervention due to early disease progression. An additional 22 patients discontinued the program prematurely, mainly due to disease progression. Median intervention adherence was 90% and no major intervention-related adverse events occurred. A goal attainment score was available for 42 patients (of whom 29 had completed the program and 13 had prematurely dropped out). Twenty-two (52%) of these patients achieved their main goal fully or largely and an additional 15 patients (36%) partially. Eighty-five percent would "definitely recommend" the program to other patients with MBC. We observed a modest improvement in patient satisfaction with physical activities (Cohen's dz 0.33). CONCLUSION: The tailored intervention program was feasible in terms of uptake, safety, and outcomes and was highly valued by patients and physical therapists. However, disease progression interfered with the program, leading to substantial dropout. TRIAL REGISTRATION: NTR register: NTR6475.

[Vertigo as the first manifestation of ovarian cancer]. / Vertigo als eerste teken van een ovariumcarcinoom.

BACKGROUND: Vertigo is a common complaint and may rarely be the presenting symptom of a paraneoplastic neurological syndrome (PNS). CASE DESCRIPTION: A 76-year-old woman presented at the ER with subacute cerebellar syndrome and severe vertigo. Laboratory testing revealed mild anaemia. A cerebral CT scan showed no intracranial pathology. The patient was admitted for observation. History-taking revealed she been suffering from general malaise and had unintentionally lost 16 kg in weight over recent months. Further PET-CT investigations revealed multiple enlarged mediastinal and abdominal lymph nodes with high metabolic activity. Histopathological investigation of a lymph node biopsy showed a malignancy originating from the genital tract. Positive anti-neuronal antibodies (anti-Yo) and an elevated CA-125 concentration were found in peripheral blood. We diagnosed paraneoplastic cerebellar degeneration as the first manifestation of hitherto undiagnosed occult ovarian cancer. CONCLUSION: In a patient with subacute, cerebellar syndrome with severe vertigo, after ruling out other causes, the diagnosis of PNS should be considered. Determination of anti-neuronal antibodies can help in the diagnosis. Early recognition of PNS is important for the diagnosis and treatment of the underlying malignancy.