Abstract P1-12-16: A Rare Case of Moderate Grade Intraductal Carcinoma in a Young Patient with known Neurofibromatosis 1

Field: Medicine (Health Sciences)

Abstract Background: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of tumors along nerves in the skin, brain, and other organs. It arises from mutations in the NF1 gene, which encodes neurofibromin, a tumor suppressor protein involved in regulating cell growth and division. NF1 patients have an increased susceptibility to various cancers, including breast cancer, though the precise mechanisms linking NF1 to breast cancer are still being investigated. Research indicates that the NF1 gene may play a role in modulating pathways involved in breast cancer development, such as the Ras signaling pathway. The risk of developing breast cancer before age 50 is estimated to increase fivefold in NF1 patients, with poor disease specific survival. Current NCCN screening guidelines suggest starting annual mammograms at age 30, with consideration of additional MRI screening. However, screening remains challenging in this patient population due to cutaneous neurofibromas, cafe-au-lait spots, and dense breast tissue. Enhancing our understanding of these connections could facilitate improved screening and management strategies for breast cancer in individuals with NF1. Case Presentation: We present a case of a 17 year old female with a confirmed pathogenic NF1 mutation diagnosed in childhood, who presented with early-onset invasive ductal carcinoma (IDC). The patient presented with new-onset symptoms of right breast bloody nipple discharge and nipple retraction. Initial work-up with breast ultrasound noted only benign simple cysts. Further diagnostic work-up with MRI breast, however, demonstrated a 2 cm mass at the 4 o'clock axis of the right breast with associated 5 cm of segmental non-mass enhancement. Diagnostic mammogram revealed correlating right breast 5.8 cm segmental pleomorphic calcifications. Stereotactic core needle biopsy of these calcifications confirmed a diagnosis of IDC, grade 2, ER/PR +, HER2+ with extensive intermediate grade ductal carcinoma in-situ (DCIS). She underwent treatment with neoadjuvant TCHP followed by right nipple sparing total mastectomy, right sentinel lymph node biopsy (SLNB), and contralateral risk reducing nipple sparing mastectomy with direct to implant reconstruction. Pathologic examination of the right breast demonstrated extensive DCIS with no residual IDC, negative margins, pathologically negative sentinel lymph nodes (ypTis N0). Multidisciplinary adjuvant treatment included adjuvant Tamoxifen and Phesgo along with recommendations for post mastectomy radiation therapy. Conclusion: Neurofibromatosis 1 and its heightened risk of early-onset breast cancer are well documented. However, diagnosing breast cancer in NF1 patients remains challenging due to prevalent cutaneous neurofibromas and dense breast tissue in young patients, which may obscure imaging and physical exam findings. While current guidelines recommend annual screening to begin at age 30, earlier initiation of high-risk screening with annual MRIs should be considered, potentially starting as early as age 18. Given the increased risk for breast cancer, it is crucial to implement age-appropriate diagnostic breast imaging in patients with known pathogenic NF1 mutations experiencing breast-specific symptoms. Citation Format: Nicholas Gore, Madeline Silva, Carissia Calvo-Strube. A Rare Case of Moderate Grade Intraductal Carcinoma in a Young Patient with known Neurofibromatosis 1 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-12-16.