Cancer biomarkers — EGFR, BRCA, HER2, MSI and why they matter

A cancer biomarker is a measurable feature of a cancer (a protein, a gene mutation, a pattern) that helps predict how the cancer will behave or which therapy will work against it. Over the last decade, biomarker-driven treatment has transformed outcomes in many cancers.

Here are the most important biomarkers patients will encounter, by category.

Hormone receptors (breast cancer)

ER (estrogen receptor) and PR (progesterone receptor) — reported as percent positive or negative. About 70% of breast cancers are ER+, meaning estrogen drives their growth. ER+ cancers often respond to endocrine therapy (tamoxifen, aromatase inhibitors) for 5–10 years.

Why it matters: ER/PR status dictates whether endocrine therapy is appropriate. It also predicts generally more favorable outcomes.

HER2 (breast, gastric, some others)

HER2 — reported as 0, 1+, 2+, or 3+ by IHC; 2+ cases get confirmed by FISH. HER2-positive cancers respond to HER2-targeted therapies (trastuzumab, pertuzumab, T-DXd). HER2-low (1+ or 2+ FISH-negative) is now actionable too, with drugs like trastuzumab deruxtecan.

Why it matters: HER2-targeted therapies have meaningfully changed breast and gastric cancer outcomes.

EGFR (lung cancer)

EGFR mutations — occur in ~15% of U.S. lung adenocarcinomas (higher in never-smokers and people of East Asian descent). EGFR-mutated lung cancers respond to EGFR tyrosine kinase inhibitors like osimertinib.

Why it matters: Targeted therapy is often the first-line treatment for EGFR-positive NSCLC, with better response rates and lower toxicity than chemotherapy.

ALK, ROS1, RET, MET, NTRK (lung cancer and other solid tumors)

Each of these represents a specific rearrangement or fusion in cancer DNA. Each has its own targeted therapy:

• ALK → alectinib, brigatinib, lorlatinib
• ROS1 → crizotinib, entrectinib, repotrectinib
• RET → selpercatinib, pralsetinib
• MET exon 14 → capmatinib, tepotinib
• NTRK → larotrectinib, entrectinib

Why it matters: These mutations collectively cover a meaningful fraction of lung adenocarcinomas. Without testing, you may miss a therapy with a high response rate.

KRAS (colorectal, lung, pancreatic)

KRAS — historically considered “undruggable,” but KRAS G12C mutations in lung cancer now have approved targeted therapies (sotorasib, adagrasib). KRAS status also affects which EGFR-directed therapies work in colorectal cancer (cetuximab and panitumumab are ineffective in KRAS-mutant colorectal).

Why it matters: KRAS testing is now standard for colorectal, lung, and pancreatic cancer.

MSI-High / MMR-Deficient (colorectal, endometrial, others)

MSI (Microsatellite Instability) and MMR (Mismatch Repair) — MSI-High (MSI-H) or MMR-deficient (dMMR) tumors have high neoantigen load and respond well to immune checkpoint inhibitors (pembrolizumab, nivolumab). MSI-H is common in Lynch syndrome–associated cancers.

Why it matters: MSI-H / dMMR testing is standard for colorectal and endometrial cancer and increasingly for other cancers. It can dramatically change first-line treatment.

PD-L1 (many cancers)

PD-L1 — the protein targeted by immune checkpoint inhibitors. Reported as a Tumor Proportion Score (TPS) or Combined Positive Score (CPS). High PD-L1 predicts better response to PD-1/PD-L1 inhibitors, though not perfectly.

Why it matters: PD-L1 testing guides first-line immunotherapy decisions in many cancers (lung, gastric, bladder, cervical, others).

Tumor Mutational Burden (TMB) — any solid tumor

TMB-High (≥10 mutations per megabase) — another indicator of response to immune checkpoint inhibitors. FDA-approved as a “tumor-agnostic” biomarker — pembrolizumab is approved for TMB-H solid tumors regardless of cancer type.

Why it matters: For patients who don’t qualify based on MSI-H or tissue-specific markers, TMB can unlock immunotherapy eligibility.

BRCA1 / BRCA2 (breast, ovarian, prostate, pancreatic)

BRCA1 / BRCA2 mutations — can be germline (inherited) or somatic (tumor-only). BRCA-mutated cancers respond to PARP inhibitors (olaparib, niraparib, talazoparib, rucaparib).

Why it matters: BRCA testing opens PARP inhibitor eligibility and informs family genetic counseling. All pancreatic and ovarian cancer patients should be tested at diagnosis.

HRD (Homologous Recombination Deficiency)

HRD-positive tumors — typically ovarian — respond to PARP inhibitors even without a BRCA mutation.

Why it matters: Extends PARP inhibitor eligibility beyond BRCA carriers.

How to make sure you’re tested

Biomarker testing should happen at diagnosis for most solid tumors before systemic therapy decisions are made. Ask your oncologist:

• “What biomarker testing are we doing on my tumor?”
• “Are we testing for all the markers I might be eligible for based on my cancer type?”
• “If my tissue is limited, can we prioritize the tests most likely to change treatment?”

If your tumor wasn’t tested, or was tested for only a limited panel, ask about repeat biopsy or liquid biopsy (blood-based testing) to fill in gaps.

Related reading

• How to read a cancer pathology report — where biomarker results appear
• How to find a clinical trial — many trials are biomarker-matched
• Questions to ask your oncologist