Breast Cancer
Breast cancer is not a single disease. Receptor status and molecular subtype divide it into groups whose biology, treatment logic and natural history differ substantially, which is why subtype is established before treatment planning rather than after it.
Disease categories
Major disease categories
- Hormone receptor positive, HER2 negative
- HER2 positive
- Triple negative breast cancer
- Ductal carcinoma in situ and other non-invasive disease
- Inflammatory and locally advanced disease
- Male breast cancer
Molecular
Molecular considerations
Oestrogen receptor, progesterone receptor and HER2 status define the principal treatment groups. Beyond these, alterations in PIK3CA, AKT1 and PTEN are relevant to the PI3K pathway; ESR1 alterations are studied in the context of acquired endocrine resistance; and germline BRCA1 and BRCA2 status carries both treatment and family implications.
Markers commonly discussed in breast cancer
- ER
- PR
- HER2
- Ki-67
- PIK3CA
- ESR1
- BRCA1/2
- PALB2
- PD-L1
- MSI / MMR
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Testing may span receptor immunohistochemistry, HER2 assessment including in-situ hybridisation where immunohistochemistry is equivocal, multigene expression assays used in some early-stage settings, and broader somatic panels in advanced disease.
Germline
Germline considerations
Germline testing is widely discussed where there is a young age at diagnosis, triple negative disease, bilateral disease, male breast cancer, or a suggestive family history. BRCA1, BRCA2 and PALB2 are the most frequently discussed genes, with implications for relatives as well as for the patient.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is studied in advanced breast cancer for the detection of alterations such as ESR1 and PIK3CA, and for tracking molecular change during endocrine therapy. Its role in early disease is an active research question rather than settled practice.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell RNA sequencing is used in breast cancer to resolve immune infiltration and to characterise the resistant subpopulations that bulk expression profiling averages into a single value. Single-cell DNA sequencing addresses a different question: whether an alteration reported at intermediate allele fraction sits in the dominant clone or in a subclone that will behave independently. On the algorithmic side, the work spans subtype classification from expression data, deconvolution of bulk samples into cell-type proportions, and models that track endocrine-resistance trajectories across serial samples.
In practice
What a review of this disease typically surfaces
The most frequent finding on review is a receptor status that was never reassessed after the disease became metastatic. Receptor discordance between primary and metastasis is well described, and a tumour that was hormone receptor positive at diagnosis may not be at relapse. The second recurring issue is a PIK3CA result reported without the specific variant, which matters because not all PIK3CA alterations carry the same weight. Cases also commonly arrive with germline testing that was never offered despite a young age at diagnosis or triple negative disease.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Does the receptor and subtype assessment agree across all available reports?
- If the tumour is hormone receptor positive, what is the evidence position for the endocrine strategy proposed?
- Is there a PIK3CA, AKT1 or PTEN alteration, and how much weight does it carry here?
- Does germline status change either treatment options or family discussions?
Resistance
Resistance and recurrence questions
- Has an ESR1 alteration emerged during endocrine therapy?
- Has receptor status been reassessed on a metastatic biopsy, and does it differ from the primary?
- Is there molecular evidence pointing to a specific resistance mechanism?
Trials
Clinical trial considerations
Trial questions in breast cancer are frequently subtype- and alteration-specific; molecular profile and prior therapy sequence both affect plausible eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.