What is the appropriate history, physical examination, investigations, and surgical staging approach for a patient presenting with a suspected breast cancer?

Breast Cancer History, Examination, Investigations, and Surgical Staging

History Taking

Obtain a complete personal and family history focusing on breast/ovarian cancer patterns to identify hereditary risk, document symptom onset and duration including erythema, peau d'orange, breast warmth, nipple discharge characteristics, and skin changes. 1, 2, 3

• Menstrual and reproductive history: Current menopausal status (measure serum estradiol and FSH if uncertain), age at menarche, parity, age at first birth, breastfeeding history 1
• Family history: First and second-degree relatives with breast/ovarian cancer, age at diagnosis, BRCA mutation status if known 1, 3
• Risk factors: Prior breast disease, hormone replacement therapy use, alcohol consumption, obesity 1
• Current symptoms: Breast mass (onset, growth rate), nipple discharge (bloody vs clear), skin changes, bone pain, respiratory symptoms, abdominal symptoms 2
• Performance status: ECOG or Karnofsky score 1, 3

Mnemonic for History: "BREAST MASS"

• Birth history (parity, age at first birth)
• Reproductive status (menopausal status)
• Exposures (HRT, radiation)
• Age at menarche
• Symptoms (mass, discharge, pain)
• Timing (onset, duration, progression)
• Medications and comorbidities
• Ancestry (family history)
• Social (alcohol, tobacco)
• Systemic symptoms (weight loss, bone pain)

Physical Examination

Perform systematic bimanual palpation of both breasts upright and supine, documenting exact location, size, consistency, mobility, and fixation of any masses, along with comprehensive assessment of axillary, supraclavicular, and infraclavicular lymph nodes. 1, 2, 3

• Inspection: Asymmetry, skin changes (erythema, peau d'orange, dimpling, ulceration), nipple retraction or deviation, visible masses 2
• Palpation technique: Examine all four quadrants plus subareolar region in both upright (arms raised, then on hips) and supine positions 2, 3
• Mass characteristics: Size (measure in cm), location (clock position and distance from nipple), consistency (hard, firm, soft), mobility, fixation to skin or chest wall 2, 4
• Lymph node examination: Axillary (all levels), supraclavicular, infraclavicular regions bilaterally - document size, number, consistency, mobility 1, 3
• Chest wall assessment: Check for fixation to pectoralis muscle (have patient press hands on hips) 1

Mnemonic for Examination: "SCALP"

• Size and shape of mass
• Consistency and contour
• Axillary and supraclavicular nodes
• Location (quadrant, clock position)
• Palpable fixation (skin, chest wall)

Investigations

Imaging Studies

Bilateral mammography and breast ultrasound are mandatory initial imaging, with MRI reserved for specific indications including dense breasts in young women, BRCA-associated familial cancer, suspected multifocality, or occult primary with positive nodes. 1, 3

Standard imaging protocol:

• Bilateral mammography: Assess tumor size, multifocality, multicentricity, contralateral disease 1
• Breast ultrasound: Characterize solid vs cystic lesions, evaluate dense breast tissue, assess axillary lymph nodes using high-resolution linear-array transducer ≥10 MHz 1, 2, 3
• Ultrasound-guided biopsy: Of suspicious axillary nodes if clinically or radiologically abnormal 1, 3

MRI indications (not routine): 1, 3

• Dense breast tissue in young women
• BRCA-associated familial breast cancer
• Silicone gel implants
• Suspected multifocality/multicentricity (especially lobular cancer)
• Occult primary with positive axillary nodes
• Before neoadjuvant chemotherapy
• Large discrepancy between clinical exam and conventional imaging

Pathological Diagnosis

Core needle biopsy obtained by ultrasound or stereotactic guidance is mandatory before any treatment, with pathology reporting histologic type, grade, ER, PR, HER2 status, and Ki67. 1

• Core needle biopsy: Minimum 2-3 cores, preferably ultrasound-guided 1, 2
• Place marker clip: At biopsy site to ensure correct surgical resection 1
• Pathology report must include: 1
  • Histologic type (WHO classification)
  • Histologic grade (Nottingham/Bloom-Richardson)
  • ER status: By immunohistochemistry with percentage of positive cells (Allred or H score)
  • PR status: By immunohistochemistry with percentage of positive cells
  • HER2 status: By IHC (0,1+, 2+, 3+); if 2+ perform FISH/CISH for gene amplification
  • Ki67 proliferation index: Percentage of positive cells

Laboratory Studies

Obtain complete blood count, comprehensive metabolic panel including liver enzymes, alkaline phosphatase, calcium, and assess menopausal status in all patients. 1

Baseline laboratory panel: 1, 2

• Complete blood count
• Liver function tests (AST, ALT, bilirubin)
• Renal function (creatinine, BUN)
• Alkaline phosphatase
• Calcium
• Serum estradiol and FSH (if menopausal status uncertain)

Cardiac function assessment: 1

• Echocardiogram or MUGA scan if planning anthracyclines and/or trastuzumab

Metastatic Workup

Routine staging imaging (chest X-ray, abdominal ultrasound/CT, bone scan) is NOT recommended for asymptomatic Stage I disease, but IS indicated for locally advanced disease (≥4 positive nodes, T3/T4 tumors, clinical symptoms, or abnormal laboratory values). 1

Indications for metastatic workup: 1, 3

• Pathological N2 (≥4 positive axillary nodes)
• T3 tumors (>5 cm) or T4 tumors
• Clinical symptoms suggesting metastases (bone pain, respiratory symptoms, neurological symptoms)
• Elevated liver enzymes or alkaline phosphatase
• Before neoadjuvant systemic therapy

Metastatic imaging when indicated: 1, 3

• Chest X-ray or CT chest
• Abdominal ultrasound or CT abdomen
• Bone scintigraphy
• PET/CT if conventional imaging inconclusive

Critical pitfall: Avoid routine bone scans, CT scans, or PET scans in asymptomatic Stage I patients - they provide no survival benefit and lead to false-positive findings requiring additional workup 3

Surgical Staging (TNM Classification)

Surgical staging uses the TNM system with pathologic assessment of the primary tumor (pT), regional lymph nodes (pN), and distant metastases (M), with sentinel lymph node biopsy recommended for clinically node-negative disease. 1

T (Tumor) Classification 1, 3

Mnemonic: "2-5-CHEST-SKIN-INFLAME"

• Tis: Carcinoma in situ
• T1: ≤2 cm (20 mm)
  • T1mi: ≤1 mm
  • T1a: >1 mm to 5 mm
  • T1b: >5 mm to 10 mm
  • T1c: >10 mm to 20 mm
• T2: >2 cm to 5 cm (>20 mm to 50 mm)
• T3: >5 cm (>50 mm)
• T4a: Extension to CHEST wall
• T4b: SKIN ulceration, satellite nodules, or edema (peau d'orange)
• T4c: Both T4a and T4b
• T4d: INFLAMEmatory carcinoma

N (Node) Classification 1, 3

Mnemonic: "1-3-4-9-10+ PLUS IM-SUPRA"

• pN0: No regional lymph node metastasis
• pN1: 1-3 axillary lymph nodes involved
• pN2: 4-9 axillary nodes OR internal mammary (IM) nodes detected clinically
• pN3: ≥10 axillary nodes OR infraclavicular nodes OR SUPRAclavicular nodes

Sentinel Lymph Node Biopsy

Perform sentinel lymph node biopsy for clinically node-negative Stage I or II disease; contraindications include palpable axillary nodes, T3/T4 tumors, multicentric tumors, prior axillary surgery, pregnancy/lactation, and inflammatory breast cancer. 1

SLNB contraindications (Mnemonic: "PALM-3-MULTI-PREG"): 1

• Palpable axillary nodes
• Axillary surgery (prior)
• Lactation
• Multicentric tumors
• 3 or T4 tumors (T3/T4)
• MULTIcentric tumors
• PREGnancy

Timing controversy: SLNB before vs after neoadjuvant chemotherapy remains debated; SENTINA and ACOSOG Z1071 studies showed lower detection rates and higher false-negatives post-chemotherapy, but post-treatment SLNB can be considered if axilla negative on pre-treatment ultrasound/PET-CT 1

Postoperative Pathology Report

The surgical pathology report must include pTNM classification, histologic type and grade, vascular/lymphovascular invasion, resection margin status with minimum margin in millimeters, total lymph nodes removed and number positive, and biomarker status. 1, 3

Required elements (Mnemonic: "MARGIN-NODES-GRADE-RECEPTORS"): 1

• MARGIN status: Minimum margin in mm and anatomical direction
• NODES: Total number removed, number positive, extent of metastases (ITC, micrometastatic, macrometastatic)
• GRADE: Nottingham/Bloom-Richardson grade
• Histologic type (WHO classification)
• Tumor size (maximum diameter in mm)
• Vascular and lymphovascular invasion
• RECEPTORS: ER, PR (percentage positive), HER2 (IHC score or FISH/CISH result), Ki67

Risk Stratification

Treatment decisions are based primarily on endocrine responsiveness (ER/PR status) and secondarily on risk of recurrence, with patients stratified into low, intermediate, and high-risk groups. 1

Risk factors for recurrence: 1

• Tumor size and grade
• Lymph node involvement (number and extent)
• Vascular/lymphovascular invasion
• ER/PR/HER2 status
• Ki67 proliferation index

Critical Pitfalls to Avoid

• Never proceed to surgery without core needle biopsy confirmation - fine needle aspiration alone is insufficient if core biopsy is technically feasible 1
• Do not perform MRI without clear indication - overuse leads to unnecessary mastectomies; never operate based solely on MRI findings without tissue confirmation 3
• Avoid routine metastatic workup in asymptomatic early-stage disease - causes false-positives and patient anxiety without survival benefit 3
• Ensure HER2 testing in accredited laboratories - use standardized protocols and experienced personnel 3
• Do not perform SLNB outside contraindications - particularly avoid in palpable nodes, T3/T4 disease, multicentric tumors 1
• Always place marker clip at biopsy site - ensures correct surgical resection, especially after neoadjuvant therapy 1