What are the next management steps for a 60‑year‑old postmenopausal woman with a 2 cm, grade II, estrogen‑receptor‑positive, progesterone‑receptor‑negative, HER2‑negative multicentric invasive ductal carcinoma and a clinically palpable 2 cm axillary lymph node (cN1) after diagnostic core‑needle biopsies have been performed?

Management of Grade II ER+/PR−/HER2− Multicentric Invasive Ductal Carcinoma with Clinically Positive Axillary Node

Mastectomy with axillary lymph node dissection is required, followed by adjuvant chemotherapy, radiation to the chest wall and regional nodes, and aromatase inhibitor endocrine therapy for at least 5 years. 1, 2

Surgical Management

Mastectomy is mandatory because multicentricity (distinct tumors in separate quadrants) is an absolute contraindication to breast-conserving surgery. 1 The presence of tumors in different breast quadrants cannot be adequately excised with clear margins while preserving acceptable cosmesis. 1

Axillary Management

• The clinically palpable 2 cm axillary lymph node must undergo preoperative tissue sampling (fine-needle aspiration or core biopsy) to confirm metastatic disease. 1, 2
• Once nodal metastasis is confirmed, perform a level I/II axillary lymph node dissection at the time of mastectomy—sentinel lymph node biopsy alone is explicitly contraindicated when a suspicious palpable node is present. 1, 2
• Do not attempt sentinel lymph node biopsy in the setting of a clinically positive axillary node; this violates ASCO guidelines and will result in inadequate staging. 1

Adjuvant Chemotherapy

Adjuvant chemotherapy is indicated for any lymph node-positive disease, regardless of hormone receptor status or patient age. 2 The combination of PR-negative status, grade II histology, and confirmed nodal involvement confers intermediate-to-high recurrence risk that mandates cytotoxic therapy. 2

• Administer a taxane-containing regimen postoperatively, such as anthracycline-taxane combinations (e.g., AC-T, TAC) or taxane-only protocols (e.g., TC). 2
• Complete chemotherapy before initiating endocrine therapy to avoid potential antagonism between concurrent cytotoxic and hormonal treatments. 2

Radiation Therapy

Post-mastectomy radiation therapy to the chest wall and comprehensive regional nodal irradiation is mandatory for clinically node-positive disease. 2

• Radiation fields must include the chest wall, supraclavicular region, and axillary apex; consider internal mammary node coverage based on tumor location and nodal burden. 2
• When ≥4 nodes are pathologically positive, post-mastectomy radiation is category 1 evidence; for 1–3 positive nodes, it remains strongly recommended. 3, 2
• Radiation therapy may be administered concurrently with endocrine therapy but must follow completion of chemotherapy. 3, 2

Endocrine Therapy

For this postmenopausal woman with ER-positive disease, an aromatase inhibitor (anastrozole, letrozole, or exemestane) is preferred over tamoxifen as first-line endocrine therapy. 3, 2 Aromatase inhibitors provide superior response rates and longer time to progression compared to tamoxifen in postmenopausal ER-positive breast cancer. 3, 2

• Continue aromatase inhibitor therapy for a minimum of 5 years, with consideration of extended treatment beyond 5 years based on individual recurrence risk. 2
• Initiate endocrine therapy immediately after completing adjuvant chemotherapy; it may run concurrently with radiation. 2
• Obtain baseline bone mineral density testing and monitor periodically during aromatase inhibitor therapy to detect osteoporosis. 2

Treatment Sequence Algorithm

1. Preoperative axillary node biopsy (FNA or core) to confirm metastatic disease 1, 2
2. Mastectomy with level I/II axillary lymph node dissection (with or without reconstruction) 1, 2
3. Adjuvant chemotherapy with taxane-containing regimen 2
4. Radiation therapy to chest wall, supraclavicular, and axillary apex regions 2
5. Aromatase inhibitor endocrine therapy for ≥5 years (may start concurrently with radiation) 2

Critical Pitfalls to Avoid

• Do not perform breast-conserving surgery for multicentric disease; this is a well-established contraindication that will result in inadequate local control. 1
• Do not rely on sentinel lymph node biopsy alone when a clinically suspicious palpable node is present; full axillary dissection is required. 1, 2
• Do not omit chemotherapy solely because the tumor is ER-positive; PR-negative status combined with grade II histology and nodal involvement necessitates cytotoxic therapy. 2
• Do not use tamoxifen as first-line therapy in a postmenopausal woman when aromatase inhibitors are available and superior. 3, 2
• Do not omit regional nodal irradiation; clinically positive nodes mandate comprehensive radiation to supraclavicular and axillary regions, not just the chest wall. 2

Follow-Up Surveillance

• Clinical examinations every 4–6 months for the first 5 years, then annually thereafter. 2
• Annual mammography of the contralateral breast for surveillance. 2
• Regular assessment of adherence to aromatase inhibitor therapy and monitoring for side effects (arthralgias, bone loss, cardiovascular effects). 2
• Periodic bone mineral density testing while on aromatase inhibitor therapy. 2
• No routine imaging (CT, PET, bone scans) in asymptomatic patients without clinical suspicion of recurrence. 4