Exam 2 lecture 3 Flashcards
Epidemiology of breast cancer
Most common malignancy in women
2nd most common cancer death
1 in 8 life time risk
Incidence and mortality of breast cancer over time? why?
incidence and mortality has decreased. Decrease in hormone replacement therapy could contribute to this.
Risk factors for breast cancer
More than 60% of pts will NOT have any risk factors
Risk increases with age
FH
personal history
Radiation
estrogen exposure (early menarche and late menopause)
exogenous estrogen (OC/HRT)
alcohol
elevated BMI
diet
What percent of breast cancers are familial
5-10%
What are the two tumor suppresor genes? Difference between them?
BRCA-1
-increased risk of ovarian cancer (40% life time risk) and breast cancer (60%)
-high prevalence of variants in jews
BRCA-2
-greater risk of breast cancer (50%) lower risk for ovarian (20%)
-greater incidence in male breast cancer
What are the different types of breast cancer?
Invasive carcinoma
non-invasive carcinoma
Inflammatory carcinoma
Define invasive carcinoma (what are the different types)
Invasive carcinoma- has invaded beyond the basement membrane of the duct or lobule
1. invasive ductal carcinoma (IDC)- most common accounting for 70% of all breast cancer
2. Invasive lobular carcinoma (ILC)- second most common type (15%)
What are the different types of non invasive breast cancer
Ductal carcinoma in situ (DCIS)- normal cells have undergone pre-malignant genetic transformation
typically see as microcalcifications on mammogra
lobular carcinoma in situ (LCIS)- has not invaded beyond the lobule basement membrane
Define inflammatory breast cancer
Looks like an orange.
Aggressive breast cancer with poor prognosis and rapid onset (days - weeks)
Edema, rendess, warmth
How does breast cancer usually present?
> 90% of patients present with a painless lump in breast.
<10% of patients have stabbing or aching pain as 1st symptom
What is FISH testing
Tests for HER2 by detecting gene amplification
prognostic tools that are used in cancer? What is it a predictor of?
Oncotype DX
Multigene assay validated for use in newly diagnosed breast cancer, stage I or II, lymph node negative and positive, ER positive, HER2 negative
good predictor of distant recurrence and classifies a patients risk as high, medium and low risk
What number is low risk and high risk for oncotype DX? What is the treatment you would use for each?
Low risk <26= hormonal therapy only
High risk>26 or += chemo and hormonal therapy
for ER and/or PR (+), HER2-, LN(-)
did medium score group benefit from chemo? (16-25)
Did women<50 y/o and score of 16-25 benefit from chemo?
Medium score group did not benefit from chemo
women<50 and score of 16-25 did incur benefit from chemi
Low risk and high risk oncotype and treatment for LN(+) disease
Low risk- <26, hormonal therapy alone
high risk- > or = 26, chemotherapy and hormonal therapy
for both pre and post menopausal patients with LN+ disease
Sites of metastasis of breast cancer?
Bone, liver, lungs, brain, distant lymph nodes and/or skin
What are the general treatment strategies of stage I, II, IIIA breast cancer
goal is cure.
-breast conserving surgery
-modified radical mastectomy
-some II and IIIA pts may have neoadjuvant chemo
-Most women will receive adjuvant therapy after surgery
Adjuvant=after surgery
General treatment strategies for stage IIIB and IIIC
Most women will have neoadjuvant chemotherapy (before surgery) followed by MRM or lumpectomy and XRT
- adjuvant therapy as appropriate
General tx strategies of stage IV
Treatment is palliative and consists of chemo, hormonal therapy, +/- biologics and immunotherapy
XRT may be used to palliate symptoms
surgery only used for symptomatic relief
When do we use neoadjuvant therapy in stage I, IIA, III disease? What are benefits of neoadjuvant chemo
For patients with larger tumors (>1cm)
Benefits
1. allows less extensive surgery
2. allows you to see response to chemo while tumor is still intact
What to do if we have a tumor <0.5 cm which is hormone positive, lymph node negative and positive, HER2 negative
Consider adjuvant endocrine therapy
What do we do if tumor >0.5cm or 1-3 positive nodes exist for a hormone positive, lymphnode negative an dpositive, HER2 NEGATIVE drug
strongly consider 21 genes RT-PCR assay
- If 21 gene RT-PCR assay isnt done, Do adjuvant endocrine therapy or adjuvant chemo followed by endocrine therapy
- If RS<26, do adjuvant endocrine therapy
- RS>or=26, do adjuvant chemo therapy followed by adjuvant endocrine therapy
What to do with hormone positive, lymph node - and +, HER2 negative premenopausal women based on RS score
<15= adjuvant endocrine therapy +/- OS
16-25= adjuvant therapy +/- OS or adjuvant chemo followed by endocrine therapy
>25= Adjuvant chemo followed by endocrine therapy
What to do with hormone positive, lymph node - and +, HER2 POSITIVE patient based on tumor size
tumor<0.5- COnsider adjuvant endocrine therapy +/- chemo with HER2 TARGETTED THERAPY
Tumor>0.6- Adjuvant chemo with HER2 targetted therapy followed by endocrine therapy
What are adjuvant hormonal therapies
Surgical ablation (oopherectomy)
LHRH analogs (goserelin, leuprolide)
SERMs (tamoxifen)
What is adjuvant hormonal therapy with regard to surgical ablation, how does it work?
Oopherectomy- removes largest source of estrogen (ovaries)
What is a SERM used as adjuvant hormonal therapy?
tamoxifen
How does tamoxifen act as an adjuvant hormonal therapy? Toxicity?
Anti estogenic effects in breast but estrogenic properties in other tissues
Reduces risk of contracting breast cancer
Major toxicity- hot flashes, endometrial cancer, DVT
What are LHRH analogs that act as adjuvant hormonal therapies? short term and long term effects in body
leuprolide, goserelin
Initially causes increased release of FSH and LH. Long term sustained exposure inhibits LH and FSH. Inhibits estrogen production by ovaries
What are aromatase inhibitors used in? When is the exception? adverse effects? What are the drugs?
USED ONLY IN POSTMENOPAUSAL PATIENTS
(WILL need ovarian suppression if in pre menoapusal women)
fewer adverse effects, no DVT/endometrial cancer, but has no bone protective effect (like tamoxifen)
Leads to osteoporosis, hot flashes, muscle aches and pains
non-steroidal- anastrazole, letrozole
steoroidal- exemestane
Adjuvant hormone therapy for premenopausal at diagnosis? What if the patient is still premenopausal after first round of treatment? What if they are post menopausal after first round of treatment
If pre menopausal at diagnosis either
1. Tamoxifen for 5 years with or without ovarian suppression (OS)
2. aromatase inhibitor for 5 years WITH OVARIAN SUPPRESSION
if premenopausal afetr these
1. Tamoxifen for 5 more years to complete a totl of 10 years or no further endocrine therapy
If post menopausal after these
1. could consider an additional 5 years to AI to total 10 years or
2. could consider tamoxifen for 5 more years
Adjuvant hormonal therapy if post menopausal at diagnosis
Aromatase Inhibitor x 5 years then consider AI for additional 5 more years (treatment of choice)
or
Tamoxifen for 2-3 years followed by AI to complete 5 years
most common adjuvant chemotherapeutic agents? What duration is ideal for adjuvant chemotherapy
Doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil, carboplatin, paclitaxel, docetaxel
durations longe rthan 3 to 6 months of adjuvant chemotherapy do not appear to improve survival
standard chemo consists of how many cycles? How often are they given?
How many cycles do neoadjuvants have?
Standard chemo consists of 4-6 cycles given every 3 to 4 weeks.
neoadjuvant consists of 4-6 cycles
adjuvant chemotherapy regimen for HER2 negative disease
Dose dense anthracycline–>paclitaxel
Doxorubicin IV
cyclophosphamide IV
repeat every 14 days x 4 (MUST GIVE GROWTH FACTORS)
followed by paclitaxel every 14 days x 4 (must give growth factor)
or
TC
Docetaxel
cyclophosphamide
repeat every 21 days x 4
From the CALBG trial, which group got the best outcome
Group 4 receiving concurrent doxorubicin and cyclophosphamide every 2 weeks X 4 followed by paclitaxel X 4
That is why it is called dose dense anthracycline
when should you avoid anthracycline based regimen and switch to non anthracycline based regimen
Cardiac risk
If cardiac problems, can consider docetaxel and cyclophosphamide (TC) chemotherapy regimen to avoid anthracyclines.
a patient has a 1.8 cm tumor and positive lymph nodes. Patient received positive lymph nodes, they received chemo consisting of dose dense doxorubicin and cyclophosphamide x 4 cycles followed by paclitaxel x 12 weeks. WHat should patient receive as pre medication with paclitaxel and why?
- Steroid (dexamethasone)
- Diphenhydramine (H1 antagonist)
- H2 antagonist
why?
to prevent hypersensitivity reactions seen with paclitaxel solubilizer
Is HER2 positive disease better treated when HER2 targeting drugs like trastuzumab are included
Yes
Drugs to use in ER/PR negative HER2+ patient
1= APT
Paclitaxel x 12 doses
trastuzumab with 1st dose of paclitaxel
followed by trastuzumab x 11 weeks
followed by 6 mg/kg every 3 weeks to complete 1 year.
2= TCH
Docetaxel day 1
Carboplatin day 1
Trastuzumab week 1
repeat every 21 days x 6
followed by 6 mg/kg every 21 days to complete 1 year of trastuzumab
3= TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year
What is triple negative breast cancer and how do we treat it
Triple breast cancer negative ER (-), PR (-), HER2 (-)
Treated by pembrolizumab+chemotherapy
Paclitaxel days 1, 8 and 15
Carboplatin on days 1, 8, 15
Pembrolizumab day 1, repeat every 21 days x 4
followed by doxorubicin day 1
cyclophosphamide day 1
pembrolizumab every 3 weeks, repeat every 21 days x 4 followed by pembrolizumab to complete 1 year of therapy
Goal of therapy for metastatic disease? Median survival time? WHich metastases respond better to hormonal therapy?
goal- palliation
median survival is 3 years
Bone and soft tissue metastases tend to have better prognosis and respond to hormone therapy
How t treat ER/PR+, bone mets, asymptomatic, visceral disease
Hormone therapy (bone disease add bisphosphonates or denosumab). Endocrine therapy +/- bisphosphonates or denosumab
ER-/PR- symptomaic visceral disease or hormone refractory question
If her2+ add anti HER2 therapy +/-chemo
if HER2-, do chemotherapy
How to decide when to give hormonal therapy vs chemotherapy
Hormonal therapy- ER and/or PR positive disease
Long disease free survival
Prior reponse to therapy
Bone only disease
Chemotherapy- ER/OR negative
Short disease free interval
rapidly progressing disease
Disease refractive to hormonal
therapy
Link between disease free length and whether we should use hormonal or chemo therapy
Long DFS (disease free state)= likely to respond to another hormonal agent
If shorter disease free interval, hormone therapy will not work, switch to chemo
single aent vs combination in chemo
COmbination offers a higher response rate but has more toxicities.
rapid response needed due to toxicities from disease, then combination chemo can be given
What is the recommended 1st line option for HER2+ metastatic disease?
Second line
Trastuzumab
pertuzumab
docetaxel
given every 3 weeks
second line- fam-trastuzumab, deruxecan NXKI
Other than 2nd line, what else is Fa-trastuzumab used for
HER2 low patients
what is 1st line for HER2(-) women that are postmenopausal. (or premenopausal receiving ovarian suppressin.
1st line- aromatase inhibitor +CDK 4/6 inhibitor (abemaciclib, palbociclib or ribocyclib)
2nd line of treatement for HER2 (-) and postmenopausal (or premenopausal receiving ovarian suppression)
fluvestrant + CDK 4/6 inhibitor (palbociclib, tibociclib) f not used before
Everolimus +endocrine therapy (exemestance, fluvestrant)
What are some CDK 4/6 inhibitors and what to monitor with each?
Abemaciclib- Monitor CBC, gives patent diarrhes
palbociclib- CBC
ribiciclib- CBC and QT prolongation
What are some pharmacologic and non pharmacologic modalities to prevent breast cancer
Non pcol- Prophylactic mastectomy (reduces risk by 90%)
Bilateral oophorectomy (reduced estrogen exposure)
pcol- tamoxifen, raloxifen, exemestance
Pros and cons of tamoxifen
Reduces risk of invasive and non invasive breast cancer in all women, reduced skeletal events
did increase endometrial cancer
did increase risk of stroke, PE and DVT
compare prevention of raloxifen and tamoxifen
Raloxifen had fewer uterin cancers and fewer blood clots, but did not reduce risk of LCIS or DCIS like tamoxifen
Women with early stage triple negative breast cancer chemo course
Paclitaxel days 1, 8 and 15
Carboplatin on days 1, 8, 15
Pembrolizumab day 1, repeat every 21 days x 4
followed by doxorubicin day 1
cyclophosphamide day 1
pembrolizumab every 3 weeks, repeat every 21 days x 4 followed by pembrolizumab to complete 1 year of therapy
Woman with early stage ER/PR negative, HER2 positive disease chemo course
3= TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year
WOman with early stage ER/PR positive, HER2 negative disease chemo treatment course
. If RS<26, do adjuvant endocrine therapy
- RS>or=26, do adjuvant chemo therapy followed by adjuvant endocrine therapy
If we do need to give chemo, we can use
Dose dense anthracycline–>paclitaxel
Doxorubicin IV
cyclophosphamide IV
repeat every 14 days x 4 (MUST GIVE GROWTH FACTORS)
followed by paclitaxel every 14 days x 4 (must give growth factor)
or
TC
Docetaxel
cyclophosphamide
repeat every 21 days x 4
Treatment course of ER/PR positive, HER2 negative metastatic disease
hormone therapy
(aromatase inhibitor with CDK4/6 inhibitor)
What would tx option for a patient with HER2 positive, ER/PR negative metastatic disease
TCH+pertuzumab (TCHP)
Docetaxel day 1
caroplatin day 1
trastuzumab week 1
pertuzumab day 1
Followed by both trastuzumab and pertuzumab to complete 1 year
