Genetic testing for cancer: Why it makes sense

The right information gives one immense power to make a wise choice. The treatment of cancer is no different. Cancer always occurs due to genetic mutations in the body, but when we say ‘genetic,’ it does not necessarily mean ‘hereditary.’ Hereditary cancer predisposition accounts for only 10-15 % of all cancers. The rest are a result of chance mutations acquired over one’s lifetime.

A genetic mutation is a disruption in the code of life written in our DNA by nature. A human cell is programmed to behave in a certain normal way throughout life. A change in the genetic code (mutation) due to several host-related and environmental influences can reprogram it to become cancerous (with uncontrolled growth).

So, the question arises: For a disease which is caused by genetic mutations, would it not make sense to perform genetic testing? Genetic testing has several important implications in the management of cancer.

Genetic testing is generally done for patients with a significant family history of cancer, or some specific patterns of presentation of cancer. If a causative germline mutation is identified, the individual’s family members are also screened for it. Thus, a cancer patient who gets suitable genetic testing done also helps save lives of family members by making them aware of any causative mutation present in their genes.

Testing for germline mutations like BRCA 1 and BRCA2 for breast and ovarian cancer, and MMR genes for colon cancer, can identify at-risk individuals. Preventive and early detection strategies can be employed in these cases to completely avoid getting cancer or treat it when it is at the earliest stage, offering more than 95% chances of cure.

For people with high-risk mutations, several strategies are used to completely prevent or detect cancer early. These include risk-reduction mastectomies (removal of breast tissue), risk-reduction oophorectomy (removal of ovaries), and hormonal therapy with simple drugs like Tamoxifen and screening MRIs.

Genetic testing is not only useful in prevention and early detection of cancer, it is also extremely important during treatment. Genetic alterations such as EGFR, ALK, ROS1 and MET in lung cancer; BRCA in breast, ovarian and prostate cancer; RAS, B-RAF and MSI in colon cancer, and B-RAF in Melanoma (skin cancer) are some examples where therapies which target these driver mutations, or act via pathways dependent on these mutations, improve survival as well as quality of life of patients.

Micro-satellite instability, higher tumour mutation burden and mutations like POLE can help inform decisions regarding using immunotherapy in suitable patients. One such example was the recent Dostarlimab study in rectal cancer which showed unprecedented responses in those with microsatellite unstable tumours. Genomic risk scores can help decide the need for add-on chemotherapy after surgery in early hormone-positive breast cancer.

For patients with blood cancer, mutations like BCR-ABL in CML and JAK2 in other myeloproliferative neoplasms (MPNs) are not only diagnostic but also confer sensitivity to targeted drugs like Imatinib (and similar drugs like Dasatinib, Nilotinib and Bosutinib) and Ruxolitinib.

Targeting FLT3 mutation in acute myeloid leukaemia (AML) has changed the outcome significantly for FLT 3 Mutated AML. Similarly, IDH inhibitors and Menin inhibitors are impacting the treatment of AML immensely in those with certain genetic mutations.

Genetic testing for blood cancers helps in stratifying these cancers into a favourable v/s unfavourable biology, helping doctors take decisions whether a particular patient will benefit with more treatment like allogenic stem cell transplant. Thorough testing can identify the reason why certain patients with acute lymphoblastic leukaemia do poorly despite otherwise having no high-risk features.

Testing hundreds of mutations together by a strategy called Next Gen Sequencing has increasingly become more and more accessible and affordable in India. Based on such ‘comprehensive genomic analysis’ where several different mutations are taken into account, approaches that utilize combinations of targeted drugs and chemotherapy/immunotherapy are sometimes able to elicit responses in relapsed / refractory cancers where routine treatment has failed. Several such strategies are currently being tested in clinical trials.

Genetic mutations are also used after treatment to monitor disease and detect recurrence or change in disease biology early, such as minimal residual disease testing in AML, T790M in lung cancer and T315I in Chronic myeloid leukaemia.

Overall, genetic testing is now an integral and essential part of treatment of cancer which guides risk reduction, screening strategies, prognosis as well as treatment and follow up.

The author is a Senior Consultant, Medical Oncology/Hematoncology/BMT, Amrita Hospital, Faridabad. View are personal. Views are personal.

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