Endocrine Abstracts (2019) 65 P150 | DOI: 10.1530/endoabs.65.P150

Breast cancer in MEN1: coincidence or association?

Seong Keat Cheah1, Chad Bisambar1, Deborah Pitfield1, Olivier Giger1, Rogier ten Hoopen1, Jose Ezequiel Martin1, Graeme Clark1, Soo-Mi Park1, Craig Parkinson2, Bejamin Challis1 & Ruth Casey1

1Addenbrooke’s Hospital (Cambridge University Hospital Trust), Cambridge, UK; 2Ipswich Hospital, Ipswich, UK

A 38 year old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.13404delG) through predictive testing, following a diagnosis of familial hyperparathyroidism. Routine screening for hyperparathyroidism and pituitary disease was negative. However, a CT thorax-abdomen-pelvis revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Biochemically, hyperinsulinaemic hypoglycaemia was confirmed following an overnight fast, and subsequently managed by diet prior to definitive surgery. Pre-operative work up with Octreotide scan demonstrated avid tracer uptake in the pancreatic lesion as well as a focal area of uptake in the left breast. Further investigation and subsequent mastectomy confirmed ductal carcinoma in situ pT2 (23 mm) grade 1, N0 (ER positive; HER2 negative). Following this, she underwent a successful pancreatectomy and splenectomy. Patchy insulin staining was seen on the pNET with no lymph node spread. MEN1’s association with breast cancer is unclear. Previously, 12 cases of breast cancer were reported in a cohort of 190 MEN1 females (Dreijerink et al. 2014). This cohort had early-onset breast cancer diagnosed at a young median age of 48 years, in line with our patient’s history. In our patient, loss of heterozygosity (LOH) at the MEN1 locus was seen in the breast tissue and pNET specimen, in keeping with a ‘two-hit’ hypothesis of oncogenesis, a suggestive but non-definitive clue for causation. However, only 3/9 cases showed loss of heterozygosity (LOH) in the Dutch cohort. Of note, somatic truncating BRCA2 and TP53 mutations were also identified in the breast tumour but the variant allele frequency of < 10% for both mutations suggesting that these mutations were sub-clonal rather than the primary genetic driver. This case highlights the need for further studies to determine the potential role of MEN1 in breast cancer development and to guide surveillance strategies.