Breast Cancer Therapeutics-Buxton Flashcards
(blank) therapy is linked to breast cancer
HRT
T or F
Breast cancer death rates are higher than those for any other cancer, besides lung cancer.
Besides skin cancer, breast cancer is the most commonly diagnosed cancer among American women. Just under 30% of cancers in women are breast cancers.
T
In TMN staging (talks about metastasis) what are the following:
T 0 to 4 indicates?
M 0 to 1 indicates?
N 0 to 3 indicates?
size
spread to organs
spread to lymph nodes and how many nodes are affected
(blank) are slightly more likely to develop breast cancer than African-American women.
However, in women under 45, breast cancer is more common in (blank) African-American women than white women.
Overall, (blank) women are more likely to die of breast cancer.
Asian, Hispanic, and Native-American women have a lower risk of developing and dying from breast cancer.
White women
African-American
African-American
where does breast cancer most commonly spread?
bone liver brain and lung
About 5-10% of breast cancers can be linked to inherited gene mutations. Mutations of the (blank) and (Blank) are most common.
WOmen with a BRCA1 mutation have a (blank) risk of developing breast cancer before age 70. For women with a BRCA2 mutation, this risk is (blank)%. What other cancers are associated with this?
BRCA1 BRCA2
BRCA1
Ovarian cancer
What do non-mutated BRCA1 and BRCA2 do?
repair double-stranded DNA breaks
About (blank) of breast cancers occur in women who have no family history of breast cancer. These occur due to (blank) that happen as a result of the aging process and life in general, rather than inherited mutations.
The most significantrisk factorsfor breast cancer are (blank and blank)
85%
genetic mutations
gender (being a woman) and age (growing older).
The (blank) consists of 10-100 acini, that drain into the terminal duct that drains into larger ducts and finally in the main duct of the lobule (or segment), that drains into the nipple
Terminal ductal lobuar unit (TDLU)
How many lobes does the breast consist of and how many lobules does each contain?
15-18 lobes
then each contain 20-40 lobules
Most invasive cancers arise from the (blank). It is also the site of origin of (blank)
TDLU (terminal ductal lobular unit)
Most calcifications in the rbeast form either within the (blank) or within the (blank)
terminal ducts (intraductal calcifications) acini (lobular calcifications)
Lobular calcification:
Calcium deposits in acini result in (blank) calcifications. When a lobule has a lot of fibrosis then what are the calcifications like?
Calcifications usually have a (blank) or (blank) distribution. Are these calcifications malignant or benign?
punctate
- calcifications are smaller and less uniform
- diffuse or scattered
- benign
What is the median age of High grade DCIS? When does this become invasive?
If it becomes invasive how do you treat them? What is the survival at 5 years?
54 years
after 3 years
-surgery, radiation, chemotherapy, prophylaxis (Tamoxifen for ER+ tumors)….
-73%
What do breast cancer patients die from?
bone, brain or liver mets
Why is breast cancer so hard to treat in the first world?
because by the time it has been detected it probaby has already entered the blood stream and traveled to distant sites i.e breast cancer patients succumb to metastatic, not local disease
How does breast cancer kill people in the third world?
Primary tumor-> exsanguination (axillary or internal mammary artery erosion) or sepsis
T or F
Primary human breast tumors suppress the growth of their own metastases
T
Without a blood supply, tumors cannot grow beyond (blank) in size. The process of blood vessel growth into a tumor, angiogenesis, is required for metastases to cause disease.
1 mm3
What is the angiogenic switch hypothesis?
that when a primary tumor is removed, distant metastases are able to attract a blood supply
What does sNDPK?
used to prevent breast cancer metastasis
- In triple negative breast cancer, it secretes sNDPK and causes endothelial cells to permit intravasation and extravasation of tumor cells. The kinase activates endothelial cells to grow as new blood vessels.
In mice carrying human triple negative tumors, blockade of sNDPK prevents (blank) in mice
lung metastases
Blocking the sNDPK pathway cures (blank) in mice.
breast cancer
Inhibiting (blank) or (Blank) activation reduced primary tumor growth and metastases while combinatorial treatment completely eradicated metastatic lung lesion.
NDPK
P2Y
What are the ER antagonists/modulators
tamoxifen raloxifene toremifene fulvestrant toremifene
What are the aromatase inhibitors?
anastrozole
exemstane
letrozole
What are the HER2 blockers?
Trastuzumab
Pertuzumab
Lapatinab
What are the blockers of DNA replication?
Doxorubicin
Epirubicin
What are the immunosuppressants used in breast cancer?
Everolimus
What are the Anti-microtubule assembly drugs?
vinblastine
eribulin
ixabepilone
What are the GnRH agonists?
-Gaserelin
What are the cell cycle interrupter drugs?
palbociclib
What are the chemotherapeutic (blockers of cell division) drugs?
Cyclophosphamide Methotrexate Paclitaxel Docetaxel Fluorouracil Capecitabine Gemcitabine
(blank) breast cancer is cancer that has spread beyond the breast. Treatment for metastatic disease usually involves some type of (blank) to try to reduce the cancer burden.
How is it usually given?
Advanced (metastatic)
chemotherapy (anti-cancer drugs)
-in combo with other drugs
How do antitumor agents (chemotherapy) work?
damage cancer cells by preventing those cells from dividing.
What are the known side effects of anti-tumor agents?
n/v, leukopenia and in some cases cardiotoxicity (doxorubicin)
What is the efficacy of chemotherapy?
What are the side effects of chemotherapy?
- decreased cancer progression
- shrinkage of tumor
SE: cardiotoxicity, leukopenia, n/v
Advanced breast cancer is (blank) but not curable. Women with advanced breast cancer have an average survival of (blank). Is chemotherapy a good treatment?
treatable
about 2 years
chemotherapy may improve survival for women with metastatic breast cancer, but it can also cause toxic side effects. i.e. it might not help and may make you feel terrible instead
T or F
there is insufficient evidence to determine if there is an impact on time to disease progression and overall survival
T
Many women like with advance disease for many years, tx is aimed at (blank) of symptoms.
The first choice tx for advanced disease is dependent on (blank) or whether the tumor overexpresses (blank) and can be treated with (blank)
alleviation rather than cure
hormone status
human epidermal growth factor receptor-2 (HER-2)
Trastuzumab (herceptin)
Is using combination chemotherapy or an intesive therapy good at treating advanced cancer?
It does reduce disease progression and shrink tumor size but adverse effects were really terrible
What is neoadjuvant therapy?
treatment given before primary therapy
Patients who have a higher risk of breast cancer recurrence are more likely to need (blank) therapy. Both prognostic and predictive factors are needed to decide which patients might benefit from adjuvant treatments.
adjuvant
Adjuvant and neoadjuvant therapies have side effects, but careful studies have shown that the risks of adjuvant therapy for breast cancer are (blank) by the benefit of treatment—that is, increasing the chance of long-term survival.
outweighed
A women may receive neoadjuvant chemotherapy for breast cancer to (blank) a tumor that is inoperable in its current state, so it can be usrgically removed
neoadjuvant
T or F
A woman whose tumor can be removed by mastectomy may instead receive neoadjuvant therapy to shrink the tumor enough to allow breast-conserving surgery
T
How does hormonal therapy work?
deprives breast cancer cells of the hormone estrogen, which many breast tumors need to grow.
What is a commonly used hormonal treatment for breast cancer?
tamoxifen (blocks estrogen activity in the body)
(blank) helps prevent the original cancer from returning and also helps to prevent the development of new cancers in the other breast; however, many women develop resistance to the drug over time.
Who do you give tamoxifen to?
Tamoxifen
-premenopausal and postemenopausal
The growth of ER postitive tumors is generally (blank) dependent
hormone
Tamoxifen when metabolized becomes (inactive/active). What cytochrome does this?
more active 4hydroxytamoxifen form
CYP2D6 and CYP3A4
Postmenopausal women may receive hormonal therapy with a drug called an (blank), either after tamoxifen therapy or instead of tamoxifen therapy.
Rather than blocking estrogen’s activity, as tamoxifen does, (blank) prevent the body from making estrogen.
aromatase inhibitor (AI) Aromatose Inhibitors
What does aromatase do?
converts testosterone to estradiol and convertes androstendione to esterone
(blank) is a non-steroidal aromatase-inhibiting drug approved for treatment of breast cancer AFTER surgery, as well as for METASTASIS in both pre and post menopausal women.
Anastrozole
Anastrozole binds (irreversibly/reversibly) to the (Blank) enzyme through competitive inhibition, inhibits the conversion of androgens to estrogens in peripheral tissues.
reversibly
aromatase
(blank) is effective as first line tx in patients with ER positive tumors but carries the risk of (blank).
anastrozole
bone fracture
Some premenopausal women may undergo ovarian ablation or suppression which greatly reduces the amount of (blank) produced by the body. What women would want to do this?
estrogen
Premenopausal women with BRCA1 and BRCA2 gene mutations who susceptibly to breast and ovarian cancer
(blank) is a monoclonal antibody that targets cancer celles that overexpress, a protein called HER2
Trastuzumab
When cancer cells overexpress HER2 protein, they are said to be HER2 positive and overexpress (blank) and grow uncontrollably as a result
EGF
Appr. (blank) percent of all breast cancers are HER2 positive
20
Clinical trials have shown that targeted therapy with (blank) in addition to chemotherapy decreases the risk of relapse for women with HER2 positive tumors
Trastuzumab
(blank) blocks DNA synthesis. It is used in the tx of metastatic breast cancer as chemotherapy when other approaches have faild
Doxorubicin
Doxorubicin is often combined with (blank) or (blank)
cyclophosphamide or a vinca alkaloid
How does doxorubicin works?
it intercalates within DNA and prevents topoimeriase II from binding the double helix together and thus inhibits cell replication
What is indicated in the tx of advanced ER/PR-positive, HER-2 negative breast cancer in postemenopausal women.
Everolimus
Everolimus is a (blank) immunosuppressant and and a mechanistic target of (blank) inhibitor which has antiproliferative and antiangiogenic properties
macrolide
Everolimus binds to (blank) binding protein-12, an intracellular protein, to form a complex that inhibits activation of (blank) activity
FK
mTOR serine-threonine kinase activity
Everolimus reduces angiogenesis by inhibiting (blank) and (blank)
vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1) expression
What are the side effects of tamoxifen?
hot flashes vaginal discharge nausea cataract development blood clot (especially if taken with chemo) uterine cancer (if still have uterus)
Since uterine cancer is increased for those taking tamoxifen, what should you do regularly?
do pelvic exams and promptly exam patients if they have any pelvic pain or any abnormal vaginal bleeding
What are the side effects of aromatase inhibitors?
hot flashes
vaginal dryness
other symp of menopause
WOmen taking aromatase inhibitors may also experience (blank) or (blank) pain during treatment
joint pain
muscle pain
Women taking aromatase inhibitors may have a higher risk of (blank) than those taking tamoxifen.
heart problems
(blank) also reduce bone densitiy and increase the risk of bone fractures
Aromatase inhibitors
When taking aromatase inhibitors should be monitored for any signs of (blank) or (Blank)
heart damange
changes in bone density
(blank) can help redue bone loss caused by aromatase inhibitors for patients at high risk of fractures
Bisphosphonates
THe most dangerous side effect of doxorubicin is (blank) leading to (blnk)
cardiomyopathy
congestive heart failure
The higher the dose, the worse the side effects
(blank) has immunosuppressant properties which may result in infection. This drug increases the risk of developing bacterial, viral, fungal, and protozoal
infections. Everolimus can lead to what dangerous problems? (x4)
Everolimus
-sepsis, respiratory failure, hepatic failure, fatality
Does everolimus cause CV problems?What are the CNS SEs of everolimus?
- yes, including angina, A fib, DVTs and PEs
- agitation, changes in behavior
What are the SEs of trastuzumab?
nausea, vomiting, hot flashes, and joint pain.
-heart problems (cardiomyopathy, but not as serious as in doxorubicin)
What is the future therapy for breast cancer?
Using viruses to kill tumor cells
thyroidal sodium iodide symporter, HIV T cells
