Breast Cancer: A Clinician’s Overview

Introduction

Breast cancer is the most commonly diagnosed malignancy in women worldwide. Although only ~1% of cases occur in men, the disease remains a significant cause of morbidity and mortality. While ductal carcinoma in situ (DCIS) is non‑fatal by definition, invasive cancers can disseminate via lymphatic and hematogenous routes, resulting in life‑threatening metastases. Incidence has risen since the late 20th century, with lifetime risk in some regions approaching 1 in 8 women.

Epidemiology and Risk Factors

• Age: Incidence rises after 25 years; peaks around 50–54; declines slightly thereafter.
• Family history: First‑degree relative with breast or ovarian cancer increases risk; clustering suggests hereditary syndromes.
• Genetics: Pathogenic variants in BRCA1/BRCA2, TP53 (Li‑Fraumeni), PTEN (Cowden), PALB2, CHEK2, ATM, etc. Hereditary breast cancer accounts for ~5–10% of cases.
• Reproductive/endocrine: Early menarche (<12), late menopause (>55), nulliparity, late first pregnancy, and lack of breastfeeding increase cumulative estrogen exposure and risk.
• Breast density: High mammographic density is an independent risk factor and reduces screening sensitivity.
• Prior breast disease: Atypical ductal/lobular hyperplasia and LCIS elevate risk.
• Exposures: Prior high‑dose chest radiation (e.g., mantle radiation), long‑term unopposed estrogen; alcohol use; postmenopausal obesity; sedentary lifestyle.

Pathology and Molecular Subtypes

• Histology: Invasive ductal carcinoma (NST) is most common; invasive lobular carcinoma follows. DCIS and LCIS are important in situ lesions.
• Receptors: ER, PR, and HER2 status define clinical behavior and guide therapy.
• Intrinsic subtypes (approximate by IHC):
• Luminal A (ER+/PR+, HER2–, low Ki‑67): best prognosis.
• Luminal B (ER+, +/- PR, HER2–/+, higher Ki‑67): intermediate.
• HER2‑enriched (ER–/PR–, HER2+): aggressive but highly targetable.
• Triple‑negative (ER–/PR–/HER2–): aggressive; chemosensitive; higher risk of early relapse.

Clinical Presentation and Diagnosis

• Symptoms: Painless breast mass, nipple retraction/discharge, skin changes (peau d’orange), axillary mass. Many are screen‑detected.
• Triple assessment: Clinical exam + imaging + pathology.
• Imaging: Mammography (screening/diagnostic), ultrasound (especially dense breasts), MRI (high‑risk screening, problem solving, neoadjuvant planning).
• Tissue diagnosis: Core needle biopsy for histology and receptor testing; vacuum‑assisted biopsy for calcifications.
• Staging: AJCC TNM staging incorporates tumor size, nodal status, metastasis, and biologic markers (ER/PR/HER2, grade).

Management Overview (Multidisciplinary)

• Surgery:
• Breast‑conserving surgery (lumpectomy) with negative margins plus adjuvant radiotherapy for suitable candidates.
• Mastectomy (simple/skin‑sparing/nipple‑sparing) when indicated; consider immediate reconstruction.
• Axillary staging with sentinel lymph node biopsy; completion axillary dissection for selected node‑positive disease.
• Radiotherapy: Adjuvant after breast‑conserving surgery; post‑mastectomy in high‑risk (T3/T4, ≥4 nodes). Hypofractionation is standard in many settings.
• Systemic therapy (guided by receptors, stage, and risk):
• Endocrine therapy: Tamoxifen or aromatase inhibitors for ER+ disease; ovarian function suppression in premenopausal high‑risk.
• HER2‑targeted therapy: Trastuzumab ± pertuzumab for HER2+ disease; antibody‑drug conjugates in selected settings.
• Chemotherapy: Anthracyclines/taxanes are common backbones; consider neoadjuvant to downstage and assess response, especially in HER2+ and TNBC.
• CDK4/6 inhibitors, PARP inhibitors (BRCA1/2), PI3K/AKT/mTOR inhibitors in appropriate subgroups.

Screening and Prevention

• Population screening: Begin biennial or annual mammography per local guidelines (often age 40–50 onward). Supplemental ultrasound/MRI for dense breasts.
• High‑risk management: Genetic counseling/testing; annual MRI + mammography; risk‑reducing endocrine therapy (tamoxifen/raloxifene/AIs) when appropriate; prophylactic mastectomy and/or salpingo‑oophorectomy for selected mutation carriers.
• Lifestyle: Limit alcohol, maintain healthy BMI, regular physical activity, and breastfeeding when possible.

Follow‑up and Survivorship

• Surveillance: History/physical every 3–6 months for 3 years, then every 6–12 months for years 4–5, then annually; annual mammography of conserved breast.
• Manage late effects: Lymphedema care, cardiotoxicity monitoring (esp. with anthracyclines/HER2 therapy), bone health, menopausal symptoms, cognitive and psychosocial issues.

Key Points

• Subtype‑driven therapy is central to modern care.
• Early detection via screening and prompt diagnosis improves outcomes.
• Multidisciplinary planning optimizes local control and systemic therapy sequencing.