Direct-to-consumer testing for hereditary cancers ‘most helpful’ when integrated with established health care practice

Approximately 10% of all breast cancer and 25% of ovarian cancer cases are hereditary.

For the past 7 years, the final week of September – known as Hereditary Breast and Ovarian Cancer Awareness Week – has served as a reminder to individuals with a family history of cancer to undergo genetic testing to determine any possible predispositions to cancer.

The week recognizes any individual affected by hereditary breast, ovarian and related cancers, including women and men with BRCA mutations, people with a family history of cancer, breast and ovarian cancer survivors, and previvors – individuals who carry a strong predisposition to cancer but have not yet developed the disease.

Patients who feel they may be predisposed to a hereditary cancer may undergo myriad genetic tests within a clinical setting to analyze their possible future risks for developing cancer.

There are concerns with access and costs associated with genetic testing, however.

Testing for abnormal breast cancer genes may cost an individual approximately $300 to $5,000 depending on what type of testing is being conducted, according to data on Breastcancer.org’s website.

Additionally, one study published in Genetics and Medicine demonstrated that access to certified clinical geneticists and genetic counselors – individuals who are best positioned to identify what genetic test results mean for patients – are primarily concentrated in larger cities, with some states having two or fewer providers.

As a result, direct-to-consumer genetic testing has emerged as a new means of obtaining genetic tests outside of a traditional clinical setting.

HemOnc Today spoke with several experts who have experience with analyzing genetic testing results, or who have conducted research about direct-to-consumer testing, about some of the highlights and concerns of this approach.

Concerns surrounding direct-to-consumer genetic testing

Jada G. Hamilton, PhD , MPH, an assistant attending psychologist at Memorial Sloan Kettering Cancer Center: Some of the concerns are related to the accuracy of direct-to-consumer genetic testing, and whether different companies are consistently and correctly interpreting the meaning of genetic changes. Other concerns deal with the way that direct-to-consumer genetic testing is marketed to the public, particularly in terms of whether there is enough evidence to support claims that these tests provide information that is useful or meaningful for people’s health. There are also important concerns that consumers may misunderstand the meaning of these results. For example, consumers may believe that a genetic change that has only a small association with disease is more powerful or predictive than it really is. Alternatively, consumers may misinterpret “normal” results as meaning that they are not at risk for disease, when in fact they likely have a level of risk that is similar to that of the average population. Such misunderstandings could lead to distress or inappropriate behavior changes.

There is a possibility that an individual would not consult with a physician or genetic counselor after receiving the results, and is inherent to the direct-to-consumer testing model which is basically designed to offer people genetic testing without the involvement of a physician or genetic counselor. What little scientific evidence there is on this topic suggests that although consumers often anticipate that they will share their direct-to-consumer genetic test results with a physician, many ultimately do not do so. Without a discussion with a healthcare provider, the potential exists for consumers to misunderstand their test results, or to make health decisions that are not necessarily appropriate. In most cases, direct-to-consumer tests provide feedback about genetic changes that have fairly small associations with disease, but healthcare providers can help consumers to put those results in context – to understand what the results mean in terms of their personal family history of disease and in relation to behavioral risk factors like diet, exercise, and smoking.

Wendy K. Kohlmann, MS, CGC, an adjunct assistant professor Huntsman Cancer Institute at the University of Utah: Concerns related to DTC testing are not necessarily unique to DTC testing and can apply to genetic testing being ordered in any setting. Challenges with the growing options for genetic testing include selection of the correct test and testing technology, classification and reporting of variants of uncertain significance by the laboratory, limited penetrance and management recommendations for some genes being included on tests, and coordination of follow-up. Interpretation of variants is variable by laboratories and may change over time. The implications of a genetic test result also often need to be determined in the context of family history and possibly also the genetic test results of other family members. A DTC approach may leave patients to navigate more of these issues on their own.

Some people may view DTC genetic testing as a way to learn if they carry a genetic mutation while keeping that information private. However, the finding of a genetic condition is only helpful if it is used to impact management. For that to happen, the findings from genetic testing need to be communicated to the healthcare providers taking care of that person and incorporated into decision making. Some DTC companies may offer consultation along with their testing services, and this can be very helpful. However, it is important to understand the extent of post-test services that will be provided and still consider who will be working with the patient to coordinate appropriate management in the long term. While the concerns about genetic testing often focus on the identification of a mutation, negative results can be equally challenging to interpret. A negative result does not necessarily rule out disease risk, and depending on the patient's personal and family history, enhanced screening and risk reducing strategies may still be appropriate. Ultimately, sharing DTC hereditary cancer test results with your healthcare providers is an important step.

Alexis Carere, ScD, CGC, a postdoctoral fellow at McMaster University: The two main concerns with DTC genetic testing, within the context of primary care, are that the results will be misinterpreted by physicians and prompt unnecessary medical interventions. For example, if a report suggests that the patient carries a risk single nucleotide polymorphism (SNP) for breast cancer, and the physician responds by ordering yearly mammograms in a 30-year-old woman. The second main concern is that consumers will use the results to manage their own care, without going through a physician. For example, a result might suggest a greater likelihood of side effects from a statin, and as a result, a patient with high cholesterol decides to stop taking their prescription statin, or to take it less regularly. A final concern, historically, is that these tests may cause undue stress or anxiety in consumers who receive unpleasant information. However, this has been shown time and time again – in a number of contexts – not to be a significant issue among individuals who make the intentional decision to undergo genetic testing. People are pretty resilient.

One of the most commonly theorized risks of DTC genetic testing is that patients will avoid consulting with a physician or genetic counselor during the process. The good news, however, is that there has been very little evidence to show that this happens. For example, if a patient receives a DTC result suggesting an increased risk of prostate cancer, they are going to need to seek out a health care provider in order to undergo PSA screening. In most cases, some discussion would ensue between patient and physician, and the hope is that ultimately a decision about whether or not to order PSA screening would be made on the totality of medical information available for that patient, not just the DTC testing. Of course, a physician may put too much stock into the DTC result, especially if they are not particularly familiar with genetic testing for prostate cancer risk, or with the benefits and limitations of prostate cancer screening. For these reasons, we would really encourage better physician education about genetics, genetic testing, and how to best incorporate genetic risk information into clinical care. But still, it is unlikely that a patient is going to undergo drastic medical interventions – such as a prophylactic mastectomy without being seen by a number of physicians, including highly specialized ones, who at some point will adequately adjudicate the relevance of the DTC results in directing that patient’s care.

An area that has perhaps been of greater concern is prescription medications, because there is somewhat less provider oversight. For example, a patient can easily cease taking a medication, or alter his or her dose, without going back to their physician. In some cases, they may even be able to order medications online to start a treatment without going through a physician. But again, the evidence hasn’t really borne this out. In a study I was involved with that was on prescription medication use following DTC genetic testing, we found that only 5.6% of 961 participants reported changing a prescription medication in the 6 months following testing, and of these, only nine reported doing so without consulting a physician. That said, among these 9 individuals, there were specific examples of people making inappropriate medication changes without physician oversight. This was a rare outcome, and it is likely that people frequently make similar decisions to stop or alter a medication dose for lots of other reasons, such as what they read on the internet, news stories, or even simply the opinions of friends and family.

Significance of receiving counseling

Hamilton: Generally speaking, pre-test genetic counseling is intended to help people understand whether and why they are a good candidate for genetic testing, and to understand what the possible implications of the test results will be so they can make an informed decision about whether to have testing or not. These implications can include what medical treatments or decisions they will be faced with if the test shows that they carry a genetic change that increases risk for disease, and what this information could mean for their family members and relationships. Post-test genetic counseling is intended to help people understand the meaning of their test results, as well as the limitations of these results. Through this counseling, people receive specific and appropriate medical recommendations based on their particular disease risk, as well as support for how to manage this information. Whether an individual must receive both traditional, in-depth pre-test and post-test genetic counseling to ensure that they are adequately informed is something of a debate and an area of active research, and can depend on factors like the health context and the medical, psychological, and social implications of the test.

Kohlmann: As with any medical procedure people need information about the benefits, limitations and risks of a procedure to make an informed decision about having the test. While often cited as a barrier to genetic testing, the idea of informed consent and decision making is not unique to genetic testing. There may be many ways to provide patients with information and to help them make decisions about having genetic testing.

Issues surrounding access to care

Hamilton: Access is an important challenge facing genetic testing and genomic medicine. The reality is that we have a limited workforce of trained genetics professionals. Research conducted by myself and others has also demonstrated that providers who do not have specific training in genetics, such as primary care providers, do not always feel prepared to address the challenges of genetic testing. Furthermore, there is variation in how genetic testing is covered by different insurance providers. There are also concerns about political threats to existing legal protections that protect people from discrimination based upon their genetic test results. No one solution will address these challenges, but finding ways to offer affordable genetic testing to individuals who are likely to benefit from the information with the support of or partnership with qualified members of the health field could certainly help.

Kohlmann: Genetic testing will be most helpful when aligned and integrated with other areas of health care, and it is important for the genetics community to find ways to facilitate that collaboration. There are concerted efforts in place to increase access to genetic services by growing the genetic counseling workforce, expansion of telephone and telemedicine services, and collaborating with other clinicians to facilitate the genetic testing process. It is important that the entire health care system be prepared to deal with genetic information from an increasing variety of sources to integrate this technology into care. Genetic counselors can play critical roles in helping patients make informed decisions about genetic testing and understand the results, and they can also help health care systems develop strategies for incorporating genetics into their services on a system-wide basis. Patients should not have to view their options for genetic testing as being either working with a genetic counselor or going at it on their own through a DTC company. Genetic counselors are resources for patients seeking information about whether genetic testing is right for them, and for those seeking help in interpreting test results.

Angela R. Bradbury, MD , of the Abramson Cancer Center at the University of Pennsylvania: Some people have said individuals should have access to their genome and there shouldn't be a gatekeeper to a certain degree, but to the extent that it is going to be used to inform a person’s medical care, a physician has to order the screening and everything that follows, there is a tension that exists there with approaching it outside of the medical system, but then bringing it into the medical system and expecting providers to act on it. I think the challenge, and we need solutions to it, is that there are many patients who don't have access to genetic counselors and if there’s a patient who is in an area where the nearest academic center or nearest genetic counselor is 2 hours away. Those patients could see a real advantage of just researching online and getting those results because other options are significant burdens if they are accessible at all. The alternative is for them to be doing this with their doctor, as opposed to doing it directly with the company. And I know some of the companies do require a physician to be involved and some of them provide a physician. What type of role that physician is playing remains a little unclear. A doctor can order a test, but are they having the conversation with the patient about what is being ordered and how to interpret the results? There's a lot of questions and potential risks and there's just very little data to know whether these risks are real or not and I don't think there's a lot of data either on how people are using this information who are the patients who are moving forward with these tests.

Understanding direct-to-consumer genetic testing

Carere: I think that we need to be very careful to specify what we mean when we talk about DTC genetic testing. In the past, this term basically referred to SNP-based tests of disease risk – such as combining odds ratios from lots of SNPs to give people an estimate of their risk of common disease. Everyone seems to accept at this point that these SNP-based estimates may or may not be accurate, and probably don't have much clinical utility or ability to change health behaviors. On the other hand, this is no longer the totality of DTC genetic testing, and much of the testing available now is quite similar – if not identical – to what an individual would receive if they visited a doctor's office or genetics department. For example, there is DTC testing for carrier status of recessive conditions – such as cystic fibrosis – which couples may want to undergo prior to having a child. These results, if performed in laboratories that meet certain quality standards, are accurate and clinically actionable prior to or during pregnancy to prevent the birth of an affected child. Of course, sharing of these results with a physician, confirmation of the results, and further counselling regarding options would be necessary before any medical intervention could take place. Another example is DTC testing for conditions like hemochromatosis, a condition caused – for the most part – by well-characterized mutations in one main gene. The DTC test is, more or less, the same test you would receive if your physician suggested, on the basis of clinical features, that you might have hemochromatosis. Much of the negative attitudes towards DTC stem from its early days, and in particular its provision of inaccurate, non-clinically meaningful information. But I do think the industry is making concerted, and conscientious, efforts to improve their offerings, and we should be welcoming of those tests that are safe and accurate.

References:

http://www.breastcancer.org/symptoms/testing/genetic/facility_cost

https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

Hock KT, et al. Genet Med. 2011; doi:10.1097/GIM.0b013e3182011636.

https://ocrfa.org/patients/about-ovarian-cancer/risk-factors/

Disclosures: Kohlmann reports receiving grant funding from the NCI for research focused on looking at patterns of genetic testing and outcomes. All other researchers report no relevant financial disclosures.

Approximately 10% of all breast cancer and 25% of ovarian cancer cases are hereditary.

For the past 7 years, the final week of September – known as Hereditary Breast and Ovarian Cancer Awareness Week – has served as a reminder to individuals with a family history of cancer to undergo genetic testing to determine any possible predispositions to cancer.

The week recognizes any individual affected by hereditary breast, ovarian and related cancers, including women and men with BRCA mutations, people with a family history of cancer, breast and ovarian cancer survivors, and previvors – individuals who carry a strong predisposition to cancer but have not yet developed the disease.

Patients who feel they may be predisposed to a hereditary cancer may undergo myriad genetic tests within a clinical setting to analyze their possible future risks for developing cancer.

There are concerns with access and costs associated with genetic testing, however.

Testing for abnormal breast cancer genes may cost an individual approximately $300 to $5,000 depending on what type of testing is being conducted, according to data on Breastcancer.org’s website.

Additionally, one study published in Genetics and Medicine demonstrated that access to certified clinical geneticists and genetic counselors – individuals who are best positioned to identify what genetic test results mean for patients – are primarily concentrated in larger cities, with some states having two or fewer providers.

As a result, direct-to-consumer genetic testing has emerged as a new means of obtaining genetic tests outside of a traditional clinical setting.

HemOnc Today spoke with several experts who have experience with analyzing genetic testing results, or who have conducted research about direct-to-consumer testing, about some of the highlights and concerns of this approach.

Concerns surrounding direct-to-consumer genetic testing

Jada G. Hamilton, PhD , MPH, an assistant attending psychologist at Memorial Sloan Kettering Cancer Center: Some of the concerns are related to the accuracy of direct-to-consumer genetic testing, and whether different companies are consistently and correctly interpreting the meaning of genetic changes. Other concerns deal with the way that direct-to-consumer genetic testing is marketed to the public, particularly in terms of whether there is enough evidence to support claims that these tests provide information that is useful or meaningful for people’s health. There are also important concerns that consumers may misunderstand the meaning of these results. For example, consumers may believe that a genetic change that has only a small association with disease is more powerful or predictive than it really is. Alternatively, consumers may misinterpret “normal” results as meaning that they are not at risk for disease, when in fact they likely have a level of risk that is similar to that of the average population. Such misunderstandings could lead to distress or inappropriate behavior changes.

PAGE BREAK

There is a possibility that an individual would not consult with a physician or genetic counselor after receiving the results, and is inherent to the direct-to-consumer testing model which is basically designed to offer people genetic testing without the involvement of a physician or genetic counselor. What little scientific evidence there is on this topic suggests that although consumers often anticipate that they will share their direct-to-consumer genetic test results with a physician, many ultimately do not do so. Without a discussion with a healthcare provider, the potential exists for consumers to misunderstand their test results, or to make health decisions that are not necessarily appropriate. In most cases, direct-to-consumer tests provide feedback about genetic changes that have fairly small associations with disease, but healthcare providers can help consumers to put those results in context – to understand what the results mean in terms of their personal family history of disease and in relation to behavioral risk factors like diet, exercise, and smoking.

Wendy K. Kohlmann, MS, CGC, an adjunct assistant professor Huntsman Cancer Institute at the University of Utah: Concerns related to DTC testing are not necessarily unique to DTC testing and can apply to genetic testing being ordered in any setting. Challenges with the growing options for genetic testing include selection of the correct test and testing technology, classification and reporting of variants of uncertain significance by the laboratory, limited penetrance and management recommendations for some genes being included on tests, and coordination of follow-up. Interpretation of variants is variable by laboratories and may change over time. The implications of a genetic test result also often need to be determined in the context of family history and possibly also the genetic test results of other family members. A DTC approach may leave patients to navigate more of these issues on their own.

Some people may view DTC genetic testing as a way to learn if they carry a genetic mutation while keeping that information private. However, the finding of a genetic condition is only helpful if it is used to impact management. For that to happen, the findings from genetic testing need to be communicated to the healthcare providers taking care of that person and incorporated into decision making. Some DTC companies may offer consultation along with their testing services, and this can be very helpful. However, it is important to understand the extent of post-test services that will be provided and still consider who will be working with the patient to coordinate appropriate management in the long term. While the concerns about genetic testing often focus on the identification of a mutation, negative results can be equally challenging to interpret. A negative result does not necessarily rule out disease risk, and depending on the patient's personal and family history, enhanced screening and risk reducing strategies may still be appropriate. Ultimately, sharing DTC hereditary cancer test results with your healthcare providers is an important step.

PAGE BREAK

Alexis Carere, ScD, CGC, a postdoctoral fellow at McMaster University: The two main concerns with DTC genetic testing, within the context of primary care, are that the results will be misinterpreted by physicians and prompt unnecessary medical interventions. For example, if a report suggests that the patient carries a risk single nucleotide polymorphism (SNP) for breast cancer, and the physician responds by ordering yearly mammograms in a 30-year-old woman. The second main concern is that consumers will use the results to manage their own care, without going through a physician. For example, a result might suggest a greater likelihood of side effects from a statin, and as a result, a patient with high cholesterol decides to stop taking their prescription statin, or to take it less regularly. A final concern, historically, is that these tests may cause undue stress or anxiety in consumers who receive unpleasant information. However, this has been shown time and time again – in a number of contexts – not to be a significant issue among individuals who make the intentional decision to undergo genetic testing. People are pretty resilient.

One of the most commonly theorized risks of DTC genetic testing is that patients will avoid consulting with a physician or genetic counselor during the process. The good news, however, is that there has been very little evidence to show that this happens. For example, if a patient receives a DTC result suggesting an increased risk of prostate cancer, they are going to need to seek out a health care provider in order to undergo PSA screening. In most cases, some discussion would ensue between patient and physician, and the hope is that ultimately a decision about whether or not to order PSA screening would be made on the totality of medical information available for that patient, not just the DTC testing. Of course, a physician may put too much stock into the DTC result, especially if they are not particularly familiar with genetic testing for prostate cancer risk, or with the benefits and limitations of prostate cancer screening. For these reasons, we would really encourage better physician education about genetics, genetic testing, and how to best incorporate genetic risk information into clinical care. But still, it is unlikely that a patient is going to undergo drastic medical interventions – such as a prophylactic mastectomy without being seen by a number of physicians, including highly specialized ones, who at some point will adequately adjudicate the relevance of the DTC results in directing that patient’s care.

PAGE BREAK

An area that has perhaps been of greater concern is prescription medications, because there is somewhat less provider oversight. For example, a patient can easily cease taking a medication, or alter his or her dose, without going back to their physician. In some cases, they may even be able to order medications online to start a treatment without going through a physician. But again, the evidence hasn’t really borne this out. In a study I was involved with that was on prescription medication use following DTC genetic testing, we found that only 5.6% of 961 participants reported changing a prescription medication in the 6 months following testing, and of these, only nine reported doing so without consulting a physician. That said, among these 9 individuals, there were specific examples of people making inappropriate medication changes without physician oversight. This was a rare outcome, and it is likely that people frequently make similar decisions to stop or alter a medication dose for lots of other reasons, such as what they read on the internet, news stories, or even simply the opinions of friends and family.

Significance of receiving counseling

Hamilton: Generally speaking, pre-test genetic counseling is intended to help people understand whether and why they are a good candidate for genetic testing, and to understand what the possible implications of the test results will be so they can make an informed decision about whether to have testing or not. These implications can include what medical treatments or decisions they will be faced with if the test shows that they carry a genetic change that increases risk for disease, and what this information could mean for their family members and relationships. Post-test genetic counseling is intended to help people understand the meaning of their test results, as well as the limitations of these results. Through this counseling, people receive specific and appropriate medical recommendations based on their particular disease risk, as well as support for how to manage this information. Whether an individual must receive both traditional, in-depth pre-test and post-test genetic counseling to ensure that they are adequately informed is something of a debate and an area of active research, and can depend on factors like the health context and the medical, psychological, and social implications of the test.

Kohlmann: As with any medical procedure people need information about the benefits, limitations and risks of a procedure to make an informed decision about having the test. While often cited as a barrier to genetic testing, the idea of informed consent and decision making is not unique to genetic testing. There may be many ways to provide patients with information and to help them make decisions about having genetic testing.

PAGE BREAK

Issues surrounding access to care

Hamilton: Access is an important challenge facing genetic testing and genomic medicine. The reality is that we have a limited workforce of trained genetics professionals. Research conducted by myself and others has also demonstrated that providers who do not have specific training in genetics, such as primary care providers, do not always feel prepared to address the challenges of genetic testing. Furthermore, there is variation in how genetic testing is covered by different insurance providers. There are also concerns about political threats to existing legal protections that protect people from discrimination based upon their genetic test results. No one solution will address these challenges, but finding ways to offer affordable genetic testing to individuals who are likely to benefit from the information with the support of or partnership with qualified members of the health field could certainly help.

Kohlmann: Genetic testing will be most helpful when aligned and integrated with other areas of health care, and it is important for the genetics community to find ways to facilitate that collaboration. There are concerted efforts in place to increase access to genetic services by growing the genetic counseling workforce, expansion of telephone and telemedicine services, and collaborating with other clinicians to facilitate the genetic testing process. It is important that the entire health care system be prepared to deal with genetic information from an increasing variety of sources to integrate this technology into care. Genetic counselors can play critical roles in helping patients make informed decisions about genetic testing and understand the results, and they can also help health care systems develop strategies for incorporating genetics into their services on a system-wide basis. Patients should not have to view their options for genetic testing as being either working with a genetic counselor or going at it on their own through a DTC company. Genetic counselors are resources for patients seeking information about whether genetic testing is right for them, and for those seeking help in interpreting test results.

Angela R. Bradbury, MD , of the Abramson Cancer Center at the University of Pennsylvania: Some people have said individuals should have access to their genome and there shouldn't be a gatekeeper to a certain degree, but to the extent that it is going to be used to inform a person’s medical care, a physician has to order the screening and everything that follows, there is a tension that exists there with approaching it outside of the medical system, but then bringing it into the medical system and expecting providers to act on it. I think the challenge, and we need solutions to it, is that there are many patients who don't have access to genetic counselors and if there’s a patient who is in an area where the nearest academic center or nearest genetic counselor is 2 hours away. Those patients could see a real advantage of just researching online and getting those results because other options are significant burdens if they are accessible at all. The alternative is for them to be doing this with their doctor, as opposed to doing it directly with the company. And I know some of the companies do require a physician to be involved and some of them provide a physician. What type of role that physician is playing remains a little unclear. A doctor can order a test, but are they having the conversation with the patient about what is being ordered and how to interpret the results? There's a lot of questions and potential risks and there's just very little data to know whether these risks are real or not and I don't think there's a lot of data either on how people are using this information who are the patients who are moving forward with these tests.

PAGE BREAK

Understanding direct-to-consumer genetic testing

Carere: I think that we need to be very careful to specify what we mean when we talk about DTC genetic testing. In the past, this term basically referred to SNP-based tests of disease risk – such as combining odds ratios from lots of SNPs to give people an estimate of their risk of common disease. Everyone seems to accept at this point that these SNP-based estimates may or may not be accurate, and probably don't have much clinical utility or ability to change health behaviors. On the other hand, this is no longer the totality of DTC genetic testing, and much of the testing available now is quite similar – if not identical – to what an individual would receive if they visited a doctor's office or genetics department. For example, there is DTC testing for carrier status of recessive conditions – such as cystic fibrosis – which couples may want to undergo prior to having a child. These results, if performed in laboratories that meet certain quality standards, are accurate and clinically actionable prior to or during pregnancy to prevent the birth of an affected child. Of course, sharing of these results with a physician, confirmation of the results, and further counselling regarding options would be necessary before any medical intervention could take place. Another example is DTC testing for conditions like hemochromatosis, a condition caused – for the most part – by well-characterized mutations in one main gene. The DTC test is, more or less, the same test you would receive if your physician suggested, on the basis of clinical features, that you might have hemochromatosis. Much of the negative attitudes towards DTC stem from its early days, and in particular its provision of inaccurate, non-clinically meaningful information. But I do think the industry is making concerted, and conscientious, efforts to improve their offerings, and we should be welcoming of those tests that are safe and accurate.

References:

http://www.breastcancer.org/symptoms/testing/genetic/facility_cost

https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

Hock KT, et al. Genet Med. 2011; doi:10.1097/GIM.0b013e3182011636.

https://ocrfa.org/patients/about-ovarian-cancer/risk-factors/

Disclosures: Kohlmann reports receiving grant funding from the NCI for research focused on looking at patterns of genetic testing and outcomes. All other researchers report no relevant financial disclosures.