Abstract P5-02-18: HER2 status and response to neoadjuvant anti-HER2 treatment among patients with breast cancer and Li-Fraumeni syndrome

Abstract Background: Breast cancer (BC) is the most common tumor in women with Li-Fraumeni syndrome (LFS), with a cumulative incidence of 85% by the age of 60 years. However, LFS-related BC characteristics are still underexplored since most data derive from small retrospective cohorts. A variable enrichment in HER2-positivity (ranging from 34 to 80%) has been reported, but information regarding the response to anti-HER2 treatments are currently lacking. Moreover, data regarding the new emerging category of HER2-low are missing. Methods: Invasive BCs diagnosed in patients (pts) with TP53 germline pathogenic/likely pathogenic variant between 2002-2022 at Institut Gustave Roussy (France), Dana-Farber Cancer Institute (USA) and Hospital Sírio-Libanês (Brazil) were included. HER2 and hormone receptor (HR) expression were retrospectively retrieved from pathology records and evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. HER2-positive cases were defined by an immunohistochemistry (IHC) score of 3+ and/or HER2 gene amplification by ISH; HER2-negative cases were classified as HER2-low (IHC 1+ or 2+ with negative ISH assay) or HER2-zero (IHC score 0). Pathologic complete response (pCR) was defined as ypT0/is and ypN0. Results: Among 197 invasive BCs identified in a total of 176 pts, 50.3% (n=99) were HER-positive. Among those, median age at BC diagnosis was 33 years (range 21-61) and the most frequent TP53 variants were missense mutations (n=68), affecting the DNA-binding domain in 70.6% of cases and the tetramerization domain in 29.4% of cases. Most BCs were invasive ductal carcinoma (n=90), with histologic grade 3 in 56.6% of cases. At diagnosis, most pts had early stage disease (34.3% stage I; 32.3% stage II; 21.2% stage III), while 6 pts presented de novo stage IV disease. Most tumors were HR-positive (76.8%, n=76), while 23.2% were HR-negative. 38 patients with HER2-positive BCs were treated with neoadjuvant therapy, 32 cases had post-neoadjuvant pathology reports available for pathological response classification. Among those, 26 (81.2%) were HR-positive and 6 (18.8%) HR-negative. Among pts with neoadjuvant treatment data, 87.1% received trastuzumab, which was combined with pertuzumab in 43.3% of cases; chemotherapy regimens included taxanes in all pts, anthracycline in 43.3% and platinum in 16.7%. 71.9% (n=23) of pts reached a pCR (69.2% among HR-positive and 83.3% among HR-negative), while 9 (28.1%) had residual disease; pCR rate was 82.4% among pts treated with an anthracycline-free regimen. At a median follow-up of 36 months, only one patient relapsed. Among HER2-negative BCs with available IHC score and ISH for HER2-low classification (n=85), 28 (32.9%) were HER2-low and 57 (67.1%) HER2-zero. Conclusions: In this first report of treatment results in BC pts with LFS, enrichment of HER2-positive BCs was confirmed and a remarkable pCR rate was observed with neoadjuvant treatment. Our findings require validation in a larger cohort, which is in progress. Collaborative efforts are essential for high quality data about BC treatment in this subgroup of pts. Citation Format: Michele Bottosso, Renata Lazari Sandoval, Benjamin Verret, Natalia Polidorio, Olivier Caron, Alessandra Gennari, Brittany Bychkovsky, Sophie Hyman, Maria Isabel Achatz, Valentina Guarneri, Fabrice Andre, Judy Garbe. HER2 status and response to neoadjuvant anti-HER2 treatment among patients with breast cancer and Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-18.