Buxton > Breast Cancer Therapeutics Flashcards
(106 cards)
1
Q
what proportion of women will develop invasive breast cancer?
A
1 in 8
2
Q
what year marked the beginning of a decrease in breast cancer incidence?
A
2000
3
Q
what caused the breast cancer decrease?
A
reduced use of HRT after WHI results
4
Q
why are breast cancer deaths in women under 50 decreasing?
A
treatment advances
earlier detection thru screening
increased awareness
5
Q
Besides lung cancer, what cancer has highest death rates?
A
breast
6
Q
besides skin cancer, what cancer is the most commonly diagnosed cancer among American women?
A
breast
7
Q
what % of cancers in women are breast cancer?
A
just under 30%
8
Q
what 3 letters are used in breast cancer staging?
A
T
N
M
9
Q
what does T represent & what are its numerical scores?
A
0-4
describes Tumor size & spread to skin or to chest wall under breast
10
Q
what does a high T score suggest?
A
large tumor or wider spread to tissues near the breast
11
Q
what does N represent & what are its numerical scores?
A
0-3
Nodes > whether cancer has spread to nodes & how many nodes are affected
12
Q
what does M represent & what are its numerical scores?
A
0 or 1
Metastasis > whether cancer has spread to distant organs (lungs, bones)
13
Q
what is stage grouping?
A
combine the T, N, & M categories
cancers w/ similar stages tend to have similar outlook & are often treated similarly
14
Q
what is the LEAST advanced stage?
A
stage I
15
Q
what is the MOST advanced stage?
A
stage IV
16
Q
what stage is non-invasive cancer?
A
stage 0
17
Q
what stage is DCIS?
A
stage 0
18
Q
what T, N, & M stages constitute stage IV?
A
any T
any N
M1
19
Q
what are the 4 most common sites of spread of breast cancer?
A
- bone
- liver
- brain
- lung
20
Q
what race is more likely to develop cancer?
A
white
21
Q
in women UNDER 45, what racial group has higher incidences of breast cancer?
A
African-American
22
Q
what racial group is more likely to DIE of breast cancer?
A
African American
23
Q
what 3 races have a lower risk of developing & dying from breast cancer?
A
Asian
Hispanic
Native-American
24
Q
T/F: the disparity for AA women does not change when income, age, or ER positivity are factored in
A
TRUE
25
what will approximately DOUBLE a woman's risk of breast cancer?
if she has a first degree relative w/ breast cancer
26
what % of women who get breast cancer have a family member dx w/ it?
15%
27
what % of breast cancers can be linked to inherited gene mutations?
5-10%
28
what mutations are the most common in breast cancer?
BRCA1 & BRCA2
29
if you have a BRCA1 mutation, what is your risk of developing breast cancer?
55-65% risk of developing breast cancer before age 70 (younger than typical)
30
what is the risk of developing breast cancer if you have a BRCA2 mutation?
45%
| + increased ovarian cancer risk
31
how do non-mutant BRCA1 & BRCA2 work?
by repairing double-stranded DNA breaks
32
what % of breast cancers occur in women w/ no family hx of breast cancer?
85%
33
what kind of mutations do women w/o family hx of breast cancer get?
genetic mutations d/t aging &/or life, NOT INHERITED
34
what are the most significant risk factors for breast cancer?
gender (female)
| age (old)
35
what is a TDLU?
terminal ductal lobular unit
36
how many acini are in one TDLU?
10-100
37
what is the drainage of an acinus?
acinus > terminal duct > larger duct > main duct of lobule or segment > nipple
38
how many lobes & lobules does a breast have?
15-18 lobes that each contain 20-40 lobules
39
where do most invasive cancers arise from?
TDLU
40
where does DCIS originate?
TDLU
41
where do most breast calcifications form?
either w/i the terminal ducts or w/i the acini
42
where do intraductal calcifications occur?
terminal ducts
43
where do lobular calcifications occur?
acini
44
are lobular calcifications benign or malignant?
often benign
45
what gives you punctate calcifications?
calcium deposits in the acini
46
when can it be hard to differentiate intra vs inter ductal calcifications?
fibrosis can make the calcifications smaller and less uniform
47
what is the usual distribution of calcifications?
diffuse or scattered
48
T/F: radiographic densities are always Calcium deposits
FALSE
49
radiographic studies find cancer w/ a high rate of false (__?__)
positives
50
what are false positive estimates of breast cancer for initial routine (radiographic) screenings?
35-50%
51
what 2 types of DCIS are considered to represent over-diagnosis?
DCIS that would not progress
OR
DCIS that would progress much later in life
52
what is the median age for high grade DCIS?
54
| range = 22-88
53
what is the median "tumor" size of high grade DCIS?
1.4 cm
| range = 0.2-15
54
what % of pts w/ high grade DCIS had a second event at 3 yrs follow-up?
6%
of that 6%,
31% was in situ
69% was invasive
55
what is the average dz-free interval if you are dx & treated for high grade DCIS?
3.5 years
56
what is survival at 5 years of high grade DCIS? (%)
73%
57
what do breast cancer pts die from?
bone, brain, or liver mets
58
who pioneered radical mastectomy?
william stewart halsted from johns hopkins
| maybe he was Hunter's grandpa or something
59
what happened to pt outcomes in response to radical mastectomy?
pt outcomes were NOT improved
60
what does "incommodus verum" mean?
the inconvenient truth
61
T/F: radical local treatment, surgery, or adjuvant radiotherapy does NOT have any influence on the appearance of distant dz & overall survival
TRUE
62
how do women w/ untreated breast cancer in the third world die?
from consequences of the PRIMARY tumor > exsanguination d/t axillary or int mammary artery erosion, sepsis (NOT METS!)
63
do breast tumors suppress their own mets?
yep (in mice)
64
what was the mouse experiment that proved that human breast tumors in mice suppress their own mets?
if you LEAVE the tumor & allow time for mets to appear, there will be FEW mets
if you REMOVE the tumor & allow time for mets, there will be MANY mets
65
what does a hazard ratio compare?
rate of recurrence vs the control group
66
what 2 things are required for metastasis?
1. uncontrolled growth
| 2. attract blood supply
67
how big can a tumor grow if it has no blood supply?
up to 1 mm^3
68
what is angiogenesis?
BV growth into a tumor
69
what is the angiogenic switch hypothesis?
tumors produce molecules that suppress BV formation
| when you remove the primary tumor, distant mets can attract a blood supply bc pro-angiogenic factors are favored
70
what do triple negative breast cancer cells secrete?
nanoparticles containing molecules that target endothelial cells > prep the metastatic niche for tumor cell arrival
71
what does the nanoparticle kinase (sNDPK) do?
cause endothelial intravasation
cause extravasation of tumor cells
activate endothelial cells to grow as new BVs
72
if you have a mouse w/ a human triple negative tumor & you block the kinase (sNDPK pathway), what happens?
you prevent lung mets
73
how does sNDPK work (3 things)?
1. acts via P2Y receptors, Src kinase, & VEGFR-2
2. stimulates intracellular MAPK pathway
3. induces angiogenesis
74
what size of tumor can release sNDPK?
16 mm^3, which is less than 1% of lethal size (& it keeps secreting sNDPK thruout its life)
75
what happens if you inhibit NDPK activity or P2YR activation?
1. DEC primary tumor growth & mets
| 2. eradicate metastatic lung lesions
76
what does Nm23 do?
secreted from breast tumor
| promotes tumor cell migration & intravasation
77
define "advanced (metastatic) breast cancer"
cancer that has spread beyond the breast
78
what does treatment for metastatic breast dz usu involve?
some type of chemo
79
how is chemo most often given?
in combo w/ other drugs
80
how do antitumor agents work?
damage cancer cells > prevent cells from dividing
| also side FX
81
what are the known side FX of antitumor agents (there are 3)
Nausea
vomiting
leukopenia
82
what does chemo improve?
time to progression & tumor response
| debatable whether it improves survival (diff slides say diff things)
83
T/F: advanced breast cancer is treatable & curable
FALSE
treatable
not curable
84
what is the average survival of women w/ advanced breast cancer?
~2 years
85
why do you treat advanced metastatic dz?
to alleviate sx
86
what 2 things are the 1st choice of treatment for advanced dz dependent on?
1. hormone status
| 2. HER-2 status
87
T/F: women receiving combo treatment experience MORE adverse fx of treatment
TRUE
88
what should you be worried about when treating advanced breast cancer (think HB)?
QoL
| balance RX & side FX
89
what is adjuvant therapy?
any treatment given after primary therapy to inc chance of long-term survival
90
what is neoadjuvant therapy?
treatment given BEFORE primary therapy
91
what group is more likely to need adjuvant therapy?
pts who have a higher risk of breast cancer recurrence
92
what 2 types of factors are needed to decide what pts might benefit from adjuvant treatments?
prognostic & predictive factors
93
T/F: the risks of adjuvant & neoadjuvant therapy outweigh their benefits
FALSE
| benefit is better
94
why would you use neoadjuvant therapy (2 situations)?
1. to shrink an inoperable tumor so that surgery is possible
| 2. to shrink a tumor eligible for mastectomy in favor of saving the breast
95
how does hormone therapy for breast cancer work?
deprives breast cells of ESTROGEN
96
what hormone do many breast tumors need to grow?
ESTROGEN
97
the growth of ER+ tumors is generally dependent on what?
hormones (probably estrogen)
98
how is tamoxifen metabolized?
via cyt P450 CYP2D6 & CYP3A4 to 4-hydroxytamoxifen
99
which is more active: tamoxifen or its metabolite 4-hydroxytamoxifen
4-hydroxytamoxifen
100
how does anastrozole bind to the aromatase enzyme?
reversibly via competitive inhibition
| inhibits androgen conversion to estrogen in peripheral tissue
101
what operation in premenopausal women can reduce the amt of estrogen pdced by the body?
oophorectomy
| ovarian ablation or suppression
102
what pt population may decide to have their ovaries surgically removed as part of adjuvant therapy?
premenopausal women w/ BRCA1 or BRCA2 gene mutations
103
surgical removal of ovaries reduces risk of breast issues & what else?
ovarian cancer (duh)
104
why does trastuzumab work?
cancer cells overexpress HER2 + EGF + grow too much
| trastuzumab blocks HER2
105
what % of breast cancers are HER2+?
20%
106
what weird therapy is showing great promise in early trials for cancer?
VIRAL
