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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bioscientifica Ltd
2021
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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 |
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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 |
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