Abstract 5801: Rates of risk reducing mastectomy in women with Li-Fraumeni Syndrome
Authors: Siegel Atara , Bremer Renee C. , Khincha Payal , Klein William , Savage Sharon A. , Loud Jennifer T. 
Published: September 2020

Introduction: Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome, primarily caused by germline pathogenic variants (PV) in the tumor suppressor gene TP53. Women with these PVs have an 85% lifetime risk of developing breast cancer (BC) and early onset BC, with a 50% risk by age 30. NCCN guidelines recommend risk-reducing mastectomy (RRM) to manage BC risk in women with LFS. However, rate of uptake of RRM, either bilateral (B-RRM) or contralateral (C-RRM), in LFS is unknown.

Methods: 205 women (≥15 years of age) with a confirmed TP53 PV enrolled in NCI's LFS study (NCT01443468) and reported lifetime BCs and mastectomies through Oct. 2019. Validated pathology reports were obtained in 86% of BCs and 74% of mastectomies. Women in the screening arm of the study were evaluated annually (clinic cohort). Remaining women completed questionnaires and provided data only (field cohort).

Results: The rate of any RRM was 40%, n=82 (Table 1). Median age at C-RRM and B-RRM was 33 (range [r]=17-65) and 37 (r= 24-52) years. Most women completed C-RRM within 1 year of BC diagnosis (77.8%, r=0-23 years) and genetic testing (69.2%, r=0-15 years), respectively. Women who chose B-RRM (mean age=43.7, SD=16.4) were older than those with no RRM (mean age=36.3, SD=8.7), t =-2.35 (31.63), p=0.025. 41.2% of women completed B-RRM within 1 year of genetic testing. Rates of C-RRM (χ2=6.54 (1), p=.011) and B-RRM (χ2=5.97 (1), p=.015) were higher in the clinic compared to the field cohort.

Rates of mastectomy among female TP53 mutation carriersFull sample (N=205)Unilateral Breast Cancer (N=105)No History of Breast Cancer (N=80)Clinic Cohort (N=81)Field Cohort (N=124)No Mastectomy38.0% (n=78)10.5% (n=11)83.8% (n=67)25.9% (n=21)46.0% (n=57)Treatment Mastectomy only22.0% (n=45)24.8% (n=26)N/A18.5% (n=15)24.2% (n=30)C-RRM31.7% (n=65)61.9% (n=65)N/A43.2% (n=35)24.2% (n=30)B-RRM8.3% (n=17)*2.9% (n=3)*16.3% (n=13)12.3% (n=10)5.6% (n=7)*3 women completed bilateral mastectomy with prophylactic intent several years after BC diagnosis. One woman completed bilateral mastectomy with prophylactic intent and bilateral BC was identified at the time of surgery.

Conclusion: Rates of C-RRM are high in women with LFS, consistent with risk reducing guidelines. Rates of B-RRM in women with TP53 PVs remain low in comparison with BRCA1/2 mutation carriers (~30-44%). Lack of LFS-specific RRM research and lack of guidelines tailored to their unique needs may contribute to low uptake. Consistent with this hypothesis, rate of RRM was higher in the clinic cohort, suggesting that counseling from LFS specialists may increase uptake. More research is needed to design and disseminate RRM guidelines accounting for unique needs of LFS women.

Citation Format: Atara Siegel, Renee C. Bremer, Payal Khincha, William Klein, Sharon A. Savage, Jennifer T. Loud. Rates of risk reducing mastectomy in women with Li-Fraumeni Syndrome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5801.