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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
Q

Adjuvant hormonal therapy

A

surgical ablation
selective estrogen receptor modulators (SERMs)
LHRH analogs
aromatase inhibitors

26
Q

Surgical ablation

A

oopherectomy: removes largest source of estrogen
only do in premenopausal women

27
Q

SERMs

A

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
Q

LHRH analogs

A

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
Q

Aromatase inhibitors

A

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
Q

Premenopausal at diagnosis

A

tamoxifen x 5 yrs +/- ovarian suppression OR aromatase inhibitor x 5yrs + OS

31
Q

Postmenopausal at diagnosis

A

aromatase inhibitor x 5 years than consider AI for additional 5 more years

32
Q

Durations of adjuvant chemo longer than _____ do not appear to improve survival

A

3-6 months

33
Q

Adjuvant chemo regimens - HER2 negative disease

A

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
Q

Adjuvant HER2+ regimen

A

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
Q

Residual disease therapy

A

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
Q

Triple negative breast cancer (TNBC): standard of care

A

now we incorporate immunotherapy into chemo regimen (ER/PR- and HER2-)
pembrolizumab should be added into chemo regimen and continues for 1 year

37
Q

Triple negative disease

A

pembrolizumab + chemo: paclitaxel, carboplatin, pembrolizumab - complete 1 year of therapy

38
Q

Metastatic disease

A

goal of therapy is palliation
symptomatic disease: chemo
bone/soft tissue metastases tend to have better prognosis and respond to hormonal therapy

39
Q

Metastatic disease: ER/PR+, bone mets, asymptomatic visceral disease

A

–> hormone therapy –> endocrine therapy +/- bisphosphonate or denosumab if bone disease present

40
Q

Metastatic disease: ER/PR-, symptomatic visceral disease, or hormone refactory

A

HER2+ –> anti-HER2 therapy +/- chemo –> anti-HER2 therapy +/- chemo
HER2- –> chemo –> chemo

41
Q

Metastatic disease: how to decide what to give

A

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
Q

Metastatic disease: single agent vs combo

A

combination therapy offers higher response rate but has more toxicities; few trials have demonstrated improved survival with combo chemo

43
Q

Options for chemotherapy

A

single vs combination
TNBC
PD-L1 status
HER2+
BRCA status

44
Q

Preferred single agent chemo - metastatic disease

A

doxorubicin, liposomal doxorubicin, paclitaxel, capecitabine, gemcitabine, vinorelbine, eribulin, sacituzumab govitecan-hziy

45
Q

1st line option for HER2+ metastatic disease

A

trastuzumab + pertuzumab + docetaxel
trastuzumab + pertuzumab + paclitaxel

46
Q

2nd line option for HER2+ metastatic disease

A

fam-trastuzumab deruxtecan-nxki

47
Q

Fam-trastuzumab deruxtecan

A

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
Q

Triple negative breast cancer in metastatic setting

A

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
Q

Hormonal therapy in metastatic setting

A

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
Q

Cyclin dependent kinases

A

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
Q

CDK 4/6 inhibitors

A

all approved in metastatic setting
abemaciclib, palbociclib, ribociclib

52
Q

Breast cancer screening

A

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
Q

Breast cancer prevention

A

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
Q

Prevention agents

A

tamoxifen and raloxifene

55
Q

Tamoxifen prevention agent

A

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
Q

Raloxifene prevention agent

A

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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