Adaptation of international coronavirus disease 2019 and breast cancer guidelines to local context

Table 8 Priorities for medical treatment of metastatic breast cancer

High priority	Medium priority	Low priority	Comments
HER2 (+) MBC: Dual anti-HER2 therapy (pertuzumab/trastuzumab) + chemotherapy is recommended in first-line HER2 (+) MBC (Yes: 100%, No: 0%)	(1) General considerations: (a) Goals for treatment in MBC: improvement of QoL, prolong survival (Yes: 100%, No: 0%); and (b) In absence of clinical infection for SARS-CoV-2, there is no specific recommendation to test a patient who initiates therapy (Yes: 89%, No: 11%); (2) Chemotherapy: (a) Consider the use of less toxic regimens (capecitabine, CM – cyclophosphamide/methotrexate) (Yes: 100%, No: 0%); and (b) If an anthracycline, a taxane, or eribulin is used, consider the concomitant use of G-CSF (Yes: 89%, No: 11%); (3) iCDK 4/6: (a) Offer clinical benefit in the first or second line in luminal MBC. They should be considered according to resources available and institutional practices[27] (Yes: 100%, No: 0%); (b) iCDK 4/6 can be deferred in selected patients if there is a high chance of controlling the disease with endocrine therapy alone (e.g., de novo luminal MBC with a low burden of disease without visceral metastases) (Yes: 100%, No: 0%); and (c) Palbociclib dose reduction does not reduce efficacy (Yes: 100%, No: 0%)[28,29]; (4) Visceral crisis: (a) In the case of a suspected visceral crisis, clinical practice guidelines recommend the use of chemotherapy immediately (Yes: 100%, No: 0%); and (b) In an established visceral crisis, chemotherapy is the treatment of choice, but this concept is actually in revision due to the use of iCDK 4/6 in clinical practice (Yes: 100%, No: 0%); (5) Luminal MBC: (a) There should be an analysis of the benefits of using iCDK 4/6 vs the risk of adverse events. Dose reduction can reduce treatment related toxicities (Yes: 100%, No: 0%); (b) In the case of premenopausal women, it is recommended to induce ovarian suppression with LHRH analogs monthly or quarterly in selected cases, to reduce hospital admissions (Yes: 100%, No: 0%); (c) First line of treatment: currently, there is insufficient evidence to discontinue treatment with iCDK 4/6 in patients with luminal MBC (Yes: 100%, No: 0%); (d) The second line of treatment: after progression to iCDK 4/6, moving to another endocrine therapy is recommended (e.g., AI or fulvestrant) (Yes: 100%, No: 0%); and (e) Other targeted therapies in luminal MBC: in second-line, consider avoiding or deferring the addition of mTOR inhibitors (everolimus induces immunosuppression and mucositis) or PIK3CA inhibitors (alpelisib induces hyperglycemia and risk of diabetes) to endocrine therapy, especially in elderly and/or comorbid patients (Yes: 100%, No: 0%); (6) HER2 (+) MBC: (a) In patients with more than 2 yr of disease control and minimal tumor burden with trastuzumab-based regimens, discontinuation of maintenance therapy may be considered[30] (Yes: 100%, No: 0%); (b) HR (+)/HER2 (+) MBC: (b1) Patients who initiate first-line treatment: Two options according to age—(i) patients < 70 yr: Consider less toxic regimens (paclitaxel every 3 wk + dual anti-HER2 blockade as a treatment option). If using docetaxel, consider the use of G-CSF from first cycle (Yes: 89%, No: 11%); and (ii) patients > 70 yr: Consider less toxic regimens (capecitabine) + dual anti-HER2 blockade. The option of using endocrine therapy associated to anti-HER2 therapy is valid if there is a low tumoral burden (Yes: 89%, No: 11%); and (b2) patients with controlled disease: Discontinuation of chemotherapy and use of oral therapy with AI +/- LHRH analogs (in premenopausal patients) may be considered as maintenance of anti-HER2 blockade (Yes: 100%, No: 0%); and (c) HR (-)/HER2 (+) MBC: (c1) In first-line setting (where an overall survival > 5 yr is expected) with a patient < 70 yr and symptomatic: Initiate taxanes every 3 wk and/or vinorelbine or capecitabine associated with anti-HER2 blockade (pertuzumab +/- trastuzumab). If using myelosuppressive regimens, consider G-CSF to reduce the risk of neutropenia (Yes: 89%, No: 11%); and (c2) Cases where the disease is in response with one line of chemotherapy + anti-HER2 therapy, in patients classified as “high groups for COVID-19” (e.g., > 65-70 yr and/or comorbidity (diabetes, hypertension, etc.): Consider maintaining anti-HER2 therapy as maintenance (Yes: 89%, No: 11%); (7) mTNBC: (a) Recommendations with use of chemotherapy: (a1) Use regimens less frequently and with less toxicity (e.g., use paclitaxel every 2 wk -Q2W- instead of docetaxel Q3W (Yes: 78%, No: 22%); (a2) Consider G-CSF to minimize the risk of neutropenia and reduce the use of corticosteroids (Yes: 89%, No: 11%); (a3) Prefer oral chemotherapy regimens (such as capecitabine) as an alternative to the EV route (if possible) (Yes: 100%, No: 0%); (a4) Consider less immunosuppressive regimens, with a preference for monotherapy regimens rather than combinations (Yes: 100%, No: 0%); and (b) For treatment with targeted therapies, it is recommended: (b1) Immunotherapy: Consider atezolizumab + chemotherapy in patients with PD-L1 (+) mTNBC (Yes: 100%, No: 0%); and (b2) PARP inhibitors (olaparib, talazoparib): Evaluate risk/benefit (myelotoxicity) and drug interactions (Yes: 100%, No: 0%); and (8) Second-line and subsequent lines: (a) Offer second-line, third-line, or subsequent lines of treatment when therapy can deliver clinical benefit and impact on outcomes (Yes: 100%, No: 0%); (b) In HER2 (+) MBC, after progression with trastuzumab, evaluate treatment with T-DM1 and/or other available therapies, always maintaining anti-HER2 blockade (Yes: 100%, No: 0%); (c) Some doses may be deferred to minimize risk of infection during the COVID-19 pandemic (Yes: 100%, No: 0%); and (d) In MBC, after a multidisciplinary discussion and according to the patient’s preferences, terms such as “therapeutic rest”, palliative therapy or maintenance regimens with dose reduction can be offered, depending on the case (Yes: 89%, No: 11%)	Bone agent therapy: Denosumab and zoledronic acid are no urgently needed (except in cases of hypercalcemia). It can be administered every 3 mo. Bone agents for patients with bone metastases should be deferred (Yes: 100%, No: 0%)	The rapidly evolving nature of the COVID-19 pandemic may change some recommendations. These will evolve over time with continuous updates

AI: Aromatase inhibitor; COVID-19: Coronavirus disease 2019; G-CSF: Granulocyte-colony stimulating factor; HR: Hormone receptor; LHRH: Luteinizing hormone-releasing hormone; MBC: Metastatic BC.