Adjuvant Treatment Plan for Stage II Invasive Ductal Carcinoma (ypT0N0M0) ER+/PR+/HER2+
For a patient achieving pathologic complete response (ypT0N0M0) after neoadjuvant therapy for ER+/PR+/HER2+ invasive ductal carcinoma, you must provide adjuvant endocrine therapy plus completion of one full year of HER2-targeted therapy with trastuzumab, with the addition of pertuzumab if the patient was node-positive at initial staging. 1
HER2-Targeted Therapy
Complete up to 1 year total of trastuzumab therapy (including any cycles administered during neoadjuvant treatment), administered as Category 1 recommendation. 1
Add pertuzumab to trastuzumab if the patient had node-positive disease at initial staging before neoadjuvant chemotherapy, continuing both agents to complete one year of dual HER2 blockade. 1, 2
- The APHINITY trial with 8.4 years median follow-up confirmed benefit of adding pertuzumab to trastuzumab plus chemotherapy in preventing recurrences in node-positive HER2+ early breast cancer. 1
- Pertuzumab dosing: 840 mg initial dose IV over 60 minutes, then 420 mg every 3 weeks over 30-60 minutes. 2
Consider extended adjuvant neratinib following completion of trastuzumab-based therapy for perceived high-risk ER+/HER2+ disease, though benefits after pertuzumab exposure remain unknown. 1
HER2-targeted therapy can be administered concurrently with both radiation therapy and endocrine therapy. 1
Endocrine Therapy
Initiate adjuvant endocrine therapy (Category 1 recommendation) for all ER+ and/or PR+ tumors, administered for 5-10 years. 1
For postmenopausal women: Aromatase inhibitors (anastrozole, letrozole, or exemestane) are preferred over tamoxifen based on superior efficacy in hormone receptor-positive disease. 1
For premenopausal women:
Endocrine therapy should be given sequentially after chemotherapy completion, not concurrently with chemotherapy, though concurrent administration with radiation therapy is acceptable. 1
Extended therapy to 10 years should be considered for higher-risk patients, though some studies indicate 7.5-8 years may provide equivalent benefit. 1
Radiation Therapy
Base radiation therapy decisions on pre-chemotherapy tumor characteristics, not on post-neoadjuvant pathology, regardless of achieving pathologic complete response. 1, 3
Post-mastectomy radiation is indicated if there were 4 or more positive axillary lymph nodes at initial presentation. 1, 3
Strongly consider post-mastectomy radiation for patients with 1-3 positive nodes at initial staging. 1
Radiation fields should include chest wall and supraclavicular lymph nodes; inclusion of internal mammary nodes can be considered but remains controversial (Category 3). 1
For patients who underwent lumpectomy, breast and regional lymph node irradiation is required based on pre-chemotherapy staging. 1
Additional Adjuvant Considerations
Consider adjuvant bisphosphonate therapy for 3-5 years in postmenopausal patients (natural or induced menopause) with high-risk node-negative or node-positive tumors for risk reduction of distant metastasis. 1
No additional chemotherapy is indicated after achieving pathologic complete response, as panel consensus states postoperative chemotherapy has no role if a full course of standard chemotherapy was completed preoperatively. 1
Critical Pitfalls to Avoid
Do not omit endocrine therapy even with pathologic complete response—ER+ disease requires hormonal suppression regardless of chemotherapy response. 1, 4
Do not base radiation decisions on post-treatment pathology—use pre-chemotherapy clinical stage and nodal status to determine radiation fields and indications. 1, 3
Do not give endocrine therapy concurrently with chemotherapy—these must be sequential with endocrine therapy starting after chemotherapy completion. 1, 4
Do not stop HER2-targeted therapy early—complete the full year of trastuzumab ± pertuzumab even with excellent pathologic response. 1
Monitor cardiac function before and during HER2-targeted therapy, as both trastuzumab and pertuzumab carry cardiac toxicity risks. 4