What is the optimal treatment for a 60‑year‑old postmenopausal woman with a 2‑cm grade II invasive ductal carcinoma of the left breast that is strongly estrogen‑receptor positive, progesterone‑receptor negative, HER2‑negative, and a clinically enlarged left axillary lymph node (≈14 × 26 mm) with no distant metastasis?

Optimal Treatment for ER+/PR-/HER2- Invasive Ductal Carcinoma with Clinically Positive Axillary Node

This 60-year-old postmenopausal woman with a 2-cm grade II ER+/PR-/HER2- invasive ductal carcinoma and clinically enlarged axillary lymph node should undergo upfront surgery (breast-conserving surgery or mastectomy) with axillary lymph node dissection, followed by adjuvant chemotherapy, radiation therapy to the breast/chest wall and regional nodes, and extended endocrine therapy with an aromatase inhibitor for at least 5 years. 1, 2, 3

Surgical Management

Primary surgery is the preferred initial approach rather than neoadjuvant therapy for this HER2-negative tumor. 1

• Neoadjuvant chemotherapy is primarily indicated for HER2-positive disease (tumors ≥2 cm and/or node-positive) where dual HER2 blockade significantly increases pathologic complete response rates 1
• For HER2-negative disease, proceeding directly to surgery allows for accurate pathologic staging to guide adjuvant therapy decisions 1

Surgical options include:

• Breast-conserving surgery with level I/II axillary lymph node dissection if tumor-to-breast ratio permits adequate margins 1, 2
• Mastectomy with level I/II axillary lymph node dissection with or without reconstruction 1, 2

Sentinel lymph node biopsy alone is insufficient given the clinically enlarged 26-mm axillary node—proceed directly to axillary lymph node dissection. 1, 3

Adjuvant Chemotherapy

Adjuvant chemotherapy is strongly indicated based on the combination of grade II histology, 2-cm tumor size, and clinically positive lymph node. 2, 3

• The European Society for Medical Oncology recommends that lymph node-positive disease warrants chemotherapy consideration despite the patient's age and hormone receptor-positive status 2
• Grade II tumors with nodal involvement have sufficient recurrence risk to justify cytotoxic therapy 4, 5
• Standard regimens appropriate for the adjuvant setting (anthracycline-taxane combinations or taxane-based regimens) should be administered 1

The PR-negative status within an ER-positive tumor suggests less endocrine responsiveness and strengthens the indication for chemotherapy. 4

Radiation Therapy

Radiation therapy to the breast (if breast-conserving surgery) or chest wall (if mastectomy) plus regional lymph nodes is mandatory. 1, 3

After Breast-Conserving Surgery:

• Whole-breast radiation therapy using hypofractionation (preferred): 42.5 Gy in 16 fractions or 40 Gy in 15 fractions 1
• Regional nodal irradiation including supraclavicular and axillary apex fields given the clinically positive node 1, 3
• Consider internal mammary node inclusion 3

After Mastectomy:

• Post-mastectomy radiation therapy to chest wall and supraclavicular nodes is indicated for node-positive disease 1, 3
• The decision for post-mastectomy radiation should be based on final pathologic nodal status: strongly indicated if ≥4 positive nodes (category 1), and should be considered for 1-3 positive nodes 1, 3

Endocrine Therapy

An aromatase inhibitor is the preferred endocrine therapy for this postmenopausal woman, superior to tamoxifen. 2, 6

• Aromatase inhibitors (anastrozole, letrozole, or exemestane) demonstrate superior response rates and time to progression compared to tamoxifen in postmenopausal women with ER+ disease 2, 6
• The ATAC trial showed anastrozole improved disease-free survival compared to tamoxifen (HR 0.87, p=0.0127) in postmenopausal women 6
• Duration should be at least 5 years; extended therapy beyond 5 years may be considered based on individual risk assessment 2, 6
• Endocrine therapy should begin after completion of chemotherapy and can be administered concurrently with radiation 1, 3

Monitor bone health with baseline and periodic bone mineral density measurements, as aromatase inhibitors increase osteoporosis risk. 2

Treatment Sequence

The recommended treatment algorithm is:

1. Surgery first (breast-conserving surgery or mastectomy + axillary lymph node dissection) 1, 2
2. Adjuvant chemotherapy (taxane-containing regimen) 1, 2, 3
3. Radiation therapy (can be given concurrently with endocrine therapy) 1, 3
4. Aromatase inhibitor for minimum 5 years (initiated after chemotherapy completion) 2, 6

Critical Pitfalls to Avoid

• Do not omit chemotherapy based solely on ER-positivity—the PR-negative status, grade II histology, and node-positive disease indicate intermediate-to-high recurrence risk that warrants cytotoxic therapy 2, 4
• Do not use tamoxifen as first-line endocrine therapy when aromatase inhibitors are available for postmenopausal women 2, 6
• Do not omit regional nodal irradiation—the clinically positive axillary node mandates treatment of the supraclavicular and axillary nodal regions 1, 3
• Do not base radiation decisions on tumor size alone—nodal involvement is the primary driver for comprehensive radiation fields 3
• Do not delay endocrine therapy initiation, though it should follow chemotherapy completion to avoid potential antagonism 3

Follow-Up

• Clinical examination every 4-6 months for 5 years, then annually 2
• Annual mammography 2
• Regular assessment of endocrine therapy adherence and side effects 2
• Periodic bone mineral density monitoring while on aromatase inhibitor 2