Breast cancer

At a glance

• The commonest cancer in Australian women, affecting about 1 in 7 by age 85. Five-year survival is about 92%, lower in Aboriginal and Torres Strait Islander women and in remote areas.
• Diagnose with the triple test: clinical examination, imaging and core biopsy. Any suspicious element means cancer until proven otherwise.
• Receptor status (ER, PR, HER2) decides treatment more than stage does.
• Early breast cancer: surgery, radiotherapy and systemic therapy (endocrine, chemotherapy, HER2-targeted, immunotherapy, CDK4/6 inhibitors, PARP inhibitors) chosen by subtype and risk.
• Metastatic disease is treatable but rarely curable. HR-positive disease often lives for years on sequential endocrine-based therapy.
• The physician's job includes bone health, cardiac monitoring, menopause symptoms, fertility and family cancer risk.

Classification

Subtype	Proportion	Key features	Main systemic therapy
HR-positive, HER2-negative	About 70%	Usually lower grade; late recurrences (beyond 5 years)	Endocrine therapy, plus CDK4/6 inhibitor if high risk; chemotherapy by risk
HER2-positive	15 to 20%	IHC 3+ or ISH-amplified; aggressive without treatment, brain metastases	Chemotherapy with trastuzumab and pertuzumab
Triple-negative	10 to 15%	Young, BRCA1, high grade, early visceral and brain relapse	Chemotherapy with pembrolizumab

• HER2-low (IHC 1+ or 2+ with negative ISH) and HER2-ultralow (faint staining in 10% of cells or fewer) are not HER2-positive, but HER2-low predicts response to trastuzumab deruxtecan in metastatic disease.
• Lobular carcinoma (E-cadherin loss) is often multifocal, harder to see on mammography, and spreads to peritoneum, GI tract and ovaries.
• Ductal carcinoma in situ (DCIS) is non-invasive and found mostly on screening. Treat with excision with or without radiotherapy; endocrine therapy lowers recurrence.

Causes and risk factors

• Hormonal: early menarche, late menopause, nulliparity or late first pregnancy, menopausal hormone therapy (combined more than oestrogen alone), alcohol, postmenopausal obesity. Breastfeeding and exercise protect.
• Chest irradiation before age 30 (Hodgkin lymphoma), with risk starting about 8 years later.
• Dense breasts raise risk and hide cancers on mammography.
• Inherited (5 to 10%):

Gene	Notes
BRCA1	Triple-negative, ovarian cancer; lifetime breast risk about 70%
BRCA2	HR-positive, ovarian, prostate and pancreatic cancer, male breast cancer
PALB2	High risk, behaves like BRCA2
TP53 (Li-Fraumeni)	Very early breast cancer, sarcoma; avoid radiotherapy where possible
CDH1	Lobular breast and diffuse gastric cancer
PTEN (Cowden), CHEK2, ATM	Moderate risk except PTEN

• Refer to a family cancer clinic when the history suggests a variant. Medicare funds germline testing for affected people meeting eligibility criteria (based on predicted probability of a variant). Carriers are offered annual MRI from their late 20s or 30s, risk-reducing mastectomy and risk-reducing salpingo-oophorectomy (BRCA1 by 35 to 40, BRCA2 by 40 to 45).

Screening

• BreastScreen Australia invites women aged 50 to 74 for a free mammogram every 2 years. Women 40 to 49 and 75 and over can attend without an invitation.
• Screening mammography cuts breast cancer mortality by about 20% in women invited, with a cost of overdiagnosis.
• Breast density: there's no national rule on reporting it yet; some state programs report it. The 2026 Strategic Framework, responding to the 2025 national review, plans a move to risk-stratified screening within 10 years, starting with annual-screening eligibility and screening at 45 to 49.
• Screening is for women without symptoms. A woman with a lump needs diagnostic imaging, not a screening appointment.
• Participation is lower in Aboriginal and Torres Strait Islander women, culturally and linguistically diverse women and remote communities.

Recognition

• Painless lump (most common), nipple inversion or bloody discharge, skin dimpling, peau d'orange, axillary mass.
• Inflammatory breast cancer: rapid erythema and oedema over a third or more of the breast, often without a lump. It's often mistaken for mastitis; a "mastitis" that fails antibiotics needs imaging and biopsy.
• Paget disease of the nipple: eczematous, unilateral nipple change; associated with underlying DCIS or cancer.
• Metastatic presentations: bone pain, hypercalcaemia, cord compression, breathlessness from effusion or lymphangitis, jaundice, headache or seizures.

Investigations

Breast imaging

Test	Use	Limits
Mammography (2D or tomosynthesis)	Screening; diagnostic imaging from age 35; shows microcalcification (DCIS)	Less sensitive in dense breasts and in young women
Ultrasound	First test under 35 and in pregnancy or lactation; characterises palpable lumps; assesses and guides biopsy of the axilla	Operator-dependent; poor at microcalcification
MRI	High-risk screening (BRCA carriers, chest irradiation), lobular extent, occult primary with axillary nodes, implant assessment, response to neoadjuvant therapy	Many false positives; Medicare funds screening MRI only for high-risk women under 50

• Imaging is reported with BI-RADS (0 incomplete, 1 negative, 2 benign, 3 probably benign, 4 suspicious, 5 highly suggestive, 6 proven cancer). Categories 4 and 5 need biopsy.
• Core needle biopsy, not FNA, of the breast lesion: it gives invasion, grade and receptors. FNA or core of suspicious axillary nodes.

Pathology and staging

• ER, PR, HER2 and Ki-67 on every invasive cancer.
• Genomic assays (Oncotype DX, MammaPrint) guide chemotherapy in HR-positive, HER2-negative disease with 0 to 3 nodes. In TAILORx, node-negative women over 50 with a recurrence score of 25 or less gained nothing from chemotherapy. In RxPONDER, postmenopausal women with 1 to 3 nodes and a score of 25 or less didn't benefit; premenopausal women did. These tests are generally self-funded in Australia.
• Staging scans (CT chest, abdomen and pelvis with bone scan, or PET-CT) for stage III, inflammatory cancer, symptoms or abnormal bloods. Not for stage I or II without symptoms.

Management of early breast cancer

Surgery and radiotherapy

• Breast-conserving surgery plus radiotherapy gives the same survival as mastectomy. Mastectomy for multicentric disease, large tumour-to-breast ratio, patient choice, or where radiotherapy is contraindicated.
• Sentinel node biopsy for clinically node-negative disease. ACOSOG Z0011: with 1 or 2 positive sentinel nodes after breast conservation and whole-breast radiotherapy, axillary dissection adds nothing. AMAROS: axillary radiotherapy matches dissection with less lymphoedema. SOUND (tumours 2 cm or less with a negative axillary ultrasound, no age or receptor limit) and INSEMA (cT1 to T2 up to 5 cm, cN0, mostly HR-positive) found omitting sentinel biopsy non-inferior. Guidelines apply this mainly to postmenopausal women with small (T1) HR-positive, HER2-negative cancers and a normal axillary ultrasound.
• Radiotherapy: hypofractionated whole-breast courses (40 Gy in 15 fractions, or 26 Gy in 5 under FAST-Forward). Can be omitted in women 65 or over with HR-positive, node-negative cancers up to 3 cm who take endocrine therapy (PRIME II, which allowed grade 3 or lymphovascular invasion but not both), at the cost of more local recurrence and no survival difference.

Neoadjuvant therapy

Standard for HER2-positive and triple-negative cancers of 2 cm or more or node-positive, and for inflammatory or inoperable disease. It shrinks the tumour, allows less surgery, and the response (pathological complete response or residual disease) decides adjuvant treatment.

Subtype	Neoadjuvant	Adjuvant
HER2-positive	Chemotherapy with trastuzumab and pertuzumab	Complete response: finish 1 year of HER2 therapy. Residual disease: T-DM1 (KATHERINE), or T-DXd (DESTINY-Breast05; FDA-approved May 2026, not PBS-listed for this)
Triple-negative	Carboplatin and paclitaxel then AC, with pembrolizumab (KEYNOTE-522: better event-free and overall survival)	Pembrolizumab to complete 1 year; residual disease: capecitabine (CREATE-X) or olaparib if germline BRCA (OlympiA)

Small node-negative HER2-positive cancers (under 2 cm) often go straight to surgery, then weekly paclitaxel with a year of trastuzumab (APT trial).

Adjuvant endocrine therapy (HR-positive)

Patient	Treatment
Premenopausal, lower risk	Tamoxifen 20 mg daily for 5 to 10 years
Premenopausal, higher risk (under 35, needed chemotherapy)	Ovarian function suppression with an aromatase inhibitor or tamoxifen (SOFT and TEXT)
Postmenopausal	Aromatase inhibitor (letrozole, anastrozole, exemestane) for 5 years, extended to 7 to 10 if higher risk

• CDK4/6 inhibitors add to endocrine therapy in high-risk disease: abemaciclib for 2 years (monarchE: 4 or more nodes, or 1 to 3 with grade 3 or a 5 cm tumour) or ribociclib for 3 years (NATALEE: stage II and III). PBAC considered ribociclib for high-risk early disease in November 2024; check the current PBS listing and restriction before prescribing. Abemaciclib causes diarrhoea; ribociclib prolongs QT and raises liver enzymes.
• Olaparib for 1 year in high-risk HER2-negative disease with a germline BRCA variant (OlympiA improved overall survival).
• Adjuvant bisphosphonate (zoledronic acid 4 mg 6-monthly for 3 years) for postmenopausal women, including those made menopausal by ovarian suppression. The EBCTCG meta-analysis showed fewer bone recurrences and breast cancer deaths.

Drug	Side effects to know
Tamoxifen	Hot flushes, VTE, endometrial cancer (postmenopausal), cataracts; protects bone after menopause
Aromatase inhibitors	Arthralgia, bone loss, vaginal dryness, raised cholesterol

Pitfall: abnormal vaginal bleeding on tamoxifen needs investigation for endometrial cancer.

Metastatic breast cancer

• Biopsy a new metastasis where safe, because receptors can change.
• HR-positive, HER2-negative: aromatase inhibitor or fulvestrant with a CDK4/6 inhibitor first line (ribociclib improved overall survival in MONALEESA-2, -3 and -7). On progression, test for ESR1 (ctDNA), PIK3CA, AKT1 and PTEN alterations: elacestrant for ESR1 mutations, capivasertib or alpelisib with fulvestrant for pathway alterations. Then chemotherapy, antibody-drug conjugates (trastuzumab deruxtecan if HER2-low, sacituzumab govitecan).
• HER2-positive: taxane with trastuzumab and pertuzumab first line (CLEOPATRA: median overall survival about 57 versus 41 months). DESTINY-Breast09 found trastuzumab deruxtecan plus pertuzumab beat taxane-trastuzumab-pertuzumab first line (median progression-free survival 40.7 versus 26.9 months, HR 0.56; overall survival immature). The FDA approved it on 15 December 2025; no TGA or PBS decision was found at review, so check the ESMO living guideline and current listing. Trastuzumab deruxtecan second line beat T-DM1 (DESTINY-Breast03). Tucatinib with trastuzumab and capecitabine for brain metastases (HER2CLIMB).
• Triple-negative: chemotherapy with pembrolizumab if PD-L1 CPS 10 or more (KEYNOTE-355); sacituzumab govitecan later (ASCENT); PARP inhibitor for germline BRCA.
• PBS: trastuzumab deruxtecan has been PBS-listed for HER2-low metastatic disease after chemotherapy since 2024. In March 2026 PBAC didn't recommend extending it to HR-positive HER2-low or ultralow disease after endocrine therapy alone.
• Bone metastases: denosumab 120 mg or zoledronic acid to reduce skeletal events; dental review first (osteonecrosis of the jaw); calcium and vitamin D (see Hypocalcaemia and hypercalcaemia).

Complications of treatment

• Cardiotoxicity: anthracyclines cause dose-related, largely irreversible cardiomyopathy; trastuzumab causes usually reversible LV dysfunction. Baseline echo and 3-monthly LVEF on trastuzumab. ESC 2022: continue with cardioprotection (ACE inhibitor and beta-blocker) and cardio-oncology review if LVEF falls to 40 to 49%; interrupt if under 40% or symptomatic heart failure (see Heart failure).
• Lymphoedema after axillary dissection or radiotherapy: early physiotherapy and compression.
• Chemotherapy-induced neuropathy (taxanes), early menopause and infertility (offer fertility preservation before chemotherapy), therapy-related myeloid neoplasms.
• Pneumonitis with trastuzumab deruxtecan: interrupt it for grade 1 (asymptomatic) and consider steroids; resume once resolved, at a reduced dose if recovery took more than 28 days. Grade 2 or worse: stop permanently and give steroids.

Special populations

• Pregnancy: ultrasound first; mammography with shielding is safe. Surgery in any trimester; anthracycline chemotherapy from the second trimester. Avoid trastuzumab (oligohydramnios), tamoxifen and radiotherapy until after delivery. In the POSITIVE trial, pausing endocrine therapy to conceive (after 18 to 30 months of it) didn't raise short-term recurrence.
• Men (about 1% of cases): think BRCA2; tamoxifen is the usual endocrine therapy (an aromatase inhibitor needs a GnRH agonist).
• Older women: geriatric assessment guides treatment; primary endocrine therapy for frail women with HR-positive cancer.
• Aboriginal and Torres Strait Islander women: later stage at diagnosis and lower survival. Culturally safe screening and care coordination matter.

Pitfalls

• Reassuring a woman with a palpable lump because her screening mammogram was normal.
• Treating persistent "mastitis" with repeated antibiotics in a non-lactating woman.
• Ordering staging CT and bone scan for asymptomatic stage I disease.
• Prescribing paroxetine or fluoxetine with tamoxifen.
• Starting zoledronic acid or denosumab without checking vitamin D, calcium and dental health.
• Not checking LVEF before and during trastuzumab.
• Forgetting family cancer referral for triple-negative cancer under 50 or male breast cancer.