Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Influence of the cone angles and the p-acceptor properties of phosphorus-containing ligands in the chemistry of dihydrogen complexes of ruthenium

A series of new dicationic dihydrogen complexes of ruthenium of the type trans-[(dppe)₂Ru(η²-H₂)(L')][BF₄]₂ (dppe = Ph₂PCH₂CH₂PPh₂; L' = PF(OMe)₂, PF(OEt)₂, PF(OⁱPr)₂) have been prepared by protonating the precursor hydride complexes trans-[(dppe)₂Ru(H)(L')][BF₄] using HBF₄·Et₂O. The precursor hydride complexes have been obtained from trans-[(dppe)₂Ru(H)(L)][BF₄] (L = P(OMe)₃, P(OEt)₃, P(OⁱPr)₃) via the substitution of a −OR group on the trans phosphorus ligand with a fluoride in the presence of HBF₄·Et₂O. Coupling of the dihydrogen ligand with the trans phosphorus moiety has been observed. In addition to the complexes bearing trans phosphite groups, the precursor hydrides containing trans phosphine ligands, viz., PMe₃ and PMe₂Ph, have also been prepared and characterized. It was found that the binding ability of the trans phosphorus ligand in both the hydride and dihydrogen complexes decreases with an increase in the steric congestion of the trans phosphorus moiety. This indicates that the stability of this series of complexes depends on the cone angles of the trans phosphorus ligand. The protonation reactions of the hydride precursors trans-[(dppe)₂Ru(H)(L)][BF₄] (L = P(OMe)₃, P(OEt)₃, P(OiPr)₃) (under certain experimental conditions in the case of P(OⁱPr)₃) result in mixtures of the new hydride complexes trans-[(dppe)₂Ru(H)(L')][BF₄] (L' = PF(OMe)₂, PF(OEt)₂, PF(OⁱPr)₂) and the trans-[(dppe)₂Ru(η²-H₂)(L')][BF₄]₂ derivatives. There is a strong dependence on the quantity of the acid used for the isolation of either the new hydrides or the corresponding dihydrogen complexes. Both dihydrogen and the new hydride complexes have been isolated and characterized. On the other hand, the protonation reactions of the starting hydrides that have trans-PMe₃, PMe₂Ph, or P(OⁱR)₃ (under certain experimental conditions) ligands gave a hydride dihydrogen complex, the structure formulation of which could not be established with certainty. The roles of the steric as well as the π-accepting properties of the trans phosphorus ligands in this series of complexes are discussed. X-ray crystal structures of trans-[(dppe)₂Ru(H)(P(OMe)₃)][BF4], trans-[(dppe)₂Ru(H)(PF(OMe)₂)][BF₄], and trans-[(dppe)₂Ru(η²-H₂)(PF(OEt)₂)][BF₄]₂ have been determined. trans-[(dppe)₂Ru(H)(L)][BF₄] (L = PMe₃, PMe₂Ph, P(OⁱPr)₃) undergoes substitution of the trans phosphorus ligand with H₂ to give trans-[(dppe)₂Ru(H)(η²-H₂)][BF₄] reversibly under very mild conditions