CancerDrs

Biomarkers

Breast Cancer biomarkers — what to test

Breast cancer is one of the most biomarker-driven cancers. Every new diagnosis should have hormone receptor status, HER2 status, and (for some subtypes) additional molecular testing before systemic therapy decisions. The results determine whether you'll receive endocrine therapy, HER2-targeted therapy, CDK4/6 inhibitors, PARP inhibitors, immunotherapy, or chemotherapy — or some combination.

Standard biomarkers

These are typically tested on every new diagnosis, or required before systemic therapy decisions, under current U.S. clinical guidelines.

Estrogen Receptor (ER) and Progesterone Receptor (PR)

Standard

What it is: Protein expression on cancer cells that indicates the tumor grows in response to estrogen and/or progesterone. Reported as percent positive on IHC.

Why test: ~70% of breast cancers are ER+. ER-positive cancers respond to endocrine (hormonal) therapy, which is effective and generally lower-toxicity than chemotherapy.

Therapies it unlocks:
  • Tamoxifen
  • Aromatase inhibitors (anastrozole, letrozole, exemestane)
  • Fulvestrant
  • CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) added to endocrine therapy
  • Elacestrant (for ESR1-mutated ER+ disease)

HER2

Standard

What it is: Human Epidermal Growth Factor Receptor 2. Tested by IHC (0, 1+, 2+, 3+) and FISH for equivocal (2+) results. HER2 gene amplification / protein overexpression drives aggressive growth.

Why test: HER2+ cancers respond dramatically to HER2-targeted therapies. HER2-low (1+ or 2+ FISH-negative) is now separately actionable with trastuzumab deruxtecan.

Therapies it unlocks:
  • Trastuzumab (Herceptin)
  • Pertuzumab (Perjeta)
  • Ado-trastuzumab emtansine (Kadcyla)
  • Trastuzumab deruxtecan (Enhertu) — including for HER2-low
  • Tucatinib
  • Neratinib
  • Margetuximab

Context-specific biomarkers

Tested depending on cancer stage, subtype, family history, or as part of broader NGS (next-generation sequencing) panels.

Ki-67

What it is: A marker of cellular proliferation (how fast cells are dividing). Reported as a percentage.

Why test: Used in some cancers with intermediate Oncotype scores or to help decide between endocrine therapy alone versus adding chemotherapy. Also relevant for CDK4/6 inhibitor choice in some settings.

BRCA1 / BRCA2 (germline)

What it is: Inherited mutations in DNA-repair genes. Tested via blood or saliva.

Why test: Opens eligibility for PARP inhibitors. Informs contralateral breast cancer risk and ovarian cancer surveillance. Has implications for first-degree family members.

Therapies it unlocks:
  • Olaparib (Lynparza)
  • Talazoparib (Talzenna)

PIK3CA

What it is: A mutation in the PI3K signaling pathway, common in ER+/HER2- advanced breast cancer.

Why test: Opens eligibility for alpelisib + endocrine therapy in advanced hormone-receptor-positive disease.

Therapies it unlocks:
  • Alpelisib (Piqray) combined with fulvestrant

PD-L1

What it is: Programmed death-ligand 1 expression on tumor or immune cells. Tested on certain subtypes.

Why test: Drives eligibility for immune checkpoint inhibitors in metastatic triple-negative breast cancer.

Therapies it unlocks:
  • Pembrolizumab (Keytruda) with chemotherapy in TNBC

Oncotype DX / MammaPrint (multigene recurrence scores)

What it is: Multi-gene panels that score recurrence risk in early-stage ER+/HER2- breast cancer.

Why test: Help decide whether chemotherapy adds benefit beyond endocrine therapy. Low scores typically skip chemo; high scores benefit from it.

Questions to ask your oncologist

  • What biomarker testing are you doing on my tumor?
  • Are there any tests we are skipping that I should consider?
  • Will we wait for results before starting systemic therapy, or start something interim?
  • Is germline genetic testing appropriate for me, given my personal and family history?
  • If a biomarker test is indeterminate, what is the plan?

Next steps

FDA-approved breast cancer drugs →

See which FDA-approved drugs match each biomarker profile above.

 Breast Cancer clinical trials →

Active recruiting trials, many biomarker-matched.

 Biomarkers explained: full guide →

Deeper background on how biomarker testing works.

 Germline genetic testing →

Different from tumor testing; addresses inherited cancer risk and family implications.

 Genetic testing cost →

What germline and tumor molecular tests cost, and how insurance covers each.

 BRCA test cost →

What patients pay in practice for BRCA1/2 testing and ACA preventive coverage rules.