Phys · oncological
Breast Cancer (Physician Perspective)
Also known as breast cancer · breast carcinoma · invasive ductal carcinoma · invasive lobular carcinoma · ductal carcinoma in situ · DCIS · lobular carcinoma in situ · LCIS · triple-negative breast cancer · TNBC · HER2-positive breast cancer · hormone receptor positive breast cancer · ER positive breast cancer · BRCA1 · BRCA2 · trastuzumab · Herceptin · tamoxifen · aromatase inhibitor · anastrozole · letrozole · exemestane · pembrolizumab · olaparib · sentinel lymph node biopsy · breast-conserving surgery
Consultant-physician guide to breast cancer — the most common cancer in women worldwide and the second leading cause of cancer death. Organised around the receptor subtype framework (ER/PR, HER2, triple-negative) that drives every systemic therapy decision. Covers epidemiology and risk factors (BRCA1/2, PALB2, reproductive and lifestyle factors), BreastScreen Australia screening and high-risk MRI surveillance, pathology (DCIS, LCIS, invasive ductal and lobular), TNM staging, surgical principles (breast-conserving therapy, sentinel node biopsy), adjuvant and neoadjuvant systemic therapy (endocrine — tamoxifen and aromatase inhibitors with ovarian suppression; HER2-targeted — trastuzumab, pertuzumab, T-DM1; immunotherapy — pembrolizumab for triple-negative; PARP inhibition — olaparib for BRCA), metastatic management by site, treatment complications (cardiotoxicity, osteoporosis, endometrial cancer, lymphoedema), and hereditary risk reduction (BRCA — bilateral mastectomy and salpingo-oophorectomy).
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Red flags
- Any new painless breast lump in a woman over 30 is breast cancer until proven otherwise — triple assessment (examination, imaging, biopsy) is mandatory
- A unilaterally bloody or serous nipple discharge is caused by an intraductal papilloma or carcinoma until excluded — investigate, do not dismiss
- Eczematous change of the nipple (Paget disease) is always associated with an underlying ductal carcinoma in over 90 percent of cases — biopsy the nipple
- Inflammatory breast cancer presents as a warm, swollen, erythematous breast with peau d'orange that mimics mastitis or cellulitis — if there is no response to antibiotics within 1 week, biopsy is mandatory
- New back pain or neurological symptoms in a woman with a history of breast cancer is spinal cord compression from vertebral metastases until proven otherwise — urgent MRI
- All triple-negative breast cancer diagnosed under age 60 should be offered germline BRCA testing — missing a BRCA1 mutation denies the patient olaparib and risk-reducing surgery
- A premenopausal woman must never receive an aromatase inhibitor without ovarian function suppression — it is ineffective and may paradoxically stimulate the ovaries
- Any postmenopausal vaginal bleeding on tamoxifen is endometrial cancer until excluded — urgent transvaginal ultrasound and biopsy
Breast Cancer (Physician Perspective)
The answer first
Breast cancer is the most commonly diagnosed cancer in women worldwide and the second leading cause of cancer death in women. In Australia, a woman has a 1 in 8 lifetime risk of developing breast cancer. Its central importance to a physician is that it is screenable, treatable, and increasingly survivable — over 90 percent five-year survival for localised disease — and the entire field turns on one idea: the receptor subtype determines the systemic therapy [1].
The single organising principle: breast cancer management is driven by the TNM stage and the receptor profile (ER, PR, HER2). Know the receptors and the stage and you know the treatment. Surgery and radiotherapy address the locoregional disease; endocrine therapy, chemotherapy, HER2-targeted therapy, immunotherapy, and PARP inhibition address the systemic risk [3][5][8].
The treatment ladder, by subtype and stage: [1]
- DCIS (stage 0) — surgery (WLE or mastectomy) plus radiotherapy after WLE; endocrine therapy for ER-positive DCIS is considered.
- Early-stage ER-positive, HER2-negative — surgery, then adjuvant endocrine therapy (tamoxifen if premenopausal, aromatase inhibitor if postmenopausal, ovarian function suppression for high-risk); chemotherapy guided by genomic assays (Oncotype DX) in node-negative disease [3][4][12].
- HER2-positive — surgery, then chemotherapy plus trastuzumab for 1 year; neoadjuvant TCHP for tumours over 2 cm or node-positive; T-DM1 for residual disease [5][7].
- Triple-negative — neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522), then adjuvant pembrolizumab; olaparib for germline BRCA carriers [8][9].
- Metastatic — systemic therapy guided by receptor subtype; bone-targeted therapy (bisphosphonates or denosumab) for bone disease; palliative radiotherapy for symptomatic sites.
DWE high-yield: The answer to almost every breast cancer management question is "determine the receptor status (ER, PR, HER2) and the stage." ER-positive gets endocrine therapy (tamoxifen if premenopausal, AI if postmenopausal, add OFS if high-risk premenopausal). HER2-positive gets trastuzumab for 1 year. Triple-negative gets pembrolizumab plus chemotherapy neoadjuvantly. BRCA-mutated HER2-negative gets olaparib. Never give an AI to a premenopausal woman without ovarian suppression [3][4][8][9].
References12ShowHide
- [1]Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin, 2024.PMID 38572751
- [2]Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials Lancet, 2011.PMID 22019144
- [3]Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer Lancet, 2005.PMID 15639680
- [4]Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer N Engl J Med, 2015.PMID 25495490
- [5]Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer N Engl J Med, 2005.PMID 16236737
- [6]Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer N Engl J Med, 2012.PMID 22149875
- [7]von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer N Engl J Med, 2019.PMID 30516102
- [8]Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer N Engl J Med, 2020.PMID 32101663
- [9]Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant Olaparib Improves Disease-Free Survival in Early, High-Risk, BRCA-Mutated, HER2- Breast Cancer Oncologist, 2021.PMID 34152054
- [10]Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial Lancet Oncol, 2010.PMID 20863759
- [11]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial JAMA, 2011.PMID 21304082
- [12]Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer N Engl J Med, 2018.PMID 29860917