Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Purpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond pro-gression on prior palbociclib-based regimen in patients with hor-mone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (ABC).Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immedi-ately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percent-age of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis.Results: Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6-53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2-27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8-6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71-282.9; P = 0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials

Neuromodulation of the Autonomic Nervous System in Chronic Low Back Pain: A Randomized, Controlled, Crossover Clinical Trial

Chronic pain is a societal concern influencing the autonomic nervous system. This system can be captured with automated pupillometry. The direct connection between the epidermal cells and the brain is presented as part of the central nervous system, reflecting the modulation of the autonomic system. This study's aim was to investigate if tape containing magnetic particles (TCMP) has an immediate effect on the autonomic nervous system (ANS) and influences chronic low back pain. Twenty-three subjects completed this study. Subjects were randomized to either receive the control tape (CT) or TCMP first. Each subject underwent a pain provocative pressure test on the spinous process, followed by the skin pinch test and automated pupillometry. Next, the TCMP/control tape was applied. After tape removal, a second provocative spinous process pressure test and skin pinch test were performed. Subjects returned for a second testing day to receive the other tape application. The results demonstrate that TCMP had an immediate significant effect on the autonomic nervous system and resulted in decreased chronic lower back pain. We postulate that this modulation by TCMP s has an immediate effect on the autonomic system and reducing perceived pain, opening a large field of future research.Sin financiación4.7 Q1 JCR 20220.897 Q1 SJR 2022No data IDR 2022UECUE

Effectiveness of Transcutaneous Neuromodulation on Abductor Muscles Electrical Activity in Subjects with Chronic Low Back Pain: A Randomized, Controlled, Crossover Clinical Trial

Introduction: Non-specific chronic low back pain (NSCLBP) is a major cause of functional impairment, resulting in consequences like job absenteeism and reduced quality of life. Risk factors such as muscle weakness and tightness have been implicated. Electromagnetic fields have therapeutic effects on human tissue, including pain relief and muscle relaxation. This study aimed to examine the impact of a tape with magnetic particles (MPT) applied to the lumbar area on abductor muscle strength and surface electromyography (sEMG) of the Gluteus Medius and Tensor of the Fascia Lata muscles in individuals with NSCLBP. Methods: It was carried out a double-blind, randomized, controlled, crossover trial and with test retest, with 41 consecutive patients younger than 65 years who previously diagnosed with NSCLBP to assess the effect of a MPT over hip abductor muscle strength and activity. sEMG and force data were obtained during the Hip Stability Isometric Test (HipSIT). The HipSIT was used to assess the abduction strength using a hand-held dynamometer and sEMG. The HipSIT uses the maximum voluntary isometric contraction (MVIC). Four trials were recorded and the mean extracted for analysis. The tape was applied with either a MPT or a sham magnetic particle tape (SMPT) bilaterally without tension on from L1 to L5 paravertebral muscles. Results: The significant increase in the recruitment of fibers and the significant increase in the maximum voluntary contraction by applying MPT with respect to the SMPT, correspond to the increases in the Peak Force and the decrease in the time to reach the maximum force (peak time) of both muscles. Conclusion: Application of a MPT in patients with NSCLBP suggests an increase in muscle strength of the Gluteus Medius and Tensor Fascia Lata bilaterally during the HipSIT test. Lumbar metameric neuromodulation with MPT improves muscle activation of the hip musculature.Sin financiación2.7 Q3 JCR 20220.667 Q2 SJR 2022No data IDR 2022UEMUE

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer.

In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤ 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤ 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

BACKGROUND. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. PATIENTS AND METHODS. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). RESULTS. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. CONCLUSION. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. IMPLICATIONS FOR PRACTICE: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis