Breast

Other carcinoma subtypes, not WHO classified

BRCA associated carcinoma


Editorial Board Member: Kristen E. Muller, D.O.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Chanchal Rana, M.D.

Last author update: 16 April 2024
Last staff update: 16 April 2024

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PubMed Search: BRCA associated breast carcinoma

Chanchal Rana, M.D.
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Cite this page: Rana C. BRCA associated carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignantbrca1.html. Accessed May 19th, 2024.
Definition / general
  • Group of inherited breast cancers attributed to mutations in the breast cancer associated genes: BRCA1 and BRCA2
  • Associated with increased risk of breast and ovarian cancers in women with BRCA germline mutations
Essential features
  • Presence of BRCA1 / 2 genes germline mutation
  • Responsible for 25 - 30% of familial breast cancers and ~2% of all breast cancers
  • Differs from sporadic breast carcinoma genotypically and phenotypically
  • Occurs at a younger age (< 50 years) with high predilection for contralateral breast involvement
  • Often well demarcated with pushing margins and medullary-like features
  • Usually high grade (poorly differentiated) and triple negative
Terminology
  • BRCA1 related breast cancer or BRCA1 germline mutation related breast cancer
  • BRCA1 / 2 associated hereditary breast and ovarian cancer syndrome
Epidemiology
Sites
  • Breast, ovarian, pancreatic, prostate and possibly other cancers can be associated with BRCA1 / 2 associated hereditary breast and ovarian cancer syndrome
Pathophysiology
Etiology
Diagrams / tables

Images hosted on other servers:
Breast cancer predisposition genes

Breast cancer predisposition genes

Clinical features
Diagnosis
Radiology description
Radiology images

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Mammogram and USG findings

Mammogram and USG findings

Circumscribed hypoechoic mass with <i>BRCA1</i> mutation

Circumscribed hypoechoic mass with BRCA1 mutation

Irregular obscured isodense mass

Irregular obscured isodense mass

Hypoechoic, irregular shape, calcifications in <i>BRCA2</i>

Hypoechoic, irregular shape, calcifications in BRCA2

Prognostic factors
  • Prognostic significance of BRCA1 / 2 mutational status on breast cancer survival is still debatable (Breast Cancer Res Treat 2010;119:13)
  • Majority of studies have failed to demonstrate a significant overall survival difference between BRCA associated breast cancer and sporadic breast cancer (Breast Cancer Res Treat 2010;119:13)
  • High risk of contralateral breast cancers (10 year risk ranging from 20 to 40%) (Breast Cancer Res Treat 2010;119:13)
  • Metastases to the CNS occur frequently in women with BRCA1 / BRCA2 germline mutations, especially with BRCA2 mutation (Cancer 2020;126:271)
  • Negative factors for overall survival may be infiltration of axillary lymph nodes, negative steroid receptor status and increased size of the primary tumor (Oncol Lett 2019;17:1986)
Case reports
Treatment
  • BRCA mutation carriers
  • BRCA mutation associated breast cancer (Onco Targets Ther 2022;15:815)
    • Total mastectomy is preferred over breast conserving surgery
    • Responsive to platinum based therapy
    • PARP inhibitors are effective in adjuvant, neoadjuvant and metastatic settings
Clinical images

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Mass in <i>BRCA</i> positive man

Mass in BRCA positive man

Gross description
  • Usually presents as well circumscribed / well demarcated fleshy mass
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Kristen E. Muller, D.O. and Chanchal Rana, M.D.
Well demarcated pushing borders

Well demarcated pushing borders

High grade nuclear features

High grade nuclear features

Lymphoplasmacytic infiltration

Lymphoplasmacytic
infiltration

Syncytial growth with necrosis

Syncytial growth with necrosis


ER negative

ER negative

PR negative

PR negative

HER2 neu negative

HER2 neu negative

Ki67

Ki67

p53 expression

p53 expression

Cytology description
  • No specific cytology findings
  • Corresponds to the histological type
Positive stains
Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

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<i>BRCA</i> pedigree

BRCA pedigree

LGRs <i>BRCA1</i>

LGRs BRCA1

LGRs <i>BRCA2</i>

LGRs BRCA2

<i>MYC</i> amplification

MYC amplification


Sample pathology report
  • Right breast mass, mastectomy:
    • Invasive breast carcinoma of no special type with medullary pattern (see synoptic report)
    • Grade III
    • Triple negative (ER / PR / HER2 neu negative)
    • Comment: In view of the presence of young age, medullary pattern and triple negativity, there is a possibility of BRCA associated breast carcinoma; genetic analysis may be advised if clinically indicated.
Differential diagnosis
Board review style question #1

Which statement about BRCA1 positive breast cancer, with histological features shown in the image above, is true?

  1. Expression of ER, PR and HER2 neu on immunohistochemistry
  2. High probability of the development of contralateral breast cancer in the future
  3. Low chance of association with ovarian cancer
  4. Patient is likely to be > 60 years of age
Board review style answer #1
B. High probability of the development of contralateral breast cancer in the future. BRCA associated breast cancer has high rates of contralateral breast cancer. Answer D is incorrect because BRCA associated breast cancer develops at a younger age, usually < 50 years. Answer A is incorrect because BRCA associated breast cancer is mostly triple negative. Answer C is incorrect because patients with BRCA associated breast cancers have a high chance of developing other cancers, especially ovarian cancer in women.

Comment here

Reference: BRCA1 associated breast carcinoma
Board review style question #2
Which of the following is the most sensitive radiological investigation to diagnose as well as follow up a patient with BRCA1 associated breast cancer?

  1. Dynamic contrast enhanced MRI
  2. Mammography
  3. Next generation sequencing
  4. Ultrasound
Board review style answer #2
A. Dynamic contrast enhanced MRI. Dynamic contrast enhanced MRI is the most sensitive screening modality, with a sensitivity of 71 - 94%. Answers B and D are incorrect because ultrasound and mammography are limited by the masking effect of dense breast tissue in young women, demarcated nature and lower incidence of ductal carcinoma in situ BRCA associated breast cancer. Answer C is incorrect because next generation sequencing is a molecular technique.

Comment here

Reference: BRCA1 associated breast carcinoma
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