What medications are required for a patient with hormone receptor-positive breast cancer being discharged after receiving trastuzumab (Herceptin), considering potential side effects and risk of recurrence?

Post-Trastuzumab Discharge Medications for Hormone Receptor-Positive Breast Cancer

For patients with HR-positive/HER2-positive breast cancer completing trastuzumab therapy, adjuvant endocrine therapy is mandatory (Category 1 recommendation), and continuation of HER2-directed therapy until completion of 1 year total duration is required. 1

Essential Discharge Medications

HER2-Directed Therapy Continuation

• Complete up to 1 year of HER2-targeted therapy with trastuzumab (Category 1), with or without pertuzumab depending on initial nodal status 1
• If node-positive at initial staging, trastuzumab + pertuzumab is the Category 1 recommendation 1
• If ado-trastuzumab emtansine (T-DM1) was discontinued for toxicity, complete up to 1 year of HER2-directed therapy with trastuzumab ± pertuzumab 1

Mandatory Endocrine Therapy

• Adjuvant endocrine therapy is Category 1 for all HR-positive disease, regardless of pathologic response 1
• Duration should be at least 5 years 2
• Aromatase inhibitors are preferred in postmenopausal women over tamoxifen 2
• Can be administered concurrently with olaparib if indicated 1

Additional Considerations Based on Risk Stratification

High-Risk HR-Positive/HER2-Positive Disease

• Consider extended adjuvant neratinib following adjuvant trastuzumab-containing therapy for patients with perceived high risk of recurrence 1
• The benefit or toxicities of extended neratinib in patients who received pertuzumab or ado-trastuzumab emtansine is unknown 1
• Neratinib requires aggressive diarrhea prophylaxis protocols, as 95% of patients experience diarrhea with 40% grade 3 toxicity 1

Residual Disease After Preoperative Therapy

• If ypN≥1 (node-positive) with residual disease and CPS+EG score ≥3, select patients may be eligible for adjuvant abemaciclib 1
• If germline BRCA1/2 mutation with ≥4 positive lymph nodes or residual disease after preoperative therapy with CPS+EG score ≥3, consider adjuvant olaparib for 1 year (Category 2A) 1

Postmenopausal Patients

• Consider adjuvant bisphosphonate therapy (such as zoledronic acid) for risk reduction of distant metastasis for 3-5 years in postmenopausal patients (natural or induced) 1
• Zoledronic acid significantly reduced risk of recurrence by 34% and risk of death by 49% in patients older than 40 years 1

Cardiac Monitoring and Supportive Care

Mandatory Cardiac Surveillance

• Cardiac monitoring must continue during and after trastuzumab therapy due to cardiotoxicity risk 1, 3, 4
• Serial LVEF measurements are required 5
• Consider prophylactic β-blockers and ACE inhibitors, which have shown effectiveness in preventing trastuzumab-related cardiotoxicity 6
• Emerging evidence supports angiotensin receptor/neprilysin inhibitors and SGLT2 inhibitors for cardioprotection 6

Bone Health Management

• Bone mineral density determination at baseline and periodically for patients on aromatase inhibitors 2
• Consider calcium and vitamin D supplementation 2

Critical Drug Interaction Warning

Anthracycline Avoidance

• If anthracyclines are needed after trastuzumab, avoid for up to 7 months after stopping trastuzumab due to increased cardiac dysfunction risk from trastuzumab's long washout period 5
• Trastuzumab combined with anthracyclines is associated with significant cardiac toxicity (27% heart failure rate) and should be avoided 1, 5
• If anthracyclines must be used, closely monitor cardiac function 5

Common Pitfalls to Avoid

• Do not discontinue HER2-targeted therapy prematurely after chemotherapy completion; continue until disease progression or completion of 1 year total duration 4
• Do not omit endocrine therapy in HR-positive disease even with complete pathologic response 1
• Do not fail to implement diarrhea prophylaxis if prescribing neratinib, as this significantly reduces grade 3 toxicity 1
• Do not neglect cardiac monitoring even after trastuzumab completion, as cardiac dysfunction may not fully recover to baseline after interruption 7
• Trastuzumab interruption occurs in 18% of patients in clinical practice, most commonly due to cardiotoxicity, with mean LVEF improving from 45% at diagnosis to 55% after interruption but not returning to baseline 63% 7