As scientific and medical advances have rapidly progressed over the past century, life-saving knowledge has been brought to humanity, but controversies have been brought on, too. Important questions addressing ethics and financial issues have arisen amidst attempts to provide often expensive and complicated diagnostic and therapeutic technology to people the world over. While we tend to think altruistically about the benefits to society from the development and availability of tests that will, for instance, help determine the risk of getting a certain cancer in the future or find a cancer in its early stages, there is money, big money, involved. And that is inherently intertwined in much of the “medical” decision-making that sets standards and guidelines the medical community abides by. Who makes the decisions that establish the standards of medical care and the guidelines for a variety of medical testing is a fascinating question. And, it’s complicated because human lives and millions of dollars are at stake.
One expensive and complicated medical technology that has emerged over the past 20 years is genetic sequencing and testing—the ability to sequence the human genome and detect now known deleterious mutations that put a cancer-affected individual at a risk for another cancer or an unaffected person at risk for a particular cancer in the future. Myriad, a molecular diagnostic company, focused this technology on the BRCA genes, which are DNA-repair genes.
Mutations in either of these genes puts a woman at a cumulative lifetime risk of ~40-85% of developing breast cancer, and 16-40% of developing ovarian cancer, compared with the 12.7% and 1.4% lifetime risk for the general population of developing breast or ovarian cancer, respectively. Myriad isolated and sequenced the genes, obtained patent applications for the sequencing technology, and gained sole control over the testing for these genetic mutations. Given Myriad’s control over testing for BRCA mutations, the question of how it would decided as to who should be genetically tested became a controversial issue. Should Myriad itself decide, given the extensive genetic information it had at its disposal? Should it be a consensus decision among various independent medical/public health organizations?
Historically, important public health decisions have been made by consensus of various large medical organizations. In the case of genetic testing, the American Cancer Society, the American Society of Clinical Oncology (ASCO), and the American Medical Association (AMA) convened to set guidelines for risk assessment and genetic testing. However, in this unique case where a private company had most of the information needed to set guidelines, it developed its own guidelines. But, did it make sense to leave the determination of such expensive testing in the hands of a company that stood to singularly gain financially from the testing?
Myriad lost its exclusive patent in 2013 when the Supreme Court ruled that human genes could no longer be patented. The company, however, still continues to maintain dominance in the genetic sequencing business by being allowed to exclusively withhold 20 years worth of genetic data on the BRCA, and not have to share them with the scientific community. Myriad has not disclosed statistical information that might be helpful to other laboratories, such as data on mutational variants of unknown significance (VUS), whose impacts are still unclear, but are being worked on by other geneticists.
Furthermore, this withholding of information makes Myriad’s analyses of BRCA mutations closed to clinical peer review, and thus patients are expected to take Myriad’s conclusions on faith. Myriad’s test though should be looked by patients with a grain of salt—it does not always detect large-scale rearrangements of the genes, and sometimes produces indeterminate or false results that can be damaging to patients’ psyches, especially for those who tested negative and later develop breast cancer. The test should be reviewed by other groups to help develop more comprehensive tests that patients can better trust.
Contrary to the recent advent of genetic testing, there has been diagnostic screening tool around for 40 years that can detect breast cancer at its early stage—the mammogram. Similar to the question of who should be genetically tested, there is the central question of when a woman should be screened. The question of whether women under 50 should be screened has remained controversial since the 1970s.
Data from the only major widespread randomized trial on mammography screening, conducted by the Health Insurance Plan (HIP) of New York, in 1963, did not demonstrated a benefit for women aged 40-49 (or even women aged 60-69 for that matter). In this study, participants began having mammograms in their late 40s, continuing to have them after they turned 50; as a result, it has remained unclear as to whether those women that were diagnosed with breast cancer were younger or older than 50 at the time.
Nevertheless, even without scientific evidence of statistically significant benefits for women aged 40-49, the American College of Radiology (ACR) and American Cancer Society (ACS) have always staunchly recommended routine annual mammograms during these years, rather than waiting to begin at age 50. Conversely, groups like the National Cancer Institute (NCI) and the U.S. Preventive Services Task Force (USPSTF) seeing that screening was not proven effective for those 40-49, considered screening during those years as ineffective. They also noted that ductal carcinoma in situ (DCIS) diagnoses were highest in the 40-49 age group, and argued that over half of the time these cases are “harmless,” and if left alone, would not progress to advanced stage breast cancer.
However, because doctors cannot tell if the DCIS is harmful, it is treated like invasive breast cancer, usually with surgical excision by lumpectomy, with or without radiation therapy, or even a mastectomy, which can cause extreme, and perhaps unnecessary anxiety in patients. Among these groups, the ACR, ACS, NCI, and USPSTF, who should have the final word on setting the screening age guidelines? Unless a randomized study is conducted for women aged 40-49, I do not think any of these groups can make the ultimate decision. There is currently not enough statistical evidence on when breast cancer rates significantly increase, and without this information, guidelines on the threshold age of screening initiation cannot be set.
Both BRCA genetic testing and mammography have the ability to create unneeded anxiety, whether it be because of a false positive, or in the case of mammography, the detection of noninvasive cancer that could have may no impact on a woman’s life if left undetected. However, both tests also allow for early detection that can save countless numbers of lives.
Ideally, patients should engage in an open dialogue with their doctors over the benefits, risks, and limitations of these tests, as well as their individual risks of breast cancer so that they can decide on what is best for themselves. This is a decision that should not be left in the hands of potentially financially motivated medical companies.
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Levy, Sharon. “Our Shared Code: The Myriad Decision and the Future of Genetic Research.”
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Reynolds, Handel. The Big Squeeze, A Social and Political History of the Controversial
Mammogram. New York: Cornell University Press, 2012.