What is the initial approach for chemotherapy, radiotherapy, and hormonal therapy in a patient diagnosed with breast cancer?

Initial Treatment Sequencing for Breast Cancer

Surgery should be performed first, followed by adjuvant chemotherapy (if indicated), then radiotherapy, with hormonal therapy initiated after chemotherapy completion or concurrently with radiotherapy for hormone receptor-positive disease. 1

Treatment Sequence Algorithm

Step 1: Establish Diagnosis and Baseline Assessment

• Obtain pathological diagnosis via surgical specimen (breast-conserving surgery or modified radical mastectomy with axillary lymph node dissection) 1
• Mandatory receptor testing: Estrogen receptor (ER), progesterone receptor (PR), and HER2 status must be determined from surgical specimens 1, 2
• Complete staging including blood counts, liver enzymes, alkaline phosphatase, calcium, chest X-ray, and contralateral mammography 1

Step 2: Surgery as Primary Treatment

• Surgery is the initial definitive treatment for non-metastatic breast cancer, establishing local control and providing tissue for complete pathological assessment 1
• Breast-conserving surgery or modified radical mastectomy with axillary dissection should be performed based on tumor characteristics 1
• Exception: Neoadjuvant chemotherapy may be considered first for locally advanced or inflammatory breast cancer to downstage disease and increase breast conservation possibilities 3, 4

Step 3: Adjuvant Chemotherapy (When Indicated)

Chemotherapy should be administered before radiotherapy to address micrometastatic disease promptly 1

For Lymph Node-Positive Disease:

• Premenopausal women (≤50 years): Chemotherapy is standard regardless of ER status 1
  • If ER-positive: Chemotherapy followed by tamoxifen 1
  • If ER-negative: Chemotherapy alone 1
• Postmenopausal women (>50 years): 1
  • If ER-positive: Tamoxifen is standard; chemotherapy is an option 1
  • If ER-negative: No standard exists; chemotherapy may be considered 1

For Lymph Node-Negative Disease:

• Risk stratification determines need for chemotherapy based on tumor size, grade, and receptor status 1

Step 4: Radiotherapy

Radiotherapy follows chemotherapy completion when both are indicated 1, 5

• For breast-conserving surgery: Radiotherapy is mandatory to reduce local recurrence 4
• Post-mastectomy radiotherapy: Indicated for high-risk features (multiple positive nodes, large tumor size, positive margins) 1
• Timing: Should commence within 7 months after surgery to maintain efficacy 5

Step 5: Hormonal Therapy

Hormonal therapy is initiated after chemotherapy completion or can run concurrently with radiotherapy for ER-positive disease 1

• Premenopausal women: Tamoxifen (typically 5 years) should only be used in association with chemotherapy when both are indicated 1
• Postmenopausal women: Third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) are preferred over tamoxifen for ER-positive disease 1, 2

Critical Sequencing Considerations

Why Chemotherapy Before Radiotherapy?

• No survival difference exists between concurrent chemoradiation, chemotherapy-first, or radiotherapy-first approaches 5
• However, chemotherapy-first allows earlier systemic treatment of micrometastatic disease 5
• Concurrent chemoradiation increases toxicity: higher rates of anemia (OR 1.54), telangiectasia (OR 3.85), and pigmentation (OR 15.96) 5
• Radiotherapy-before-chemotherapy increases neutropenic sepsis risk (OR 2.96) 5

Multidisciplinary Planning

• Treatment planning must be multidisciplinary before initiating any therapy to determine the necessity and extent of all modalities 1
• This prevents suboptimal sequencing and ensures coordinated care 6

Common Pitfalls to Avoid

• Do not delay chemotherapy for radiotherapy when both are indicated—this may allow micrometastatic progression 5
• Do not use tamoxifen alone in premenopausal women with node-positive disease requiring chemotherapy; it must be combined with chemotherapy 1
• Do not start radiotherapy beyond 7 months post-surgery as this may compromise local control 5
• Do not skip receptor reassessment if recurrence occurs, as receptor status changes in 20-40% of cases due to clonal evolution 2