Table 1B. Tailored recommendations for systemic therapy in breast cancer patients during the COVID-19 pandemic according to tumor biology.

Breast cancer biology	Recommendations	Notes	Ref.
Atypical hyperplasia− ER+ LCIS− ER+ DCIS	Effectively treated with either tamoxifen or aromatase inhibitors ER+ DCIS: consider preoperative endocrine therapy for 6 months		[24,25,27,28]
Low-risk luminal BC (stage I–II, ER+/HER2−, low-grade, lobular BC, oncotype score <25, luminal A signature)	Consider neoadjuvant endocrinal treatment for 6–12 months or till maximum response Consider omitting adjuvant chemotherapy	These low-risk patients do not usually benefit from chemotherapy	[24,25,26,50]
Premenopausal BC patients who are planned for LHRH agonists	Consider applying /3 months dosing, to reduce patient visits Consider monthly home administration by the patient or visiting nurse		[24,50]
Non-metastatic HER2+ BC	Should be treated with chemotherapy and anti-HER2 therapy T1aN0: consider omission of chemotherapy and anti-HER2 therapy Low-risk or elderly patients with cardiovascular or other comorbidities: consider discontinuation of anti-HER2 agents after 6 months instead of 12 months of treatment Stage I: consider substituting trastuzumab-DM1 instead of paclitaxel/trastuzumab Consider delaying cardiac monitoring (echo etc.) during anti-HER2 therapy, for clinically stable patients	Anti-HER2 agents (trastuzumab and pertuzumab) should be safe to use; they are unlikely to affect immune function Based on data from prospective randomized trials Based on randomized trial favoring patient safety	[24,25,50]
TNBC	Platinum should not be used routinely in the adjuvant setting Consider chemotherapy plus atezolizumab in PD-L1+ advanced TNBC after weighing benefits vs risks	Close monitoring for specific symptoms of infection or pneumonitis	[25,28]
Metastatic HER2+ BC patients	Consider early introduction of anti-HER2 agents (e.g., pertuzumab/trastuzumab) Consider giving anti-HER2 agents at longer intervals (i.e., /4 weeks) Consider discontinuation of maintenance anti-HER2 agents (e.g., trastuzumab, pertuzumab) for patients with minimal burden and disease control for ≥2 years	This is more likely to improve outcomes without impact on the immune system.	[24,25,50]
Metastatic ER+HER2− BC patients	Consider delaying adding CDK4/6, mTOR, or PIK3CA inhibitors to endocrine therapy, especially in elderly patients with comorbidities, in the following situations: 1. Where endocrine-therapy alone is providing effective tumor control 2. In first line 3. Low disease burden or bone-only disease Dose reduction of palbociclib does not decrease efficacy	Use of these agents must be weighed against the increased risk of adverse events (e.g., neutropenia, pneumonitis) Endocrine therapies can be safely used (e.g., tamoxifen, aromatase inhibitors, fulvestrant) with no effect on immune function Fulvestrant needs monthly application	[24,25,50]

AC: Adriamycin and cyclophosphamide; ANT: Anthracyclines; BC: Breast cancer; CMF: Cyclophosphamide, methotrexate, fluorouracil; DCIS: Ductal carcinoma in situ; DM1: Ado-trastuzumab emtansine; EC: Epirubicin, cyclophosphamide; ER: Estrogen receptor; LCIS: Lobular carcinoma in situ; LHRH: Luteinizing-hormone releasing hormone; PD-L1: Programmed death-ligand 1; TNBC: Triple-negative breast cancer; 5-FU: 5-fluorouracil.