Breast Cancer — Risk Factors, Receptors, TNM Staging, Surgery and Systemic Therapy

Breast cancer is the most common cancer in women and the second commonest cause of cancer death in women worldwide. Most tumours arise in the ductal epithelium; fewer arise in the lobules. Most breast cancers are sporadic (90–95%) — only 5–10% carry an identifiable inherited mutation, although inherited cases make up a larger share (about 25%) in women under 30.

• Invasive ductal carcinoma (no special type): 50–75% of invasive cancers; felt as a hard lump because of the fibrotic reaction.
• Invasive lobular carcinoma: 10–15%; cells infiltrate in single file, so the tumour is often clinically and mammographically occult; more often multifocal and bilateral; characteristically E-cadherin negative.
• Mucinous (colloid) carcinoma: 2–5%; well demarcated, older women.
• Tubular carcinoma: 1–2%; small glands with minimal atypia.
• Medullary carcinoma: poorly differentiated; more common in BRCA carriers and younger patients.

Every invasive cancer is tested for oestrogen receptor (ER), progesterone receptor (PR) and HER2, along with grade and Ki-67. These markers define the molecular subtypes, which predict behaviour and choose the systemic drugs.

Breast cancer is diagnosed by three arms used together — clinical examination, breast imaging and tissue biopsy — often called triple assessment. Examination covers both breasts in sitting, standing and supine positions, the skin (peau d'orange, ulceration), the nipple and all regional nodal basins.

• Mammography is the most widely used test for screening and diagnosis. Abnormal findings: a mass, calcifications or architectural distortion. It is less useful in dense breasts and younger women.
• Ultrasound has similar sensitivity, suits younger or dense breasts and guides biopsy. MRI is the most sensitive study but is costly and less available.
• Findings are reported with BI-RADS categories 0 to 6, linking the image to a probability of cancer and a next step.
• Core needle biopsy (image-guided) is superior to fine needle aspiration and should be done whenever possible; a marker clip is placed at the site. Clinically positive nodes get an ultrasound-guided core biopsy.
• The biopsy must include ER, PR and HER2 testing. Routine staging scans are not needed for operable, asymptomatic early cancer; advanced disease gets CT chest–abdomen–pelvis with bone scan, or PET.

Stage groups follow: stage 0 is DCIS (non-invasive); stages I, IIA and IIB are early invasive cancer; IIIA, IIIB and IIIC are mostly locally advanced disease; stage IV is any metastatic cancer. Clinical staging is done before treatment; pathological staging after surgery.

Breast-conserving surgery (BCS) — lumpectomy or partial mastectomy with a margin of healthy tissue — can be offered to most patients with tumours under 5 cm if the breast is large enough for a good cosmetic result. BCS must be followed by whole-breast radiotherapy with a boost to the tumour bed to reduce local recurrence. Non-palpable lesions are localised before surgery with a wire or radioactive seed.

• Contraindications to BCS / indications for mastectomy: large tumour, large tumour-to-breast ratio, chest wall or skin involvement, multifocal cancer, inflammatory cancer and inability to receive radiotherapy.
• Post-mastectomy radiotherapy is added in selected cases: tumour over 5 cm, chest wall or skin invasion, multifocal tumour, or 4 or more positive nodes.
• Axillary dissection preserves the long thoracic nerve and the thoracodorsal nerve.
• Complications of axillary dissection include lymphoedema, nerve injury, chronic pain and, rarely, lymphangiosarcoma.

The sentinel node is the first node to receive lymph from the tumour. A radiotracer and/or blue dye is injected near the tumour or under the areola, and the 1–3 nodes that are hot or blue — usually in level I or II of the axilla — are removed. SLNB is the staging procedure for a clinically node-negative axilla in early invasive cancer, and it spares most women the morbidity of a full dissection.

Endocrine therapy is indicated in all hormone receptor-positive patients and is given for 5 to 10 years; it reduces both recurrence and death. The choice depends mainly on menopausal status.

About 17% of breast cancers overexpress HER2. Added to chemotherapy in early HER2-positive disease, trastuzumab cut the risk of recurrence by 52% and of death by 33% compared with chemotherapy alone. Other targeted options: CDK4/6 inhibitors (palbociclib) for HR-positive, HER2-negative tumours; pembrolizumab for triple-negative disease; PARP inhibitors for BRCA carriers. All triple-negative tumours over 1 cm receive chemotherapy, and neoadjuvant chemotherapy is increasingly used in triple-negative and HER2-positive early cancer and in locally advanced cancer (over 5 cm or clinically node-positive).