Breast cancer in multiple endocrine neoplasia type 1 (MEN1)

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 imagi...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheah, Seong Keat, Bisambar, Chad Ramese, Pitfield, Deborah, Giger, Olivier, Hoopen, Rogier ten, Martin, Jose-Ezequiel, Clark, Graeme R, Park, Soo-Mi, Parkinson, Craig, Challis, Benjamin G, Casey, Ruth T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115436/
https://www.ncbi.nlm.nih.gov/pubmed/33960322
http://dx.doi.org/10.1530/EDM-20-0196
_version_ 1783691221519040512
author Cheah, Seong Keat
Bisambar, Chad Ramese
Pitfield, Deborah
Giger, Olivier
Hoopen, Rogier ten
Martin, Jose-Ezequiel
Clark, Graeme R
Park, Soo-Mi
Parkinson, Craig
Challis, Benjamin G
Casey, Ruth T
author_facet Cheah, Seong Keat
Bisambar, Chad Ramese
Pitfield, Deborah
Giger, Olivier
Hoopen, Rogier ten
Martin, Jose-Ezequiel
Clark, Graeme R
Park, Soo-Mi
Parkinson, Craig
Challis, Benjamin G
Casey, Ruth T
author_sort Cheah, Seong Keat
collection PubMed
description 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 .
format Online
Article
Text
id pubmed-8115436
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Bioscientifica Ltd
record_format MEDLINE/PubMed
spelling pubmed-81154362021-05-17 Breast cancer in multiple endocrine neoplasia type 1 (MEN1) Cheah, Seong Keat Bisambar, Chad Ramese Pitfield, Deborah Giger, Olivier Hoopen, Rogier ten Martin, Jose-Ezequiel Clark, Graeme R Park, Soo-Mi Parkinson, Craig Challis, Benjamin G Casey, Ruth T Endocrinol Diabetes Metab Case Rep Unique/Unexpected Symptoms or Presentations of a Disease 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 . Bioscientifica Ltd 2021-05-05 /pmc/articles/PMC8115436/ /pubmed/33960322 http://dx.doi.org/10.1530/EDM-20-0196 Text en © 2021 The authors https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Unique/Unexpected Symptoms or Presentations of a Disease
Cheah, Seong Keat
Bisambar, Chad Ramese
Pitfield, Deborah
Giger, Olivier
Hoopen, Rogier ten
Martin, Jose-Ezequiel
Clark, Graeme R
Park, Soo-Mi
Parkinson, Craig
Challis, Benjamin G
Casey, Ruth T
Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title_full Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title_fullStr Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title_full_unstemmed Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title_short Breast cancer in multiple endocrine neoplasia type 1 (MEN1)
title_sort breast cancer in multiple endocrine neoplasia type 1 (men1)
topic Unique/Unexpected Symptoms or Presentations of a Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115436/
https://www.ncbi.nlm.nih.gov/pubmed/33960322
http://dx.doi.org/10.1530/EDM-20-0196
work_keys_str_mv AT cheahseongkeat breastcancerinmultipleendocrineneoplasiatype1men1
AT bisambarchadramese breastcancerinmultipleendocrineneoplasiatype1men1
AT pitfielddeborah breastcancerinmultipleendocrineneoplasiatype1men1
AT gigerolivier breastcancerinmultipleendocrineneoplasiatype1men1
AT hoopenrogierten breastcancerinmultipleendocrineneoplasiatype1men1
AT martinjoseezequiel breastcancerinmultipleendocrineneoplasiatype1men1
AT clarkgraemer breastcancerinmultipleendocrineneoplasiatype1men1
AT parksoomi breastcancerinmultipleendocrineneoplasiatype1men1
AT parkinsoncraig breastcancerinmultipleendocrineneoplasiatype1men1
AT challisbenjaming breastcancerinmultipleendocrineneoplasiatype1men1
AT caseyrutht breastcancerinmultipleendocrineneoplasiatype1men1