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PHRM 864 > Lecture 11 - Breast Cancer > Flashcards

Lecture 11 - Breast Cancer Flashcards

1
Q

What is the #1 cancer in females

A

breast cancer
#2 in deaths in females

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2
Q

Lifetime risk of developing breast cancer

A

1 in 8 women

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3
Q

Reducing hormone replacement therapy has contributed to

A

a decrease in mortality of breast cancer

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4
Q

Risk factors

A

more than 60% of pts will NOT have any risk factors
increased age, family/personal history, radiation, estrogen exposure (early menarche and late menopause), exogenous estrogen (oral contraceptives/hormone replacement therapy), alcohol (decreased hepatic metabolism of estrogen), prior breast biopsies with proliferative history, nulliparity or age > 30 yrs old before first birth, elevated BMI (estrogen stores in adipose tissue), diet (soy/tofu are protective)

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5
Q

Genetics

A

only ~5-10% of breast cancers are familial

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6
Q

Genetics: tummor suppressor gene BRCA-1

A

increased risk of ovarian and breast cancers

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7
Q

Genetics: tummor suppressor gene BRCA-2

A

greater risk for breast cancer, lower risk for ovarian
greater incidence in male breast cancer

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8
Q

Types: invasive breast cancer

A

invasive carcinoma: has invaded beyond basement membrane of duct or lobule
invasive ductal carcinoma (most common), invasive lobular carcinoma (2nd most common)

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9
Q

Types: non-invasive

A

ductal carcinoma in situ
lobular carcinoma in situ

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10
Q

Ductal carcinoma in situ

A

normal cells have undergone pre-malignant genetic transformation; typically seen as microcalcifications on mammogram

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11
Q

Lobular carcinoma in situ

A

has not invaded beyond lobule basement membrane

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12
Q

Types: inflammatory

A

aggressive form of breast cancer with rapid onset and poor prognosis; onset typically days and weeks
pt present with edema, redness, warmth, inflammation, peau d’orange (orange peel look)
delayed in diagnosis bc most often thought of as cellulitis

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13
Q

FISH testing

A

can test for HER2 status in 2 different ways: immunohistochemistry - detects protein overexpression: 1+ (low tx group), 2+ (give FISH test), 3+ (give HER2 therapy); fluorescence in-situ hybridization: detects gene amplification

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14
Q

Prognostic tools: oncotype DX

A

genetic test for expression of 21 genes which gives a recurrence score; determines likelihood that breast cancer will return and whether the pt is likely to benefit from chemo
multi-gene assay validated for use in: newly diagnosed pts, stage I or II, lymph node (-) and (+), ER+, HER2(-)

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15
Q

Oncotype DX: TAILORx

A

low risk (<26) = hormonal therapy only
high risk (>/= 26) = chemo and hormonal therapy
however women < 50 with score of 16-25 did incur benefit from chemo
spares ~85% of people from getting chemo

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16
Q

General treatment strategies for stages I, II, and IIIA

A

goal is cure
breast conserving surgery: lumpectomy + XRT
modified radical masectomy
some pts have neoadjuvant chemo before surgery
most will receive adjuvant therapy after surgery

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17
Q

General treatment strategies for stages IIIB and IIIC

A

goal is cure
most women have neoadjuvant chemo followed by MRM or lumpectomy and XRT
adjuvant therapy as appropriate

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18
Q

General treatment strategies for stage IV

A

metastatic - treatment is palliative and primarily consists of chemo, hormonal therapy, +/- biologics, +/- immunotherapy
XRT may be used to palliate sx; surgery only for symptomatic relief

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19
Q

Neoadjuvant treatment

A

chemo, hormonal therapy, biologic therapy, immunotherapy

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20
Q

Adjuvant treatment

A

chemo, hormonal therapy, biologic therapy, immunotherapy, radiation

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21
Q

Metastatic treatment

A

chemo, hormonal therapy, biologic therapy, immunotherapy, radiation

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22
Q

Neoadjuvant therapy for stage I, IIA, IIB, III disease

A

goal of therapy is to achieve cure
neoadjuvant therapy: for pts with larger tumors (>1cm) - benefits: allows less extensive surgery, allows you to see response to chemo while tumor still intact

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23
Q

Systemic adjuvant therapy for stage I, IIA, IIB, III disease - hormone +, lymph node - and +, HER2 -

A

if tumor </-0.5 cm –> consider adjuvant endocrine therapy
if tumor > 0.5 cm or 1-3 positive nodes –> strongly consider 21 gene RT-PCR assay –> not done –> adjuvant endocrine therapy or chemo followed by endocrine therapy; if RS < 26 –> adjuvant endocrine therapy; if RS >/= 26 –> adjuvant chemo followed by adjuvant endocrine therapy

24
Q

Systemic adjuvant therapy for stage I, IIA, IIB, III disease - hormone +, lymph node - and +, HER2 +

A

tumor </= 0.5 cm –> lymph positive or negative –> consider adjuvant endocrine therapy +/- chemo with HER2 targeted therapy
tumor > 0.6 –> lymph positive or negative –> adjuvant chemo with HER2 targeted therapy followed by endocrine therapy

25
Adjuvant hormonal therapy
surgical ablation selective estrogen receptor modulators (SERMs) LHRH analogs aromatase inhibitors
26
Surgical ablation
oopherectomy: removes largest source of estrogen only do in premenopausal women
27
SERMs
tamoxifen: anti-estrogenic effects in breast, but estrogenic properties in other tissues (bones, lipids) used in pre and post-menopausal women toxicities: hot flashes, endometrial cancer, DVT
28
LHRH analogs
leuprolide and goserelin initially causes increased release of FSH and LH, but long-term sustained exposure inhibits LH and FSH --> inhibiting estrogen production by ovaries used in pre-menopausal
29
Aromatase inhibitors
blocks androgens --> estrogens use only in postmenopausal pts; need to use ovarian suppression (LHRH agonist) if in premenopausal fewer AEs: no DVT/endometrial cancer, not protective effect on bone (like tamoxifen has); osteoporosis, hot flashes, muscle aches/pains anastrozole, letrozole, exemestane
30
Premenopausal at diagnosis
tamoxifen x 5 yrs +/- ovarian suppression OR aromatase inhibitor x 5yrs + OS
31
Postmenopausal at diagnosis
aromatase inhibitor x 5 years than consider AI for additional 5 more years
32
Durations of adjuvant chemo longer than _____ do not appear to improve survival
3-6 months
33
Adjuvant chemo regimens - HER2 negative disease
dose dense doxorubicin and cyclophosphamide - repeat every 14 days x 4, (must give growth factors!) followed by paclitaxel if there's a risk of cardiotoxicity --> docetaxel and cyclophosphamide
34
Adjuvant HER2+ regimen
paclitaxel + trastuzumab (for people with more comorbidities or are older) docetaxel, carboplatin, trastuzumab docetaxel, carboplatin, trastuzumab, pertuzumab (harder to tolerate) use trastuzumab for 1 year following chemo
35
Residual disease therapy
katherine trial: HER2+ with residual disease found on pathology after surgery - received ado-trastuzumab emtansine (TDM-1) or trastuzumab IV TDM-1 = risk of recurrence of death was 50% lower compared to trastuzumab alone if no residual disease, continue trastuzumab +/- pertuzumab x total 1 year
36
Triple negative breast cancer (TNBC): standard of care
now we incorporate immunotherapy into chemo regimen (ER/PR- and HER2-) pembrolizumab should be added into chemo regimen and continues for 1 year
37
Triple negative disease
pembrolizumab + chemo: paclitaxel, carboplatin, pembrolizumab - complete 1 year of therapy
38
Metastatic disease
goal of therapy is palliation symptomatic disease: chemo bone/soft tissue metastases tend to have better prognosis and respond to hormonal therapy
39
Metastatic disease: ER/PR+, bone mets, asymptomatic visceral disease
--> hormone therapy --> endocrine therapy +/- bisphosphonate or denosumab if bone disease present
40
Metastatic disease: ER/PR-, symptomatic visceral disease, or hormone refactory
HER2+ --> anti-HER2 therapy +/- chemo --> anti-HER2 therapy +/- chemo HER2- --> chemo --> chemo
41
Metastatic disease: how to decide what to give
hormonal therapy: ER/PR+, long disease-free survival, prior response to therapy, bone only disease chemo: ER/PR-, short disease-free interval, rapidly progressing disease, disease refractive to hormonal therapy
42
Metastatic disease: single agent vs combo
combination therapy offers higher response rate but has more toxicities; few trials have demonstrated improved survival with combo chemo
43
Options for chemotherapy
single vs combination TNBC PD-L1 status HER2+ BRCA status
44
Preferred single agent chemo - metastatic disease
doxorubicin, liposomal doxorubicin, paclitaxel, capecitabine, gemcitabine, vinorelbine, eribulin, sacituzumab govitecan-hziy
45
1st line option for HER2+ metastatic disease
trastuzumab + pertuzumab + docetaxel trastuzumab + pertuzumab + paclitaxel
46
2nd line option for HER2+ metastatic disease
fam-trastuzumab deruxtecan-nxki
47
Fam-trastuzumab deruxtecan
HER2 low pts; don't have to be HER2+ to get drug 1+ on IHC or 2+ on IHC and lacked gene amplification interstitial lung disease SE!
48
Triple negative breast cancer in metastatic setting
platinum agents have shown benefit: carboplatin single agent - 1st line or cisplatin single agent - 1st line pembrolizumab + chemo is better than chemo alone in pts with combined positive score of >/=10; if no positivity, then platinum-based chemo is preferred
49
Hormonal therapy in metastatic setting
HER2 negative and postmenopausal or premenopausal receiving ovarian suppression 1st line: aromatase inhibitor + CDK 4/6 inhibitor (abemaciclib, palbociclib, ribociclib) 2nd line: fulvestrant + CDK 4/6 inhibitor if not used before or everolimus + endocrine therapy (exemestane, fulvestrant, tamoxifen)
50
Cyclin dependent kinases
block conversion of G1 --> S phase play an important role in drug resistance and its action can reverse some acquired resistance to previous hormone therapy
51
CDK 4/6 inhibitors
all approved in metastatic setting abemaciclib, palbociclib, ribociclib
52
Breast cancer screening
self breast exams and clinical exams have been removed from the screening guidelines breast self exam at age >/=20 years: discuss benefits and limitations clinical breast exam: not recommended mammogram: age 40-44: opportunity for annual exams, age 45-54: annual mammograms; age >/= 55 biennial mammograms
53
Breast cancer prevention
high-risk pts: discussion about risk reduction surgeries is warranted - BRCA mutations prophylactic mastectomy can decrease risk by ~90% bilateral oophorectomy can decrease estrogen exposure and decrease risk by ~50%
54
Prevention agents
tamoxifen and raloxifene
55
Tamoxifen prevention agent
decreased risk of invasive and noninvasive breast cancer in all women, decreased skeletal events, increased endometrial cancer, increased risk of stroke, PE and DVT
56
Raloxifene prevention agent
decreased incidence of breast cancer, as effective as tamoxifen, both reduced cancer by 50% had fewer uterine cancer and blood clots; did not reduced risk of LCIS or DCIS like tamoxifen

PHRM 864 (20 decks)

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