Lynch Syndrome and Breast Cancer Risk
The statement "Lynch syndrome does not have breast cancer" is incorrect—breast cancer has been reported in Lynch syndrome families, but it is NOT currently considered part of the established Lynch syndrome tumor spectrum based on major clinical guidelines. 1
Guideline Position on Breast Cancer in Lynch Syndrome
The established Lynch syndrome-associated cancers include:
- Colorectal cancer (30-80% lifetime risk) 1
- Endometrial cancer (25-60% lifetime risk) 1
- Ovarian cancer (4-24% lifetime risk) 1
- Gastric, urinary tract, small intestine, pancreatic, biliary tract, brain, and sebaceous tumors 1
Breast cancer is explicitly NOT included in the diagnostic Lynch syndrome disease spectrum. 1 The 2006 JAMA guidelines state that while breast cancers have been reported in Lynch syndrome families, "no studies have been reported that verify that these sites are statistically more frequent than in the general population and they are not currently considered as diagnostic components of the Lynch syndrome disease spectrum." 1
Current Screening Recommendations
There is insufficient evidence to support breast cancer screening above average-risk recommendations for Lynch syndrome patients. 1 The NCCN guidelines from 2016 explicitly state that despite suggestions of increased breast cancer risk, there is insufficient evidence to support enhanced screening beyond standard population-based recommendations. 1
Emerging Research Evidence Shows Conflicting Data
While guidelines do not recognize breast cancer as part of Lynch syndrome, recent research suggests potential gene-specific associations:
MSH2 Mutation Carriers:
- A 2017 Canadian study found MSH2 carriers had a 22% lifetime cumulative incidence of breast cancer (SIR 3.11,95% CI 1.95-4.71), significantly elevated compared to the general population. 2
- A 2015 UK study found MSH2 carriers had an 11.2% cumulative risk to age 70, not significantly elevated. 3
MLH1 Mutation Carriers:
- A 2015 UK cohort study demonstrated MLH1 carriers had an 18.6% cumulative breast cancer risk to age 70 (95% CI 11.3-25.9), significantly higher than MSH2 carriers (11.2%, p=0.014) and the UK population risk of 7.5-8%. 3
PMS2 Mutation Carriers:
- A 2020 study found 27% of women with PMS2 mutations were diagnosed with breast cancer, compared to only 3-9% in other MMR gene mutations (p=0.0043). 4
- However, a 2018 large international study found no clear evidence of increased breast cancer risk in PMS2 carriers. 5
Clinical Implications
Despite emerging research, clinical management should follow current guidelines:
- Do NOT offer enhanced breast cancer surveillance (such as MRI screening) based solely on Lynch syndrome diagnosis. 1
- Assess breast cancer risk independently using standard risk assessment tools (e.g., Tyrer-Cuzick model). 4
- Consider that 16.5-24.4% of Lynch syndrome patients may independently qualify for breast-specific genetic testing (BRCA1/2) based on personal/family history. 4
- If a Lynch syndrome patient has additional breast cancer risk factors or family history meeting criteria for enhanced surveillance, manage according to those separate indications, not the Lynch syndrome diagnosis itself. 4
Important Caveats
The discrepancy between research findings and guideline recommendations reflects:
- Small sample sizes in individual studies 3, 2
- Potential ascertainment bias in clinic-based cohorts 5
- Gene-specific heterogeneity that may not apply uniformly across all MMR mutations 4, 3, 2
- Lack of prospective validation studies demonstrating mortality or morbidity benefit from enhanced breast surveillance in this population 1
Until prospective data demonstrate benefit from enhanced breast cancer screening in Lynch syndrome, standard population-based breast cancer screening remains appropriate. 1