Lucan · Conditions

Breast cancer

Australian guidance: Cancer Council Australia + iPrevent + RACGP breast cancer pathways

1. Definition and epidemiology

Breast cancer is a malignant neoplasm arising from the epithelial cells of the breast ductal or lobular system, encompassing a spectrum from non-invasive in situ disease to invasive and metastatic carcinoma. In Australia it is the most common cancer in women, accounting for more than 29 per cent of all newly diagnosed cancers, and is second only to lung cancer as the leading cause of cancer death in women. The absolute lifetime population risk in Australian women is 12 per cent, with average risk defined as less than 1.5 times population risk, moderate risk as 1.5 to 3 times, and high risk as greater than 3 times population risk.

2. Pathophysiology

Most breast cancers arise from luminal epithelial cells lining the terminal duct lobular unit. Accumulation of somatic mutations in proto-oncogenes (including HER2 amplification on chromosome 17q12) and tumour suppressor genes (TP53, RB1, BRCA1/2) drives clonal expansion, loss of normal cell polarity, and ultimately basement membrane invasion. Oestrogen receptor (ER) signalling is central in luminal A and B subtypes, with oestrogen promoting transcription of cyclin D1 and other proliferative targets. HER2-positive tumours overexpress a receptor tyrosine kinase that activates the RAS/MAPK and PI3K/AKT pathways independently of ligand. Triple-negative breast cancer (ER negative, progesterone receptor negative, HER2 negative) lacks these targetable receptors, relies heavily on aberrant BRCA1 pathway dysfunction, and pursues an aggressive phenotype with basal-like features on gene expression profiling. Non-invasive precursors include ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS); DCIS carries direct malignant transformation potential whereas LCIS is primarily a marker of elevated bilateral risk. Lymphovascular invasion and lymph node seeding are the dominant early mechanisms of spread, with haematogenous dissemination to bone, lung, liver, and brain occurring in advanced disease.

3. Clinical presentation and diagnostic criteria

Classic presentation is a persistent, painless, unilateral breast lump, but any of the following should prompt urgent assessment: change in breast size or shape, nipple change including inversion or ulceration, spontaneous nipple discharge, skin dimpling or peau d'orange thickening, redness, or an axillary mass. Inflammatory breast cancer presents with rapid breast enlargement, warmth, and erythema without a discrete lump and can mimic mastitis; failure to respond to antibiotics within 1 to 2 weeks should prompt imaging and biopsy. Phyllodes tumour and fat necrosis are important differentials. At least one-third of Australian breast cancers are detected through asymptomatic screening. A patient with symptoms should be seen by a general practitioner within two weeks of symptom onset.

4. Investigations and AU-specific cutoffs

Assessment follows a structured triple test approach:

1. Medical history and clinical breast examination.
2. Imaging: bilateral mammography and/or ultrasound as first-line modality. Magnetic resonance imaging (MRI) is reserved for cases where conventional imaging is insufficient, for staging locally advanced disease, or for high-risk surveillance.
3. Non-excision tissue sampling: core biopsy is preferred over fine-needle aspiration cytology because it enables histological grading and receptor profiling. Core biopsy allows determination of ER, progesterone receptor (PR), and HER2 status via immunohistochemistry funded through the Medicare Benefits Schedule.

All tests should ideally be completed within two weeks of initial GP consultation. A positive result on any single component of the triple test warrants specialist surgical referral regardless of the other components. Axillary ultrasound with fine-needle aspiration of suspicious nodes is performed at the specialist stage. Routine staging computed tomography (CT) and bone scan are not recommended for early breast cancer; staging is reserved for confirmed locally advanced or nodal disease, or clinical suspicion of metastatic spread. Positron emission tomography (PET) scan may be most appropriate for distant staging.

BreastScreen Australia offers two-yearly screening mammography to asymptomatic women aged 50 to 74 years, with access available from age 40 on request. A GP referral is not required for BreastScreen attendance. Risk stratification tools endorsed in Australia include iPrevent, the IBIS tool, and the CanRisk Web Tool.

5. Management

Management is determined by cancer subtype, stage, receptor profile, and patient factors, and should be planned at a multidisciplinary meeting (MDM) ideally prior to surgery or neoadjuvant chemotherapy.

Surgery for early breast cancer involves breast-conserving surgery or mastectomy, sentinel node biopsy plus or minus axillary dissection, and oncoplastic or reconstructive options. Surgery should occur within five weeks of the decision to treat for invasive disease.

Neoadjuvant chemotherapy is appropriate for triple-negative or HER2-positive cancers, locally advanced or inflammatory breast cancer, and large operable tumours where tumour downstaging is the aim. Neoadjuvant therapy should commence within four weeks of the treatment decision.

Adjuvant systemic therapy: all patients with invasive cancer should be considered for systemic therapy. Hormone receptor-positive cancer warrants endocrine therapy. Endocrine therapy should start as soon as appropriate after completing surgery, chemotherapy, or radiation therapy. Adjuvant chemotherapy for triple-negative and HER2-positive disease should begin within four weeks of surgery; adjuvant chemotherapy for other subtypes should begin within six weeks of surgery.

Radiation therapy is indicated after breast-conserving surgery and in selected patients after mastectomy. It should begin within eight weeks of surgery for patients without adjuvant chemotherapy, or three to four weeks after chemotherapy completion.

Adjuvant bisphosphonates improve survival and should be considered for selected patients treated with curative intent.

For metastatic disease, management follows the ESO/ESMO Advanced Breast Cancer guidelines and is directed by receptor profile, prior therapy, and performance status.

6. Pharmacology and AU PBS notes

Endocrine therapy (ER-positive disease): - Premenopausal: tamoxifen 20 mg orally daily for 5 to 10 years (PBS listed; first-line standard). Ovarian suppression with goserelin (Zoladex) combined with an aromatase inhibitor for higher-risk premenopausal women. - Postmenopausal: aromatase inhibitors (letrozole [Femara], anastrozole [Arimidex], exemestane [Aromasin]) are preferred over tamoxifen in most postmenopausal patients. All are PBS listed for adjuvant use. - Tamoxifen is also used for risk reduction in moderate-to-high-risk women via iPrevent-guided clinical decisions.

HER2-positive disease: - Trastuzumab (Herceptin; PBS listed for adjuvant and metastatic HER2-positive breast cancer) 3-weekly for 12 months adjuvant. - Pertuzumab (Perjeta; PBS listed for neoadjuvant and adjuvant high-risk HER2-positive) in combination with trastuzumab and chemotherapy.

Chemotherapy backbones: anthracycline and taxane regimens (e.g., AC-T: doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel) are standard for high-risk early breast cancer. Carboplatin is added for BRCA-mutated triple-negative disease.

CDK4/6 inhibitors (metastatic ER-positive HER2-negative): palbociclib (Ibrance; PBS listed), ribociclib (Kisqali; PBS listed), abemaciclib (Verzenio; PBS listed) combined with an aromatase inhibitor or fulvestrant.

PARP inhibitors: olaparib (Lynparza; PBS listed for germline BRCA-mutated HER2-negative high-risk early breast cancer adjuvant following chemotherapy) and for metastatic germline BRCA-mutated disease.

7. Complications and monitoring

Treatment-related complications: - Lymphoedema: risk increases with axillary lymph node dissection and radiation; patients require physiotherapy referral and education. - Cardiotoxicity: anthracyclines cause dose-dependent cardiomyopathy; trastuzumab causes reversible cardiac dysfunction. Echocardiogram monitoring is required during HER2-targeted therapy. - Premature menopause and bone loss: ovarian suppression and aromatase inhibitors cause oestrogen deprivation, accelerating osteoporosis. Bone density scanning and bisphosphonate consideration are standard. - Peripheral neuropathy from taxanes. - Cognitive effects and fatigue are common during and after chemotherapy.

Surveillance schedule after curative treatment: - Clinical review every 3 to 6 months for the first 3 years, then every 6 to 12 months for years 4 to 5, then annually thereafter. - Annual ipsilateral breast (post-conservation) and contralateral mammography for life. - Bone density scan at baseline and periodically for patients on aromatase inhibitors or ovarian suppression. - Patients on tamoxifen require awareness of endometrial cancer risk; gynaecological review for any abnormal bleeding. - Psychosocial and supportive care needs assessment at each review, including screening for anxiety and depression. - Recurrence is detected most often through routine follow-up or patient-reported symptoms; rapid re-entry pathways should be established.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.