Wk 7 Breast Cancer Flashcards
3 endocrine risk factors for breast cancer
- later age at first pregnancy
- early menarche & late menopause
- HRT
Breast cancer genetics
BRCA1 and BRCA2
-there are other less penetrant inherited genes
-all acount for less than 10%
Breast cancer genetics
BRCA1 and BRCA2
-there are other less penetrant inherited genes
-all acount for less than 10%
General breast cancer risk factors
- older age
- endocrine factors
- obesity
- diet,EtOH use, sedentary lifestyle
- genetics BRCA1, BRCA2
What is the UofU mammography recommendation?
40, yearly
What info do we want from pathology?
- histologic type
- tumor size
- grade
- margin status
- hormone receptor status
- HER2 status
What is breast tissue analogy and parts?
Like a specialized sweat gland w/ ducts and secretory glands (lobules)
-like a bunch of grapes w/ lobules = grapes, ducts = stems
Breast tissue histology at various ages
Categories of breast pathology
Breast Pathology Categories
Classification of breast lesions according to risk of invasive cancer
What meds are used for breast cancer?
For localized:
tamoxifen
anastrozole
How are estrogen and progesterone markers measured?
- immunohistochemistry
- gene expression
What is HER2 gene?
Encodes a transmembrae protein tyrosine kinase
-related to EGFR
-tumor expression may predict poor px
Ab med to know for HER2
Trastuzumab
Pertuzumab (don’t need to know)
-there are others too!
How is HER2 measured?
IHC (measures the membrane protein)
FISH (looking for extra copies of the gene)
-expressed in 15-20% of invasive breast cancers
IHC testing for HER2 expression
Adjuvent therapies, might be NED but high prevalence of recurrence
- radiation - local
- systemic therapies:
-chemo
-hormonal (ER/PR+): tamoxifen, aromatase inhibitors (only post-menopausal)
-trastuzumab (HER2+)
Adjuvent therapies, might be NED but high prevalence of recurrence
- radiation - local
- systemic therapies:
-chemo
-hormonal (ER/PR+): tamoxifen, aromatase inhibitors (only post-menopausal)
-trastuzumab (HER2+)
Research results from adjuvant radiation therapy
No change in overall deaths
but dramatic decrease in recurrences
Research effects of chemotherapy
30% reduction in recurrence
25% reduction in death
What type of breast cancer is tamoxifen used for?
ER+
What is the chemotx regimen for metastatic breast cancer?
Hormone receptor +: tamoxifen or aromatase inhibitors
Hormone receptor negative, HER2 negative = “triple negative breast cancer” - chemotherapy, many agents
HER2 + - trastuzumab or newer anti-HER2 agents
Breast cancer tx flow chart
Where does breast cancer often spread?
Bone
Mucinous Carcinoma
excellent px
-tumor cells stuck in mucous, can’t go anywhere
-usually in elderly women
What is DCIS?
Ductal carcinoma in situ
=malignant prolif of cells in ducts w/ no invasion of basement membrane
-detected as calcification on mammography that is dystophic calcification on top of necrotic cells in center
-more likely ipsilateral
*calcifications are not always malignant (ex fat necrosis and sclerosing adenosis)
-TX: surgery and tamoxifen for ER+
What is the functional unit of the breast?
Terminal duct lobular unit
-lobule has glands (produce milk)
w/ cancer, can get malignant prolif of cells in the duct (DCIS) bound by basement membrane
What are 4 main subtypes of breast cancer?
- DCIS (ductal carcinoma in situ)
- Paget’s disease of the nipple (a type of DCIS that walked it’s way up to the nipple) - IDC (invasive ductal carcinoma) - cells invade basement membrane
- LCIS (lobular carcinoma in situ)
- ILC (invasive lobular carcinoma)
What is Comedo type DCIS?
High-grade cells w/ necrosis and dystrophic calcification in center of ducts
What is Paget’s Disease of the breast?
DCIS that extends up ducts to nipple skin
-presents as nipple ulceration and erythema
-almost always associated w/ an underlying carcinoma
Invasive Ductal Carcinoma
-forms duct-like structures in desmoplastic stroma (CT grows w/ tumor as structural support)
-most common type of invasice carcinoma
-presents as mass (PE or mammo)
-advanced can -> dimpling skin or retraction of nipple
What are 4 subtypes of invasive ductal carcinoma?
- tubular carcinoma
- mucinous carcinoma
- medullary carcinoma
- inflammatory carcinoma
Tubular carcinoma
-malignant
-desmoplastic stroma
-2nd cell type is absent (should be epithelial cell and myoepithelial cell)
-good px
What makes up the breast stroma?
adipose tissue, fibrous tissue, BVs, lymphatic channels
What makes up the TDLU?
=terminal duct lobular unit
1. 2 cell layers:
-luminal cell, myoepithelial cell
2. intralobular duct
3. intralobular specialized stroma
What age range does this breast tissue represent?
pre-menarche
Age range w/ associated breast tissue?
premenopausal
Age range w/ associated breast tissue?
premenopausal
Age range/functional status associated w/ breast tissue?
lactation
Fxnal status of breast tissue?
Postmenopausal
Apocrine metaplasia and cysts
=fibrocystic changes
myoepithelial cells are present
-no atypia
-no risk of malignancy
Proliferative disease w/o atypia
Proliferative disease w/ atypia
-atypical lobular hyperplasia (ALH) is E-caderin negative
-4-5x relative lifeteim risk for developing cancer
What are 3 types of biphasic lesions?
- fibroadenoma
- phyllodes tumor
- gynecomastia
What is a fibroadenoma?
-most common benign breast tumor
-20’s-30’s
-often multiple and bilateral
-hormonally responsive
-well-circumscribed mass w/ prolif of epithelial and stromal componenets
What is gynecomastia?
-benign condition in males
-uni- or bilateral
-due to increased circulating estrogens
-endogenous causes: cirrhosis, decreased testosterone, Klinefelter syndrome or fxning testicular tumors
-exogenous: EtOH, drugs
-expansion of stroma w/ mild epithelial hyperplasia
What is Phyllodes tumor?
-affects older women
-rapid growth of stromal component w/ leaf-like architecture
-benign, borderline and malignant forms
What are the 2 categories of malignant breast neoplasms?
- in situ carcinoma (usually doesn’t present as a mass)
- invasive carcinoma
What are 3 pathways of sporadic breast cancer?
- ER+, HER2-: germline BRCA2 -> PIK3CA mutations ->atypical hyperplasia -> DCIS (50-65% of cancers)
- ER-, HER2-: germline BRCA1 mutations -> TP53 mutations -> BRCA inactivation -> DCIS (15% of cancers)
- HER2+: germline TP53 mutations -> HER2 amplification->DCIS (20% of cancers)
Lobular carcinoma in situ
LCIS (ER+, e-cadherin-)
-diffuse multicentric and bilateral
-LCIS treated as a disease marker b/c associated risk of invasive cancer similar in both breasts
-more likely both breasts
-TX: surveillance, tamoxifen
Major histological marker of invasive breast carcinoma
loss of myoepithelial cells
Grading Invasive Carcinomas
Carcinoma histology
Histology of ER positive slide
