Breast Cancer: Basic Science and Clinical Management Flashcards
What is the most common malignancy in women in the United States AND the second leading cause of cancer deaths after lung cancer
Breast
What hormone causes worsening breast cancer
Estrogen
What is the peak age for incidence in breast cancer
60-70
What are estrogen-related risks that increase likelihood of breast cancer
early menarche (age 9), nulliparity (never given birth), late menopause
What are estrogen-related risks that decrease likelihood of breast cancer
late menarche, pregnancy before age 25, bilateral oophorectomy, early menopause
What are modifiable breast cancer risk factors
Diet/obseity,, alcohol consumption, physical activity, exogenous estrogen exposure
What are the non-modifiable breast cancer risk factors
Age, gender, family history, genetic factors, endogenous hormones
What are the gene most associated with breast and ovarian cancers, what ways would mutations be handled if discovered early
BRACA1 and BRCA2/ proplylactic mastectomy or oophorectomy, chemoprevention with tamoxifen or raloxifene
What does BRCA do
Repair DNA damage
What are the screening recomendations for clinical breast exam, mammogram, MRI, Breast awareness
Every 1-3 years (25-39) or every year once 40 and older, annually at age 40 and older, women with greater than 20% lifetime risk or BRCA mutations, age25 and older
What is the gold standard for breast cancer detection
MMMOGRm
What is the most common breast cancer
Invasive ductal carcinoma
T/F: If there are a large number of lymph nodes involved there is an increase in risk of recurrence
True
What marker is used to predict the tumor cell proliferation
Ki-67
What hormone receptors are important for knowing response to breast cancer in patient
estrogen and progesterone receptors
What gene is overexpressed 25-35% of the time and may mark how aggressive the tumor is
HER2
What is TNM classification
T: tumor size
N: Nodal status
M: Distant metastasis
What is the staging classificaion of breast tumor
Stage 1: Tumor confined to the breast
Stage 2:Tumor has spread to movable ipsilateral axillary nodes
Stage 3: Tumor has spread to the superficial structures of the chest wall
Stage 4: Metastasis
What are other considerations needed for breast cancer characteristics
Tumor grade: a measurement of how much the cancer cells look like normal cells
Estrogen and progesterone receptor status
HER2 status
Oncotype DX score
T/F: All stages of breast cancer have a cure
False: Stage 1 and stage 2 is highly curable while stage 3 does have a cure but STAGE 4 IS NOT CURABLE
What part of the estrogen receptor plays a large part in whether a ligand binds, what happens when a ligand binds
Helix 12, alpha helix snaps shut trapping the ligand in place while attracting co activators to aid in transcription
What are actions of the coactivators
Binds to the LBD of the receptor when agonsits are bound, histone acetyltrasnferase activity, recruit ubiquittous coactivator for several transcription factors
What do corepressors do, how are they recurited
Histone deacetylase activity, antiestrogen binds to prevent transcriptional activation
T/F: Estrogen receptor Alpha deals with breast cancer
True
What are the other ways estrogen receptor can signal
Indirect tethering to other transcription factors. membrane-initiatied or non-genomic signaling (phosphorylation cascades), ligand-independent (initiated through growth factor receptor)
What are the three types of endocrine therapy that target estrogen or the receptor
SERM: blocks the ER in the breast and prevents signaling, SERD: removes the ER by degredation, Aromatase inhibitors: blocks the synthesis of estrogen
What the SERM used in breast cancer, how
Tamoxifen: all stages but principally used to treat premenopausal patients
Raloxifene: breast cancer prevention
Tormifene: treatment of metastatic breast cancer
T/F: All of the SERMs have different efficacy
False: Toremifene and Raloxifene do not have improved efficacy over tamoxifen
What are the adverse effects of tamoxifen
Hot flahses, increased bone density, endometriosis (endometrial cancer)
What are the aromatase inhibitors, when are they used
Arimidex, femara, aromasin/ for women who have gone through menopause
What do aromatase inhibitors do
Block convervsion of testosterone to estrogen through inhibition of aromatase
What is the mutation that is associated with aromaste inhibitor therapy, what happens
ESR1, result in decreased sensitivity to ER antagonists including tamoxifen and fulvestrant abd stimulation of the receptor when no estrogen is present
What is the on SERD approved
Fulvesterant
