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Breast malignant, males, children

Carcinoma subtypes

BRCA1 associated breast carcinoma

Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 15 November 2012, last major update March 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Definition
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● BRCA1 is a tumor suppressor gene at 17q21 (OMIM 113705); may interact with p53 (Cancer Lett 2008;268:137)
● Germline mutations occur in 0.1% of Caucasians but in 2% of Ashkenazi Jews

Terminology
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● BRCA1 associated breast carcinoma is not part of WHO breast classification

Epidemiology
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● 12% of women referred for genetic testing have BRCA1/BRCA2 deleterious mutations, rate is similar among different enthnicities (Cancer 2009;115:2222), but higher in Ashkenazi Jewish women
● Inherited in autosomal dominant manner
● BRCA1 mutations are present in 10% of women with (a) no family history, (b) breast cancer onset by age 40 years, and (c) high grade, triple negative tumors (BMC Cancer 2009;9:86)
● 56-68% of BRCA1 carriers with germline mutations get breast cancer by age 70 years, 80% by age 80, but usually at ages 40-59 (BMC Cancer;2008:8;155)
● Most effective predictor of BRCA1 mutations in breast cancer is age of onset < 50 years, HER2 status (negative), and either ER or PR status (negative), as compared with sporadic or non-BRCA1/BRCA2 cancers (Breast Cancer Res 2008;10:R17)
● The Manchester scoring system is a risk assessment model which may be applied to evaluate an individual’s risk of having a BRCA1 or BRCA2 mutation (J Med Genet 2009;46:811)
● 60% chance of mutation if 4+ family members had breast cancer prior to age 60 years (Eur J Cancer 1999;35:1954)
● Not cost effective to screen if only 10% risk of having a BRCA1/2 mutation (Value Health 2009;12:207)

Treatment and prognosis
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● Carriers: close follow up or prophylactic mastectomy (reduces risk of cancer by 85-90%, Ann Surg Oncol 2007;14:3335)
● Tumors: tamoxifen may prevent bilateral breast cancers in ER alpha negative tumors that are ER beta+ (BMC Cancer 2008;8:100)
● Tumors: increased risk of recurrence after breast conserving surgery (Ann Surg Oncol 2009;16:3380)
● Tumors: BRCA1 status does not appear to affect death rates (N Engl J Med 2007;357:115), but is associated with resistance to docetaxel based chemotherapy (Med Sci Monit 2008;14:SC7)

Case reports
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● BRCA1 carrier with primary ovarian carcinoma and metastases 3 and 6 years later, due to occult breast carcinoma (Hum Pathol 2004;35:629)

Micro description
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● Usually high grade (basal-like phenotype) with abundant intra- and peritumoral lymphocytes, but no syncytial growth pattern, no fibrous capsule (Mod Pathol 2005;18:1321)
● Greater incidence of medullary tumors
● High incidence of DCIS (Cancer Prev Res (Phila Pa) 2009;2:122)

Micro images
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Various images and immunostains

   
ER alpha (left) and beta (right)

Positive stains
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● p53 and P-cadherin (Hum Pathol 2008;39:857), also Ki-67 (Cancer Genet Cytogenet 2009;189:105)
● ER beta positive in 44% (BMC Cancer 2008;8:100), although usually ER alpha negative
● CK14 in 39% (Breast Cancer Res 2008;10:R17), although expression of basal cytokeratins and EGFR does not predict BRCA1 status in women with triple negative tumors (Am J Surg Pathol 2009;33:1093)

Negative stains
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● Usually triple negative (ER alpha negative in 85%, PR-, HER2-), but often ER beta positive
● Androgen receptor negative

Additional references
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● Arch Pathol Lab Med 1999;123:1023, Wikipedia, National Cancer Institute

End of Breast malignant, males, children > Carcinoma subtypes > BRCA1 associated breast carcinoma

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