A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA).

BACKGROUND: BRCA1/2-related metastatic breast cancers (mBC) are sensitive to DNA-damage agents and show high tumor-infiltrated lymphocytes. We hypothesized that the association between pembrolizumab and carboplatin could be active in BRCA-related mBC. PATIENTS AND METHODS: In this phase II Simon's design multicenter single-arm study, BRCA1/2-related mBC patients received carboplatin at area under the curve 6 every 3 weeks for six courses associated with 200 mg pembrolizumab every 3 weeks until disease progression or unacceptable toxicity. The primary aim at first stage was overall response rate (ORR) ≥70%. Disease control rate (DCR), time to progression (TTP), duration of response (DOR), and overall survival (OS) were the secondary aims. RESULTS: Among 22 patients enrolled at the first stage, 5 BRCA1 and 17 BRCA2, 16 (76%) were luminal tumors and 6 (24%) triple-negative BC (TNBC). In 21 patients, ORR and DCR were 43% and 76% (47% and 87% in luminal, 33% and 50% in TNBC), respectively. TTP was 7.1 months, DOR was 6.3 months, and median OS was not reached. Grade ≥3 adverse events (AEs) or serious AEs occurred in 5/22 patients (22.7%). Since the primary aim was not met, the study was terminated at the first stage. CONCLUSIONS: Although the primary aim was not reached, data on efficacy and safety of pembrolizumab plus carboplatin in first-line visceral disease BRCA-related luminal mBC were provided and they need to be further investigated.

Unscented transform-based uncertainty analysis of rotating coil transducers for field mapping.

The uncertainty of a rotating coil transducer for magnetic field mapping is analyzed. Unscented transform and statistical design of experiments are combined to determine magnetic field expectation, standard uncertainty, and separate contributions of the uncertainty sources. For nonlinear measurement models, the unscented transform-based approach is more error-proof than the linearization underlying the "Guide to the expression of Uncertainty in Measurements" (GUMs), owing to the absence of model approximations and derivatives computation. When GUM assumptions are not met, the deterministic sampling strategy strongly reduces computational burden with respect to Monte Carlo-based methods proposed by the Supplement 1 of the GUM. Furthermore, the design of experiments and the associated statistical analysis allow the uncertainty sources domain to be explored efficiently, as well as their significance and single contributions to be assessed for an effective setup configuration. A straightforward experimental case study highlights that a one-order-of-magnitude reduction in the relative uncertainty of the coil area produces a decrease in uncertainty of the field mapping transducer by a factor of 25 with respect to the worst condition. Moreover, about 700 trials and the related processing achieve results corresponding to 5 × 10(6) brute-force Monte Carlo simulations.

A rapid genetic counselling and testing in newly diagnosed breast cancer is associated with high rate of risk-reducing mastectomy in BRCA1/2-positive Italian women.

BACKGROUND: Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant. PATIENTS AND METHODS: This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT. RESULTS: In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention. CONCLUSIONS: Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization.