The Breast Flashcards
What are the two major structures of the breast?
Ducts
Lobules
What are the two types of epithelial cells of the breast?
Luminal
Myoepithelial
What are the two types of stroma of the breast?
Interlobular
Intralobular
What structural changes occur in the breast during the 1st half of the menstrual cycle?
Lobules are relatively quiescent
What happens to the structure of the breast after ovulation?
Cell proliferation and the number of acini per lobule increases
INtralobular stroma becomes edematous
What happens to the structure of the breast during menstruation?
Regression of the lobules and the disappearance of edema
What happens to the breast pre-puberty?
Lactiferous ducts are formed at birth but lobules remain underdeveloped until puberty
What happens to breast during puberty?
Ovarian ESTROGEN and PROGESTERONE induces branching of the ductal system and development of lobules
What happens to the breast during pregnancy?
Progesterone and prolactin induce complete maturation of the breast at the time of the first full-term pregnancy
Permanent increase in number and size of lobules
Oxytocin induces myoepithelial proliferation and differentiation
Following lactation, total breast size decreases due to apoptosis of epithelium and lobule atrophy
What happens to the breast during aging and menopause?
Lobular and ductal atrophy occurs
Interlobular stroma decreases in fibrous connective tissue and increase in adipose tissue content
What are the three classifications of benign breast lesions?
Non-proliferative
Proliferation without atypia
Atypical hyperplasia
What is non-proliferation benign breast lesions associated with?
Simple breast cysts
NOT associated with an increased risk of breast cancer
What is a simple breast cyst?
Fluid-filled masses derived from teh terminal duct lobular unit
What is proliferation without atypia benign breast lesions associated with?
Fibroadenoma
Small increased risk of developing breast cancer
What is atypical hyperplasia benign breast lesions associated with?
Substantial increased risk of developing breast cancer
Multifocal lesions
What is a simple fibroadenoma?
Benign solid tumors containing glandular as well as fibrous tissue
What is the etiology of simple fibroadenoma?
Not known but likely a hormonal relationship
What is the classification of simple fibroadenomas?
Proliferation without atypia
What is a complex fibroadenoma?
Associated with a slightly increased risk of cancer when multicentric proliferative changes are present
What causes fibroadenomas?
Estrogen, progesterone, and lactation during pregnancy
Some have receptors on their surface and respond to human epidermal factor (EGH) and growth hormone
What is the cause of calcified fibroadenomas seen in older patients?
Increased stromal growth
Necrosis
What is the most common type of breast carcinoma?
Adenocarcinoma
What are the two types of in situ breast carcinomas?
Ductal (DCIS) (aka introduction carcninoma)
Lobular
What are the two types of invasive breast carcinomas?
Infiltrating ductal
Invasive lobular
What is the human epidermal growth factor receptor 2 (HER2) oncogene?
Encodes for the HER2 receptors which belongs to the epidermal growth factor receptor (EGFR) family
What does the HER2 receptor do?
Controls epithelial cell growth and differentiation
Maybe angiogenesis
What percentage of human breast cancers have amplification/overexpression of HER2?
18-20%
What are the three major genetic pathways of carcinogenesis?
ER +, HER2 -
HER2 +
ER -, HER2 -
What major genetic pathway of carcinogenesis is the most common?
ER +, HER2 -
What pathway is associated with HER2 + breast carcinogenesis?
Cancers arise through a pathway that is strongly associated with amplifications of the HER2 gene
What pathway is associated with ER -, HER2 - genetic pathways of carcinogenesis?
Cancers arise through a distinct pathway that is independent of ER-mediated changes in gene expression and HER2 gene amplifications
What are triple negative breast cancer cells negative for?
Progesterone
ER
HER2
What are the dominant drivers of cell proliferation and survival in the majority of human breast cancers?
ER and/or HER2 signaling pathways
What are the clinical implications of HER2-ER crosstalk?
Resistance can occur to broth endocrine and HER2 therapies
What is Carcinoma in Situ/Ductal Carcinoma in Situ?
Malignant clonal proliferation of epithelial cells limited to ducts and lobules by the basement membrane
What are the three main categories of CIS/DCIS?
HIgh grade
Low grade
Intermediate grade
What is High grade CIS/DCIS?
Lesions lack estrogen and progesterone receptors
High proliferative rate
Overexpression of the HER2 oncogene
P53 mutations
Angiogenesis
What is low grade CIS/DCIS?
Lesions are estrogen and progesterone receptor positive
Low proliferative rate
Rarely (if ever) show abnormalities of the HER2/new or p53
What are intermediate grade CIS/DCIS?
Somewhere between low and high grade
What are the three invasive (infiltrating) breast carcinomas?
ER positive, HER2 negative - low proliferation
ER positive, HER2 negative - high proliferation
HER2 positive
ER negative, HER2 negative
What is ER positive, HER2 negative, low proliferation invasive breast carcinomas?
Respond well to hormonal treatment and long survival with metastatic disease is possible, despite the fact that incomplete responses to chemotherapy are the rule
What is ER positive, HER2 negative, high proliferation invasive breast carcinomas?
10% of these carcinomas show a complete response to chemotherapy
What is HER2 positive invasive breast carcinomas?
Second most common molecular subtype
What is ER negative, HER2 negative invasive breast carcinomas?
Basal-like triple negative carcinoma
Third major molecular structure
What mutations represent 80-90% of familial breast cancers?
BRCA1 and BRCA2
What are BRCA1 and BRCA2 genes?
Genes that produce tumor suppressor proteins which help to repair damaged DNA
What are the major risk factors for sporadic breast cancer?
Hormone Exposure!
Gender Age at menarche and menopause Reproductive history Breastfeeding Exogenous estrogens Radiation exposure Exposure to chemicals with estrogen like effects
How does hormonal exposure cause sporadic breast cancer?
By stimulating breast growth during puberty, menstrual cycles, and pregnancy thereby increasing the number of cells that can potentially give rise to a cancer
