What neoadjuvant chemotherapy regimen is appropriate for a fit 72‑year‑old woman with a 2.9 cm invasive lobular, clinically node‑positive, HER2‑negative breast cancer?

Neoadjuvant Chemotherapy for 72-Year-Old with Node-Positive Invasive Lobular Carcinoma

For a fit 72-year-old woman with 2.9 cm invasive lobular, node-positive, HER2-negative breast cancer, neoadjuvant chemotherapy is generally NOT recommended; primary surgery followed by adjuvant chemotherapy and endocrine therapy is the preferred approach.

Why Neoadjuvant Chemotherapy Has Limited Benefit in Invasive Lobular Carcinoma

Poor Response Rates in ILC

• Invasive lobular carcinoma demonstrates pathologic complete response (pCR) rates of only 3.4% with neoadjuvant chemotherapy, compared to significantly higher rates in invasive ductal carcinoma 1
• Even among molecularly high-risk ILC cases, the nodal conversion rate from clinically node-positive to pathologically node-negative is only 40.9%, compared to 51.2% in non-lobular tumors 2
• ILC patients receiving neoadjuvant chemotherapy have worse overall survival (10-year OS 54.4%) compared to those receiving adjuvant chemotherapy (65.1%), with an adjusted hazard ratio of 1.38 for death 1

Surgical Outcomes Are Not Improved

• Neoadjuvant chemotherapy does not reduce mastectomy rates in ILC patients (81.8% mastectomy rate with neoadjuvant vs 74.5% with adjuvant chemotherapy) 1
• ILC patients initially ineligible for breast-conserving surgery downstage to eligibility in only 16% of cases after neoadjuvant chemotherapy, compared to 48% in invasive ductal carcinoma 3
• Positive margin rates after lumpectomy are significantly higher in ILC (21.2% vs 7.9% in non-lobular) even after neoadjuvant therapy 2

Recommended Treatment Approach

Primary Surgery First

• Proceed directly to mastectomy with sentinel lymph node biopsy or level I/II axillary dissection 4
• Given the 2.9 cm tumor size and node-positive status, this represents stage IIA-IIB disease requiring comprehensive surgical staging 5
• ILC frequently has more extensive nodal involvement than clinically apparent; patients with any lobular component and positive sentinel nodes are upstaged to pathologic stage IIIA in 30.9% of cases 6

Adjuvant Systemic Therapy Sequence

For ER+/PR+/HER2- Disease (Most Likely Scenario):

• Deliver adjuvant chemotherapy first, followed sequentially by endocrine therapy 4
• Standard chemotherapy regimens include:
  • Dose-dense AC-T: Doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² every 14 days × 4 cycles with G-CSF, followed by paclitaxel 175 mg/m² every 14 days × 4 cycles 4, 7
  • TAC regimen: Docetaxel 75 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m² every 21 days × 6 cycles 4, 7
• Despite age 72, fit elderly patients should receive full-dose standard multidrug regimens identical to younger patients; single-agent therapy is inferior 4

Endocrine Therapy:

• Aromatase inhibitor for at least 5 years is preferred over tamoxifen in postmenopausal women 4, 8
• Consider extended endocrine therapy beyond 5 years given high-risk features (node-positive, tumor >2 cm) 4, 8
• Bisphosphonates (zoledronic acid) should be added for bone health and potential anti-tumor benefit 4

For Triple-Negative Disease (If Applicable):

• If the tumor is ER-/PR-/HER2-, the calculus changes: neoadjuvant chemotherapy with pembrolizumab becomes standard 4, 7
• Regimen: Pembrolizumab + carboplatin + paclitaxel followed by AC, then continued pembrolizumab for 1 year total 4, 7

Radiation Therapy

• Post-mastectomy radiation to chest wall, infraclavicular, and supraclavicular nodes is mandatory with node-positive disease 4, 5
• Strongly consider internal mammary node irradiation given nodal involvement 4
• Radiation should follow completion of chemotherapy 4, 5

Critical Caveats and Pitfalls

When Neoadjuvant Therapy Might Be Considered

The only scenarios where neoadjuvant chemotherapy could be justified in this ILC patient:

• If hormone receptor status is negative (triple-negative), making the tumor more chemotherapy-sensitive 3
• If the tumor is high-grade/poorly differentiated AND progesterone receptor-negative, which predicts better response (62% downstaging rate vs 29% in PR+/low-grade) 3
• If genomic testing (e.g., 70-gene assay) demonstrates high-risk biology despite lobular histology 2

Avoid These Common Errors

• Do not assume neoadjuvant chemotherapy will facilitate breast conservation in ILC—it rarely does, and attempting it may delay definitive surgery without benefit 3, 1
• Do not underestimate nodal burden based on clinical examination—ILC has occult nodal disease more frequently than ductal carcinoma, with higher rates of upstaging at surgery 6
• Do not use single-agent chemotherapy (capecitabine or docetaxel monotherapy) in fit elderly patients—standard multidrug regimens are required 4
• Do not omit chemotherapy based solely on age—at 72 years with node-positive disease, chemotherapy benefit outweighs risks in fit patients 4, 8

Monitoring Requirements

• Baseline and periodic cardiac function monitoring (LVEF) before and during anthracycline therapy 4
• Bone mineral density assessment at baseline and periodically on aromatase inhibitor therapy 8
• Clinical follow-up every 4-6 months for 5 years, then annually 8