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Guidelines on Risk Assessment for Hereditary GynCa November 4, 2007

Posted by ramunas in BRCA, breast cancer, cancer genetics, colorectal cancer, genetic testing, hereditary cancer, HNPCC, ovarian cancer.

Recently guidelines on risk assessment for inherited gynecologic cancer (Hereditary Breast/Ovarian Cancer (HBOC) and the Lynch/Hereditary Non-Polyposis Colorectal (HNPCC)) predispositions were published by The Society of Gynecologic Oncologists (SGO).

Hereditary cancer risk assessment is a process that includes assessment of risk, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained (ref).

Genetic risk assessment enables physicians to provide individualized evaluation of the likelihood of having one of these gynecologic cancer predisposition syndromes, as well the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes (ref).

Up to 10% of breast cancer and 10-15% of ovarian cancer cases are related to BRCA 1/2 genes mutations (“faulty genes”), so called HBOC syndrome.

Mutations in BRCA1 genes 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 BRCA2 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 (ref., subscription needed).

For comparison, overall life time breast cancer risk in the western population is 10-12%, and ovarian 1,5-2%.

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.”(ref.)

It is a new thing (“20-25%”) for me, because to my knowledge, a guidelines in USA set by the American Society of Clinical Oncology (ASCO) suggested a 10% likelihood of finding BRCA1/2 mutations to undertake genetic testing. A stringent 20% likelihood threshold of having BCRA mutations is already applied in UK.

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 MSH6 includes 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 (via).

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.

“revised Amsterdam criteria” for HNPCC are as follows (ref.):

  • 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.

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.

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. (ref.)



1. Steven Murphy MD - November 6, 2007

Excellent post. I had just finished reading the article when I found your post. Excellent assessment. I think that this stringent guideline is not what is being called for hereas there is some wiggle room i.e. 10%. Traditionally counselors had been offering at 10-15% here. If you look at a retrospective analysis of SGO guidelines for referral for adnexal masses you find that they miss early tumors. I think if you useboth sets of guidelines for identifying at risk and afflicted you will be missing the boat.

2. ramunas - November 10, 2007

Thank you Steven!! Yes, I agree that strict adherence to some guidelines has the potential to miss some cases. Better is to use combination of different approaches, imho.

3. Meg - April 16, 2008

It’s nice to know that more information is coming out about the Genetic problem that I have (Lynch/HNPCC syndrome)
in the last two years since being diagnosed with the faulty gene I’ve been trying to find out as much information about it as I could.
So much so that when I Doctor’s I tend to give them more information about it then they give me, which was the case with my GP, I still have a laugh about it now.

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