Genetic Testing - The Information May Surprise You

The following are some of the misconceptions about genetic testing and what it can presently provide to individuals with concerns about hereditary cancer risk:

Misconception #1: Family History Analysis Can Accurately Determine Those Likely To Benefit From Genetic Testing

  Analysis of family history can usually determine those likely to be at increased risk due to hereditary factors. However, in some families there may not be a sufficient number of individuals to rule out increased hereditary risk. In others, a new mutation may have occurred, with only a single affected individual present in the family. One study of women diagnosed with breast cancer before age 50, who were chosen without regard for family history, found that 4% had a BRCA1 mutation. Among those of Ashkenazi Jewish descent the rate was higher - 16% (see table below ).

  Therefore, it is unwise to assume that those who have only a single affected relative do not have an increased hereditary risk. On the other hand, not all individuals who have a strong family history of cancer may not obtain useful information from genetic testing, since not all mutations that increase hereditary risk have been discovered. In one study, only 7% of the families in which breast cancer alone was present were found to have a BRCA1 mutation. Even when both breast and ovarian cancer were in the family, a mutation was found in only 40% (see table below ).

Misconception #2: Genetic Testing Provides Clinically Accurate Information About Cancer Risk

  The commonly stated 85% risk of breast cancer and 63% risk of ovarian cancer to age 70 for women with a BRCA1 mutation cannot be accurately applied to an individual patient with a strong family history of cancer or even to a woman who is found to have a BRCA1 mutation, since these figures are: a) based on specially chosen research families, and b) the families from which the risks are derived are a heterogeneous group. In fact, other researchers, using different methods, found an 87% risk of a breast cancer and a 44% risk of ovarian cancer to age 70 in these same families.
  As shown in the figure below, in some families, only breast, in some only ovarian, and in others both breast and ovarian cancer are found. The risks cited above were derived by combining these three different family types. The risks therefore overestimate the risk of breast cancer for those from families in which only ovarian cancer has been found, and underestimate the breast cancer risk for those from families in which only breast cancer is present. Until more studies are done on risks associated with specific mutations within the BRCA1 gene, the conglomerate risks should be used with great caution and explanation.

  The conglomerate figures do, however, provide important information. For example, they show that much of the risk of breast and ovarian cancer occurs after age 50 (see table below).

Misconception #3: Genetic Testing Results Are Not Clinically Useful At the Present Time

  Test results may be of limited importance when considering breast cancer risk, since many studies show that breast cancers of small size are associated with an excellent prognosis (for example, see table below). Remember that not all of these women had access to today’s care, so a woman recently diagnosed may have an even better prognosis.

  Not all breast tissue can be removed in a mastectomy, so following prophylactic mastectomy, women still need to be vigilant in order to detect a small lump that could occur in the renaming tissue.

  Many of my patients with a family history of breast and ovarian cancer or ovarian cancer alone do find genetic testing to be quite useful. For example, one woman age 32 has two sisters, a mother and an aunt diagnosed with ovarian cancer. She did not want to have her ovaries removed unless she was found to have a mutation increasing her risk, or if testing proved to be uninformative in her family. One of her affected sisters was tested and a BRCA1 mutation was detected. When my patient was tested, she was found not to have the mutation, and so is not at significantly increased risk of ovarian cancer due to hereditary factors. She is no longer considering prophylactic oophorectomy (removal of ovaries before a cancer has been detected).
  One of the issues to be discussed when a woman is considering prophylactic oophorectomy is the risk of later developing peritoneal cancer [the peritoneum is the inner lining of the abdominal cavity and is derived from the same embryological tissue as the ovary.] This risk appears to be quite low. The Gilda Radner tumor registry reports that of 324 women with a strong family history of ovarian cancer who had prophylactic oophorectomy, some followed for 25 years, only 6 subsequently developed peritoneal cancer. At least 40 and as many as 90 ovarian cancers would have been expected in this group.

  Information about risk and genetic testing is dense and sophisticated. To help individuals understand the ramifications and to make informed decisions, they need information about all the relevant risks associated with the cancers of concern, not just hereditary risks. For example, a woman with benign breast disease needs information about risks associated with this condition. Someone contemplating prophylactic oophorectomy needs detailed information on breast cancer risks associated with taking hormones at menopause, particularly studies of women with a family history of breast cancer. As shown in the table below, at least four studies have shown no increased risk to women with a family history of breast cancer who take hormones compared to non-users with a similar family history. In one study an increased risk of breast cancer was found in those who did not use hormones.

  Because individuals differ in the way they learn and make decisions, information and decision making help needs to be provided in a way that is appropriate to the individual patient. Past experiences with cancer generally influence the way in which people hear and interpret risk, so this factor must be taken into account. Unless care is taken, emotional reactions can act as barriers to understanding.

Other Points to Remember about Genetic Testing

1. Usually the DNA of one affected person in a family must be analyzed to determine if testing is currently informative for that family (see figure below).

2. A negative finding in the first person tested in a family is not evidence of low or absent hereditary risk.
3. Risks obtained from study families may not be applicable to other mutation carriers, due to special selection of study families
4. A negative family history (no cancer is present) is no guarantee that a germline mutation is absent.
5. Genetic testing is more likely to be useful when it is conducted within the context of cancer risk assessment and counseling services.

For more information about hereditary and non-hereditary breast and other cancer risks, genetic testing, and training programs for health professionals in Cancer Risk Assessment, contact: Patricia T. Kelly, Ph.D., Medical Geneticist

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