Introduction

In 2020, the predicted number of new breast cancer cases was 2.3 million worldwide, with an estimated age-standardized rate (ASR) incidence of 47.8 per 100,000 person-years and ASR mortality of 13.6 per 100,000 person-year with 684,996 deaths predicted 1. The COVID-19 pandemic has challenged the medical community on many fronts, having a significant impact on access to cancer diagnosis and treatment 2. The fear of becoming infected while using healthcare facilities, fueled by the rising number of infected individuals seeking medical care, is one of the main factors delaying cancer diagnosis and treatment 3–5. A significant decrease in cancer diagnoses has been observed during the COVID-19 pandemic, with the most marked decline seen in breast cancer care (51.8%) 6.
Surgery remains the main curative treatment for breast cancer 7.  However, due to the COVID-19 pandemic, breast cancer teams have been forced to review triage for surgical procedures in a bid to optimize clinical resource usage. This move has entailed assessing risks and deciding which surgery cases should be postponed 8, such as elective surgeries 9 and taking preventive measures for potentially infected non-deferrable surgery candidates 10,11. Brazil is currently facing one of the worst moments of the pandemic, with almost 500,000 deaths registered 12. The purpose of this review is to provide an evidence-based update of the management of early breast cancer during COVID-19 outbreak, with a particular emphasis on avoiding risks to both patients and healthcare professionals (HCP).

Methods

With the aim of pooling information on the host of clinical scenarios in which early breast cancer patients may present during the COVID-19 pandemic, a group of specialists in Brazil were invited to join an expert panel. In order to ensure the most clinically-relevant information was addressed, essential information was drawn from several of the latest national and international guidelines and from other technical documents 4,9,10,13–31. The data gathered were discussed on an online platform (Within3 ®) covering topics regarding diagnosis, treatment, and management of breast cancer patients in clinical settings routinely encountered by HCPs amid the COVID-19 pandemic.
Fourteen recognized experts joined an online expert panel and worked collaboratively in five virtual closed sessions from November 18th to May 25th, 2021, in five virtual closed sessions.  A three-step process was conducted: [1] Prework, in which all relevant material was shared, and notes on crucial aspects acknowledged; [2] Steering Committee meeting, where participants discussed and shared clinical expertise, drafting recommendations; [3] Meeting convening all experts, in which a comprehensive review of all evidence provided was performed online, and resultant recommendations discussed and refined.  

Clinical Presentation of Breast Cancer

Breast cancer (BC) is a heterogeneous disease with different subtypes. Most patients with breast cancer are asymptomatic (findings from screening mammography) while others may present with a palpable lump at diagnosis. Early breast cancer (eBC; stages I and II) represents more than 75% of cases in most parts of the world 32. The management of eBC is well-defined according to international protocols 13,14,33. HER2-positive and triple negative (TN) BC are biologically more aggressive tumors whereas luminal cancers (which express hormone receptors) are more indolent 34. Based on the Ki-67 proliferation index, the St Gallen Consensus defines two luminal subtypes: luminal A (better prognosis) and luminal B (more aggressive disease)34. Surgery is the mainstay treatment for eBC, and the procedure may be performed upfront or after neoadjuvant therapy (chemotherapy or endocrine therapy). As a rule, HER2-positive, luminal B and TN patients are priority categories for urgent breast cancer therapy 33.

Pathophysiology

Cancer patients have dysregulated immunity with depleted immune cells, such as CD8+ Tcells, CD4+ Tcells, NK cells and others 35. COVID-19 infection in cancer patients significantly increases inflammatory factors and cytokines (high-sensitivity C-reactive protein, procalcitonin, IL-2, IL-6, IL-8), possibly explaining the poorer prognosis in individuals with cancer relative to those without cancer 36. SARS-CoV-2 can enter the cell by mediating spike proteins using the angiotensin-converting enzyme 2 (ACE2) receptor via plasma membrane fusion or endosomes 37.  SARS-CoV-2 stimulates the innate immune system and antigen-specific responses of B and T cells through a mechanism similar to that seen for the influenza virus 38.  The development of virus-neutralizing antibodies is essential for protection against viral infections, and clinical studies of SARS-CoV-2 vaccines have been pursuing this therapeutic target 39.

Management

Assessment and Diagnosis

In the context of the COVID-19 pandemic, the management of patients with eBC has become more complex, as patients can present in any of three clinical situations: asymptomatic patients with no known exposure to SARS-CoV-2, asymptomatic patients exposed to SARS-CoV-2, and symptomatic patients with suspected SARS-CoV-2 infection (Table 1) 40