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Block 10 Week 3 > Buxton > Breast Cancer Therapeutics > Flashcards

Buxton > Breast Cancer Therapeutics Flashcards

1
Q

what proportion of women will develop invasive breast cancer?

A

1 in 8

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2
Q

what year marked the beginning of a decrease in breast cancer incidence?

A

2000

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3
Q

what caused the breast cancer decrease?

A

reduced use of HRT after WHI results

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4
Q

why are breast cancer deaths in women under 50 decreasing?

A

treatment advances
earlier detection thru screening
increased awareness

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5
Q

Besides lung cancer, what cancer has highest death rates?

A

breast

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6
Q

besides skin cancer, what cancer is the most commonly diagnosed cancer among American women?

A

breast

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7
Q

what % of cancers in women are breast cancer?

A

just under 30%

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8
Q

what 3 letters are used in breast cancer staging?

A

T
N
M

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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

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10
Q

what does a high T score suggest?

A

large tumor or wider spread to tissues near the breast

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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

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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)

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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

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14
Q

what is the LEAST advanced stage?

A

stage I

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15
Q

what is the MOST advanced stage?

A

stage IV

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16
Q

what stage is non-invasive cancer?

A

stage 0

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17
Q

what stage is DCIS?

A

stage 0

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18
Q

what T, N, & M stages constitute stage IV?

A

any T
any N
M1

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19
Q

what are the 4 most common sites of spread of breast cancer?

A
  1. bone
  2. liver
  3. brain
  4. lung
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20
Q

what race is more likely to develop cancer?

A

white

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21
Q

in women UNDER 45, what racial group has higher incidences of breast cancer?

A

African-American

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22
Q

what racial group is more likely to DIE of breast cancer?

A

African American

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23
Q

what 3 races have a lower risk of developing & dying from breast cancer?

A

Asian
Hispanic
Native-American

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24
Q

T/F: the disparity for AA women does not change when income, age, or ER positivity are factored in

A

TRUE

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25
Q

what will approximately DOUBLE a woman’s risk of breast cancer?

A

if she has a first degree relative w/ breast cancer

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26
Q

what % of women who get breast cancer have a family member dx w/ it?

A

15%

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27
Q

what % of breast cancers can be linked to inherited gene mutations?

A

5-10%

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28
Q

what mutations are the most common in breast cancer?

A

BRCA1 & BRCA2

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29
Q

if you have a BRCA1 mutation, what is your risk of developing breast cancer?

A

55-65% risk of developing breast cancer before age 70 (younger than typical)

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30
Q

what is the risk of developing breast cancer if you have a BRCA2 mutation?

A

45%

+ increased ovarian cancer risk

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31
Q

how do non-mutant BRCA1 & BRCA2 work?

A

by repairing double-stranded DNA breaks

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32
Q

what % of breast cancers occur in women w/ no family hx of breast cancer?

A

85%

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33
Q

what kind of mutations do women w/o family hx of breast cancer get?

A

genetic mutations d/t aging &/or life, NOT INHERITED

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34
Q

what are the most significant risk factors for breast cancer?

A

gender (female)

age (old)

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35
Q

what is a TDLU?

A

terminal ductal lobular unit

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36
Q

how many acini are in one TDLU?

A

10-100

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37
Q

what is the drainage of an acinus?

A

acinus > terminal duct > larger duct > main duct of lobule or segment > nipple

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38
Q

how many lobes & lobules does a breast have?

A

15-18 lobes that each contain 20-40 lobules

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39
Q

where do most invasive cancers arise from?

A

TDLU

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40
Q

where does DCIS originate?

A

TDLU

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41
Q

where do most breast calcifications form?

A

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

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42
Q

where do intraductal calcifications occur?

A

terminal ducts

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43
Q

where do lobular calcifications occur?

A

acini

44
Q

are lobular calcifications benign or malignant?

A

often benign

45
Q

what gives you punctate calcifications?

A

calcium deposits in the acini

46
Q

when can it be hard to differentiate intra vs inter ductal calcifications?

A

fibrosis can make the calcifications smaller and less uniform

47
Q

what is the usual distribution of calcifications?

A

diffuse or scattered

48
Q

T/F: radiographic densities are always Calcium deposits

A

FALSE

49
Q

radiographic studies find cancer w/ a high rate of false (__?__)

A

positives

50
Q

what are false positive estimates of breast cancer for initial routine (radiographic) screenings?

A

35-50%

51
Q

what 2 types of DCIS are considered to represent over-diagnosis?

A

DCIS that would not progress
OR
DCIS that would progress much later in life

52
Q

what is the median age for high grade DCIS?

A

54

range = 22-88

53
Q

what is the median “tumor” size of high grade DCIS?

A

1.4 cm

range = 0.2-15

54
Q

what % of pts w/ high grade DCIS had a second event at 3 yrs follow-up?

A

6%
of that 6%,
31% was in situ
69% was invasive

55
Q

what is the average dz-free interval if you are dx & treated for high grade DCIS?

A

3.5 years

56
Q

what is survival at 5 years of high grade DCIS? (%)

A

73%

57
Q

what do breast cancer pts die from?

A

bone, brain, or liver mets

58
Q

who pioneered radical mastectomy?

A

william stewart halsted from johns hopkins

maybe he was Hunter’s grandpa or something

59
Q

what happened to pt outcomes in response to radical mastectomy?

A

pt outcomes were NOT improved

60
Q

what does “incommodus verum” mean?

A

the inconvenient truth

61
Q

T/F: radical local treatment, surgery, or adjuvant radiotherapy does NOT have any influence on the appearance of distant dz & overall survival

A

TRUE

62
Q

how do women w/ untreated breast cancer in the third world die?

A

from consequences of the PRIMARY tumor > exsanguination d/t axillary or int mammary artery erosion, sepsis (NOT METS!)

63
Q

do breast tumors suppress their own mets?

A

yep (in mice)

64
Q

what was the mouse experiment that proved that human breast tumors in mice suppress their own mets?

A

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
Q

what does a hazard ratio compare?

A

rate of recurrence vs the control group

66
Q

what 2 things are required for metastasis?

A
  1. uncontrolled growth

2. attract blood supply

67
Q

how big can a tumor grow if it has no blood supply?

A

up to 1 mm^3

68
Q

what is angiogenesis?

A

BV growth into a tumor

69
Q

what is the angiogenic switch hypothesis?

A

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
Q

what do triple negative breast cancer cells secrete?

A

nanoparticles containing molecules that target endothelial cells > prep the metastatic niche for tumor cell arrival

71
Q

what does the nanoparticle kinase (sNDPK) do?

A

cause endothelial intravasation
cause extravasation of tumor cells
activate endothelial cells to grow as new BVs

72
Q

if you have a mouse w/ a human triple negative tumor & you block the kinase (sNDPK pathway), what happens?

A

you prevent lung mets

73
Q

how does sNDPK work (3 things)?

A
  1. acts via P2Y receptors, Src kinase, & VEGFR-2
  2. stimulates intracellular MAPK pathway
  3. induces angiogenesis
74
Q

what size of tumor can release sNDPK?

A

16 mm^3, which is less than 1% of lethal size (& it keeps secreting sNDPK thruout its life)

75
Q

what happens if you inhibit NDPK activity or P2YR activation?

A
  1. DEC primary tumor growth & mets

2. eradicate metastatic lung lesions

76
Q

what does Nm23 do?

A

secreted from breast tumor

promotes tumor cell migration & intravasation

77
Q

define “advanced (metastatic) breast cancer”

A

cancer that has spread beyond the breast

78
Q

what does treatment for metastatic breast dz usu involve?

A

some type of chemo

79
Q

how is chemo most often given?

A

in combo w/ other drugs

80
Q

how do antitumor agents work?

A

damage cancer cells > prevent cells from dividing

also side FX

81
Q

what are the known side FX of antitumor agents (there are 3)

A

Nausea
vomiting
leukopenia

82
Q

what does chemo improve?

A

time to progression & tumor response

debatable whether it improves survival (diff slides say diff things)

83
Q

T/F: advanced breast cancer is treatable & curable

A

FALSE
treatable
not curable

84
Q

what is the average survival of women w/ advanced breast cancer?

A

~2 years

85
Q

why do you treat advanced metastatic dz?

A

to alleviate sx

86
Q

what 2 things are the 1st choice of treatment for advanced dz dependent on?

A
  1. hormone status

2. HER-2 status

87
Q

T/F: women receiving combo treatment experience MORE adverse fx of treatment

A

TRUE

88
Q

what should you be worried about when treating advanced breast cancer (think HB)?

A

QoL

balance RX & side FX

89
Q

what is adjuvant therapy?

A

any treatment given after primary therapy to inc chance of long-term survival

90
Q

what is neoadjuvant therapy?

A

treatment given BEFORE primary therapy

91
Q

what group is more likely to need adjuvant therapy?

A

pts who have a higher risk of breast cancer recurrence

92
Q

what 2 types of factors are needed to decide what pts might benefit from adjuvant treatments?

A

prognostic & predictive factors

93
Q

T/F: the risks of adjuvant & neoadjuvant therapy outweigh their benefits

A

FALSE

benefit is better

94
Q

why would you use neoadjuvant therapy (2 situations)?

A
  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
Q

how does hormone therapy for breast cancer work?

A

deprives breast cells of ESTROGEN

96
Q

what hormone do many breast tumors need to grow?

A

ESTROGEN

97
Q

the growth of ER+ tumors is generally dependent on what?

A

hormones (probably estrogen)

98
Q

how is tamoxifen metabolized?

A

via cyt P450 CYP2D6 & CYP3A4 to 4-hydroxytamoxifen

99
Q

which is more active: tamoxifen or its metabolite 4-hydroxytamoxifen

A

4-hydroxytamoxifen

100
Q

how does anastrozole bind to the aromatase enzyme?

A

reversibly via competitive inhibition

inhibits androgen conversion to estrogen in peripheral tissue

101
Q

what operation in premenopausal women can reduce the amt of estrogen pdced by the body?

A

oophorectomy

ovarian ablation or suppression

102
Q

what pt population may decide to have their ovaries surgically removed as part of adjuvant therapy?

A

premenopausal women w/ BRCA1 or BRCA2 gene mutations

103
Q

surgical removal of ovaries reduces risk of breast issues & what else?

A

ovarian cancer (duh)

104
Q

why does trastuzumab work?

A

cancer cells overexpress HER2 + EGF + grow too much

trastuzumab blocks HER2

105
Q

what % of breast cancers are HER2+?

A

20%

106
Q

what weird therapy is showing great promise in early trials for cancer?

A

VIRAL

Block 10 Week 3 (7 decks)

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