What is the recommended treatment approach for a patient with clinical stage T2 (cT2) breast cancer?

Treatment of Clinical Stage T2 (cT2) Breast Cancer

For cT2 breast cancer (tumor >2 cm but ≤5 cm), treatment depends critically on receptor status, nodal involvement, and patient candidacy for neoadjuvant therapy, with the primary goal of achieving optimal local control while minimizing recurrence and maximizing survival.

Initial Diagnostic Requirements

Before initiating treatment, comprehensive pathologic assessment is mandatory:

• Core needle biopsy must establish histological diagnosis, tumor grade, and complete biomarker profile including ER, PR, HER2 status, and Ki67 proliferation index 1
• TNM staging should be completed with clinical examination, imaging of the breast, and axillary assessment 2, 1
• Axillary ultrasound is recommended for staging in clinically node-negative patients with T2 tumors, with biopsy confirmation if suspicious nodes are identified 2

Treatment Algorithm Based on Tumor Biology

HER2-Positive cT2 Breast Cancer

Neoadjuvant chemotherapy is strongly preferred for HER2-positive T2 tumors:

• Trastuzumab plus pertuzumab plus taxane should be administered for at least 9 weeks preoperatively, as this represents the standard first-line regimen for HER2-positive disease 2
• Complete all planned chemotherapy (preferably preoperatively), followed by surgery, then complete up to 1 year of trastuzumab therapy 2
• Radiation therapy follows surgery based on pre-chemotherapy tumor characteristics 2
• Add endocrine therapy if hormone receptor-positive (ER+ and/or PR+), administered sequentially after chemotherapy or concurrently with trastuzumab 2

Hormone Receptor-Positive, HER2-Negative cT2 Breast Cancer

Treatment approach depends on risk stratification:

For low-risk patients (favorable biology, low Ki67, small T2 tumors):

• Primary surgery (lumpectomy or mastectomy) with sentinel lymph node biopsy if clinically node-negative 2
• Adjuvant endocrine therapy is mandatory (category 1 recommendation) 2
• Consider adjuvant chemotherapy based on genomic testing results and clinical-pathologic features 3
• Radiation therapy after breast-conserving surgery 2

For high-risk patients (higher grade, elevated Ki67, larger T2 tumors, or node-positive):

• Neoadjuvant chemotherapy followed by surgery may be preferred to assess treatment response 2
• Sequential endocrine therapy following chemotherapy completion 2
• Radiation therapy based on final pathologic staging 2

Triple-Negative cT2 Breast Cancer

Neoadjuvant chemotherapy is the standard approach:

• Chemotherapy regimens should include anthracycline and taxane-based combinations 2, 3
• Consider adding immunotherapy if PD-L1 positive 1
• Surgery follows chemotherapy completion 2
• Radiation therapy is administered postoperatively based on pre-treatment tumor characteristics 2
• Triple-negative tumors have higher recurrence risk (85% 5-year survival for stage I) compared to other subtypes, making aggressive systemic therapy critical 3

Surgical Considerations for cT2 Tumors

Axillary Management

For clinically node-negative patients:

• Sentinel lymph node biopsy (SLNB) is the standard approach if primary surgery is performed 2
• Use single tracer (radiocolloid) for primary surgery; dual tracer if low-volume center 2
• If 1-2 positive sentinel nodes and planning breast-conserving therapy with radiation, axillary lymph node dissection (ALND) may be omitted 2
• If mastectomy with 1-2 positive nodes, ALND should be performed on a case-by-case basis 2
• If ≥3 positive nodes, complete ALND is recommended 2

For clinically node-positive patients:

• Lymph node biopsy should confirm diagnosis before treatment 2
• Neoadjuvant chemotherapy is preferred 2
• Post-chemotherapy axillary staging may include SLNB or level I/II dissection 2

Breast Surgery Options

• Breast-conserving surgery is appropriate for most T2 tumors if adequate margins can be achieved 2, 1
• Mastectomy is indicated when breast conservation is not feasible due to tumor-to-breast size ratio, multicentric disease, or patient preference 1
• Delayed breast reconstruction may be considered after mastectomy 2

Radiation Therapy Guidelines

Post-lumpectomy:

• Whole-breast radiation is mandatory after breast-conserving surgery 2, 1
• Regional nodal irradiation (RNI) should be added if ≥4 positive nodes or other high-risk features 2

Post-mastectomy:

• Chest wall and regional nodal radiation is recommended for ≥4 positive axillary nodes or T3 tumors with positive nodes 1
• Strongly consider internal mammary node radiation if involved; consider even if not clinically involved (category 2B) 2
• Radiation decisions should be based on pre-chemotherapy tumor characteristics when neoadjuvant therapy is used 2

Critical Pitfalls to Avoid

• Do not perform SLNB before neoadjuvant chemotherapy except in special circumstances after multidisciplinary discussion, as post-chemotherapy SLNB is feasible and provides prognostic information 2
• Do not omit HER2 testing or use inadequate tissue for biomarker assessment, as this fundamentally alters treatment strategy 1
• Do not delay trastuzumab in HER2-positive disease—it should be incorporated into neoadjuvant regimens for at least 9 weeks preoperatively 2
• Do not give chemotherapy and endocrine therapy concurrently—they must be administered sequentially with endocrine therapy following chemotherapy 2
• Do not base radiation decisions on post-chemotherapy staging when neoadjuvant therapy is used—use pre-treatment tumor characteristics 2

Follow-Up Protocol

• Clinical examination every 3-6 months for 3 years, then every 6-12 months thereafter 2
• Annual mammography for surveillance 1
• Document normalization of parameters affected by chemotherapy at first follow-up 2
• Monitor for late effects of therapy and recurrence 1