The Impact of Next Generation Sequencing on Women-Focused Cancers


Kamala Maddali, vice president for Biopharma Collaborations & Companion Diagnostics at Cancer Genetics, discusses what impact next generation sequencing (NGS) stands to have on cancers that affect women.


NGS technology allows for the rapid and accurate sequencing of many genes at once

2018 saw an estimated 18 million cancer cases around the world. Of these, 9.5 million cases were in men and 8.5 million in women. Lung and breast cancers were the most common cancers worldwide, each contributing 12.3 percent of the total number of new cases diagnosed in 2018.1 With this growing global burden, a huge focus is on early detection and prevention of cancer, in addition to cancer treatment. This is one of the most significant public health challenges of the 21st century.


Higher incidence of cancers in related individuals has uncovered an inheritance pattern in underlying genetic lesions. Hereditary cancers represent five to ten percent of all cancers and the inherited mutations are generally not insufficient for cancer development but increase the risk, and/or predispose the carrier individuals to cancer (while some mutations are inherited). Also, some other mutations may arise due to various extraneous factors such as stress, diet, behaviour and exposure to changing environments. Therefore, identification of the set of driver mutations and the overall mutational landscape of tumours allows for more precise diagnosis, prognosis, and theranosis to optimize treatment outcomes. This is where Precision Medicine is set to play a crucial role. In general, precision medicine is a medical model that proposes the customization of healthcare, focusing on identifying which approaches will be effective for which patients, based on genetic, environmental, and lifestyle factors. This leads to medical decisions, treatments, practices, or products being tailored to the individual patient.


The continued reduction in the cost of DNA sequencing is expected to make early and comprehensive testing more affordable. As precision medicine takes centre stage in the 21st century, there are a few key challenges that lie ahead of us. Arguably, the overall goal of precision medicine would be to have the analyzed entire genome of an individual available at the physician’s fingertips to facilitate the best available and most cost-effective therapeutic path for the patient. Next-generation sequencing (NGS) technology allows for the rapid and accurate sequencing of many genes at once. While NGS has been tested across multiple health care settings, its use is most advanced in oncology with physicians sequencing their patients’ tumours to match them to therapies designed to target the genetic alterations driving the tumour’s growth. The growing significance of NGS was illustrated in December 2017 by the first FDA approval of a large panel, Foundation Medicine’s ‘FoundationOne companion diagnostic’ (F1CDx) test, which detects mutations in 324 genes and 2 genomic signatures in any tumour type.


Again, precision medicine promises entirely new comprehensive approaches to detect, monitor, and treat illness, based on a patient’s genetic, environmental, and lifestyle profile. The effort is massive, requiring a deep understanding of patient biology at a molecular level not feasible before. By taking a peek at a patient’s comprehensive and unique molecular profiles, the field of medicine will morph into a dramatically different landscape in the next 5 to 10 years.


Right now, precision medicine is enabling collaborators across many sectors (academia, life sciences, pharmaceutical, and healthcare) to join forces to accelerate the movement of innovation from research labs to clinical settings. Also, the role of patient advocacies is pivotal to adopting precision medicine in the community at a much faster and more effective pace.


The use of NGS to sequence a few genes can help confirm that the patient will respond favourably to the drug and make the therapy more efficient. Such innovation lies at the heart of improving cancer care and disrupting the invasion of cancer. We know that different populations have different genetic markers that affect incidence, progression and response to therapy.


Its biggest impact has been in the area of offering NGS based diagnostic panels. Several companies now offer NGS testing for a selection/panel of genes involved in hereditary cancers, genes that are most commonly mutated in solid tumours, and a few panels representing the most frequently mutated genes in specific cancers, e.g. myeloid malignancies and breast cancer.


In the context of cancer, which is driven by genetic aberrations in multiple genes, this presents great advantages over the traditional sequencing technology of one gene or few at a time. Several public and private initiatives quickly adopted the new NGS platforms to establish mutational landscapes of several tumour types by sequencing the entire genomic DNA content of tumour tissues. Intuitively, the scale of this research has created a data deluge that many people continue to sift through to categorize the mutations into four relatively distinct classes of mutations.


  • Germline versus somatic mutations
  • Driver versus passenger mutations
  • Prognostic mutations
  • Pharmacogenomic/theranostic mutations


Advancements include Nextgen sequencing tests to guide relevant breast cancer therapies based on genetic mutations, 3D mammography, circulating DNA tests, surgical advancements such as mastectomy, lumbectomy, and reconstructive micro surgery.


This level of diagnostic, prognostic, theranostic, and molecular tissue-typing approach is the centrepiece of the emerging field of precision medicine and NGS plays a vital role in empowering doctors to use actionable genetic information for the most effective clinical management of cancer. NGS has already been instrumental in the discovery phase of cancer diagnostics and continues to fuel clinically relevant research that will increase personalization of diagnosis and treatment of cancer.


This is why building a knowledge base that allows effective use of such differences to guide decision making in the clinical context will increase the efficacy and accuracy of precision oncology.


With collaboration between multiple stakeholders, the innovation from precision medicine is, and will continue to, give more hope to good community health globally




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