Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data

Background: About 5% of all breast cancer cases are attributable to germline mutations in BRCA1 or BRCA2 genes. BRCA mutations in suspected carriers, however, may be missed, which hampers genetic counselling. Materials and methods: Different clinicopathological features were compared between 22 breast cancers from carriers of proved BRCA1 mutations and 604 cancers from sporadic controls. In addition, 5 BRCA2-related breast cancers and 66 breast cancers of untested patients at intermediate risk and 19 breast cancers of untested patients at high risk of hereditary disease on the basis of family history were evaluated. Results: A “probably sporadic” class (age ⩾54 years and epidermal growth factor receptor (EGFR) negative; 68% of cases) with a 0% chance of BRCA1-related breast cancer containing 79% of the sporadic cases was yielded by using a decision tree with age, Ki67 and EGFR. A 75% chance of BRCA1-related breast cancer was shown by the “probably BRCA1-related” class (age <54 years and Ki67 ⩾25%; 8% of cases) with 82% of the BRCA1-related cases but only 1.4% of the sporadic cases. Most cases at intermediate or high risk of hereditary disease on the basis of family history could be classified with high probability as either probably BRCA1 related or probably sporadic. Conclusion: Breast carcinomas can be classified with a high level of certainty as sporadic or related to BRCA1 germline mutations by using a decision tree with age, Ki67 and EGFR. This can be clinically useful in mutation analysis in families with a borderline risk of hereditary disease.

[1]  J. Benítez,et al.  The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications , 2005, Modern Pathology.

[2]  I. Bedrosian.  The prognostic implication of the basal-like (cyclin Ehigh/ p27low/p53+glomeruloid-microvascular-proliferation +) phenotype of BRCA1-related breast cancer , 2005 .

[3]  H. Nevanlinna,et al.  Relationship of patients' age to histopathological features of breast tumours in BRCA1 and BRCA2 and mutation-negative breast cancer families , 2005, Breast Cancer Research.

[4]  A. Ashworth,et al.  Hallmarks of 'BRCAness' in sporadic cancers , 2004, Nature Reviews Cancer.

[5]  William D. Foulkes,et al.  Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer , 2004 .

[6]  L. Bégin,et al.  The Prognostic Implication of the Basal-Like (Cyclin Ehigh/p27low/p53+/Glomeruloid-Microvascular-Proliferation+) Phenotype of BRCA1-Related Breast Cancer , 2004, Cancer Research.

[7]  J. Benítez,et al.  Re: Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. , 2004, Journal of the National Cancer Institute.

[8]  L. Bégin,et al.  Advances in Brief The Prognostic Implication of the Basal-Like ( Cyclin Ehigh / p 27 low / p 53 / Glomeruloid-Microvascular-Proliferation ) Phenotype of BRCA 1-Related Breast Cancer , 2004 .

[9]  M. Ringnér,et al.  Molecular classification of familial non-BRCA1/BRCA2 breast cancer , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Daniel J Schaid,et al.  Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers , 2003, Cancer.

[11]  Marcel J T Reinders,et al.  Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors. , 2002, Cancer research.

[12]  J. Savulescu,et al.  No consent should be needed for using leftover body material for scientific purposes , 2002, BMJ : British Medical Journal.

[13]  A. Whittemore,et al.  Comparison of DNA‐ and RNA‐Based Methods for Detection of Truncating BRCA1 Mutations , 2002, Human mutation.

[14]  M. J. van de Vijver,et al.  The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Nazneen Rahman,et al.  Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations , 2002, Nature Genetics.

[16]  P. V. van Diest,et al.  Cyclin A is a prognostic indicator in early stage breast cancer with and without tamoxifen treatment , 2002, British Journal of Cancer.

[17]  Yudong D. He,et al.  Gene expression profiling predicts clinical outcome of breast cancer , 2002, Nature.

[18]  D. Venter,et al.  The pathology of inherited breast cancer , 2002, Pathology.

[19]  P. V. van Diest,et al.  Survival analysis in familial ovarian cancer, a case control study. , 2001, European journal of obstetrics, gynecology, and reproductive biology.

[20]  Å. Borg,et al.  Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. , 2001, Journal of the National Cancer Institute.

[21]  G. Casey,et al.  Breast tumor immunophenotype of BRCA1-mutation carriers is influenced by age at diagnosis. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  D. Santini,et al.  Quantitative p21WAF‐1/p53 immunohistochemical analysis defines groups of primary invasive breast carcinomas with different prognostic indicators , 2001, International journal of cancer.

[23]  K. Phillips.  Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  P. Chappuis,et al.  Clinico-pathological characteristics of BRCA1- and BRCA2-related breast cancer. , 2000, Seminars in surgical oncology.

[25]  J. Klijn,et al.  Survival in hereditary breast cancer associated with germline mutations of BRCA2. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  S. Lakhani.  The pathology of familial breast cancer: Morphological aspects , 1999, Breast Cancer Research.

[27]  Y. Miki,et al.  Clinicopathologic analysis of BRCA1‐ or BRCA2‐associated hereditary breast carcinoma in Japanese women , 1999, Cancer.

[28]  G. Giles,et al.  Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. , 1999, Cancer research.

[29]  P. V. van Diest,et al.  Differences between hereditary and sporadic ovarian cancer. , 1999, European journal of obstetrics, gynecology, and reproductive biology.

[30]  D. Berry,et al.  Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history. , 1998, Journal of the National Cancer Institute.

[31]  L. Norton,et al.  BRCA-associated breast cancer: absence of a characteristic immunophenotype. , 1998, Cancer research.

[32]  M. Stratton.  Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases , 1997, The Lancet.

[33]  D. Abeliovich,et al.  [Inherited breast cancer]. , 1996, Harefuah.

[34]  W. Thompson,et al.  The genetic attributable risk of breast and ovarian cancer , 1996, Cancer.

[35]  N. Risch,et al.  Autosomal dominant inheritance of early‐onset breast cancer. Implications for risk prediction , 1994 .

[36]  J. Peterse,et al.  Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. , 1992, Human pathology.