How precision medicine and genomics aid in cancer care
Therapies now are targeted based on the tumor’s genetic profile rather than on the site where the disease presents.
Cancer specialists have long been the standard-bearers of precision medicine. Oncology was one of the first clinical areas to recognize the role genetic variations play in disease risk and causation. Subsequent progress has brought us to our current state, where oncologic therapies are targeted based on the tumor’s genetic profile, rather than on the site where the disease presented itself.
Consider these realities:
Somatic results are not enough
The results of somatic testing, which reveals genetic markers of the tumor tissue, has added great value to cancer treatment. Oncologists use these insights to more precisely diagnose a patient’s disease and devise a care plan tailored to the unique molecular profile of the cancer. While incredibly important in the treatment of a specific incidence of cancer, somatic information does not provide information about the patient’s “native” genetic profile; a tumor’s characteristics are unique unto itself. Therefore, somatic data provides limited information about the overall patient and other factors that might affect their care and wellbeing now and into the future.
As standard bearers, oncologists must look beyond somatic information, seeking and using a broader range of genomic data including germline and pharmacogenomic information to deliver the most effective care possible.
Leveraging pedigree and germline data
Four specific areas come to mind, when we consider how oncology can maximize the value of genomics beyond the somatic view – which will lead to better outcomes and quality of life for patients.
Pedigree documentation to identify risk for prevention and earlier intervention. Not long ago, I saw a young female patient who mentioned several family members had been diagnosed with breast cancer and ovarian cancer. We discussed benefits of genetic screening as well as other aggressive prophylactic options. While contemplating, she underwent mammography that unfortunately revealed Stage III cancer.
This was a sad and unnecessary outcome. Electronic health records should be capable of capturing critical family history enabling providers to spot areas of risk and concern – but, unfortunately, they do not. Instead, we need to leverage precision medicine tools designed to map a detailed patient pedigree so all providers, from PCPs to specialists, can assess heritable risk early, implementing in-time preventative and diagnostic measures.
The value extends beyond the patient him or herself, as well. Complete and detailed pedigree information can be shared with family members (and their providers) so they, too, can easily review familial patterns and more effectively identify genetic risk sooner.
The impact pharmacogenomic (PGx) information could have on the medications the oncologist prescribes. Of course, somatic data can help the oncologist decide on the best treatment. Perhaps the patient’s tumor exhibits markers like those examined in the TAILORx study4 for breast cancer – which means she does not need chemotherapy following surgery but would benefit equally well with hormone therapy (typically Tamoxifen). If the oncologist also had access to full PGx information, however, he would discover variants in the patient profile indicating she may not metabolize Tamoxifen well. With this information in hand, he can prescribe a different medication (such as an aromatase inhibitor) to manage her condition long term – and with greater success – instead.
PGx test results can reveal which nausea and pain drugs the patient metabolizes best, as well. This enables the oncologist to order the medications that will provide greatest relief with fewest side effects – the first time around, without time-consuming and frustrating trial and error.
Germline insights into co-morbidities and concurrent therapies. When an oncologist refers only to somatic data, he or she sees a thin representation of the patient’s overall situation. But it stands to reason that other diseases and treatments could impact the oncology care plan – and vice versa (cancer care could impact other clinicians’ decisions and therapies). Access to full germline data, as well as treatment plans, means the oncologist can make more informed decisions about the best way forward. For example…
Perhaps the cancer patient is also being treated for depression. The oncologist could refer to PGx information to guard against potential drug-drug-gene interactions between the antidepressant the patient takes and the aromatase inhibitor being used to support the patient’s long-term, cancer-free survival.
Perhaps a breast cancer patient has also been diagnosed with rheumatoid arthritis. What are the implications of concomitant methotrexate therapy?
Future decisions about cancer care. The goal of oncology treatment is partial or complete remission wherever possible. Nevertheless, it is not uncommon for the disease to recur or for a patient to develop a different type of cancer. Oncologists can better prepare for, and respond to, these occurrences when they have access to the patient’s full germline data. (The somatic information they relied upon during the first course of treatment is no longer relevant.)
It is important to keep in mind that germline data is static. It rarely changes over time, which means a patient needs to undergo genomic testing only once. However, two other factors impacting health care are highly dynamic: 1] the patient’s phenotype (observable characteristics and new symptoms) and 2] the body of knowledge around disease and treatment.
Oncologists who have ordered full germline testing and/or have access to these results are able to re-interrogate the data as the patient’s phenotype changes and science discovers more about genetic influence and targeted molecular therapies (provided their precision medicine software incorporates up-to-date knowledgebases). This means the oncologist can more quickly identify what the patient’s emerging symptoms mean and what the most current therapeutic options are.
Precision medicine is undoubtedly becoming the new standard of care. Oncology forged healthcare’s path into genomics and is poised to show the industry how to derive even greater benefit by leveraging insights from the full genome and by demanding tools that make the information actionable – both in today’s environment and as tomorrow’s scientific discoveries make their way into clinical practice.
Consider these realities:- BRCA 1 (associated with breast cancer) was discovered in 1994—a full 25 years ago—and BRCA 2 was identified just a year later.
- Since then, it has been discovered that more than 50 cancer syndromes are affected by mutations in specific genes.
- In 2017, pembrolizumab became the first tumor-agnostic drug approved by the FDA. Since then, several more have entered the market, including nivolumab and larotrectinib. The trend towards targeted molecular therapy is expected only to accelerate.
Somatic results are not enough
The results of somatic testing, which reveals genetic markers of the tumor tissue, has added great value to cancer treatment. Oncologists use these insights to more precisely diagnose a patient’s disease and devise a care plan tailored to the unique molecular profile of the cancer. While incredibly important in the treatment of a specific incidence of cancer, somatic information does not provide information about the patient’s “native” genetic profile; a tumor’s characteristics are unique unto itself. Therefore, somatic data provides limited information about the overall patient and other factors that might affect their care and wellbeing now and into the future.
As standard bearers, oncologists must look beyond somatic information, seeking and using a broader range of genomic data including germline and pharmacogenomic information to deliver the most effective care possible.
Leveraging pedigree and germline data
Four specific areas come to mind, when we consider how oncology can maximize the value of genomics beyond the somatic view – which will lead to better outcomes and quality of life for patients.
Pedigree documentation to identify risk for prevention and earlier intervention. Not long ago, I saw a young female patient who mentioned several family members had been diagnosed with breast cancer and ovarian cancer. We discussed benefits of genetic screening as well as other aggressive prophylactic options. While contemplating, she underwent mammography that unfortunately revealed Stage III cancer.
This was a sad and unnecessary outcome. Electronic health records should be capable of capturing critical family history enabling providers to spot areas of risk and concern – but, unfortunately, they do not. Instead, we need to leverage precision medicine tools designed to map a detailed patient pedigree so all providers, from PCPs to specialists, can assess heritable risk early, implementing in-time preventative and diagnostic measures.
The value extends beyond the patient him or herself, as well. Complete and detailed pedigree information can be shared with family members (and their providers) so they, too, can easily review familial patterns and more effectively identify genetic risk sooner.
The impact pharmacogenomic (PGx) information could have on the medications the oncologist prescribes. Of course, somatic data can help the oncologist decide on the best treatment. Perhaps the patient’s tumor exhibits markers like those examined in the TAILORx study4 for breast cancer – which means she does not need chemotherapy following surgery but would benefit equally well with hormone therapy (typically Tamoxifen). If the oncologist also had access to full PGx information, however, he would discover variants in the patient profile indicating she may not metabolize Tamoxifen well. With this information in hand, he can prescribe a different medication (such as an aromatase inhibitor) to manage her condition long term – and with greater success – instead.
PGx test results can reveal which nausea and pain drugs the patient metabolizes best, as well. This enables the oncologist to order the medications that will provide greatest relief with fewest side effects – the first time around, without time-consuming and frustrating trial and error.
Germline insights into co-morbidities and concurrent therapies. When an oncologist refers only to somatic data, he or she sees a thin representation of the patient’s overall situation. But it stands to reason that other diseases and treatments could impact the oncology care plan – and vice versa (cancer care could impact other clinicians’ decisions and therapies). Access to full germline data, as well as treatment plans, means the oncologist can make more informed decisions about the best way forward. For example…
Perhaps the cancer patient is also being treated for depression. The oncologist could refer to PGx information to guard against potential drug-drug-gene interactions between the antidepressant the patient takes and the aromatase inhibitor being used to support the patient’s long-term, cancer-free survival.
Perhaps a breast cancer patient has also been diagnosed with rheumatoid arthritis. What are the implications of concomitant methotrexate therapy?
Future decisions about cancer care. The goal of oncology treatment is partial or complete remission wherever possible. Nevertheless, it is not uncommon for the disease to recur or for a patient to develop a different type of cancer. Oncologists can better prepare for, and respond to, these occurrences when they have access to the patient’s full germline data. (The somatic information they relied upon during the first course of treatment is no longer relevant.)
It is important to keep in mind that germline data is static. It rarely changes over time, which means a patient needs to undergo genomic testing only once. However, two other factors impacting health care are highly dynamic: 1] the patient’s phenotype (observable characteristics and new symptoms) and 2] the body of knowledge around disease and treatment.
Oncologists who have ordered full germline testing and/or have access to these results are able to re-interrogate the data as the patient’s phenotype changes and science discovers more about genetic influence and targeted molecular therapies (provided their precision medicine software incorporates up-to-date knowledgebases). This means the oncologist can more quickly identify what the patient’s emerging symptoms mean and what the most current therapeutic options are.
Precision medicine is undoubtedly becoming the new standard of care. Oncology forged healthcare’s path into genomics and is poised to show the industry how to derive even greater benefit by leveraging insights from the full genome and by demanding tools that make the information actionable – both in today’s environment and as tomorrow’s scientific discoveries make their way into clinical practice.
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