Genetics and Genomics in Cancer: Key Facts Everyone Should Know 2025

In the ever-evolving field of oncology, understanding genetics and genomics is crucial for patients, families, and healthcare providers alike. Genetics focuses on the study of genes and their role in inheritance—how certain traits or conditions are passed from one generation to the next. Genetic testing identifies inherited mutations present in every cell of the body since birth (known as germline testing). This can be performed via a blood test, cheek swab, or saliva sample. In cancer care, it's vital because it detects inherited predispositions to specific cancers, such as those linked to BRCA1/2, ATM, PALB2, CHEK2, BRIP1, Lynch syndrome, and others. These insights inform treatment choices, surveillance strategies, risk-reduction measures, and family testing recommendations.

Genomics, on the other hand, examines a person's entire genome. In cancer, genomic testing analyzes the tumor cells to pinpoint gene or protein alterations that distinguish them from healthy cells. By sequencing the tumor (from tissue or blood), we gain insights into what drives cancer growth, resistance mechanisms, and potential targeted therapies. It also determines eligibility for clinical trials. Often called somatic testing, genomic profiling, biomarker testing, or next-generation sequencing (NGS), this can involve tumor tissue or a "liquid biopsy" via blood. Together, genetics and genomics provide a comprehensive approach to personalized cancer care.

When to Consider Genetic TestingGenetic testing is recommended for individuals with a personal or family history suggestive of hereditary risk, early-onset diagnosis, specific cancer subtypes (e.g., triple-negative breast cancer), or when results could influence treatment decisions.
Per the National Comprehensive Cancer Network (NCCN) guidelines, testing is indicated if:

• A blood relative has a known mutation in a cancer susceptibility gene.
• Results could guide systemic therapy or surgical decisions (e.g., PARP inhibitors for BRCA-related breast cancer).
• A mutation found in tumor genomic testing has implications if confirmed as germline (e.g., BRCA).

NCCN offers tailored criteria based on cancer type, such as breast, prostate, or ovarian. Testing typically uses multigene panels to screen multiple genes simultaneously.It's essential to consult a genetic counselor or experienced clinician for pretest counseling, which includes a thorough review of family, medical, and surgical history. This helps select the appropriate test and educates on benefits, risks, and limitations, empowering informed decisions about testing and screening. Posttest counseling interprets results, outlines medical risks, and provides personalized care recommendations.Possible Genetic Testing ResultsGenetic tests yield one of three main outcomes:

1. Pathogenic Variant (Mutation) Identified: A DNA change in a gene is confirmed to increase risk for cancer or other conditions.
2. Negative: No variants are found in the tested genes. Note that most cancers are sporadic, not hereditary, so this doesn't eliminate all cancer risk.
3. Variant of Uncertain Significance (VUS): A gene change is detected, but its impact on health or cancer risk is unknown. Most VUS are later reclassified as benign. Labs notify patients of updates, but periodic check-ins with a genetic counselor are advisable. VUS typically doesn't alter management plans.

Should You Repeat Genetic Testing?If your prior testing was limited—e.g., only checking common BRCA mutations or a single gene—consider retesting with modern multigene panels. This is especially relevant if testing occurred over a decade ago, as technology has advanced. Discuss with your healthcare team or genetic counselor. Remember, hereditary cancer testing differs from prenatal genetic screening or tumor-specific biomarker tests.Understanding Cancer GenomicsGenomic testing offers a detailed view of the tumor's molecular makeup and can be performed at diagnosis, progression, or recurrence. For instance, in metastatic breast cancer, it may reveal:

• Actionable mutations like PIK3CA/AKT/PTEN (targeted by alpelisib or capivasertib).
• ESR1 mutations (targeted by elacestrant).
• MSI-high or high tumor mutational burden (TMB) for immunotherapy.

Other examples include Oncotype DX or MammaPrint for early-stage breast cancer to inform chemotherapy needs, or somatic BRCA testing in ovarian cancer for PARP inhibitors. The timing and type depend on the cancer and how results guide treatment.Tissue vs. Liquid Biopsy for Genomic Testing

• Tissue Biopsy: Analyzes surgical or biopsy samples for mutations, copy number variations, and fusions.
• Liquid Biopsy: A blood-based test detecting circulating tumor DNA (ctDNA). It's minimally invasive, repeatable, and useful for monitoring evolution in metastatic cases. Turnaround: 1–4 weeks.

Common platforms include Caris, Guardant, Tempus, and FoundationOne; some institutions use in-house assays. Single-gene tests suit suspected alterations, while NGS panels scan hundreds of genes for broader insights. AI is increasingly enhancing analysis.Navigating Financial AspectsCost can be a barrier, but options exist:

• Insurance Coverage: Most plans cover germline testing if NCCN criteria are met; tumor testing varies.
• Out-of-Pocket Costs: Range from low to thousands of dollars.
• Support Programs: Labs often provide financial aid, payment caps, or free testing if denied by insurance.

Key questions for your team:

• Does my insurance cover this?
• Will the lab verify coverage beforehand?
• What's the maximum out-of-pocket expense?
• Are there assistance programs or financial counselors available?
• What if I don't meet criteria or lack insurance?

Addressing Common Questions"I have a strong family history of breast cancer, but genetic testing was negative. Should I repeat it?"
It depends on when and what was tested. If limited to one gene or common mutations years ago, retesting with updated panels may be warranted. Consult a genetic counselor. Even with negative results, high-risk screening could still apply. Use CLIA-certified labs for reliability—avoid direct-to-consumer kits.
"Why isn't somatic tumor testing routine for every new diagnosis?"
It varies by test and context. For example, Oncotype in early breast cancer differs from mutation hunting in metastatic disease. Testing is prioritized when it directly informs therapy or trials.
"My genetic testing was negative, but I had two breast cancers. Why?"
Most breast cancers aren't inherited; other factors play a role. Current tests don't cover all genes, and new discoveries continue. Negative results reduce but don't eliminate risk.This overview highlights the transformative role of genetics and genomics in cancer. For personalized advice, consult your healthcare provider.

Source and Reference: https://drteplinsky.substack.com/p/genetics-and-genomics-in-cancer-important