What are the treatment options for a patient with breast (Ca breast) cancer?

Treatment Options for Breast Cancer

Breast cancer treatment requires a multidisciplinary approach with therapy determined by stage, molecular subtype (hormone receptor and HER2 status), and patient-specific factors, with the primary goal of maximizing survival while maintaining quality of life. 1, 2

Initial Diagnostic Work-Up

Before initiating any treatment, the following assessments are mandatory:

• Pathological confirmation via core needle biopsy or surgical specimen to establish histology according to WHO classification 1, 3
• Biomarker assessment including estrogen receptor (ER), progesterone receptor (PR), and HER2 status is essential for treatment planning 1, 4
• Staging evaluation using TNM classification with complete blood counts, liver enzymes, alkaline phosphatase, calcium levels, chest X-ray, and contralateral mammography 1, 3
• Cardiac function assessment (LVEF) is required before initiating HER2-targeted therapy 4
• Additional biomarkers including germline BRCA1/2 mutation status in HER2-negative disease, PD-L1 status in triple-negative breast cancer, and PIK3CA mutations in ER-positive/HER2-negative disease should be evaluated 1

Treatment by Stage

Stage 0: Ductal Carcinoma In Situ (DCIS)

Breast-conserving surgery with clear margins followed by whole breast radiation therapy is the preferred treatment for DCIS when complete excision with satisfactory cosmetic results is achievable. 5

• Lumpectomy with radiation therapy is standard when the tumor can be completely excised 5
• Post-operative mammography must verify absence of residual microcalcifications 5
• Modified radical mastectomy is indicated for widespread microcalcifications, inability to achieve clear margins, or patient preference 5
• Radiation boost to the tumor bed is mandatory for patients under 50 years and optional for those over 50 with risk factors 5
• Axillary lymph node dissection is not indicated for pure DCIS 5
• Endocrine therapy should be added if ER-positive 2, 6

Stage I-II: Early Invasive Breast Cancer

Treatment consists of three phases: preoperative (neoadjuvant), surgical, and postoperative (adjuvant).

Preoperative/Neoadjuvant Therapy

For HER2-positive T2 or node-positive disease, neoadjuvant chemotherapy with dual HER2 blockade (pertuzumab + trastuzumab + docetaxel) is the standard first-line approach, achieving pathologic complete response rates of 45.8-66.2%. 7, 3

• Neoadjuvant therapy allows tumor downstaging, in vivo assessment of chemosensitivity, and early treatment of micrometastatic disease 7
• For hormone receptor-positive disease, endocrine therapy may be considered preoperatively 2
• Triple-negative breast cancer requires chemotherapy as the only preoperative systemic option 2, 8

Surgical Management

Breast-conserving surgery with radiation therapy and mastectomy have equivalent survival rates; the choice depends on tumor size, location, and patient preference. 2, 8

• Sentinel lymph node biopsy is standard for clinically node-negative patients 3, 6
• Axillary lymph node dissection is required for N2 disease even after excellent neoadjuvant response 7
• Modified radical mastectomy includes axillary lymph node dissection 1

Postoperative/Adjuvant Therapy

Adjuvant systemic therapy is determined by lymph node status, hormone receptor status, HER2 status, and menopausal status. 1

For node-positive, premenopausal, hormone receptor-positive disease:

• Chemotherapy plus tamoxifen is standard 1
• Alternative options include chemotherapy with ovarian suppression ± tamoxifen, or ovarian ablation ± tamoxifen without chemotherapy 1

For node-positive, postmenopausal, hormone receptor-positive disease:

• Chemotherapy plus tamoxifen is standard 1
• Aromatase inhibitors are preferred over tamoxifen for postmenopausal women 7

For HER2-positive disease:

• Complete 1 year total of trastuzumab-based therapy 7, 4
• Switch to trastuzumab emtansine for 14 cycles if residual disease is present after neoadjuvant therapy 7

Radiation therapy:

• Whole breast radiation is mandatory after breast-conserving surgery 5, 3
• Post-mastectomy radiation to chest wall and regional nodes is indicated for ≥4 positive axillary nodes 3
• Radiation decisions must be based on pre-chemotherapy clinical stage, not post-neoadjuvant pathology, even if pathologic complete response is achieved 7

Stage III: Locally Advanced Breast Cancer

Neoadjuvant chemotherapy is the standard approach for stage III disease to downsize tumors and facilitate surgical resection. 1

• For T0, N2-N3, M0 disease, neoadjuvant chemotherapy with trastuzumab and endocrine therapy should be considered, followed by axillary nodal dissection and mastectomy 1
• Inflammatory breast cancer requires induction chemotherapy followed by mastectomy (not breast-conserving surgery), axillary lymph node dissection, and chest wall radiation 6
• Systemic therapy follows recommendations for stage II-III disease based on biomarker status 1

Stage IV: Metastatic Breast Cancer

For newly diagnosed or recurrent metastatic breast cancer, biopsy should be performed to confirm histology and re-assess ER, PR, and HER2 status, as tumor biology may change from the primary tumor. 1

• Treatment goals shift to prolonging survival and maintaining quality of life, as metastatic disease is treatable but not curable 2, 8
• Minimum staging includes CT chest/abdomen and bone scintigraphy, or 18F-FDG PET-CT as an alternative 1
• If discordance exists between primary and metastatic biomarkers, treatment should be considered when ER/PR or HER2 are positive in at least one biopsy 1

Treatment by molecular subtype:

• Hormone receptor-positive/HER2-negative: Endocrine therapy with targeted agents (CDK4/6 inhibitors, PI3K inhibitors) 1, 9
• HER2-positive: Anti-HER2 targeted therapy combined with chemotherapy or endocrine therapy 1, 9
• Triple-negative: Chemotherapy with or without immune checkpoint inhibitors based on PD-L1 status, or antibody-drug conjugates 1, 9

Follow-Up Protocol

Clinical examination every 3-6 months for 3 years, then every 6-12 months thereafter, with annual mammography for surveillance. 1, 3

• Document normalization of parameters affected by chemotherapy at first follow-up 1
• Routine imaging for metastatic surveillance is not recommended in asymptomatic patients 1
• Contralateral breast surveillance with clinical examination and mammography at same frequency 1

Critical Pitfalls to Avoid

• Never omit radiation therapy after breast-conserving surgery - this substantially increases local recurrence risk 5
• Never base radiation therapy decisions on post-neoadjuvant pathology - always use pre-treatment clinical stage 7
• Never perform sentinel node biopsy alone in N2 disease at presentation - axillary dissection remains necessary even after excellent response 7
• Never perform axillary dissection for pure DCIS - it provides no benefit and adds morbidity 5
• Never omit cardiac monitoring during HER2-targeted therapy - trastuzumab can cause cardiomyopathy 4
• Never forget to verify pregnancy status before initiating trastuzumab - it causes embryo-fetal toxicity 4
• Never accept positive surgical margins - re-excision or mastectomy is required 5