Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations
Abstract
BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. METHODS: Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. RESULTS: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. CONCLUSIONS: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.
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BRCA2 mutation carriers present tumours with pathologic features similar to those of sporadic tumours.
“BRCA2 mutation carriers, on the contrary, present tumours with pathologic features similar to those of sporadic tumours [2-10].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [8]
BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation.
“Several studies suggest that BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation [5-12].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [8]
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- Authors
- Lakhani, S. R., Jacquemier, J., Sloane, J. P., Gusterson, B. A., Anderson, T. J., van de Vijver, M. J., Farid, L. M., Venter, D., Antoniou, A., Storfer-Isser, A., Smyth, E., Steel, C. M., Haites, N., Scott, Goldgar, D., Neuhausen, S., Daly, P. A., Ormiston, W., McManus, R., Scherneck, S., Ponder, B. A. J., Ford, D., Peto, J., Stoppa-Lyonnet, D., Bignon, Y.-J., Struewing, J. P., Spurr, N. K., Bishop, D. T., Klijn, J. G. M., Devilee, P., Cornelisse, C. J., Lasset, C., Lenoir, G., Barkardottir, R. B., Egilsson, V., Hamann, U., Chang-Claude, J., Sobol, H., Weber, B., Stratton, M. R., & Easton, D. F.
- Affiliations
- University College London (GB)
- Inserm (FR)
- University of Liverpool (GB)
- Institute of Cancer Research (GB)
- University of Edinburgh (GB)
- University of Pennsylvania (US)
- The University of Melbourne (AU)
- University of Cambridge (GB)
- Western General Hospital (GB)
- University of St Andrews (GB)
- University of Aberdeen (GB)
- Centre international de recherche sur le cancer (FR)
- University of Utah (US)
- Trinity College Dublin (IE)
- Max Delbrück Center (DE)
- Addenbrooke's Hospital (GB)
- Centre Jean Perrin (FR)
- National Cancer Institute (US)
- St James's University Hospital (GB)
- Daniel den Hoed Kliniek (NL)
- Leiden University (NL)
- German Cancer Research Center (DE)
- Corresponding author
- Lakhani, S. R.
- ORCID
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-08-05
- Volume
- 90
- Issue
- 15
- Pages
- 1138-1145
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2112187879
- Cited by
- 707
- References
- 39
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 12 · 2023: 18 · 2022: 26 · 2021: 14 · 2020: 22 · 2019: 16 · 2018: 15 · 2017: 19 · 2016: 18 · 2015: 20 · 2014: 19 · 2013: 15 · 2012: 28
- FWCI
- 18.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health (7r01ca061231-03)
- National Cancer Institute (CA-61231)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- breast cancer, BRCA1 mutation, BRCA2 mutation, hereditary breast cancer, sporadic breast cancer, tumor histology, mitotic count, lymphocyte infiltration, tubule formation, tumor grade, family history (medicine)
- MeSH terms
- Adult, Age Factors, Aged, Breast Neoplasms, Female, Humans, Middle Aged, Mutation, Neoplasm Proteins, Transcription Factors, Multivariate Analysis, Genes, BRCA1, BRCA2 Protein
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