Which feature best distinguishes BRCA1-associated breast cancer from BRCA2-associated breast cancer in terms of tumor biology and clinical presentation?
A. BRCA1 mutations are autosomal recessive, whereas BRCA2 mutations are autosomal dominant
B. BRCA1 tumors are typically triple-negative (ER−, PR−, HER2−), whereas BRCA2 tumors are often hormone receptor–positive
C. BRCA2 mutations are associated with male breast cancer, whereas BRCA1 mutations rarely cause male breast cancer
D. BRCA1 mutations confer higher lifetime breast cancer risk (70%) compared to BRCA2 (45%)
Explanation
Distinguishing BRCA1 from BRCA2 Tumors
Key Molecular Difference
Key Point
BRCA1-associated breast cancers are characteristically triple-negative (estrogen receptor–negative, progesterone receptor–negative, HER2-negative), reflecting a distinct molecular phenotype. BRCA2-associated breast cancers are more often hormone receptor–positive, resembling sporadic luminal breast cancers.
Comparative Table
Table
Feature
BRCA1-Associated
BRCA2-Associated
ER/PR status
Predominantly negative
Often positive
HER2 status
Negative
Variable
Molecular subtype
Triple-negative (basal-like)
Luminal A/B or HER2+
Grade
High grade (poorly differentiated)
Variable
Age of onset
Younger (<50 years, often <40)
Younger but slightly older than BRCA1
Male breast cancer
Rare (<5%)
Common (5–10%)
Ovarian cancer risk
High (40–50%)
Lower (10–20%)
Pancreatic cancer risk
Moderate (2–3%)
Moderate (2–7%)
Prostate cancer risk (males)
Low
Elevated
Inheritance
Autosomal dominant
Autosomal dominant
Why This Matters
High-YieldNEET PG
BRCA1 loss impairs homologous recombination repair (HR) and also functions in transcriptional regulation and cell-cycle checkpoint control. The loss of these pleiotropic functions drives a basal-like, triple-negative phenotype. BRCA2 is primarily an HR repair gene; its loss does not enforce a specific hormone receptor phenotype, so BRCA2 tumors resemble sporadic breast cancers more closely.
Clinical Pearl
A 35-year-old woman with triple-negative breast cancer and a strong family history of breast/ovarian cancer → BRCA1 mutation likely. A 50-year-old man with hormone receptor–positive breast cancer and a family history of breast cancer → BRCA2 mutation likely.
Mnemonic
BRCA1 = "Basal-like, Receptor-negative, Cancer-aggressive" vs. BRCA2 = "Breast-cancer-2, (also) male breast cancer"
Robbins 10e Ch 7
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