Buxton: Breast Cancer Therapeutics

Question 1

1 in (blank) women will develop invasive breast cancer over the course of her lifetime

Answer 1

8

Question 2

Why did breast cancer incidence begin decreasing in 2000, after increasing for the previous two decades?

Answer 2

reduced use of hormone replacement therapy

**the results of the Women’s Health Initiative study suggested a connection b/w HRT & increased breast cancer risk

Question 3

Breast cancer death rates are higher than those for any other cancer, besides (blank). Besides (blank) cancer, breast cancer is the most commonly diagnosed cancer among American women

Answer 3

lung cancer; skin

Question 4

Describe the TNM staging system for breast cancer

Answer 4

T: from 0-4 indicating the tumor’s size & spread to the skin or to the chest wall under the breast (higher T means a larger tumor or wider spread to tissues near the breast)

N: from 0-3 indicating whether or not the tumor has spread to lymph nodes near the breast & how many lymph nodes are affected

M: 0 or 1 indicating whether the tumor has spread to distant organs

Question 5

Stage is expressed from 1 to 4, with 1 being (blank) and 4 being (blank)

Answer 5

least advanced; most advanced

Question 6

Where is breast cancer most likely to met?

Answer 6

bone
brain
liver
lung

Question 7

How does breast cancer disproportionately affect white women vs african american women? Which groups have the lowers risk of developing & dying from breast cancer?

Answer 7

white women more likely to develop breast cancer than AA, but in women under age 45, breast cancer is more common in AAs
Also, AA women are more likely to die of breast cancer

Asians, Hispanics, & Native American women have a lower risk!

Question 8

The actuarial risk for death from Stage I BrCa is highest for (blank) women. (blank) women have a lower actuarial risk of death that whites

Answer 8

African American; Asian

Question 9

A woman’s risk of breast cancer approximately (blank) if she has a first-degree relative (mother, sister, daughter) who has been diagnosed with breast cancer.

Answer 9

doubles

Question 10

Women with a (blank) mutation have a 55-65% risk of developing breast cancer before age 70, and often at a younger age that it typically develops.

Answer 10

BRCA1

Question 11

For women with a (blank) mutation, this risk is 45%. An increased ovarian cancer risk is also associated with these genetic mutations.

Answer 11

BRCA2

Question 12

What does non-mutant BRCA1&2 do?

Answer 12

repairs double-stranded DNA breaks

Question 13

About (blank)% of breast cancers occur in women who have no family history of breast cancer. These occur due to genetic mutations that happen as a result of the aging process and life in general, rather than inherited mutations.

Answer 13

85%

Question 14

What are the most significant risk factors for breast cancer?

Answer 14

gender

age

Question 15

Where do most invasive cancers arise from in the breast? & DCIS!

Answer 15

TDLU (terminal ductal lobular unit)

Question 16

Where do most calcifications in the breast form?

Answer 16

w/i the terminal ducts or w/i the acini

Question 17

Are radiographic densities always calcium deposits?

Answer 17

no!

Question 18

T/F: There are many false positives in radiographic studies of the breast. May lead to unnecessary treatment

Answer 18

True

Question 19

Does early detection find cancer? Why is this question controversial?

Answer 19

Ethical factors make it impossible to do any sort of natural experiment to assess the rate at which untreated DCIS evolves into invasive cancer.
Some DCIS cases either would not develop into invasive disease or would do so much later in life, perhaps never becoming clinically relevant.
Thus, DCIS that would either not progress or progress much later in life, if ever, is often considered to represent over-diagnosis.

Question 20

What do breast cancer patients die from?

Answer 20

mets to bone, brain or liver

Question 21

Did patient outcomes improve with the use of radical operation to remove primary breast tumors? Why?!

Answer 21

no - patients still developed distant mets

**Radical local treatment or surgery or radiotherapy does not have any influence on the appearance of distal disease & overall survival!!!

Question 22

Do breast tumors suppress their own metastases?

Answer 22

Studies in mice confirm that primary human breast tumors suppress the growth of their own metastases!

**with removal of the initial tumor, many mets vs leaving tumor in place (few mets)

Question 23

T/F: Tumor cells that lie dormant must acquire the ability to grow uncontrollably & attract a blood supply

Answer 23

True

Question 24

What is the angiogenic switch hypothesis that explains how tumor mets cause disease?

Answer 24

suggests that tumors produce molecules that suppress blood vessel formation, and when the primary tumor is removed, distant mets are able to gain a blood supply bc pro-angiogenic factors are then favored

Question 25

Inhibitors of (blank), which is secreted by human breast carcinoma cells, may be indicated in treatment of breast cancers. It works in mice!

Answer 25

sNDPK (which acts on P2y receptors) **holds significant potential to lead to therapies capable of reducing breast cancer mortality since blocking P2Y signaling can prevent metastasis in the mouse.

Question 26

Do chemotherapy drugs show an increase in survival? Do they have an increase in side effects?

Answer 26

fail to show a benefit in survival higher rate of side effects * *the addition of chemo to a regimen caused greater shrinkage of the tumor, but increased toxicity * *use needs to be carefully weighed against the risks

Question 27

Advanced breast cancer is treatable but not curable. Why? | What is the average survival of women with advanced breast cancer?

Answer 27

treatment is aimed at alleviated symptoms | ~2yrs

Question 28

What does the first choice of treatment for advanced disease depend on?

Answer 28

``` hormone status (ER+/-, PR+/-) HER-2+/- (tells whether the tumor can be treated with trastuzumab - Herceptin) ```

Question 29

Is using a more intensive regimen (more than one chemotherapy drug) better than the single agent treatment for women with advanced disease? What is one downside?

Answer 29

some evidence says yes! combo treatments were associated with better time to progression & response (tumor gets smaller w treatment) however, women receiving combo treatment experience more adverse effects of treatment - increased hair loss, nausea & vomiting

Question 30

What happens to QOL with increasing combo therapy?

Answer 30

survival gains with combination therapy came at the cost of a significant increase in toxicity and impact on other psychological and social factors which are known to contribute to a sense of quality of life for this group of women. **these women need to be educated on the potential negative effects of combo therapy (with small gains in survival)

Question 31

How does adjuvant therapy differ from neoadjuvant therapy?

Answer 31

adjuvant - any treatment given after primary therapy to increase the chance of long-term survival neoadjuvant - given BEFORE primary therapy

Question 32

T/F: Adjuvant and neoadjuvant therapies have side effects, but careful studies have shown that the risks of adjuvant therapy for breast cancer are outweighed by the benefit of treatment—that is, increasing the chance of long-term survival

Answer 32

true

Question 33

When would neoadjuvant treatment be warranted?

Answer 33

to shrink a tumor that in inoperable in its current state so that it can be surgically removed - possibly allows some breast-conservation

Question 34

This drug deprives breast cancer cells of estrogen, which many tumors need to grow Helps prevent the original cancer from returning & prevents the development of new cancers

Answer 34

Tamoxifen

Question 35

Antagonist of the ER in breast tissue. Acts as an agonist on ER in endometrium and is thus called a SERM. Selective ER modulator. First line adjuvant treatment in pre-menopausal patients with ER positive breast cancers. Can also be used in post-menopausal patients

Answer 35

Tamoxifen

Question 36

Postmenopausal women may receive hormonal therapy with a drug called a (blank), either after tamoxifen therapy or instead of tamoxifen therapy. Rather than blocking estrogen's activity, as tamoxifen does, these drugs prevent the body from making estrogen.

Answer 36

aromatase inhibitors

Question 37

Clinical trials suggest that (blank) may be more effective than tamoxifen in preventing breast cancer recurrence in some women.

Answer 37

aromatase inhibitors

Question 38

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 Binds reversibly to the aromatase enzyme through competitive inhibition, inhibits the conversion of androgens to estrogens in peripheral tissues. Effective as first line treatment in patients with ER positive tumors but carries the risk of bone fractures

Answer 38

Anastrozole

Question 39

Some premenopausal women may undergo this procedure, which greatly reduces the amount of estrogen produced by the body, either permanently or temporarily. Can decrease risk of breast cancer recurrence & ovarian cancer

Answer 39

oophorectomy (removal of the ovaries)

Question 40

A monoclonal antibody that targets cancer cells that overexpress, a protein called HER2. When cancer cells overexpress HER2 protein, they are said to be HER2 positive and overexpress EGF and grow uncontrollably as a result. Approximately 20 percent of all breast cancers are HER2 positive.

Answer 40

Trastuzumab

Question 41

Clinical trials have shown that targeted therapy with (blank) in addition to chemotherapy decreases the risk of relapse for women with HER2-positive tumors.

Answer 41

trastuzumab

Question 42

Blocks DNA synthesis Interacts with DNA by intercalation and inhibition of DNA biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of cell replication.

Answer 42

Doxorubicin

Question 43

Indicated in the treatment of advanced ER/PR-positive, HER2-negative breast cancer in postmenopausal women. A macrolide immunosuppressant and a mechanistic target of rapamycin (mTOR) inhibitor which has antiproliferative and antiangiogenic properties. The drug binds to FK binding protein-12, an intracellular protein, to form a complex that inhibits activation of mTOR serine-threonine kinase activity. Reduces angiogenesis by inhibiting vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1) expression

Answer 43

Everolimus

Question 44

Most common side effects of hormonal therapy?

Answer 44

hot flashes vaginal discharge cataracts

Question 45

Most serious side effects of Tamoxifen?

Answer 45

those w/ a hysterectomy are at risk of developing uterine cancer greater risk of developing a blood clot

Question 46

Side effects of aromatase inhibitors? What can they be prescribed with to prevent one adverse effect?

Answer 46

``` hot flashes vaginal dryness join/muscle pain higher risk of heart problems reduced bone density ``` can be prescribed w/ bisphosphonates to prevent bone fractures

Question 47

The most dangerous side effect of doxorubicin is (blank)

Answer 47

cardiomyopathy, leading to congestive heart failure

Question 48

Side effects of Everolimus?

Answer 48

increases the risk of developing bacterial, viral, fungal, and protozoal infections Adverse cardiovascular side effects CNS side effects including agitation and changes in behavior are possible.

Question 49

Side effects of trastuzumab? (anti-HER2)

Answer 49

nausea, vomiting, hot flashes, and joint pain. Trastuzumab can also increase the risk of heart problems. Women receiving trastuzumab should be monitored closely for any cardiomyopathy, both during and after treatment. This effect is not a prominent as the concern with doxorubicin treatment.