Tag: genetic testing

If Whole Genome Sequencing is So Cheap and Quick, Why Shouldn’t Everyone Have It Done?

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This post is a part of our Bioethics in the News series

By Leonard M. Fleck, PhD

The headline in New York Times Magazine reads: “Scientists can now sequence an entire genome overnight.” This is amazing. It took ten years and $3 billion to do the first mapping of the human genome, all three billion base pairs. Today the entire genome of any individual can be mapped for less than $1000. Why is that important? There are preventative, diagnostic, therapeutic, reproductive, and public health reasons. The public health reasons are most evident with the speed with which all the variants of COVID-19 have been mapped.

Having one’s genome mapped can provide an individual with some foreknowledge of health risks to which they might be vulnerable (always keeping in mind environmental factors linked to inherent genetic risks, also keeping in mind the uncertainty and probabilities associated with the vast majority of health risks identified in this way). The risks of medical harm related to genetic ignorance can be reduced. A family of genes referred to as P450 determine whether we are normal, fast, or slow metabolizers of drugs. If we are fast metabolizers, a normal dose will be metabolized too quickly with diminished effectiveness. If we are slow metabolizers, a normal dose will accumulate to potentially life-threatening levels in some cases. Roughly 7% of 1200 FDA approved medications are affected by actionable germline inherited pharmacogenes. Even more importantly, 18% of outpatient U.S. prescriptions (more than four billion per year) are affected by actionable germline pharmacogenomics.

Whole Genome Sequencing (WGS) can assist future possible parents to determine the best reproductive option if they know they represent specific genetic risks to future possible children, e.g., if each were a carrier for a mutated cystic fibrosis gene. In addition, WGS can be used to make accurate diagnoses of very rare disorders that would otherwise require harmful, invasive, diagnostic odysseys. This will be very important in the context of infants in the NICU or children in the PICU.

A technician who has long dark hair and is wearing safety glasses, a white coat, and purple gloves, loads DNA samples into a desktop genomic sequencing machine
Image description:  A technician loads DNA samples into a desktop genomic sequencing machine at the Cancer Genomics Research Laboratory, part of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics (DCEG). Image source: Daniel Sone/National Cancer Institute/Unsplash.

I remind students that unlike normal medical tests that only yield information about the person who has the test, genetic tests tell us about genetic features of a range of close relatives. Hence, if a genetic test identifies a serious health vulnerability in me, that information can be used to alert other family members of that same vulnerability of which they might otherwise have been ignorant (and which might well be medically manageable before clinical symptoms emerge that might then suggest an irreversible disease process). The therapeutic potential of WGS is most evident today in the case of metastatic cancer. WGS can provide base-pair resolution of an entire tumor genome in a single run, thereby revealing the unique mutations and genomic alterations in the cancer tissue. This will often allow the identification of a targeted cancer therapy, such as imatinib, that targets the distinctive genetic features of a cancer, such as chronic myelogenous leukemia.

In the reproductive context WGS can be used as a non-invasive prenatal screening tool to offer a comprehensive assessment of the fetus. Likewise, WGS could be used at birth as a screening tool to offer a more comprehensive assessment of the infant than the current gene panel, which is only looking for fifty-six rare genetic disorders. This increases the opportunities for timely therapeutic interventions, when available.

Given all these potential therapeutic benefits, what would be the potential ethical challenges? Cost is an issue that raises health care justice problems. Though the sequencing itself costs less than $1000, the analysis, interpretation and counseling bring the cost to $3000 (though in the case of cancer treatment the cost will be $10,000). Few health insurers cover these costs. Should access to WGS then be publicly funded, as a matter of health care justice, perhaps as part of a basic benefit package guaranteed to all? If all 330 million Americans wanted WGS, the cost would be $990 billion. Would that be either a wise or just use of limited health care resources, given all sorts of other unmet health care needs in our society?

One of the main rationales for doing WGS is preventive, i.e., to identify significant health vulnerabilities whose risk of actualization can be reduced by behavioral change. However, the critical question is whether we can be very confident that most patients would commit to the required behavioral changes. Available medical evidence suggests pessimism in this regard, which would imply that WGS with this expectation represented a poor use of social resources. No one believes McDonald’s business plans are threatened by WGS.

If WGS is used to replace current neonatal screening practices, are the privacy rights of newborns put at risk, given later in life genetic vulnerabilities that would be revealed? Would these concerns be mitigated if only medically actionable information were revealed to parents, all other information being set aside until that child reached adulthood? However, what exactly is the scope of “medical actionability?” That child might be vulnerable to some serious genetic disorders much later in life. This would not be a concern for the child as a child. But that child might have older relatives for whom this information would have considerable potential relevance. What are the ethical issues associated with either revealing or failing to reveal that information to potentially “at-risk” relatives?

A very important feature of genetic information gleaned from neonatal WGS (and all WGS for that matter) is that the vast majority of that information will be either of unknown or highly uncertain significance. This will be especially true because of the thousands of mutations that would be part of anyone’s DNA. For parents of a newborn, such uncertainty could be distressing for years and years. However, there is also the uncertainty associated with the responsibilities of primary care physicians in this regard. Who is supposed to have responsibility for tracking changes in genetic knowledge regarding those genetic variations in an individual as medical research advances? And who would be responsible for conveying this new information to parents or adult children, and judging what should be told and when? This is a very complex medical information management problem, relative to which current physician complaints regarding the electronic medical record would fade into insignificance.

Let us assume that WGS is going to be done more thoughtfully and more parsimoniously, such as a diagnostic or therapeutic context where such information would be most useful. What will still happen is the discovery of all sorts of incidental genetic information, sometimes with frightening potential consequences. Imagine this bit of medical dialogue: “Mr. Smith, we were looking for the genetic roots of your heart disease (which we found), but we also discovered your genetic vulnerability to an early-onset form of dementia.” Many patients would not want to know this. How is a physician supposed to know what a patient does or does not want to know in this regard?

Finally, WGS could generate new problems of health care justice. Imagine that the incidental finding in the prior paragraph was a 10% lifetime risk of some serious but treatable cancer. I personally would not be especially distressed by such a finding. However, other individuals might be especially anxious and demand all manner of expensive diagnostic tests on a semi-annual basis to rule out any indications of disease initiation. Would that individual have a just claim to such resources at social expense?

To return to the title of this essay, perhaps the fact that WGS is quick, easy to do, and relatively inexpensive is insufficient reason to justify the promiscuous promulgation at social expense of this technology. Perhaps more thoughtful social and professional deliberation regarding the issues identified in this essay would yield less ethically fraught uses of WGS. Then again there could be the 2030 version of the electronic medical record with room for terabytes of genetic information and thousands of new tabs and subtabs!

Leonard Fleck photo

Leonard M. Fleck, PhD, is Professor in the Center for Bioethics and Social Justice and the Department of Philosophy at Michigan State University.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, May 6, 2021. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

More Bioethics in the News from Dr. Fleck: Religious Coercion of Physicians: Whose Conscience Is It Anyway? Health Care and Social Justice: Just Take Two Aspirin for Your Tumor If You Cannot Afford Your Cancer Care; Medicare For All: This Is Going to Hurt; Greed Is God: The Divine Right to Avaricious Drug Pricing; Gene Editing: God’s Will or God’s Won’t

Click through to view references

Dr. Fleck facilitates occupational and environmental medicine workshop at Michigan conference

Leonard Fleck photoCenter Acting Director and Professor Dr. Len Fleck held a workshop at the annual Michigan Occupational Health Conference in Grand Rapids, MI on September 28. Dr. Fleck’s workshop was on “Occupational and Environmental Medicine: Ethical Challenges.”

The primary ethical challenge for physicians in occupational medicine is the dual loyalty challenge. More specifically, they are employed by (or contracting with) some large company to address health issues related to employees. In the workshop itself, attendees considered several concrete examples of this challenge, in particular, what might be regarded as emerging challenges related to emerging genetic technologies. A concern in many workplace situations that involve numerous chemicals is the health and safety of workers. Some workers may be susceptible to serious medical disorders related to such exposures for genetic reasons, but the required exposure might have to be over a prolonged period of time. An employer might offer to pay for whole genome sequencing to identify workers with such risks, in part for morally sound reasons (not wanting to cause avoidable harm to these workers), in part for more selfish economic reasons (not wanting to be at risk for large future health costs). An occupational physician would receive that information, and be expected to pass it along to an employer (who paid for it).

However, there are privacy rights that seem to be at risk; there are also issues of respect for patient autonomy. One worker, in the example Dr. Fleck gave to the audience, was found to be at 30% increased risk for colorectal cancer after ten years of exposure to a specific chemical. He did not want the physician to report that genetic vulnerability to his employer for fear of losing his job. He was willing to accept the risk. What is the right thing to do, all things considered? Several physicians said their responsibility extended only to determining “fitness to work.” And this worker was not going to drop dead next month or next year as a result of this vulnerability. So they would not report that result. Others asked about the details of the agreement with the company. Should the occupational physician strongly counsel this patient? One response was that this was the job of the primary care physician that this individual might have. In brief, discussion was vigorous and interesting.

How do we explain to patients what genetic test results might mean for their baby when they have only been validated in other populations?

Bioethics Brownbag & Webinar Series logoExpanded Carrier Screening for an Increasingly Diverse Population: Embracing the Promise of the Future or Ignoring the Sins of the Past?

Event Flyer

Race and ethnic groups have been tracking heritable conditions endemic within their communities for decades, but past public health screening programs—e.g., sickle cell testing for African Americans 1970s—were adopted with little thought to scientific accuracy or potential discrimination. Currently, carrier genetic testing is generally offered under professional guidelines aiming to balance potentially clinically actionable information with concerns about healthcare costs and patient anxiety: recommended testing on the basis of family history, self-reported race or ethnicity, or for a condition deemed worthy of universal screening. But some private companies have begun to offer expanded carrier screening, testing all conditions for all patients. Scientists at one such company reported in 2016 in JAMA that expanded carrier screening might increase detection of potentially serious genetic conditions. But what are the implications of returning ancestry information when patients seek medical advice? How do we explain to patients what results might mean for their baby when they have only been validated in other populations? This talk will explore policy options at the intersection of race, reproduction, and commercial use of data.

sept-13-bbagJoin us for Kayte Spector-Bagdady’s lecture on Wednesday, September 13, 2017 from noon till 1 pm in person or online.

Kayte Spector-Bagdady, JD, MBioethics, is a Research Investigator in the Department of Obstetrics and Gynecology at the University of Michigan Medical School and also leads the Research Ethics Service in the Center for Bioethics and Social Sciences in Medicine (CBSSM). Her current research explores informed consent to emerging technologies with a focus on reproduction and genetics. Kayte received her J.D. and M.Bioethics from the University of Pennsylvania Law School and School of Medicine respectively after graduating from Middlebury College. She is a former drug and device attorney and Associate Director of President Obama’s Bioethics Commission.

In person: This lecture will take place in C102 East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

Can’t make it? All webinars are recorded! Visit our archive of recorded lectures. To receive reminders before each webinar, please subscribe to our mailing list.

Announcing the Fall 2017 Bioethics Brownbag & Webinar Series

bbag-icon-decThe Center for Ethics and Humanities in the Life Sciences at Michigan State University is proud to announce the 2017-2018 Bioethics Brownbag & Webinar Series, featuring a wide variety of bioethics topics. The fall series will begin on September 13, 2017. You are invited to join us in person or watch live online from anywhere in the world! Information about the fall series is listed below. Please visit our website for more details, including the full description and speaker bio for each event.

Fall 2017 Series Flyer

sept-13-bbagExpanded Carrier Screening for an Increasingly Diverse Population: Embracing the Promise of the Future or Ignoring the Sins of the Past?
How do we explain to patients what results might mean for their baby when they have only been validated in other populations?
Wednesday, September 13, 2017
Kayte Spector-Bagdady, JD, MBioethics, is a Research Investigator in the Department of Obstetrics & Gynecology and leads the Research Ethics Service at the Center for Bioethics & Social Sciences in Medicine at the University of Michigan Medical School.

oct-11-bbagCrossing the Biology to Pathobiology Threshold: Distinguishing Precision Health from Precision Medicine
What level of risk will be tolerated for interventions that are developed for treating “pre-diseased” patients?
Wednesday, October 11, 2017
Christopher H. Contag, PhD, is a John A. Hannah Distinguished Professor of Biomedical Engineering and Microbiology & Molecular Genetics, Chair of the Department of Biomedical Engineering, and Director of the Institute for Quantitative Health Science and Engineering at Michigan State University.

nov-29-bbagProspects, Promises and Perils of Human Mind-Reading
What are the prospects for such technology to be widely used?
Wednesday, November 29, 2017
Mark Reimers, PhD, is an Associate Professor in the Neuroscience Program in the College of Natural Science at Michigan State University.

In person: These lectures will take place in C102 (Patenge Room) East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

Can’t make it? Every lecture is recorded and posted for viewing in our archive. If you’d like to receive a reminder before each lecture, please subscribe to our mailing list.

Misconceptions: Ethics and the Rejection of Reproductive Roulette

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Leonard Fleck, Ph.D.

In a recent story in the New York Times, Gina Kolata reports the story of Amanda Kalinsky, age 30, who had been told four years ago that she had the gene for Gerstmann-Straussler-Scheinker [GSS] disease. This is a very rare neurological disorder that will result in a slow and terrible death, likely before she is fifty years old. Her father was dying of this disorder at that time. She very much wanted to have children but she could not bear the thought of passing on GSS to them. She had then learned of the option of pre-implantation genetic diagnosis [PGD]. This involved her being given a drug causing her to hyperovulate. Multiple ova would be surgically removed from her, inseminated by her husband, and result in the creation of 12 embryos. Over two days those embryos would grow to the eight-cell stage, at which point a cell would be removed from each and genetically analyzed for the GSS mutation. Six of her embryos had the GSS mutation. Those embryos were discarded. She successfully bore twins free of GSS and another child, also free of GSS. She and her husband paid over $20,000 for PGD.

Ethically speaking, how should individuals who wish to be just and caring and genetically responsible think about this procedure? How should citizens in a liberal, pluralistic society think about PGD? Should this be a covered benefit under the Affordable Care Act, at least for couples who know they are at risk of having a child with a serious genetic disorder that could very adversely affect the length or quality of life of a future possible child?

Advocates for a Right to Life position would surely object because the procedure necessarily involves the destruction of genetically flawed or excess embryos. They would further object to paying taxes to support access to the procedure for couples like the Kalinskys because this deeply violated their conscientious beliefs. The same is true for many advocates for persons with disabilities who regard this procedure as necessarily diminishing the value of persons with disabilities. Should we have a public policy that would ban this procedure, period?

Let me suggest two responses to the objections that have been raised. And let me also suggest why we should have a policy that would publicly subsidize the cost of the procedure for couples like the Kalinskys. First, what is being disvalued is the disability itself, not persons with disabilities. This can be understood more clearly with a brief thought experiment. Imagine that in the future regenerative medicine is able to use modified embryonic stem cells to restore mobility to individuals who have suffered severe spinal cord injuries. The cost of the procedure might be $100,000. I would argue that a just and caring society ought to underwrite that cost. Some persons with quadriplegia might refuse the procedure. Many others might gratefully accept it. There would be fewer immobile individuals in the world, but it surely seems that would be a good thing from the point of view of those newly mobile patients.

Advocates for a Right to Life position might argue that if a couple knows they are at risk for having a child with, say, cystic fibrosis, they ought either forego having children or accept having a child with cystic fibrosis. A child with cystic fibrosis may have lifetime medical costs in excess of $1 million, not to mention diminished length and quality of life. Those costs will largely be socially borne, as opposed to being borne by the parents. I would argue that the social acceptance of these costs is what a just and caring and liberally respectful society ought to do. However, others might see this a bit differently.

Others might regard such a couple as being thoughtless and irresponsible, both because of the preventable harm they are imposing on that child and the costs that are imposed on society. I would argue that such thoughts are illiberal. Those choices ought to be respected. But if that is true, then a liberal society is nothing if not mutually respectful. In other words, an advocate of a Right to Life position as well as advocates for persons with disabilities ought to respect the Kalinsky’s right to make their choice not to have children with GSS. Further, such advocates should also accept a democratically-legitimated policy that would pay the costs of PGD for couples like the Kalinskys, especially those not as economically well off as the Kalinskys. In both cases advocates for either point of view are paying taxes to support services they judge to be conscientiously troubling. But this is what mutual respect and fair treatment often means in a liberal pluralistic democratic society.

Perhaps I am wrong in my judgments here; perhaps advocates for a Right to Life position are wrong. If we both righteously insist on our rightness, then the practical consequence will be unnecessary suffering and premature death for many future possible children. Perhaps the better choice would be mutual respect and continued efforts at mutual understanding.

References:

Kolata, Gina. “Ethics Questions Arise as Genetic Testing of Embryos Increases.” New York Times 03 Feb 2014. Retrieved from http://www.nytimes.com/2014/02/04/health/ethics-questions-arise-as-genetic-testing-of-embryos-increases.html?hp&_r=3

Related reading:

Fleck smallLeonard Fleck, Ph.D., is a Professor in the Center for Ethics and Humanities in the Life Sciences at Michigan State University and the author of Just Caring: Health Care Rationing and Democratic Deliberation.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, March 6, 2014. With your participation, we hope to create discussions rich with insights from diverse perspectives. You must provide your name and email address to leave a comment. Your email address will not be made public.

Welcome to FDA Enforcement

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Kayte Spector-Bagdady, J.D., M.Bioethics

 “This is me, my DNA. It helps make me who I am…I might have an increased risk of heart disease, arthritis, gallstones, hemochromatosis…hundreds of things about my health. Getting my 23andMe results, it really opened my eyes. The more you know about your DNA, the more you know about yourself. I do things a little differently now…”

On November 22, 2013, 23andMe (the leading direct-to-consumer (DTC) genetic testing company), received a “Warning Letter” from FDA—a first for the DTC genetic testing industry. In this letter, FDA requested that 23andMe discontinue marketing its personal genome service until further authorization and end its TV campaign excerpted above (now the YouTube video is marked “private”). 23andMe’s official FDA response might not be public, but on December 5, 2013, 23andMe did announce publicly that it was going to stop selling new customers its DTC health-related genetic test. Unlike, for example, an X-ray, “DTC” tests are those available directly to purchasers, like a pregnancy test. While there are many benefits to having certain diagnostic tests available directly to consumers without a trained intermediary, there are also concerns about giving laypersons medical information without specific guidance from a healthcare practitioner.

This is not the DTC genetic testing industry’s first tango with the U.S. federal government. In 2006 the Government Accountability Office (GAO) released a report on nutrigenetic testing which found that companies were selling $1,200/year vitamins (actually worth $35/year in a local drug store) to “fix” DNA. In 2010 a GAO investigator was advised by an industry representative that her BRCA mutation, associated with an increased risk of breast cancer, meant that she was “in the high risk of pretty much getting” the disease (GAO did not reveal company identities for either of its reports).

In fact, just a few years ago, nearly thirty DTC companies offered 400 discrete genetic tests—until Pathway Genomics announced in 2010 that it was going to start offering its previously web-based product in Walgreens across the country. This got the attention of FDA, which eventually sent 23 “Untitled Letters” (for a violation not quite as significant as those triggering a “Warning Letter”) stating that these products were in fact medical devices and had to receive FDA clearance or approval. Soon thereafter many DTC genetic testing companies either altered their model by requiring a physician order or collapsed entirely—leaving 23andMe to dominate the industry.

In 2007, 23andMe offered thirteen health reports for $999. As of December 2, 2013, 23andMe offered over 250 health reports for $99—including reports regarding a higher risk for Alzheimer’s Disease to whether your cilantro will taste soapy—all in a colorful box promising “Welcome to you.”

As of today, for the same $99, 23andMe is selling an analysis of your ancestral origins and lineage  and “raw genetic data” “without 23andMe’s interpretation” but have suspended their health-related genetic information service “to comply with [FDA’s] directive to discontinue new consumer access during our regulatory review process.”

FDA’s jurisdiction hinges on whether the 23andMe’s product can appropriately be considered a medical device under the Food, Drug, and Cosmetic Act. There has been a lot of interesting debate in the tweetisblogosphere regarding whether 23andMe is marketing their test as their terms of service state, for “research and educational use only,” or, as the TV adds promised, to tell you “hundreds of things about your health” so you can do things “a little differently.” But another possible consequence of 23andMe canceling their health analysis is the unintended encouragement of a new DTC genetic industry—one providing genetic medical information only.

Last year, Gene By Gene started the trend by offering consumers genomic sequencing only: a raw data file of As, Ts, Cs, and Gs without any interpretation. Think this. But, for the majority of consumers, raw sequence data services require a parallel offering of interpretation-only services to provide a marketable product.

FDA has stated that it’s not interested in regulating raw genomic data as a medical device, but entities that provide genomic interpretation (see, e.g., openSNP) can reveal more sensitive medical information about an individual’s propensity to develop disease and pharmacogenomic information about the efficacy of particular drugs given a particular genetic makeup—which places these services squarely within FDA’s area of interest. 23andMe has always offered customers their raw data as part of its package, but it’s the genetic risk and drug responses (i.e., analyzed information) that FDA cited as concerning in its letter.

But just as FDA begins to seriously grapple with the DTC genetic testing industry, open-source, web-based platforms that interpret genomic data free of charge are going to pose further challenges to the limits of FDA’s ability to regulate (potentially non-commercial) speech, and effectively utilize enforcement mechanisms made for tangible money-making products on information and open-sourced platforms.

The interpretation of FDA’s Warning Letter may be clear, but the future of DTC genetic testing might instead lie in how you interpret the letters “A, T, C, and G.”

(Still interested? Read more on the topic from me and my co-author Lizzy Pike here).

References:

Letter from Alberto Gutierrez, Dir., Office of In vitro Diagnostics and Radiological Health, Ctr. for Devices & Radiological Health, Food & Drug Admin., U.S. Dep’t of Health & Human Services, to Ann[e] Wojcicki, C.E.O., 23andMe, Inc. (Nov. 22, 2013).

U.S. Gov’t Accountability Office, GAO-06-977T, Nutrigenic Testing: Tests Purchased from Four Web Sites Misled Consumers, Testimony Before the S. Special Comm. on Aging (July 27, 2006).

U.S. Gov’t Accountability Office, Highlights of GAO-10-847T, Direct-to-Consumer Genetic Tests: Misleading Results are Further Complicated by Deceptive Marketing and Other Questionable Practices (July 22, 2010).

kayte-spector-bagdadyKayte Spector-Bagdady, J.D., M.Bioethics, is Associate Director at the Presidential Commission for the Study of Bioethical Issues where she managed the Commission’s reports on Privacy and Progress in Whole Genome Sequencing and Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts.*

Join the discussion! Your comments and responses to this commentary are welcomed. The author will not, unfortunately be able to respond to all comments, but will read input with interest. With your participation, we hope to create discussions rich with insights from diverse perspectives. You must provide your name and email address to leave a comment. Your email address will not be made public.

* The findings and conclusions in this blog are those of the author and do not necessarily represent the official position of the Presidential Commission for the Study of Bioethical Issues or the Department of Health and Human Services. Use of official trade names does not mean or imply official support or endorsement by the author.

The “Jolie Effect”: Managing Awareness, Risk, and Personal Choices

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Monica List, DVM, MA

On May 14, actress Angelina Jolie published an op-ed article in the New York Times (Jolie, 2013). In this article, entitled “My Medical Choice”, Jolie narrates her experience of going through genetic screening for the BRCA-1 gene mutations,1 and after testing positive, and in light of her family history of breast cancer, deciding on a bilateral prophylactic mastectomy (BPM) followed by breast reconstruction.

A deluge of media attention quickly followed. Jolie’s NYT op-ed received 1,712 reader comments, a significant number, compared to, for instance, 170 reader comments for the editorial on the Boston Marathon bombings published by the NYT Editorial Board within hours of that event. The reports and opinions that followed Jolie’s article were both positive and negative, but there is fair certainty that the vast majority approved of, and even praised both Jolie’s decision to have a BPM, and her decision to go public. Supporters commended the actress not only for publicly sharing such a personal decision, but for bringing even more visibility to the issue of breast cancer.

The less numerous critical comments focused on questions such as whether or not her decision was medically warranted, and the potential impact that her public disclosure may have on services and procedures such as genetic screening, genetic counseling, BPM, and contralateral preventive mastectomy (CPM). An additional point of concern raised by Peggy Ornstein in an article also published in the NYT (Ornstein, 2013), is that while fear of cancer is legitimate, the ways in which information about breast cancer prevention, screening, and treatment is packaged and sold to us can result in disproportionate fear and anxiety, which not only has a negative effect on women’s quality of life, but can lead to radical decisions that are not always medically necessary. Todd Tuttle, lead author of a study on CPM, refers to this phenomenon as “breast cancer over-awareness”; in her NYT article, Ornstein quotes him as saying “It’s everywhere. There are pink garbage trucks. Women are petrified.”

In Jolie’s case, the decision to undergo mastectomy seems to be medically justified – she carries the defective BRCA-1 gene, and had already lost her mother to breast cancer in 2007, at the age of 56. Shortly after the publication of her op-ed, she also lost an aunt to the same disease. However, as Norah Essali points out in the “Students 4 Best Evidence” blog, there are reasons to think that the decision may not be as unequivocal as it seems; even for a high-risk patient such as Jolie, the choice to undergo BPM is more based on risk assessment than on actual evidence (Essali, 2013). Essali’s point is supported by a systematic review published by Lostumbo (Lostumbo, et al., 2010), which analyzes data from 39 observational studies on women who underwent either BPM or CPM. The authors conclude that although BPM may reduce the incidence of breast cancer and improve survival in women with high breast cancer risk, further studies are required to obtain more conclusive evidence. In the case of CPM, the authors straightforwardly claim that there is simply insufficient evidence to prove that CPM improves survival. They suggest that the best way to gather this evidence would be through randomized clinical trials (RCT), which are sorely lacking for most if not all of the approaches to breast cancer risk assessment and management.

While the issue of using randomized clinical trials raises important ethical questions, perhaps it is necessary to take a step back, and think more broadly about the ethical dimensions of breast cancer risk assessment and management. If, as Angelina Jolie states in her article, opting for BPM, or any other form of breast cancer prophylaxis or treatment is a personal choice, and, if Todd Tuttle is correct in saying that we are in the midst of a breast cancer over-awareness epidemic (Ornstein, 2013), then improving the ways in which individual patients can make informed choices should be a high priority on the breast cancer research agenda, and perhaps gathering more and better evidence in some areas is not enough.

While it is generally accepted that scientific uncertainty is unavoidable, there is also a tendency to believe that as the body of evidence for a particular issue grows, uncertainty will tend to decrease, and that this will allow for better risk management, and ultimately, a reduction of risk for that particular issue. However, as Silbergeld points out, there are different kinds of scientific uncertainty; systematic uncertainty arises from limitations related to the type of knowledge being sought, in this case, factors that increase the risk of breast cancer, and actions to decrease that risk (Silbergeld, 1991). Specific uncertainty, on the other hand, is related to limitations of the protocols, experimental designs, and inference processes that we use to turn data into scientific evidence.

For the issue of breast cancer risk, clearly there are both systematic and specific uncertainties. More importantly, no amount of evidence will ever address the uncertainty that stems from each woman’s individual combination of risk factors, and also importantly, her values and actions with respect to those factors. According to Prado and colleagues (Prado, 2010), 75% of breast cancer patients are classified as “sporadic”, meaning that they have no family history of breast cancer, and no proven genetic risk. These authors also call attention to the fact that while models for breast cancer risk assessment take into account multiple factors, they have poor or no capability to predict individual risk.

My point is not to say that any quest for better evidence for breast cancer prevention, diagnosis, and treatment is useless in the face of uncertainty. Rather, I mean to call attention to the importance of the role of values not only in patients’ individual decisions about healthcare, but also at the scientific and policy-making levels. In 2010, federal funds for breast cancer research amounted to $631 M;2 meanwhile, a report published in the NYT in February of this year questions research priorities, arguing that priorities failed to include, for instance, prevention oriented research, as well as research on environmental risk factors (Grady, 2013).

Certainly, for women like Jolie, who carry the BRCA-1 or BRCA-2 mutations, being able to know that they are at a high risk for breast cancer before it even develops is a life-saving advantage, and a choice like PBM is one they can make (provided that they have financial access to the necessary medical care). However, the number of women who are able to know their risk for breast cancer, and make a choice about it, and more importantly, the number of women who are able to act on that choice, needs to increase exponentially if our war on breast cancer is going to move on beyond what Peggy Ornstein refers to as “a feel good” enterprise. A more careful examination of the values that influence and shape research priorities, as well as research design and implementation is an important step in this direction.

1 For more information on BRCA-1 and BRCA-2 genetic testing, visit: http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA

2 http://www.cancer.gov/cancertopics/factsheet/NCI/research-funding

References:

list-cropMonica List, DVM, MA, Monica List is a doctoral student in the Department of Philosophy at Michigan State University. She earned a veterinary medicine degree from the National University of Costa Rica in 2002, and an MA degree in bioethics, also from the National University, in 2011.

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