How to Manage a Patient with Lynch Syndrome
Patients with Lynch syndrome are unique in that Lynch syndrome is very prevalent, but still receives little notoriety. Lynch originally was termed as HNPCC, hereditary non-polyposis colorectal cancer, and therefore still is often considered a colon cancer syndrome, regardless of implications with gynecological cancers and more. Lynch can predispose someone to colon and/or endometrial cancer, but also stomach, liver, ovarian, kidney, bladder, skin and more. Lynch does not 100% guarantee a person’s potential to get cancer, but the percentages are significantly higher than the average person, and usually at a younger age. Previvor is a term for someone who has a Lynch mutation, but has not had cancer yet.
Physicians should be proactive in dealing with Lynch syndrome, both before and after diagnosis. A thorough family health history remains the best step in diagnosing a potential Lynch syndrome patient. It is not uncommon for a patient to be unfamiliar with the exact type of cancer family members have had but asking the questions can be determinant if a test for Lynch is warranted. Obviously in the instances where the patient themselves have had cancer, especially at a younger age than normal, genetic testing is warranted, and should be pursued, either using saliva or blood. In addition, tumors should be sequenced to determine genetic profile.
Lynch syndrome, as an autosomal dominant mutation, can be inherited from either parent. In the instances where a patient has been diagnosed with Lynch syndrome, a discussion needs to take place around care for the patient, as well as a discussion around the direct family members. Often the first patient diagnosed with Lynch syndrome sets off a series of tests for family members who may not have considered themselves candidates for genetic testing (cascade screening), including the patient’s parents. For the patient, and any subsequent family members who have tested positive for a Lynch syndrome variant, a series of screenings can and should be undertaken right away. The traditional screening rules and timeframes are expedited, as Lynch syndrome manifests itself early. Lynch syndrome is considered a mismatch-repair deficiency, meaning some sort of environmental factor causes the body to not repair itself.
A standard set of Lynch syndrome screening guidelines includes colonoscopy/endoscopy every 1-2 years, a cystoscopy (timeframe TBD), MRCP (timeframe TBD), CT scans of chest/abdomen/pelvis (timeframe TBD), whole body skin examination, and an endometrial biopsy/pelvic ultrasound. While a physician, typically a high-risk oncologist, will recommend a schedule of screenings, typically a baseline screen is done to start. Obviously in cases where cancer has already occurred and/or there is a history of cancer in certain locations in family members, there may be a decision to focus on one or more areas more frequently. Breast cancer is not typically included in Lynch syndrome prevalence, but physicians may opt for mammograms earlier more frequently, including men. It is not uncommon for a Lynch syndrome patient (survivor or previvor) to have an oncologist, gastroenterologist, urologist, primary care physician, and a gynecologist, with whom they visit on a regular basis.
Women may consider having a hysterectomy and oophorectomy as a preventative measure. This is a significant decision, and issues such as child-bearing and/or hormone replacement therapies need to be discussed beforehand. While gastrointestinal cancer is prevalent in those with Lynch, an ostomy is not always needed and/or recommended.
On a more positive note (pun intended), recent technological advances have shown some patients with Lynch syndrome have a certain genetic makeup that conveys promise for future treatment. “Microsatellite instability” (MSI) is a term to describe the genetic makeup of tumors, and Lynch patients produce MSI-High tumors. These tumors have had good results using immunotherapy, so a Lynch patient can and should discuss immunotherapy with their physician, either before or after a cancer diagnosis. Recent studies with aspirin have shown prevention benefits as well. The dose and frequency of aspirin’s effectiveness are to be determined still, but again, they show promise. Genetic alterations/modification are also possibilities, both currently and in the future. PGD, pre-implantation genetic diagnosing, is a mechanism for IVF physicians to work with families looking to have children without Lynch syndrome in the future. PGD does tend to be expensive and time-consuming, so a conversation with an experienced IVF physician would be recommended.
A certified genetic counselor (GC) is often a good person to review Lynch syndrome with a patient. Learning that you have Lynch syndrome can be emotional in multiple ways. A patient can feel guilt for potentially passing on their mutation to children, a person can express fear about their future of getting cancer and/or multiple cancers and there’s the concern of discussing with family. At the same time, a Lynch diagnosis can be liberating, once they understand why cancer has run in their family and they can plan for their future. A GC can communicate percentages, options and next step recommendations with a patient, usually virtually, based upon the patient’s specific mutation. Direct to consumer testing has not been shown to be clinically appropriate for diagnosing Lynch syndrome and other hereditary cancers. It is recommended that a clinically valid hereditary cancer test performed by a CLIA approved clinically valid lab, such as the ExpedioTM Cancer Screening Test, be performed under the guidance of a GC and appropriate physician.
Whatever clinician is interacting with a Lynch syndrome patient should be upfront about the information available, allowing a patient to make an educated decision about their care moving forward.