What is the recommended neoadjuvant treatment regimen for a patient with locally advanced breast cancer, considering factors such as HER2 (Human Epidermal growth factor Receptor 2) status and hormone receptor status?

Neoadjuvant Treatment for Locally Advanced Breast Cancer

Treatment Selection Based on Receptor Status

For HER2-positive locally advanced breast cancer, the standard neoadjuvant regimen is concurrent taxane-based chemotherapy with dual HER2 blockade using trastuzumab and pertuzumab, followed by sequential anthracycline-based chemotherapy. 1

HER2-Positive Disease

Dual HER2 blockade with pertuzumab plus trastuzumab and docetaxel achieves pathologic complete response (pCR) rates of 45.8-66.2%, significantly higher than trastuzumab plus docetaxel alone (29%). 1, 2

Recommended Regimen Structure:

• Initial therapy: Pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) plus docetaxel (75-100 mg/m² every 3 weeks) for 3-6 cycles preoperatively 1, 2
• Anthracycline administration: When anthracyclines are used, they must be given sequentially (not concurrently) with anti-HER2 therapy to minimize cardiac toxicity 1
• Post-operative completion: Continue trastuzumab (with or without pertuzumab) to complete 1 year total of HER2-directed therapy 1

Alternative HER2-Positive Regimens:

• FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by docetaxel, trastuzumab, and pertuzumab 1
• Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCH-P regimen, achieving 66.2% pCR) 1

Hormone Receptor-Positive, HER2-Negative Disease

For HR-positive, HER2-negative locally advanced breast cancer, treatment choice depends on disease aggressiveness, tumor grade, and patient factors. 1

Chemotherapy Approach:

• Anthracycline and taxane-based regimen is recommended for most patients with locally advanced disease 1
• Sequential administration: anthracyclines followed by taxanes for up to 8 cycles 1, 3
• Standard regimens include AC (doxorubicin/cyclophosphamide) or FEC followed by taxane 1

Endocrine Therapy Alternative:

• Neoadjuvant endocrine therapy may be considered in postmenopausal women with strongly hormone receptor-positive, lower-grade tumors who are not candidates for or decline chemotherapy 1
• Aromatase inhibitors (anastrozole or letrozole) are superior to tamoxifen for neoadjuvant endocrine therapy, providing higher rates of breast-conserving surgery 1
• Endocrine therapy requires longer duration (typically 3-6 months) to assess response compared to chemotherapy 1

Triple-Negative Breast Cancer

For triple-negative locally advanced breast cancer, anthracycline and taxane-based chemotherapy is the standard initial treatment. 1

• Platinum agents (carboplatin or cisplatin) may be combined with taxanes to potentially improve pCR rates 1
• Sequential anthracycline followed by taxane regimens are recommended 1
• Triple-negative patients who achieve pCR have significantly better outcomes than those with residual disease 3

Treatment Duration and Monitoring

Neoadjuvant chemotherapy should be administered for 3-6 cycles (approximately 4-6 months) preoperatively. 1

• Response evaluation should occur after 2-3 cycles of chemotherapy through clinical assessment and imaging 1
• For HER2-positive disease, cardiac function (LVEF) must be evaluated prior to initiation and every 3 months during HER2-targeted therapy to monitor for cardiotoxicity 4, 2

Surgical Approach After Neoadjuvant Therapy

Following effective neoadjuvant therapy, surgery consists of mastectomy with axillary dissection in the majority of cases, though breast-conserving surgery may be possible in selected patients with good response. 1

• For patients with low axillary burden at presentation (cN0-cN1) who achieve complete response (ycN0), sentinel lymph node biopsy is an option if dual tracer technique is used, positive nodes were clipped/marked, and minimum of three sentinel nodes are identified 1
• For inflammatory breast cancer, mastectomy with axillary dissection is recommended even with excellent response to neoadjuvant therapy 1

Post-Surgical Adjuvant Therapy

After surgery, complete planned systemic therapy if not finished preoperatively. 1

• For HER2-positive disease: Complete 1 year total of trastuzumab-based therapy (may include pertuzumab for node-positive disease at diagnosis) 1, 4
• For hormone receptor-positive disease: Initiate endocrine therapy (aromatase inhibitor for postmenopausal women, tamoxifen or ovarian suppression plus endocrine therapy for premenopausal women) 1
• Radiotherapy: Chest wall and regional nodal irradiation is required for locally advanced disease, even if pCR is achieved 1

Critical Pitfalls to Avoid

Do not administer anthracyclines concurrently with trastuzumab or pertuzumab due to significantly increased cardiac toxicity risk; always use sequential administration 1

Do not discontinue HER2-targeted therapy after completing chemotherapy; continue until 1 year total duration is reached 1

Do not omit radiotherapy in inflammatory breast cancer even when pCR is achieved, as locoregional control requires radiation 1

For patients who fail to respond or progress during neoadjuvant chemotherapy, consider alternative chemotherapy agents and/or preoperative radiotherapy before proceeding to surgery 1