SAT-298 - Multiple Endocrine Neoplasia Type 4 in A Young Female with Grade III Invasive Ductal Carcinoma and Pathogenic CDKN1B Mutation (C.388_392Del)

Multiple Endocrine Neoplasia type 4 (MEN4) is a rare hereditary syndrome caused by germline mutations in the CDKN1B gene encoding the cell cycle regulator p27^Kip1^. Its clinical features overlap with MEN1 but remain less well defined due to limited reported cases. We describe a 31-year-old female diagnosed with grade III triple-negative invasive ductal carcinoma (IDC) who was found to harbor a pathogenic CDKN1B mutation (c.388_392del), broadening the recognized tumor spectrum of MEN4 to include breast malignancy.

The patient presented with a palpable right breast mass; biopsy confirmed high-grade IDC. She completed neoadjuvant chemotherapy with adriamycin, cyclophosphamide, and paclitaxel. MRI brain showed no pituitary lesion, and CT chest/abdomen/pelvis revealed no pancreatic or adrenal tumors but identified a sclerotic femoral lesion, subsequently biopsied. Germline testing demonstrated a pathogenic CDKN1B frameshift deletion consistent with MEN4. Endocrine evaluation showed mild elevations in chromogranin A and IGF-1. Chromogranin A normalized on repeat testing and was deemed nonspecific, with no evidence of carcinoid syndrome. IGF-1 elevation may indicate a future risk for acromegaly, although the patient remains asymptomatic. Elevated insulin levels were attributed to insulin resistance associated with obesity. Upper and lower endoscopy findings were unremarkable. She remains under multidisciplinary surveillance with oncology, endocrinology, and gastroenterology, with biochemical monitoring every six months.

MEN4 is an autosomal dominant syndrome accounting for < 5% of MEN cases. Parathyroid and pituitary adenomas are the most common manifestations, but recent reports suggest associations with non-endocrine tumors, including breast carcinoma. The CDKN1B c.388_392del mutation causes a frameshift and premature truncation of p27^Kip1^, disrupting G1/S checkpoint regulation and promoting unrestrained cellular proliferation. The diagnosis of aggressive IDC at age 31 suggests a possible role of CDKN1B loss in breast tumorigenesis.

This case expands the phenotypic spectrum of MEN4 and emphasizes the need to consider breast cancer surveillance in CDKN1B mutation carriers alongside traditional endocrine screening. Ongoing documentation of such cases is essential to refine cancer risk assessment and surveillance strategies in MEN4.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*