Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

A flexible, highly stable electrochemical scanning probe microscope for nanoscale studies at the solid-liquid interface.

This work describes the design, fabrication, and application of an ultrastable scanning probe microscope for nanoscale studies at the solid-liquid interface, specifically in electrolyte environments. Quantification of system noise limits in the tunneling mode, mechanical drift rates, and lowest mechanical resonance provided values of < or = 10 pA/Hz(1/2), 2 nm/min (XY) and 0.15 nm/min (Z), and 7.9 kHz, respectively. Measurement of the closed-loop transfer function in the tunneling condition demonstrated linear feedback responses up to 4.2 and 2.5 kHz in ambient and electrochemical conditions. Atomic and molecular resolution imagings have been achieved in ambient, in situ, and electrochemical imaging environments at scan rates up to 80 lines/s. A modular design approach has produced a highly flexible microscope capable of imaging and spectroscopy in tunneling, tapping force [amplitude modulation atomic force microscopy (AFM)], and noncontact force (frequency modulation-AFM) modes.