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Genetic Testing Challenges in Oncology: Lynch Syndrome Patient Has Ovaries, Uterus Removed at Age 22

Precision Oncology News and My Gene Counsel have partnered to produce the "Genetic Testing Challenges in Oncology" series to highlight real-world issues that genetics experts and medical professionals are encountering as genetic tests are increasingly used in cancer care. Experts submit anonymized case reports to My Gene Counsel, and based on the details in these reports, Precision Oncology News writes a feature that describes the case history, challenges encountered by professionals in dealing with the case, and strategies they used in response to challenges or errors. The features also include a discussion with My Gene Counsel genetic counseling experts on better approaches that could be considered if similar cases are encountered in the future. In publishing this series, our aim is to educate experts in the field and foster discussion. If you would like to submit a case report, please email [email protected].

What happened?

After seeing multiple members of a family with late-stage cancers at young ages, their oncologist suspected that these malignancies may be due to Lynch syndrome. The hereditary cancer syndrome is known to increase genetic risk for certain types of cancers. The mother of the family was diagnosed with ovarian cancer when she was 55 years old and died at the same age. Her son was diagnosed at age 28 with stage IV small bowel cancer and her daughter was diagnosed with stage IV colon cancer at age 23. Her husband and three other daughters did not have any experience with cancer. 

Although the mother had never gotten genetic testing, the oncologist told the family that their cancer history was suspicious for Lynch syndrome and referred them to a genetic counselor, who ordered genetic testing for the father and his five children. Genetic testing identified a pathogenic MLH1 variant in the son with bowel cancer and the daughter with colon cancer. The youngest daughter, who was 21 years old at the time of genetic testing and had never had cancer, also had the same pathogenic variant.

The genetic counselor provided the family information about Lynch syndrome and discussed the National Comprehensive Cancer Network's management guidelines. The genetic counselor also referred the 21-year-old unaffected daughter, who had never seen a gynecologist, to see a gynecologist to discuss routine care and have a point of contact for discussing screening and preventive options for ovarian and uterine cancers when appropriate. Subsequently, the genetic counselor learned that the gynecologist recommended the patient undergo a hysterectomy and oophorectomy soon, earlier than often recommended.  

How was this case resolved?

The genetic counselor was surprised by this recommendation for surgery for someone so young, particularly since hysterectomy and oophorectomies were not discussed as surgeries to consider in the near term during the genetic counseling session. Thinking there may be some confusion, the genetic counselor provided the gynecologist her counseling clinic notes and the NCCN's management guidelines.

According to the NCCN guidelines for managing the risk of Lynch syndrome-associated gynecologic cancers, patients should discuss with a gynecologist the signs and symptoms of endometrial and ovarian cancers; available screening approaches, such as transvaginal ultrasound, endometrial biopsy, and CA-125 testing; and opportunities for risk reduction through oral contraceptives. Hysterectomy and oophorectomy could also be considered, according to the guidelines. The NCCN guidelines also contain information on the average age at which endometrial and ovarian cancers are diagnosed, as well as ovarian cancer risks by decade.

Although the NCCN doesn't cite a specific age when hysterectomy and oophorectomy should be considered for a Lynch syndrome patient, historically, in practice, doctors typically begin considering a hysterectomy for managing Lynch syndrome-associated uterine cancer risk in patients after they've completed childbearing or from age 35 to 40. The NCCN guidelines currently recommend that timing of surgery be based on a nuanced discussion with the patient that addresses factors, such as family planning, medical history, family history, and specific genetic test results. Possible negative health impacts of these surgeries should also be part of the discussion.

In this case, according to the genetic counselor, the gynecologist recommended the surgery be considered soon since the young woman and her father were very fearful that so many family members had been diagnosed with late-stage cancers.

The genetic counselor further learned from the gynecologist that this young woman had a hysterectomy and oophorectomy at age 22.  

Why is this case concerning?

"The timing of risk-reducing hysterectomy and oophorectomy is complicated," said Meagan Farmer, a genetic counselor and genetic clinical operations director at My Gene Counsel. Although the details of what the gynecologist discussed with the patient are not known, "on the surface, this surgery recommendation is at a younger age than I would expect," Farmer said.

The recommendation is concerning because there are immediate and long-term effects on a woman's health after a hysterectomy and oophorectomy that should be carefully discussed with patients. After these surgeries a woman is unable to have biological children, though it is possible that this young woman told her gynecologist that she didn't want to have biological children. However, the surgeries can also result in the sudden onset of menopause, which has implications for heart, bone, and sexual health, and can impact memory.

The genetic counselor who reported this case recognized that for this young woman, fear and anxiety related to the death of her mother from ovarian cancer, and the late-stage cancer diagnoses of two siblings when they were in their 20s, played a role in her decision to take preventive action at such an early age. However, the genetic counselor was also under the impression that the young woman's gynecologist did not have a very nuanced discussion with her about the risks of these surgeries, including how the risks at her age differ compared to her lifetime risk, as well as the potential implications of surgery and timing, Farmer said.

What could have been done differently?

Ultimately, it is the doctor who can make a medical recommendation to the patient about how to manage cancer risk, but a genetic counselor can educate and prepare the patient for that conversation. While Farmer was not privy to the details of the conversation between the young woman and her gynecologist, she said that during genetic counseling she would have discussed data related to ovarian cancer risk by age as compared to lifetime risk and talked about timing of preventive surgery within this framework.

The risk of uterine cancer for someone who is MLH1-positive and has Lynch syndrome is between 43 percent and 57 percent by age 70, and the average age of diagnosis is 49. The risk of ovarian cancer for someone with Lynch syndrome is between 5 percent and 20 percent by age 70, and the average age of diagnosis is between 44 and 47 years old.

Additionally, for this woman in her 20s, Farmer would also share data on how her ovarian cancer risk would change as she got older. Her risk for ovarian cancer would be very low, around 0 percent and 1 percent, at age 40, but would increase each decade. By age 50, someone with Lynch syndrome has between a 4 percent and 7 percent risk of ovarian cancer, by age 60, between 9 percent and 15 percent, and by age 60, between 11 and 20 percent.

"I'd want to show her that the risk climbs to that level over time, and that her risk while she's in her 20s is not the same as when she is 45," Farmer said, noting that this additional information may be a way to help her feel like she has some time to consider her options, "instead of feeling like she has to have surgery now because she watched her mom die of ovarian cancer."

Even if the gynecologist felt the need to take some medical action because this patient was so fearful of cancer, before suggesting hysterectomy and oophorectomy, the doctor might have considered short-term screening strategies starting in a few years, or cancer risk-reducing approaches such as birth control pills, Farmer said. Even if the evidence supporting the use of measures like endometrial biopsy or transvaginal ultrasound to detect cancer early is weak, "if you have a very anxious patient, is that something you consider doing in lieu of surgery in her 20s?" she posited.

Finally, it is also worth considering if this young woman would benefit from having her anxiety about cancer addressed. Farmer said that perhaps a referral to a mental health professional might have helped her deal with her fear, while she considered her risk management options.