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

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      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.
    • Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      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.
    • Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      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.
    • Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      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.
    • Correction: Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-04-12)
      A Correction to this paper has been published: https://doi.org/10.1038/s41416-021-01378-x
    • Publisher Correction: Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK 'Alert Level 4' phase of the B-MaP-C study.

      Dave, Rajiv V; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O'Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P; Kirkham, Jamie J; Camacho, Elizabeth M; Fairbrother, Patricia; Sharma, Nisha; et al. (2021-06-23)
    • Publisher Correction: Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK 'Alert Level 4' phase of the B-MaP-C study.

      Dave, Rajiv V; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O'Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P; Kirkham, Jamie J; Camacho, Elizabeth M; Fairbrother, Patricia; Sharma, Nisha; et al. (2021-06-23)
    • Publisher Correction: Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-06-23)
    • Rivaroxaban compared to no treatment in ER-negative stage I–III early breast cancer patients (the TIP Trial): study protocol for a phase II preoperative window-of-opportunity study design randomised controlled trial

      Castle, John; Blower, Emma; Bundred, Nigel J.; Harvey, James R.; Thachil, Jecko; Marshall, Andrea; Cox, Karina; Cicconi, Silvia; Holcombe, Chris; Palmieri, Carlos; et al. (BioMed Central, 2020-08-27)
      Abstract: Background: Breast cancer patients are at a four-fold increased risk of developing a venous thromboembolism (VTE), a major cause of death in this group. Conversely, coagulation factors promote tumour growth and metastasis. This has been evidenced in preclinical models, with an inhibitory effect of anticoagulants on cancer growth through proliferative, angiogenic, apoptotic, cancer stem cell and metastatic processes. The extrinsic clotting pathway is also more upregulated in patients in the relatively poorer prognosis oestrogen receptor (ER)-negative breast cancer subgroup, with increased tumour stromal expression of the coagulation factors Tissue Factor and thrombin. Rivaroxaban (Xarelto®, Bayer AG, Leverkusen, Germany) is a direct oral anticoagulant (DOAC). It is a Factor Xa inhibitor that is routinely prescribed for the prevention of stroke in non-valvular atrial fibrillation and for both VTE prophylaxis and treatment. This trial will assess the anti-proliferative and other anti-cancer progression mechanisms of Rivaroxaban in ER-negative early breast cancer patients. Methods: This UK-based preoperative window-of-opportunity phase II randomised control trial will randomise 88 treatment-naïve early breast cancer patients to receive 20 mg OD Rivaroxaban treatment for 11 to 17 days or no treatment. Treatment will be stopped 24 h (range 18–36 h) prior to surgery or repeat core biopsy. All patients will be followed up for 2 weeks following surgery or repeat core biopsy. The primary endpoint is change in tumour Ki67. Secondary outcome measures include tumour markers of apoptosis and angiogenesis, extrinsic clotting pathway activation and systemic markers of metastasis, tumour load and coagulation. Discussion: Laboratory evidence supports an anti-cancer role for anticoagulants; however, this has failed to translate into survival benefit when trialled in patients with metastatic disease or poor prognosis cancers, such as lung cancer. Subgroup analysis supported a potential survival benefit in better prognosis advanced disease patients. This is the first study to investigate the anti-cancer effects of anticoagulants in early breast cancer. Trial registration: UK National Research Ethics Service (NRES) approval 15/NW/0406, MHRA Clinical Trials Authorisation 48380/0003/001-0001. The sponsor is Manchester University NHS Foundation Trust, and the trial is co-ordinated by Cancer Research UK Liverpool Cancer Trials Unit (LCTU). EudraCT 2014-004909-33, registered 27 July 2015. ISRCTN14785273.