Genetic Screening for Breast Cancer Genes: Weighing the Pros and Cons
Knowledge is power. But sometimes knowledge can become a tyrannical master.
Genetic testing can help predict many diseases and one day may help prevent them, but privacy concerns and fears of abuse could derail the technology's potential... the American Cancer Society said that a woman has a 12 percent chance of developing breast cancer in her lifetime. That risk jumps to between 50 percent and 85 percent if the woman is genetically predisposed to the disease.
CNN, Genetic Tests may Bring Hope, Inspire Fear, January 29, 2007
There are very few personal repercussions for testing positive for recessively inherited diseases, such as Tay-Sachs or cystic fibrosis, since the person himself is not sick. (See "The Ethics of Genetic Screening"). While the finding of an abnormal recessive gene raises the specter of disease in the patient's offspring, the repercussions of finding a harmful dominant gene is that the patient himself is at risk for developing a deadly disease.
For instance, most cases of breast cancer arise in women without first-degree relatives (e.g. mother or sister) who have previously developed the disease. Nevertheless, a small percentage of cases of breast cancer are believed to be caused by dominantly inherited abnormal genes called BRCA1 and BRCA2, which have a higher frequency in the Ashkenazi Jewish population than in the general population. The gene, which affects men and women, is passed from one of the parents to the offspring. A woman with one of the BRCA genes has a significantly increased risk of breast and ovarian cancers during her lifetime.
Screening for genes such as BRCA1 or BRCA2 that predispose to dominantly inherited disease raises an additional, even more difficult, set of ethical problems that do not apply to Tay-Sachs testing.
Advantages and Disadvantages of Mass Screening
There are good reasons to encourage mass screening of women for the breast and ovarian cancer genes. If women who test positive are alerted to their increased risk of developing potentially deadly cancers, they may practice increased diagnostic vigilance. They may begin a strict mammography regimen to detect breast cancer early and undergo periodic pelvic ultrasounds to detect ovarian cancer. Genetic screening might also allow for implementation of preventive measures such as prophylactic mastectomy and oophorectomy (removal of the ovaries) in women testing positive. Additionally, the patient might be better informed to decide on therapy if she develops breast cancer.
The reasons to discourage mass screening are multiple. At the present, despite advances in mammography and ultrasound, there is no absolutely reliable method of early diagnosis, nor is there an absolutely reliable method of prevention of breast or ovarian cancer. 1 Even prophylactic bilateral total mastectomy, a very invasive and disfiguring operation that Jewish law permits in certain situations, 2 cannot completely eliminate the risk of breast cancer.
Removal of both ovaries, in addition to being abdominal surgery, exposes the woman to the morbidity of estrogen deficiency (premature menopause) and the associated increased risks of osteoporosis. Nevertheless, prophylactic surgery does significantly decrease the probability of developing breast or ovarian cancer.
It is important to recognize that prophylactic removal of the ovaries presents a more serious question in Jewish law, since although most leading rabbis hold that sirus ("castration") in a woman is a rabbinic prohibition, others, such as the Vilna Gaon (Rabbi Eliyahu Kremer), ruled that it is a Biblical prohibition. "Thus one has to have a sufficiently good reason to permit it and, in the case of the BRCA genes, the reasons are not compelling enough." 3
Even if we decide that it is advisable to screen for the BRCA genes, it is debatable which groups we should screen. Our choices range from the entire population, men and women, to only the highest risk populations. Screening the entire population would offer a very low yield for very high cost. It is currently considered most prudent to only screen men or women with a significant family history of specific cancers, minimizing the occurrences of false negatives, 4 allowing those testing positive to be extra vigilant, and offering at least some relief to those testing negative for these particular genes. 5
There is also a very real fear of the social and economic repercussions of testing positive for an autosomal dominant gene such as a BRCA gene. The test might cause stigmatization of the patients themselves and their children. 6 Issues of confidentiality arise, including the availability of the test results to employers and insurance companies, potentially making the patient unemployable and less insurable. 7 While 41 states have laws against some types of genetic discrimination, no federal law yet exists to deal with the problem.
If a woman carried a 50% chance of developing breast cancer, would a man marry her?
There are members of Congress who have been working for over 10 years to pass legislation that would prevent health insurers and employers from asking for or using genetic testing and that would block insurers from raising premiums based on test results. While such a bill did pass the House of Representatives in 2005, it failed to pass the Senate. 8 On January 16, 2007, The Genetic Information Nondiscrimination Act (GINA) was introduced in the House of Representatives with 143 co-sponsors, indicating renewed interest in solving the problem of stigmatization that genetic testing can cause.
It is important to realize that legislation to protect people from having employers or insurance companies use genetic information to discriminate against them is a two-edged sword. Positive results could lead to discrimination and increased insurance premiums, yet it is important to recognize that insurance companies currently use family history, a very inexact form of genetic information, to make actuarial decisions. If genetic screening results were available to insurance companies, a test that confirms the absence of a deleterious gene in a member of a BRCA-affected family may cause a person's insurance premiums to decrease!
From an emotional perspective, the person testing positive for a BRCA gene is faced with life-long fear and might even have the feeling that they are being treated as a "genetic time-bomb." Were a prospective suitor to know that a woman carried a greater than 50% chance of developing breast cancer during her life, would he date or marry her?
Implications in Jewish Law
Does the Biblical obligation to guard health 9 include genetic testing for the potential presence of a dominant, possibly life-threatening trait? Does the approximately 2% carrier frequency in the Ashkenazi Jewish population constitute a "risk to life" which would require screening by Jewish law? It is important to remember that the presence of the BRCA1 or BRCA2 gene does not imply that the patient will develop breast or ovarian cancer, only that she is at a much higher risk for these diseases. A predisposition is not the same as a diagnosis.
As we shall see, since the presence of a BRCA gene only creates a statistical risk of cancer, it would be hard to argue from a Jewish perspective that there is an absolute obligation to test. Nevertheless, if a woman did choose to test for such a gene before marriage and was found to possess one of the BRCA genes, she would almost certainly be required to tell her prospective spouse of the results.
Rabbi Moshe Feinstein 10 was asked whether a man with Marfan syndrome (a debilitating dominantly inherited disease) must marry. He answered in the affirmative, but was careful to point out that the wife could have the marriage annulled if she was not informed of his condition before marriage. 11 He must find a woman to marry him who is cognizant of his disease and the repercussions for their children.
The woman is therefore caught in the between a rock and a hard place. If she tests before marriage, she creates a potential impediment to marriage. If she waits until afterwards, she pushes off the age at which she would find out her status. If she marries at a young age, the risk of postponing screening is small, but if she marries later, the risk increases. Compounding this dilemma is the argument that she may be obligated to inform a potential spouse that she is at high risk of having one of the BRCA genes even if she has not been tested.
We are left with the reality that testing before marriage raises issues of premarital disclosure, but earlier gene detection presumably should lead to early cancer detection. However, earlier gene detection still may lead to greater anxiety.
It is important to realize that a woman with a strong family history of breast and ovarian cancer may certainly follow a rigorous monitoring program of mammograms and pelvic ultrasounds without knowing her BRCA status. But certainly, she would be much less likely to consider bilateral mastectomy or oophorectomy unless she knew that she had one of the BRCA genes, even with a strong family history.
Informing Family Members
If a woman tests positive for one of the BRCA genes, must she inform her immediate relatives 12 who are automatically at much increased risk for having the gene themselves?
There are two major conflicts that arise, one from the side of the relative and one from the side of the woman known to be BRCA positive.
By informing a sister, are we unjustly robbing her of the right to remain blissfully ignorant?
Perhaps the relative does not want to know if they are at increased risk for breast and ovarian cancer. By informing a sister of the BRCA positive woman's status, are we unjustly robbing her of the right to remain blissfully ignorant? How are we to know if someone does not want to know important information about themself? While we could ask them, it is very difficult to do so without telling what information we would be offering them.
A second concern introduces the issue of confidentiality, a matter taken very seriously in Jewish law (See "Professional Confidentiality in Jewish Law") What if the woman does not want anyone to know that she is positive for the BRCA gene? It would be virtually impossible to inform a close relative about their increased risk of breast cancer without informing them of the affected woman's own cancer history. Such a case occurred several years ago in a hospital in Jerusalem. The woman who tested positive for a BRCA gene after developing breast cancer at a young age refused to inform her family of her cancer or her BRCA status. Additionally, she forbade the physicians to inform anyone in her family of the need for genetic testing, including her younger sister!
If we respect her privacy, are we transgressing the biblical commandment to not standing idly by as our neighbor is harmed 13 On the other hand, if we do inform the sister, we are breeching the confidentiality of the affected sister. If we merely suggest genetic screening to the sister (without mentioning the sister with breast cancer), she will surely ask why this suggestion is being made to her.
The Torah strictly limits disclosure of private information to a third party, even though the information is true and no malice is intended, regardless of how or where the information is obtained. This would include divulging medical information to anyone other than the patient. The result is a code of professional and personal confidentiality that is generally stricter than its secular counterpart. Nevertheless, Judaism recognizes situations in which disclosure of confidential material is required.
The Torah writes: "Do not go as a tale-bearer among your people, do not stand idly by the blood of your neighbor..." (Leviticus 19:16). Two apparently unrelated concepts are juxtaposed in one biblical command. This teaches us that while there are two separate obligations, confidentiality of communications and protecting others from harm, they are nevertheless intricately related. Because of the potential damage that may occur if pertinent information is not disclosed, the Code of Jewish Law explains that one may not keep a confidence if doing so will lead to harming someone. In such a case one must divulge secrets.
Due to the potential for psychological harm, one is not obligated to test for BRCA genes.
Dr. Avraham Avraham, author of Nishmat Avraham, reports that he asked Rabbi Yosef Sholom Elyashiv, a leading rabbinic authority in Israel, what the Jewish law would be if a BRCA carrier refused to give permission to contact their close relatives. Rabbi Elyashiv pointed out that there are several uncertainties involved in the scenario that would lead to a ruling allowing the patient to maintain her confidentiality. First, the risk to each family member is not definite, as not every family member necessarily carries the gene. Second, even if a relative did carry the gene, it is not certain that they will develop cancer. Last, there is no completely preventative or assuredly curative treatment for cancer in those relatives who would test positive. Therefore, there would be no obligation to test other family members. As Dr. Avraham wrote: 14
It is only a possibility that another carries the gene, and even if she does, it is not certain that she will have breast cancer later. Also, the lack of a method of completely preventing the disease coupled with the stress inflicted on the person carrying the abnormal gene for the rest of her life, make the situation one of multiple uncertainties. Therefore, one may not do anything without the patient's express permission. Similar considerations would also apply to other diseases and a recognized posek must be consulted first.
Why doesn't the need to inform close relatives supersede the confidentiality rights of the individual? It appears that Rabbi Elyashiv's decision is predicated upon the conclusion that the individual herself has no obligation to test! Due to the potential for psychological harm and the reality that there is a limited amount that can be done to mitigate disease, even if it were present, one is not obligated to test oneself for the BRCA genes. Such a level of uncertainty is not included in the biblical requirement to guard one's health. Therefore, there is no imperative in Jewish law to inform relatives that would supplant the prohibition of lashon hara, derogatory speech, involved in informing others of the patient's medical condition.
A Final Thought
We generally approach knowledge as a liberating force. Knowledge is power. Knowledge makes us the master of our fate. But sometimes knowledge becomes the master and makes us the servants. Rabbi Moshe Dovid Tendler, chairman of biology at Yeshiva University, once described genetic testing for BRCA genes as an issue of "tyranny of knowledge." He rightly stated that when information causes anxiety, but offers no way to reduce that anxiety, it controls us. In the case of screening for the BRCA genes, where no absolutely reliable diagnostic tool exists, the patient is faced with the prospect that she may develop breast or ovarian cancer, diseases which she cannot guard against without radical prophylactic surgery. Nevertheless, increased diagnostic vigilance may be helpful, and while invasive, prophylactic mastectomy and oophorectomy do seem to increase survival rates. If the positive results of BRCA screening are used to improve health, then the tests are justified. But if they only increase anxiety, they serve no useful purpose.
The famed folk-singer Woody Guthrie, author of "This Land is Your Land," died in 1967 of the dominantly inherited disease called Huntington's disease, the same disease that had killed his mother. When Arlo Guthrie, the singer's son, (now a grandfather without signs of the disease) was offered the chance to be tested for the lethal gene after his father's death, he reportedly refused. He questioned the value of finding out whether he was destined to die of this terrible debilitating neurological disease, when there was no way to prevent it. Can anyone blame him?
- While bilateral mastectomy substantially decreases the risk of breast cancer, it does not completely eliminate it. The emotional, psychological, and physiologic disadvantages of such a procedure must also be considered. See the editorial in the iJournal of Clinical Oncology, Vol 22, No 6 (March 15), 2004: pp. 981-983 by Lynn C. Hartmann, Amy Degnim, Daniel J. Schaid entitled: “Prophylactic Mastectomy for BRCA1/2 Carriers: Progress and More Questions.” (http://www.jco.org/cgi/content/full/22/6/981). Also see Hanne Meijers-Heijboer, M.D, et al, “Breast Cancer after Prophylactic Bilateral Mastectomy in Women with a BRCA1 or BRCA2 Mutation,” New England Journal of Medicine, Volume 345:159-164, Number 3, July 19, 2001. (http://content.nejm.org/cgi/content/abstract/345/3/159)
- Personal communication with Dr. Avraham Avraham, February 16, 2007. Dr. Avraham explained that because this surgery would be prophylactic and not treatment for a known illness, the husband and wife would need to agree on the surgery.
- Personal communication with Dr. Avraham Avraham, February 16, 2007.
- The sensitivity of a test measures how many truly sick people the test will identify as sick. Specificity measures how many healthy people will be identified as healthy by the test. A test with 100% sensitivity will identify every sick person who is tested (even though it may identify some healthy people as sick). A test with 100% specificity will identify every healthy person as healthy (even though it may identify some sick people as healthy). An ideal test (which does not exist) has 100% sensitivity and 100% specificity. That is, it correctly identifies every ill person, but identifies no healthy person as being ill. A result that erroneously identifies someone as healthy when they are actually ill is called a false negative. A result that erroneously identifies someone as sick when they are actually healthy is called a false positive.
- It is also important to understand how the limitations of the screening test can wreak havoc with people’s lives. Every screening test has a less than perfect sensitivity and specificity. Let us consider testing 100 million women in the United States being tested for a rare (1 in 1000) hypothetical gene causing a deadly disease. For instance, even if a test has a 99% sensitivity and 99% specificity, it would carry a 1% false positive rate. Even with such a small false positive rate, only 99,000 of the 1.1 million positive results would be “true positives.” 91% (one million) of the women whose tests were positive would actually not be carrying the dangerous gene and 1,000 women with the deadly gene would be told that they did not have it. Such errors can have devastating effects. For this reason, any screening test intended for the general population, must have a virtually 100% sensitivity and specificity. Lower specificities can be tolerated if there is a more accurate follow-up test for those who test positive on the initial screening. Since the test for BRCA genes is for the gene itself, and not just for a gene marker, the specificity of the test is virtually 100%. Nevertheless, any false positive results if mass testing were initiated (particularly in those patients without a family history of breast or ovarian cancer), would unnecessarily increase mental distress and possible unnecessary mastectomies and oophorectomies. In the case of the BRCA genes, we test for the specific mutations that are common among Ashkenazi Jews. However, there are other mutations that can cause a defect in the normal gene. If just Ashkenazi Jews at high risk were tested, then the sensitivity of the test would be very high, since we are testing for the mutations that they are most likely to have (i.e. very few people with unidentified defects in the normal gene would be missed). However, if we tested the whole population, we would miss anyone who has a different mutation than the ones that we are testing for and they would believe that they are not at increased risk of developing breast and ovarian cancer (in women). This is because there are many changes in the BRCA genes known to be pathological mutations. Some other gene changes have not yet been proven to be pathological. In some families where it seems that a gene mutation should be present based on family history, none is found. It is therefore possible that there are other breast cancer disposition genes that have not yet been identified.
- It is important to recognize that the BRCA genes cause an increased risk of various cancers in men also.
- A spokeswoman for America's Health Insurance Plans, which represents almost 1,300 health insurers, said she does not know of any genetic discrimination cases. Nevertheless, a recent article on the topic of genetic discrimination reported: "America's Health Insurance Plans believes that genetic testing is important to help guide treatment decisions and options and to improve the quality of care," Susan Pisano said. "Our understanding is that health insurance plans do not use results from genetic tests for rate setting or underwriting." But in 2001, in what is believed to be the largest reported case, a railroad company agreed to pay $2.2 million to settle a lawsuit alleging that it secretly conducted genetic tests on workers who filed medical claims for carpal tunnel syndrome – a repetitive-stress injury. In settling the case, the Burlington Northern and Santa Fe Railway Co. became one of the first firms to admit conducting genetic tests on its workers.” http://www.cnn.com/2007/HEALTH/01/18/genetic.testing/index.html
- It is questionable whether the obligation to guard health would apply to testing for a recessive trait which will not directly cause harm to the person being screened.
- Igros Moshe, Choshen Mishpat II:73
- A Jewish marriage can be annulled if it took place under false pretenses, such as one of the spouses lacking information that would have caused them to choose not to enter into the marriage. The concept applies in other areas of Jewish law and is called “mekach ta’os,” or “a faulty purchase.”
- It is important to recognize that the BRCA genes also may occur in men and increase their risk of various cancers.
- Leviticus 19:16. The Torah commands us to do whatever is necessary to prevent harm from befalling a fellow Jew.
- Nishmat Avraham, Volume 3 (Even Ha’Ezer and Choshen Mishpat), p. 302, Mesorah Publications, 2004.