Breast cancer in multiple endocrine neoplasia type 1 (MEN1)

Abstract

Summary A 38-year-old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.1304delG) through predictive genetic testing, following a diagnosis of familial hyperparathyroidism. Routine screening for parathyroid and pituitary disease was negative. However, cross-sectional imaging by CT revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed the lesion to be a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Biochemically, hyperinsulinaemic hypoglycaemia was confirmed following an overnight fast, which was subsequently managed by diet alone prior to definitive surgery. Pre-operative work-up with octreotide SPECT CT demonstrated avid tracer uptake in the pancreatic lesion and, unexpectedly, 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 mastectomy, our patient underwent a successful distal pancreatectomy to resect the pNET. Loss of heterozygosity (LOH) at the MEN1 locus was found in both the breast tumour and pNET, thereby in keeping with a 'two-hit' hypothesis of oncogenesis, a suggestive but non-definitive clue for causation. To obtain further support for a causative relationship between MEN1 and breast cancer, we undertook a detailed review of the published literature which overall supports the notion that breast cancer is a MEN1-related malignancy that presents at a younger age and histologically, is typically of ductal subtype. Currently, clinical guidance regarding breast cancer surveillance in MEN1 does not exist and further research is required to establish a clinical and cost-effective surveillance strategy). Learning points We describe a case of pNET and breast cancer diagnosed at a young age of 38 years in a patient who is heterozygous for a pathogenic MEN1 variant. Loss of the wild-type allele was seen in both breast tissue and pNET specimen. Breast cancer may be an under-recognised MEN1-associated malignancy that presents at a younger age than in the general population with a relative risk of 2–3. Further research is required to determine the cost-effectiveness of breast cancer surveillance approach at a younger age in MEN1 patients relative to the general population .

Coincidental Occurrence of Multiple Endocrine Neoplasia Type 1 and Breast Cancer in a Young Saudi Girl: A Case Study and Genetic Analysis

“…Jeong et al described a case where a previously healthy 45-year-old woman presented MEN-1 symptoms first through a breast mass [ 13 ]. Cheah et al discussed a woman in her thirties with MEN-1 who developed a histologically confirmed ductal breast tumor [ 14 ]. Notably, most reported cases in young women were also histologically ductal.…”

Beyond the “3 Ps”: A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1

“…Most recently, it has been proposed that the risk of breast carcinoma is heightened in females with MEN1. To date, there have been approximately 90 or fewer cases of breast carcinoma in women with MEN1 reported in the literature (24,43,44,51,72,81,87,95,99,(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150); breast cancer has not yet been reported in a man with MEN1. The exact number of cases is difficult to determine due to the likely overlap of cases in the published literature and the lack of specific case numbers in one publication.…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…MEN1 pathogenic variants in exon 2, 9, and 10 are prone to a more aggressive pancreatic NET behavior [ 72 ]. Other nonendocrine components have been placed in relationship with MEN1 like breast cancer or melanoma, but currently, there is insufficient statistical evidence to directly connect them with the MEN1-associated picture [ 89 , 90 ].…”