What adjuvant therapy is recommended for a postmenopausal patient with Estrogen Receptor (ER) positive, Progesterone Receptor (PR) positive, and Human Epidermal growth factor Receptor 2 (Her2neu) positive breast cancer, status post Modified Radical Mastectomy (MRM)?

Adjuvant Therapy for ER+/PR+/HER2+ Breast Cancer Post-MRM

For a postmenopausal patient with ER+/PR+/HER2+ breast cancer after modified radical mastectomy, you must provide dual-targeted therapy: HER2-directed therapy (trastuzumab or T-DM1 if residual disease after neoadjuvant therapy) combined with endocrine therapy (aromatase inhibitor preferred over tamoxifen), as both pathways drive this cancer and must be blocked simultaneously to optimize survival. 1

HER2-Targeted Therapy Selection

If the patient had neoadjuvant chemotherapy with residual invasive disease:

• Administer T-DM1 for exactly 14 cycles, which reduces recurrence or death risk by 50% compared to continuing standard trastuzumab 1
• Do not re-examine hormone receptor or HER2 status in residual disease—base treatment on initial diagnostic biopsy results 1

If the patient had upfront surgery without neoadjuvant therapy:

• Administer adjuvant chemotherapy plus trastuzumab for one year (52 weeks) for tumors >1 cm or node-positive disease 2
• For tumors 0.6-1.0 cm and node-negative, consider adjuvant chemotherapy plus trastuzumab, recognizing limited trial data in this population 2

Concurrent Endocrine Therapy (Mandatory)

Aromatase inhibitor therapy is preferred for postmenopausal patients:

• Initiate an aromatase inhibitor (anastrozole, letrozole, or exemestane) concurrently with HER2-directed therapy 2, 1
• Continue endocrine therapy for 5-10 years total duration, extending beyond completion of HER2-directed therapy 1
• Aromatase inhibitors reduce annual odds of recurrence by approximately 5% in absolute terms compared to tamoxifen in postmenopausal women 2

Alternative option if aromatase inhibitor is contraindicated:

• Tamoxifen 20 mg daily can be administered concurrently with T-DM1 or trastuzumab and continued for total duration of 5-10 years 1, 3

Critical Principle: Do Not Withhold Endocrine Therapy

• Adjuvant endocrine therapy is recommended for all patients with ER-positive breast cancer regardless of HER2 status, patient age, lymph node status, or whether adjuvant chemotherapy is administered 1
• The presence of HER2-positive status does not negate the need for endocrine therapy—both pathways must be targeted 1

Sequencing When Chemotherapy Is Indicated

If adjuvant chemotherapy is needed (based on tumor size, grade, nodal status):

• Administer chemotherapy first, followed by sequential trastuzumab (or T-DM1 if post-neoadjuvant with residual disease) 1
• Begin endocrine therapy after chemotherapy completion, administered concurrently with HER2-directed therapy 2
• Preferred chemotherapy regimens include anthracycline-based followed by taxanes (AC→paclitaxel or docetaxel) or docetaxel-cyclophosphamide 4

Mandatory Cardiac Monitoring

• Perform left ventricular ejection fraction (LVEF) assessment before starting, during treatment (every 3 months), and following HER2-targeted therapy 1
• Patients with clinical congestive heart failure or significantly compromised LVEF require case-by-case evaluation before initiating HER2-targeted therapy 1
• The combination of anthracyclines, trastuzumab, and aromatase inhibitors increases cardiac toxicity risk, necessitating vigilant monitoring 2

Duration of Therapy

HER2-directed therapy:

• T-DM1: exactly 14 cycles (approximately 10.5 months) 1
• Standard trastuzumab: 52 weeks (one year) 2

Endocrine therapy:

• Minimum 5 years, with consideration for extension to 10 years for node-positive disease to reduce late recurrence risk 2, 1
• Extended therapy beyond 5 years reduces late recurrence in hormone receptor-positive disease 2

Common Pitfalls to Avoid

• Do not continue standard trastuzumab in patients with residual disease after neoadjuvant therapy—this represents suboptimal care given the 50% reduction in recurrence risk with T-DM1 1
• Do not omit endocrine therapy based on HER2-positive status—hormone receptors mandate endocrine therapy regardless of HER2 status 1
• Do not use tamoxifen as first-line in postmenopausal women when aromatase inhibitors are available—aromatase inhibitors provide superior disease-free survival 2
• Do not administer chemotherapy and endocrine therapy concurrently—chemotherapy must be completed first, then endocrine therapy follows sequentially 2, 4

Adjuvant Bisphosphonate Consideration

• Consider adjuvant bisphosphonate therapy in postmenopausal (natural or induced) patients receiving adjuvant endocrine therapy 2