With an epicentre in the Hubei Province of the People’s Republic of China, the current outbreak of the novel coronavirus SARS‐CoV‐2 (coronavirus disease 2019, COVID-19), has spread world-wide. In January 2020, the WHO Emergency Committee declared a global health emergency (1). By the 31st of March, 2020, there were 788,522 cases confirmed worldwide, with 37,878 deaths (2). COVID-19 has led to worldwide repercussions in healthcare delivery, including that of cancer care (3).
1.2 Statements from professional bodies
1.2.1 Association of Breast Surgery
The Association of Breast Surgery published a guidance statement on 15th March 2020 in response to the ongoing threat of COVID-19 and the likely changes required to the management of patients presenting with breast symptoms and those with confirmed breast cancer. This included triage of all referrals to breast clinic, and precautionary advice to those patients with a high index of suspicion of breast cancer, who should continue to attend. There have been reports of suspension of all follow-up clinics and high risk surveillance nationally, and there is suspension of breast screening. A new model of telephone clinics has been employed.
Management of patients confirmed to have breast cancer may involve an adjusted treatment pathway (referred to as “COVID-altered” in this protocol). In the event of an anticipated shortage of theatre space, there will be prioritisation of patients being offered surgery. This will likely lead to more widespread use of primary and neoadjuvant endocrine therapy, and reduced use of neoadjuvant chemotherapy, which will likely be reserved for patients with inoperable disease, rather than for down-staging for breast and axillary conservation.
Specific guidance for patients diagnosed with breast cancer during the pandemic have been circulated to the ABS membership (4):
- Clip put in all cancers when biopsy performed.
- Aim for day case surgery in majority of patients.
- If theatre space is limited, surgical priority given to oestrogen receptor (ER) negative patients first, then HER2+ patients and then pre-menopausal ER+ patients.
- For ductal carcinoma in situ (DCIS) patients if theatre space available prioritise high grade DCIS.
- Neoadjuvant chemotherapy only for inoperable disease, NOT to downstage from mastectomy to BCS or to perform axillary conservation in ER- or human epidermal growth factor receptor 2 (HER2+) patients.
- No immediate breast reconstruction. Mastectomy and delayed reconstruction to be offered at a later date.
- If insufficient theatre capacity, post-menopausal ER+ patients to be commenced on primary endocrine therapy. If not enough theatre capacity premenopausal ER+ patients may also have to be commenced on primary endocrine therapy.
- Discuss with oncology whether all grade 3 or node positive ER+ positive patients should have genomic testing performed on the core biopsy. If a high score to have surgery as would normally need adjuvant chemotherapy. Currently genomic testing is not reimbursed in this situation, but this will need to be re-considered.
1.2.2 National Coordinating Committee for Breast Pathology (NCCBP)
The NCCBP have published specific guidance (5) to protect staff during preparation of large breast samples, for example by avoiding submission of fresh specimens being submitted to the laboratory and should instead be placed in formalin as soon as possible and all slicing should be carried out in a Microbiological Safety Cabinet. Guidelines have also been developed for reporting of pathological specimens in the event that a specialist breast pathologist is unavailable.
1.2.3 Royal College of Radiology
International guidelines have been published on radiation therapy for breast cancer during the COVID-19 pandemic (6). In addition to this, the Royal College of Radiologists (RCR) have published national guidelines on the rationalisation of radiotherapy for breast cancer patients during the pandemic (7).
- Omit radiotherapy (RT) for patients 65 years and over (or younger with relevant co-morbidities) with invasive breast cancer that are up to 30 mm with clear margins, grade (G) 1-2, ER+, HER2- and node negative who are planned for treatment with endocrine therapy.
- Deliver RT in 5 fractions only for all patients requiring RT with node negative tumours that do not require a boost. Options include 28-30 Gy in once weekly fractions over 5 weeks or 26 Gy in 5 daily fractions over 1 week as per the FAST and FAST Forward trials respectively.
- Boost RT should be omitted to reduce fractions and/or complexity in the vast majority of patients unless they are 40 years old and under, or over 40 years with significant risk factors for relapse.
- Nodal RT can be omitted in post-menopausal women requiring whole breast RT following sentinel lymph node biopsy and primary surgery for T1, ER+, Her2, G1-2 tumours with 1-2 macrometastases.
- Consider delivering RT, 26 Gy in 5 fractions for patients requiring nodal radiotherapy who would have fulfilled the eligibility for the FAST Forward nodal subgroup study (not internal mammary chain (IMC) irradiation) and where nodal RT is still considered necessary during the COVID-19 pandemic.
Further guidelines have been published regarding the use of pre-operative breast radiotherapy in patients whose surgery is postponed (8).
- Newly diagnosed invasive breast cancer with no systemic therapy options (chemotherapy or endocrine) e.g. patient with ER- breast cancer but deemed unsuitable for chemotherapy as significantly increased risk of COVID-19 mortality.
- Completion of all neoadjuvant therapy with no option of endocrine and/or HER2 directed therapy e.g. patients with triple negative breast cancer.
- Loco-regional cancer progression/poor response despite use of all available neo-adjuvant therapies including Her2 directed and/or endocrine therapy.
1.2.4 Cancer Core Europe
The ‘Cancer Core Europe (CCE)’ consortium have published a ‘roadmap’ for care of cancer patients during the COVID-19 pandemic (9). These are general consensus measures taken by CCE centres during the COVID-19 pandemic, which include re-structuring of service provision and amendments to usual protocols of radiation therapy and chemotherapy, with a clearly defined prioritisation scheme for anti-cancer therapy based on anticipated outcome. They offer opinion on critical research priorities, which includes to ‘collect real-world data on the effects of adjustment and de-escalation of treatment regimens on the outcomes of patients with cancer.’
1.3 The impact of COVID-19 on working patterns and treatment pathways
The attendance at multi-disciplinary team (MDT) meeting will be minimal, in accordance with ABS guidelines, and it is likely that the primary treating clinician will not be present at the MDT. It is vital that the clinicians not present at MDT have an understanding of the altered decision making process. Therefore, there is a need to contemporaneously capture standard and COVID-altered management decisions, not only to document the changes in treatment provision, but also to ensure that these decisions were deliberate, and not made in error (given increased pressures). This would ideally be performed prospectively, if only to develop an ‘aspirational’ datasetfor further audit / interrogation. However, considering the pressures on the service currently, this can be done retrospectively.
1.4 Possible breast cancer management scenarios during the COVID-19 pandemic
1.4.1 Pre-operative setting
- Omitted/incomplete neoadjuvant chemotherapy, in particular for patients with HER2+ cancers and triple-negative cancers.
- No neoadjuvant chemotherapy for patients requiring down-staging to accommodate breast conserving surgery or axillary conservation
- Patients with hormone receptor positive cancers having primary/neoadjuvant endocrine therapy with a view to delayed surgery once the pandemic is under control.
- Patients having delayed surgery due to insufficient theatre capacity
- Changes to pre-op assessment, including altered imaging protocols and biopsy of ‘incidental lesions’
1.4.2 Operative setting
- Patients having delayed (>31 days) surgery
- Patients having simple mastectomy, who have requested / would usually be offered immediate reconstruction, who are now having simple mastectomy
- Patients having mastectomy due to omission of RT, who would otherwise have been offered breast conserving surgery.
- Patients who are at high risk (>1:4 lifetime risk of developing breast cancer) who have developed unilateral breast cancer would otherwise be offered synchronous contralateral mastectomy but will denied this option due to the strained service provision.
- Patients who would usually have margin re-excision surgery for close margins or completion axillary node clearance if significant nodal disease found at sentinel lymph node biopsy (based on local protocols), who do not have further surgery.
1.4.3 Post-operative setting
– Patients having breast conserving surgery who would usually have adjuvant RT to the breast +/- axilla, which has been omitted, potentially due to newly enforced protocols on patient selection
– Patients who would usually be offered adjuvant chemotherapy +/- targeted anti HER2 therapy, not having this, potentially due to a newly introduced significant increase in the threshold of chemotherapy benefit secondary to a concern of the consequences of chemotherapy immunosuppression during the COVID-19 pandemic
– Patients having genomic testing (e.g. ONCOTYPE), which has been used outside of NICE guidelines (2018) to direct adjuvant chemotherapy
1.5 Research collaboratives
There is a well-tested route for delivery of high-quality cohort/audit studies in the UK.
The first surgical trainee research collaborative was formed in the West Midlands, however, the collaborative network now has almost universal coverage of the UK (10). Specialty surgical trainee collaboratives have also emerged in neurosurgery, plastic surgery and are forming in other sub-specialties supported by the Royal College of Surgeons (11, 12). These collaborations have the capacity to generate meaningful large scale data with the potential to inform or change clinical practice (13-15). There have been several successful breast surgery related trainee collaborative studies, such as ibra (16) , ibra-2 (17), and TeaM (18) and other national non-trainee collaborations, including the Sloane project (19) and National Audit of breast cancer in older patients (NABCOP)(20).
- Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020;25(3):278-80.
- Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020.
- Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R, et al. Clinical characteristics of COVID-19-infected cancer patients: A retrospective case study in three hospitals within Wuhan, China. Ann Oncol. 2020.
- Coles CE, Aristei C, Bliss J, Boersma L, Brunt AM, Chatterjee S, et al. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic. Clin Oncol (R Coll Radiol). 2020;32(5):279-81.
- van de Haar J, Hoes LR, Coles CE, Seamon K, Fröhling S, Jäger D, et al. Caring for patients with cancer in the COVID-19 era. Nature Medicine. 2020.
- Bhangu A, Kolias AG, Pinkney T, Hall NJ, Fitzgerald JE. Surgical research collaboratives in the UK. Lancet (London, England). 2013;382(9898):1091-2.
- Kolias AG, Cowie CJ, Tarnaris A, Hutchinson PJ, Brennan PM. Ensuring a bright future for clinical research in surgery with trainee led research networks. BMJ (Clinical research ed). 2013;347:f5225.
- Kolias AG, Jones TL, Cowie CJ, Coulter IC, Afshari FT, Tarnaris A, et al. A report from the inaugural meeting of the British Neurosurgical Trainee Research Collaborative held in the Royal College of Surgeons of England, 19 October 2012. British journal of neurosurgery. 2013;27(3):307-10.
- Pinkney TD, Calvert M, Bartlett DC, Gheorghe A, Redman V, Dowswell G, et al. Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI Trial). BMJ (Clinical research ed). 2013;347:f4305.
- Ferguson HJ, Hall NJ, Bhangu A. A multicentre cohort study assessing day of week effect and outcome from emergency appendicectomy. BMJ quality & safety. 2014;23(9):732-40.
- Multicentre observational study of performance variation in provision and outcome of emergency appendicectomy. The British journal of surgery. 2013;100(9):1240-52.
- Potter S, Conroy EJ, Cutress RI, Williamson PR, Whisker L, Thrush S, et al. Short-term safety outcomes of mastectomy and immediate implant-based breast reconstruction with and without mesh (iBRA): a multicentre, prospective cohort study. Lancet Oncol. 2019;20(2):254-66.
- O’Connell RL, Rattay T, Dave RV, Trickey A, Skillman J, Barnes NLP, et al. The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study. Br J Cancer. 2019;120(9):883-95.
- O’Connell RL, Baker E, Trickey A, Rattay T, Whisker L, Macmillan RD, et al. Current practice and short-term outcomes of therapeutic mammaplasty in the international TeaM multicentre prospective cohort study. The British journal of surgery. 2018;105(13):1778-92.
- Dodwell D, Clements K, Lawrence G, Kearins O, Thomson CS, Dewar J, et al. Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project. Br J Cancer. 2007;97(6):725-9.
- Jauhari Y, Gannon MR, Dodwell D, Horgan K, Tsang C, Clements K, et al. Addressing frailty in patients with breast cancer: A review of the literature. Eur J Surg Oncol. 2020;46(1):24-32.