Ovarian,Breast cancer Screening
October 24, 2007 — The Society of Gynecologic Oncologists (SGO) has developed guidelines for medical professionals’ use in identifying women most likely to benefit from assessment for genetic predispositions to gynecologic cancers. Published online October 17 in Gynecology Oncology, the guidelines address patients at risk for hereditary breast/ovarian cancer (HBOC) and Lynch/hereditary non-polyposis colorectal cancer (HNPCC) syndrome, the most common cancer susceptibility syndromes for women.
The statement will also appear in the November print issue of the journal.
In an email to Medscape Pathology, Ilana Cass, MD, from the division of gynecologic oncology, department of obstetrics and gynecology, Cedars-Sinai Medical Center, Los Angeles, California, a member of the SGO Education Committee, described her goal for the statement: “The entire medical community needs to be educated about these syndromes so we can recognize the red flags that should prompt a physician to think about ordering genetic testing for the appropriate patient.”
HBOC: Breast and Ovarian Cancers
HBOC involves mutations in genes BRCA1 or BRCA2. The former confers a 39% to 46% chance of a woman developing ovarian cancer and a 65% to 85% risk of a woman developing breast cancer by age 70 years. The latter gene is associated with an ovarian cancer risk for 10% to 27% and a breast cancer risk for 45% to 85% by age 70 years.
The SGO guidelines recommend genetic risk assessment for women with a 20% to 25% likelihood of having BRCA1 or BRCA2 mutations. For patients whose probability of predisposition is greater than 5% to 10%, the guidelines suggest that genetic risk assessment “may be helpful.”
Guidelines for both levels of risk are based on personal, family, and ethnic factors and draw on extensive literature review and input from experts in the field. Guidelines indicating a 20% to 25% probability of predisposition to HBOC consider both more ovarian cancer involvement and a personal history of both breast and ovarian cancer in the patient, compared with a greater focus on breast cancer for those patients who have a 5% to 10% probability of predisposition.
Combining the guidelines for breast and ovarian cancers “came naturally,” said Thomas Herzog, MD, director of the division of gynecologic oncology and professor of clinical oncology and obstetrics, department of obstetrics and gynecology, Columbia University Medical Center, New York City, who is another member of the SGO Education Committee, in his email to Medscape Pathology.
Lynch/HNPCC: Colorectal/Endometrial Cancers
Combining the colorectal/endometrial cancer guidelines also was a natural result of their common genetic origin. These guidelines address Lynch/HNPCC syndrome, which includes a predisposition to both endometrial and colorectal cancers. Referring to both syndromes addressed by the SGO guidelines, Dr. Herzog noted, “The grouping was due to the recognized risks around the 2 distinct defects for the [tumor suppressor gene] BRCA and Lynch II.”
Lynch/HNPCC syndrome is caused by germline mutations in genes that oversee DNA mismatch repair. The family predisposition conferred by mutations in genes MLH1, MSH2, or MSH6includes not only colorectal cancer and cancers of the endometrium but also cancers of the ovary, stomach, small intestine, and other organs. Women with one of these mutations have a 42% to 60% likelihood of developing endometrial cancer and a 9% to 12% chance of developing ovarian cancer by the age of 70 years. Their lifetime risk for colorectal cancer is 40% to 60%.
The SGO statement divides the Lynch/HNPCC guidelines into those for patients with a 20% to 25% chance of having the inherited predisposition and those with a greater than 5% to 10% chance. The guidelines reflect both personal and family profiles, with the “revised Amsterdam criteria” included for the higher-risk group.
Developed in 1990 by the International Collaborative Group meeting in Amsterdam, the Amsterdam criteria were revised in 1999. The revised criteria, as included in the SGO guidelines, identify HNPCC patients as follows:
- Patients have at least 3 relatives with a Lynch/HNPCC-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis) in 1 lineage,
- One affected individual should be a first-degree relative of the other 2,
- At least 2 successive generations should be affected, and
- At least 1 HNPCC-associated cancer should be diagnosed before age 50 years.
The SGO statement adds criteria related to specific cancers and evidence of mismatch repair defects. For the group with a 5% to 10% chance of having a predisposition to Lynch/HNPCC, the guidelines focus on patient and family history and omit evidence of mismatch repair defects.
Benefits for Patients, Clinicians, and the Public
The statement emphasizes that the assessment of risk should be accompanied by education and counseling carried out by a clinician, counselor, or other personnel well-trained in cancer genetics. Genetic testing can be carried out only with informed consent of the patient.
Dr. Cass elaborated on the value of the assessments for both patients and clinicians: “Performing the genetic testing and finding out that a patient does or does not have a genetic mutation can allow us to reduce risks for other related cancers, and can have tremendous impact for the patient’s family members if a mutation is found.”
Considering this effect, the statement affirms that “a physician’s principal responsibility is to the individual patient in their care.” However, patients should be “strongly encouraged” to communicate the results of their genetic testing to family members to whom it may be important.
When assessments identify women at high risk for these cancers, they could receive magnetic resonance imaging breast screening, colorectal screening with colonoscopy, and preventive surgery, but the medical community must become aware of the importance of these strategies in improving individual outcomes. Another member of the SGO Education Committee, Noah D. Kauff, MD, director of the Ovarian Cancer Screening and Prevention Program at Memorial Sloan-Kettering Cancer Center, New York City, outlined in an email to Medscape Pathology the steps SGO is taking to publicize the guidelines.
“In addition to publishing the guidelines in…Gynecologic Oncology, the complete guidelines are available as a free download on the SGO Web site,” Dr. Kauff said. “SGO has also issued a press release and provided spokespeople for both the medical and lay press.” SGO is also discussing, with other societies concerned with women’s healthcare, ways to disseminate these guidelines to their member physicians.
Adoption of these guidelines holds promise for the patient community. Dr. Kauff noted that risk reduction strategies already exist for most cancers associated with HBOC and Lynch/HNPCC syndromes. “We would expect, if these guidelines are followed rigorously, to see a decrease in the number of inherited cancers diagnosed at all of these sites as well as an improved prognosis in the remaining cancers that are diagnosed.”
Dr. Cass, Dr. Herzog, and Dr. Kauff have disclosed no relevant financial relationships.
Gynecol Oncol. 2007;107:159-162.
Clinical Context
Women with germline mutations in the cancer susceptibility genes BRCA1 or BRCA2 associated with the HBOC syndrome have an 85% lifetime risk for breast cancer and up to a 46% lifetime risk for ovarian cancer, whereas those with mutations in the DNA mismatch repair genes MLH1, MSH2, or MSH6 associated with the HNPCC syndrome have a 40% to 60% lifetime risk for both endometrial and colorectal cancer and a 9% to 12% lifetime risk for ovarian cancer. Risk assessment is a process that includes education, counseling, and genetic testing if indicated.
This is a guideline of the SGO Education Committee developed by a consensus panel through face-to-face and conference calls; synthesis of research literature; and comments from experts in gynecology, oncology, genetics, and other professions. The final recommendations were approved by the panel membership and the Executive Committee of the SGO.
Study Highlights
- Hallmarks of hereditary cancer syndromes include multiple affected family members, early age of onset, and the presence of multiple and/or bilateral primary cancers.
- Women with BRCA1 susceptibility (the HBOC syndrome) have a 65% to 85% risk for breast cancer and a 39% to 46% risk for ovarian cancer by age 70 years.
- Women with mutations in BRCA2 have risks for breast and ovarian cancer by age 70 years of 45% to 85% and 10% to 27%, respectively.
- Women with HNPCC have a 40% to 60% lifetime risk for colorectal cancer in addition to endometrial and ovarian cancer risks.
- Tailored screening can help reduce morbidity.
- Risk-reducing interventions can alter the natural history of the inherited conditions.
- Strategies that have been shown to improve outcomes for individuals include breast cancer screening with magnetic resonance imaging, colorectal cancer screening with colonoscopy, and prophylactic surgery.
- Genetic testing for cancer predisposition requires informed consent, pretest education and counseling, posttest counseling, and appropriate genetic tests.
- Pretest counseling should include education on the limitations of testing, false-negative results, risk for stress, change in family dynamics, and potential for health insurance discrimination.
- The Health Insurance Portability and Accountability Act of 1996 prohibited a genetic test result in the absence of symptoms from being classified as a preexisting condition.
- Patients should be strongly encouraged to share genetic test results with appropriate family members.
- Genetic risk assessment is recommended for the following groups:
- Women with a 20% to 25% chance of having an inherited predisposition to breast and ovarian cancer with the following: personal history of both breast and ovarian cancer and ovarian or breast cancer in a close relative younger than 50 years of age, ovarian cancer at any age in women of Ashkenazi Jewish ancestry, breast cancer at age 50 years or younger and a close relative with ovarian or breast cancer at any age, and Ashkenazi descent and breast cancer at age 40 years or younger or first- or second-degree relative with BRCA1 or BRCA2 mutation.
- Those with 20% to 25% chance of having a genetic predisposition to endometrial, colorectal, and related cancers with the following: meet the revised Amsterdam criteria, synchronous or metachronous endometrial and colorectal cancer with the first cancer diagnosed before age 50 years, synchronous or metachronous ovarian and colorectal cancer with the first cancer diagnosed before age 50 years, and colorectal or endometrial cancer with evidence of mismatch repair defect or family history of a relative with known mismatch repair gene mutation.
- Women with greater than 5% to 10% risk for an inherited predisposition to breast, ovarian, endometrial, colorectal, and related cancers should be considered for genetic risk assessment.
- A lower threshold for genetic risk assessment should be applied in the following situations: families with few female relatives because this may lead to underrepresentation of cancers, hysterectomy or oophorectomy at a young age in multiple family members because this may mask the risk for cancer, and the presence of adoption in the lineage.
- Risk of developing either syndrome is very low in women younger than age 21 years, and the committee does not recommend genetic testing for either HBOC or HNPCC in the absence of a family history of extremely early-onset cancer.
Pearls for Practice
- Women with the HBOC syndrome have an 85% lifetime risk for breast cancer and up to a 46% lifetime risk for ovarian cancer, whereas those with the HNPCC syndrome have a 40% to 60% lifetime risk for both endometrial and colorectal cancer and a 9% to 12% lifetime risk for ovarian cancer.
- Genetic testing for cancer predisposition requires informed consent, pretest education and counseling, posttest counseling, and appropriate genetic tests.