Genetic testing for breast cancer (BC)

1 in 10

About 1 in 10 women are diagnosed with breast cancer during their lifetime. 5% to 10% of all women with breast cancer may have a germline mutation of BRCA1 and BRCA2 genes. Invasive ductal carcinoma is the most common type of breast cancer.

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About two-thirds of breast cancers have estrogen and/or progesterone receptors called «hormone receptor-positive».

10–20%

About 10% to 20% of breast cancers are caused by alterations in the gene called human epidermal growth factor receptor 2 (HER2). These tumors are «HER2 positive» and have many copies of the HER2 gene (HER2 amplification) or overexpression of HER2 protein.

15–20%

Tumors that don’t have ER, PR, and HER2 expressions are called «triple-negative». Triple-negative breast cancer comprises about 15-20% of invasive breast cancers. It seems to be more common among younger women and women with a mutation in the BRCA1 gene.

What is genetic testing for breast cancer?

An NGS-based assay includes a panel of genes concurred with the clinical use of approved targeted drugs and drugs from prospective clinical trials for breast cancer.

Alterations in these genes lead to tumor development and are used as diagnostic, prognostic, and predictive cancer markers.

"First Genetics Lab" performs testing using the high‑throughput sequencing system named "F‑Genetics" and reagents for high‑throughput next generation sequencing (NGS) of genes associated with human cancer genesis, that are registered as medical devices (Federal Service for Surveillance in Healthcare: РЗН 2020/10521, РЗН 2022/16970)

The assay detects:

Hotspots (SNV/InDels)
Copy number variations (CNV)
Chromosomal aberrations (Gene fusions)

Consulting with a clinical geneticist and an oncologist to interpret test results and select cancer therapy is required

Hotspots (SNV/InDels)

8 genes

AKT1

ERBB2

ERBB3

FGFR2

FGFR3

KRAS

NRAS

PIK3CA

Copy number variations (CNV)

9 genes

CCND1

ERBB2

FGFR1

FGFR2

FGFR3

FGFR4

KRAS

MYC

PIK3CA

Chromosomal aberrations (Gene fusions)

7 genes

ERBB2

FGFR1

FGFR2

FGFR3

NTRK1

NTRK2

NTRK3

Indications for testing

For patients diagnosed with breast cancer for:

Therapy selection
Therapy monitoring and correction if the cancer recurrence occurs
Clinical trials enrollment

Targeted therapy

Targeted therapy is the type of treatment that targets specific molecules/proteins on the cancer cell surface or inside the cancer cells, blocking the growth and spread of cancer cells and limiting damage to healthy cells.

Not all tumors have the same targets. Genetic tests are used to find out what treatment is the most effective. Many clinical studies are underway.

Targeted therapy. Indications for drugs

TARGETED THERAPIES FOR RECURRENT UNRESECTABLE OR STAGE IV (M1) breast cancer
(NCCN Guidelines Version 3.2022)

Breast Cancer Subtype	Biomarker	FDA-Approved Agents
Любой	HER2	Trastuzumab Pertuzumab Margetuximab Ado-trastuzumab emtansine Fam-trastuzumab deruxtecan-nxki
Any	BRCA1/BRCA2 mutation	Olaparib Talazoparib
HR-positive/HER2-negative	PIK3CA activating mutation	Alpelisib + fulvestrant
TNBC	PD-L1 expression	Pembrolizumab + chemotherapy (albumin-bound paclitaxel, paclitaxel, or gemcitabine and carboplatin)
Any	NTRK fusion	Larotrectinib Entrectinib
Any	MSI-H/dMMR*	Pembrolizumab Dostarlimab-gxly
Any	TMB-H (≥10 mut/Mb)**	Pembrolizumab

* microsatellite instability / deficiency of the DNA mismatch repair system

** high tumor mutation burden

NGS method

NGS can simultaneously read hundreds of millions of short sequences of DNA and detect all types of mutations, including

Hotspots (SNV/InDels)

Copy number variations (CNV)

Chromosomal aberrations (Gene fusions)

Advantages

High sensitivity and specificity of the method
Fast turnaround time
Simultaneous detection of all types of mutations, including chromosomal aberrations
Minimum requirements for sample quantity and quality
Shorter testing times