Breast cancer Flashcards
What are the two main cncers that have the expression of HER-2?
xcxcxcxcxc
breast cancer and Gastric cancer
Receptors we can see in breast cancer?
HER-2
ER
PR
What is the MOA of Trastuzumab?
Binds EC portion of HER-2 receptor, blocking typically and almost exclusively the homodimerization
Trastuzumab works better in association with another drug, which one?
Pertuzumab
MOA of Pertuzumab?
blocks heterodimerization of HER2-HER3
What drugs represent the first line of treatment for metastatic HER-2 positive tumors?
Trastuzumab and Pertuzumb
What treatment can we give for post-menopausal patient, metastatic HER-2 positive?
Trastuzumab + Aromatase inhibitors
An important side effect of Trastuzumab ?
Cardiotoxicity, in the form of heart failure.
what is the mechanism that can cause heart failure with trastuzumab?
Down regulates Neuregolin-1
what type of drug is Ado-Trastuzumab ?
Chemically bound Trastuzumab to DM1 (Emtansine)
Cytoskeleton drug
Does pertuzumab binds to the same receoptor site as trastuzumab ?
No
cyclins 2/4/6 regulate which phase of the cell cycle?
Transition phase from G1 to S
MOA of cyclin 4/6 inhibitors ?
Inhibiting the cyclin D, it blocks the activity of E2F (transcription factor)
Indication of Lapatinib?
- HER-2 positive breast K, that became resistent to Trastuzumab (associated to Capecitabin)
- Pr+ breast K, associated to Aromatase inhibitors
What kind of agent is DM1 ?
Chemotherapeutic
can we use DM-1 alone?
No, it is too toxic
In what process does BRCA 1/2 proteins are involved?
DNA repair
What is one of the principal risk factors for Mammarian carcinoma?
Estrogenic stiumuli
which drug is able to reduce by 38% the incidence of mammary carcinoma?
Tamoxifen 20 mg/d
secondary prevention in breast K?
Mammography screening
In asymptomatic women between the ages of 50-69, every two years
How screening for breast K is performed in younger women ?
Ultrasound, in familial cases and px with risk factors
younger patients have a denser tissue (glandular)
What is the principal prognostic factor in breast K?
Metastasis to axilary lymph nodes
When do we have an elevated risk of relapse in axilary lymph node metastasis from breast K?
4 or more lymph nodes
Which protein are we looking for in immunohistochemistry of breast K, that the higher it’s concentration, the higher the chance for relapse?
Ki67
Does high percentage of hormonal receptors in breast (ER, PR) improve or worsens prognosis?
Improves, it lowers the risk of relapse.
Which breast tumors are more chemo-sensitive but less endo-sensitive ?
Tumors with high proliferation index (Ki67)
What is luminal A breast K?
Positive for ER and/or PgR
Negative for HER2
What is luminal B breast K?
Positive for ER and/or PgR
Positive for HER2
What is Basal like breast K?
Triple negative
What is HER2-like breast K?
HER2 positive and negative ER and PgR
Which drug for breast cancer is the most frequently used in pre-menopause?
Tamoxifene
What is the indication for Tamoxifene ?
is it pre/post menopausal?
both prevention and treatment of breast K
ER+, pre menopause
what is the MOA of Tamoxifene ?
Inhibiting the AF2 domain
what is the most important side effect of Tamoxifen?
Increased risk of endometrial cancer, by stimulating the proliferation of the uterine mucosa
How efficient are the aromatase inhibitors?
Like tamoxifen, but without the estrogenic activity on the endometrial mucosa.
what generation is Anastrazole (aromatase inhibitor) ?
III
Main indication for aromatase inhibitors?
ER positive breast cancer
Important side effects of Aromatase inhibitors ?
Osteoporosis
Arthralgia (especially in the small articulations)
what is the purpose of systemic neoadjuvant therapy?
Reduce the dimensions of the tumor before the surgical operation
Targeted therapies in metastatic breast cancer?
“TAAL”
Trastuzumab
Ado-trastuzumab
Anti-VEGF
Lapatinib
When do we use aromatase inhibitors? post/pre menopause?
post menopausal
