74 Questions
What are the three major subtypes of breast cancers distinguished by gene expression?
Luminal, basal-like, and Her2+
What is the median age of diagnosis of breast cancer?
63
What percentage of breast cancers are associated with inherited genetic mutations?
10%
What is the most commonly diagnosed cancer in women in the United States?
Breast cancer
Which gene mutations are responsible for 80-90% of hereditary breast cancer cases?
BRCA1 and BRCA2
A mutation in which of these genes is LEAST likely to be found in a case of sporadic breast carcinoma?
BRCA1
Which gene mutation is associated with the hereditary diffuse gastric cancer syndrome?
CDH1
Which risk factor is associated with a higher risk of breast cancer in postmenopausal women?
Higher BMI
What is the main molecular mechanism for HER2 overexpression in HER2-positive carcinomas?
Gene amplification
Which gene encodes a transmembrane protein that forms adherens junctions?
CDH1
What is the main function of translation products from BRCA1 and BRCA2?
Repair double-stranded DNA breaks through homologous recombination
Which gene mutation is associated with Cowden syndrome?
PTEN
Which is the most common type of breast carcinoma associated with mutations in the PIK3CA gene?
Luminal (ER-positive) carcinomas
Which factor is associated with a higher breast cancer risk in women with denser breasts?
Mammographic breast density
Which gene mutation is associated with Peutz-Jeghers syndrome?
STK11
Which risk factor is associated with a higher risk of breast cancer due to cumulative lifetime exposure to estrogen?
All of these
Which type of breast carcinoma accounts for 70–85% of all invasive lesions?
Invasive ductal carcinoma
Where do papillary carcinomas and Paget disease of the breast originate?
Major lactiferous ducts
What does carcinoma in situ refer to?
Presence of apparently malignant epithelial cells that have not penetrated the basement membrane
Which architectural subtype of ductal carcinoma in situ (DCIS) is characterized by a uniform population of cells forming a sieve-like arrangement with rounded secondary lumens?
Cribriform variant
What is the histological appearance of cells in LCIS?
Uniform small nuclei with evenly distributed chromatin
What is the minimum diameter of a dilated structure that qualifies a lesion as ductal carcinoma in situ (DCIS)?
2 mm
Which type of breast lesion is recognized only by abnormalities seen in mammogram, such as small clusters of calcifications with irregular shapes and sizes?
DCIS
What is a prominent factor in the architectural subtype of comedocarcinoma in ductal carcinoma in situ (DCIS)?
Necrotic debris undergoing dystrophic calcification
Which variant of ductal carcinoma in situ (DCIS) features epithelial tufts with no fibrovascular cores projecting into the lumen?
Micropapillary variant
What is the main difference in the expansion pattern between ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS)?
DCIS involves spread of malignant-looking cells through the ducts and lobules to unfold the terminal duct lobular unit.
What is the distinguishing feature of the solid variant of ductal carcinoma in situ (DCIS)?
Proliferating cells completely filling and distorting the duct lumen
Which type of breast carcinoma accounts for 70–85% of all invasive lesions?
Infiltrating ductal carcinoma
Where do papillary carcinomas and Paget disease of the breast originate?
Major lactiferous ducts
Which architectural subtype of ductal carcinoma in situ (DCIS) is characterized by delicate fibrovascular cores lined by tall columnar cells extending into the duct lumen?
Papillary variant
What is a prominent factor in the architectural subtype of comedocarcinoma in ductal carcinoma in situ (DCIS)?
Dystrophic calcification
Which type of breast lesion is recognized only by abnormalities seen in mammogram, such as small clusters of calcifications with irregular shapes and sizes?
Ductal carcinoma in situ (DCIS)
What is the most common type of breast carcinoma associated with mutations in the PIK3CA gene?
Invasive ductal carcinoma
What is the characteristic gross appearance of invasive ductal carcinoma, no special type (NST)?
Hard, gray-white, gritty masses with irregular, stellate shape and small foci of calcification
What is the microscopic characteristic of invasive ductal carcinoma, no special type (NST)?
Presence of tubules or glands with visible lumens admixed with solid cords and nests of tumor cells lacking lumens
What is responsible for the clinically and grossly palpable mass, the radiologic density, and ultrasound characteristics of typical invasive ductal carcinomas?
Tumor cells inducing a fibrosclerotic response as they infiltrate the breast parenchyma
Why is invasive ductal carcinoma called 'no special type' (NST)?
Because the cancer cells have no histologic features that class them as a special type of breast cancer
Which histologic type of invasive breast carcinoma is characterized by small, minimally branched, round, well-formed structures with gaping lumens infiltrating the stroma?
Tubular carcinoma
What is the distinguishing feature of invasive lobular carcinoma on light microscopy?
Discohesive epithelial cells of low nuclear grade
What type of breast cancer is associated with small clusters of uniform, round cells with minimal amounts of cytoplasm and a grossly gelatinous appearance?
Mucinous (colloid) carcinoma
Which histologic type of invasive breast carcinoma is not as frequently associated with desmoplastic response in the adjacent stroma as ductal carcinoma?
Invasive lobular carcinoma
What type of breast carcinoma forms solid syncytium-like sheets of large cells with vesicular nuclei containing prominent nucleoli and frequent mitoses with negligible stroma?
Medullary carcinoma
What is the most common location for breast cancer metastasis?
Axillary lymph nodes
Which biological subtype is associated with bone metastases as the most frequent primary site of metastasis?
Luminal A subtype
Which subtype is mostly associated with lung metastases?
Triple negative subtype
What type of profiling has been used in addition to conventional histological classification and immunohistochemical analysis of hormone receptors to characterize breast cancers?
Genomic profiling
Which subtype of breast cancer is characterized by being ER+, PR+, HER2‒, low Ki-67, and well-differentiated with a good prognosis?
Luminal A subtype
Which subtype of breast cancer is more prevalent in certain ethnic groups, mostly triple-negative, and exhibits aggressive behavior?
Basal-like subtype
What is the distinguishing feature of luminal B tumors?
Lower ER-related gene expression
What is the usual ER and PR expression of breast cancer that is characterized by aggressive tumor growth, poor clinical outcome, and is treatable with anti-HER2 receptor antagonists?
ER- PR-
Which breast cancer subtype is most commonly associated with BRCA-1 mutations?
Basal-like subtype
Which subtype of breast cancer is characterized by higher ER-related gene expression, higher Ki-67, and tends to be PR positive or negative with a worse prognosis?
Luminal B subtype
What is the characteristic of luminal A tumors?
Low Ki-67 and well-differentiated
Which subtype of breast cancer is associated with aggressive behavior and is mostly triple-negative?
Basal-like subtype
What is the distinguishing feature of luminal B tumors?
Higher Ki-67
What is the term used for tumors that present with a swollen, erythematous breast?
Inflammatory carcinoma
In countries with established breast cancer screening programs, how do most patients present due to an abnormal mammogram?
With smaller cancers and without local or distant metastases
What is the characteristic appearance referred to as peau d'orange caused by in invasive breast carcinoma?
All of these
What is the name of the rare form of breast cancer characterized by proliferation of malignant glandular epithelial cells in the nipple areolar epidermis?
Paget disease of the breast
What does a malignant mammographic mass most often appear as?
Mass with irregular spiculated margins
What do clustered microcalcifications represent histologically?
Intraductal calcifications in areas of necrotic tumor
What is the histologic hallmark of Paget disease of the breast (PDB)?
Presence of malignant, intraepithelial adenocarcinoma cells occurring singly or in small groups within the epidermis of the nipple and/or areola
What is responsible for the clear appearance of cytoplasm in Paget cells?
Abundant content of mucus
What color does the cytoplasm of Paget cells assume with PAS staining?
Purple-magenta
What percentage of Paget disease of the breast (PDB) cases overexpress HER2?
Up to 90%
What is the hallmark of PDB's clinical presentation?
Scaly, raw, vesicular, or ulcerated lesion on the nipple spreading to the areola
What symptoms are commonly associated with Paget disease of the breast (PDB)?
Pain, burning, and/or pruritus
What percentage of patients with Paget disease of the breast (PDB) have a palpable mass in the underlying breast tissue?
About 50%
What is the origin of Paget cells in Paget disease of the breast (PDB)?
Arise from an underlying mammary adenocarcinoma
What is the hallmark of Paget disease of the breast (PDB)'s clinical presentation?
Scaly, raw, vesicular, or ulcerated lesion that begins on the nipple and then spreads to the areola
What is the main cause of the worse prognosis reported for invasive breast cancer with Paget disease?
HER2 overexpression
What are the characteristics of Paget cells in the epidermis of the nipple and/or areola?
Large cells with abundant pale cytoplasm and large nuclei with prominent nucleoli
What is the most common histologic subtype of breast cancer in men?
Invasive ductal carcinoma
What is the most common molecular subtype of breast cancer in men?
ER-positive
Study Notes
Breast Cancer: Overview and Classification
- Breast cancer is a heterogeneous disease with at least 20 different histological types described by the WHO.
- The molecular classification of breast cancers distinguishes three major subtypes: luminal, basal-like, and HER2-positive.
- In the United States, breast cancer is the most commonly diagnosed cancer in women and the second-leading cause of cancer deaths after lung cancer.
- Approximately 1% of breast cancers occur in males.
- 10% of all breast cancers are associated with inherited genetic mutations, with BRCA1 and BRCA2 responsible for 80-90% of hereditary cases.
- In sporadic breast cancer, mutational inactivation of BRCA1/2 is rare, and three main genetic pathways resulting in different types of breast carcinoma have been identified.
- Risk factors for sporadic breast cancer include gender, age, BMI, height, benign breast disease, hormonal factors, menarche/menopause, parity, age at first full-term pregnancy, family history, alcohol use, smoking, and mammographic breast density.
- Breast cancer can be categorized into in situ carcinoma and invasive carcinoma, with the major invasive tumor types including ductal carcinoma, lobular carcinoma, and special histologic types like mucinous, tubular, medullary, and papillary carcinomas.
Breast Cancer Molecular Subtypes
- Pathological analysis of breast cancer biopsy determines hormone receptor status: ER-positive (ER+), PR-positive (PR+), and HER2-positive (HER2+).
- Molecular classification of breast carcinomas has significant therapeutic and prognostic consequences.
- Luminal subtypes: Most common, characterized as luminal A (40% of breast cancers) and luminal B (20% of breast cancers), both ER-positive.
- Luminal A tumors: ER+, PR+, HER2‒, low Ki-67, well-differentiated, good prognosis.
- Luminal B tumors: ER+, lower ER-related gene expression, higher Ki-67, tend to be PR positive or negative, worse prognosis.
- HER2-enriched subtype: 10-15% of breast cancers, aggressive tumor growth, poor clinical outcome, treatable with anti-HER2 receptor antagonists.
- Basal-like subtype: 10-20% of breast cancers, more prevalent in certain ethnic groups, mostly triple-negative, aggressive behavior.
- Basal-like carcinomas may represent tumors that arise due to inherited predilection for carcinogenesis.
- Triple-negative breast cancer: High histologic grade, high mitotic index, no approved targeted treatments available other than chemotherapy.
- Most BRCA-1-mutated cancers are basal-like.
- Invasive ductal carcinoma and invasive lobular carcinoma are composed of tumors in all molecular categories.
- Triple-negative breast cancer is more commonly diagnosed in women younger than 40 years compared with hormone-positive breast cancer.
Test your knowledge about breast cancer with this quiz covering the overview, classification, and molecular subtypes of this heterogeneous disease. Learn about the different histological types, molecular classification, and subtypes such as luminal, basal-like, HER2-enriched, and triple-negative breast cancer.
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