Breast cancer 2 Flashcards
biopsy type for breast mass
core needle biopsy
HER2 scoring system
0 to 1+ = “HER2 negative.”
2+ = “borderline,” requiring FISH
3+ = “HER2 positive.”
Classic features of cancerous breast lesion on exam
Hard + immobile + irregular borders
Skin findings that suggest inflammatory breast cancer
Erythema, thickening, or dimpling of overlying skin
Classic mammography findings of breast cancer
Soft tissue mass or density + grouped micro calcifications
MRI features of breast cancer
Irregular or spiculated mass + heterogeneous internal enhancement + enhancing internal septa
Other malignancies that can occur in the breast outside of breast cancer
(think about other tissue types in the breast)
- breast sarcoma
- paget disease
- phyllodes tumors
- lymphoma
Definition of ER-positivity
IHC for ER and PR in more than 1% of tumor cells
Definition of multifocal and multicentric disease
Multifocal = several areas within a single quadrant (so prob represents disease along an entire duct) Multicentric = multiple areas within different quadrants (so disease prob involves multiple ducts)
notation of clinical stage
cTNM = clinical stage pTNM = pathologic stage ypTNM = final pathologic stage after undergoing NAC
Test characteristics of physical exam for lymph node staging + why
Poor NPV (metastatic lymph nodes are often not palpable and reactive lymph nodes may be mistaken for mets)
- PPV = 61-84%
- NPV = 50-60%
Tamoxifen mechanism
SERM – selective estrogen receptor modulator
- Mixed ER antagonistic and agonistic properties
Palbociclib/ribociclib/abemaciclib mechanism
CDK 4/6 inhibitors
Targeted therapies for metastatic breast cancer?
- CDK 4/6 inhibitors
- PI3K
- mTOR
- EGFR
First line *regimens for HER2-negative, hormone receptor positive Stage IV BC
Endocrine therapy + targeted therapy typically
AI + CDK4/6 inhibitor
OR
Fulvestrant + CDK4/6 inhibitor
OR
Selective ER down-regulator + non-steroidal AI
Lapatinib mechanism
TKI of HER2 and EGFR pathways
Axillary imaging modality
US or MRI
Workup of stage IV disease
- Chest CT/abdomen/pelvis with contrast
- IF CNS symptoms – brain MRI
- IF back pain or cord compression symptoms – spine MRI
ER/PR/HER2 status of metastatic tumor
Definition of visceral crisis in breast cancer
Severe organ dysfunction
Preferred regimen for hormone receptor negative, HER2 positive stage IV
pertuzumab + trastuzumab + taxane
median overall survival of metastatic breast cancer
??
2 major phenotypes in metastatic breast cancer
1) Visceral metastases (aggressive phenotype)
2) Bone metastases (indolent phenotype)
Management of stage IV hormone receptor positive, HER2 negative BC
Initial treatment with endocrine therapy, unless visceral crisis, in which case chemo is used
Tumor markers that can be trended for response assessment in MBC (if elevated)?
CA 15-3
CA 27.29
CEA
What are the standardized criteria for determining response to therapy in solid tumors called?
Response Evaluation Criteria in Solid Tumors (RECIST)
Management of AI-induced arthralgia
Switch to a different AI, if persistent, then start tamoxifen
Receptor status of most BRCA 1 tumors
Triple negative
Receptor status of most BRCA 2 tumors
ER+
who needs genetic testing per NCCN
1) triple negative BC
2) male
3) Younger than age 45
4) over 51 + close relative with breast, ovarian, pancreatic cancer
5) some other indications
Adjuvant for ER+ with negative surgical margins
???
- no indication for tamoxifen (no remaining breast tissue)
Margin size to be considered negative for DCIS
2 mm (optimal surgical margin for DCIS)
Indications for post mastectomy radiation
More than 3 lymph nodes involved OR involved margins
First step following disease progression
ALWAYS BIOPSY (receptor status can change)
TDM drug type
HER2 ADC
Problem with breast MRI
high false positive rate
Surveillance modality
Mammography
Management points for localized breast cancer arising from radiation from previous treatment (Eg hodgkin’s)
- can’t reirradiate
- so have to do mastectomy (lumpectomy requires RT)
Relative contraindications to RT for breast cancer
- SLE
- scleroderma and other - connective tissue disease
negative margins broadly speaking with lumpectomy or mastectomy
*Unlike DCIS, you don’t need 2 mm of negative margins
No ink on tumors means
negative margins
Management of HER2+ via IHC
FISH testing (HER2 is intermediate so you need confirmatory testing)
Management of ER/PR positive BC after mastectomy in old patient who values quality of life + intermediate oncotype
Anastrozole, no chemo (noninferior in trials to chemo in terms of disease free survival and OS at 9 years)
When oncotype 21 is used
ER/PR positive AND node negative
Indications for RT in breast cancer
>5cm T4 disease Inflammatory breast cancer nodal involvement positive margins after mastectomy
Breast cancer management in pregnant woman
- Radiation is contraindicated
- Can give chemo during second trimester
- Can’t give tamoxifen
To know about workup in pregnant women
Blue dye is contraindicated during SLNB
ER/PR positive management in men after mastectomy
Tamoxifen (you can’t given an AI because it won’t inhibit testicular production)
Most common phenotype
ER+ (70-80% of breast cancer)
What is the goal of neoadjuvant systemic therapy?
Treat occult micrometastatic disease + surgical minimization
Why is neoadjuvant chemo important?
Surgical minimization (50% of people with node positive disease will be converted to node negative, therefore won’t need axillary dissection)
Why is neoadjuvant endocrine therapy not standard?
Can reduce tumor size, but pCR is rare so it’s not standard
Management of triple negative residual disease
chemo escalation (add capecitabine)
Therapy with more activity for ER+, HER2- negative
- Endocrine therapy has a greater impact than chemo
Neoadjuvant chemo for ER+, HER2-?
Less commonly used since pCR is rare (hence little surgical benefit)
What are the prognostic genomic assays available?
- oncotype
- mammaprint
- prosigna
What is the point of oncotype?
- ER+ derives more benefit from endocrine therapy. Oncotype predicts recurrence + response to chemo, so it is used to determine patients that will benefit and those who derive minimal benefit from chemo and for whom toxicity outweighs benefit
Supportive care for hair loss
- cold caps or scalp cooling device (highly effective in 50-60% of women)
Definition of hormone receptor positive
ER or PR greater than 1% on IHC
Management of vaginal dryness from AI’s
topical moisturizers/lubricants
Main reason for discontinuation of AI’s
MSK symptoms
Phenotype in which late relapse is more commonly seen?
ER+, seldomly seen in ER-
When to extend adjuvant endocrine therapy after 5 years?
- Stage 3 and many Stage 2
- Stage 1 on an individual basis and considering secondary prevention
- patient has tolerated treatment
How long do you extend endocrine therapy?
Typically not longer than 10 years total
How long is trastuzumab given?
1 year (duration given in trial)
Adjuvant treatment of hormone receptor positive breast cancer
- Leuprolide + aromatase inhibitor (exemestane) (ovarian suppression + an aromatase inhibitor has been shown to have a survival benefit over ovarian suppression alone)
When is breast cancer screening recommended after chest wall radiation?
25 or 8 years after completion of radiation therapy, whichever is last
*correct answer
*MRI before 30, only start mammograms at age 30
Management of woman requiring chemo who wants to preserve fertility
Delay chemo until patient can meet with fertility specialist
Fulvestrant generic name
Faslodex
Role for fulvestrant
- HR+ metastatic breast cancer with disease progression
- HR+, HER2 negative advanced BC in combination with palbociclib
Denosumab mechanism of action
RANKL inhibitor
atezolizumab indication
Stage IV, PD-L1 expression greater than 1%
Diagnosis of inflammatory breast cancer
CLINICAL (dermal lymphatic involvement not needed)
- erythema and edema of more than a third of the breast
Clinical course of inflammatory breast cancer
- very aggressive, rapidly proliferates
First step in management of inflammatory BC
- Neoadjuvant chemo (athracyclines and taxanes)
Why you can’t give AI’s in male breast cancer
- won’t inhibit testicular estrogen production
adjuvant hormonal treatment of early stage favorable histology BC
consider/offer adjuvant tamoxifen or AI
What are the favorable histology breast cancers?
- papillary
- tubular
- mucinous
Phyllodes tumor management
Primary surgery: Wide excision of the tumor (greater than 1), no axilla staging needed (no lymphatic spread)
Stage IV HER2+, ER+ treatment
Triplet therapy – docetaxel + trastuzumab + pertuzumab
- then typically drop docetaxel, and transition to hormonal therapy
- HER2 therapy markedly improves outcomes
- Currently unclear as to whether it is better to use HER2-directed therapy + chemo vs. endocrine therapy first-line
Oncotype testing is only indicated
ER+ AND *HER2 negative AND node negative
Stage IV management of ER+/HER2 -
IF no visceral crises –> initial anti estrogen therapy with letrozole +
letrozole mechanism
AI
SE to know about with CDK4/6 inhibitors
neutropenia
Treatment of patient with residual invasive breast cancer after NAC plus HER2+ targeted therapy
TDM-1
Adjuvant treatment of triple negative early stage
IF less than 0.5 cm – no adjuvant chemo
IF greater than 1 cm – adjuvant chemo
Utility of MRI for screening
- Reserved for those at high risk (Known BRCA carriers, first degree relatives of BRCA carriers, Li-Fraumeni syndrome, a few others)
- Per ASCO – Not indicated for dense breasts on exam
leuprolide MOA
- GNRH agonist (thus inhibits gonadotrope secretion of LH and fFSH, subsequently suppresses gonadal sex steroid production) (this is why used in both breast and prostate)
Treatment of cold agglutinin disease
- Cold avoidance
- rituximab
Treatment of early stage laryngeal cancer
RT alone
Why do you test for RAS in metastatic CRC?
Candidacy for EGFR inhibitors (cetuximab or panitumumab)
Palbociclib mechanism
CDK4, CDK6 inhibitor
Patients who need NAC
1) IBC
2) bulky or matted cN2 axillary nodes (cN3, CT4)
3) HER-2 positive disease
4) TNBC, if cT greater than 2 or cN greater than 1
5) large primary tumor relative to breast size in a patient who desires breast conservation
6) cN+ disease likely to become cN0 with preoperative systemic therapy
what are the CDK4/6 inhibitors
- abemaciclib
- palbociclib
- ribociclib
fulvestrant mechanism
SERM (selective ER down-regulator)
Regimens for stage IV HER2-positive disease
- pertuzumab + trastuzumab + taxane (docetaxel or paclitaxel)
IBC is
inflammatory breast cancer
Neoadjuvant management of locally advanced endocrine positive BC
Chemo rather than neoadjuvant endocrine therapy (associated with higher response rates in a shorter time period)
Role for PARP inhibitors in locally advanced
Adjuvant for triple negative with residual disease
Fulvestrant mechanism vs. tamoxifen or raloxifene
- tamoxifen or raloxifene are SERMS, fulvestrant down-regulates estrogen receptor
Why CDK4-6, PIK3CA inhibitors, and mTOR inhibitors are given with estrogen therapy
- trials have shown they mechanistically work in different ways and can enhance benefit of ET aloen
Criteria for ER positivity based on IHC
0-1% = negative
1-9% = positive BUT may be less likely to be effective
Greater than 10% = positive
Drug approved for PIK3CA positive BC
alpelisib
Taxotere generic name
Docetaxel
when to extend ET in ER+ breast cancer
- node-positive
- node-negative patients at higher recurrence risk
- benefits are modest in lower risk node-negative or limited node-positive cancers, so approach is individualized
high risk features of early stage hormone receptor-positive cancers
- high grade
- large tumor size (greater than 2 cm)
- nodal involvement
- high 21-gene recurrence score
prognostic factors for recurrence after 5 years of ET
- nodal status
- tumor size
- higher grade
- low levels of ER expression
- higher score on genomic assays
Margin required for DCIS
2 mm
Typical recurrence pattern of ER positive
- often bone recurrence
Late recurrence in breast cancer?
- not uncommon
Tumor type that develops as secondary malignancy from radiation
- sarcoma
extension of endocrine therapy has been shown to be beneficial in what disease state?
locally advanced
Benefit of tamoxifen for DCIS
Reduces ipsilateral recurrence risk, no OS benefit
First line for stage IV hormone AND HER2 positive
Taxane + pertuzumab + trastuzumab
*no endocrine therapy
CPS warranting addition of pembro to NAC in triple negative BC
None, irrespective in trial
*CPS greater than 10 in setting of metastatic disease
IBC diagnosis
Clinical
*negative skin biopsy does not rule it out
Inflammatory breast cancer management
NAC
Mastectomy w/ axillary lymph node dissection
Adjuvant radiation therapy
management of adenoid cystic carcinoma
Local therapy alone (surgery)
No adjuvant chemo
Adjuvant management of hormone receptor positive tumor with high Ki-67 (greater than 20%)
AI + abemaciclib
Third line regimens for HER2+
T-DM1 (very well tolerated. Used to be standard second line) (EMILIA trial – OS 30.9 months)
Given brain mets, tucatinib/capecitabine/trastuzumab (HER2 climb)
DCIS primary management
BCS (lumpectomy with radiation) vs. mastectomy
First line for triple negative MBC management
single agent chemotherapy – docetaxel, platinum, capecitabine
Management of locoregionally recurrent triple negative breast cancer
NAC + surgery
Common toxicity seen with pertuzumab
Diarrhea
Common cause of diarrhea after chemotherapy
Bacterial overgrowth
Benefit of adjuvant radiation and endocrine therapy for DCIS
Reduced recurrence risk, NO proven survival benefit
BI-RADS scores
1-2 = normal or benign
3 = probable benign
4 = suspicious for malignancy
5 = highly suggestive of malignancy
Staging of newly diagnosed breast cancer
Given absence of cough or hemoptysis on ROS and pulmonary exam within normal limits, no indication for CT abdomen/pelvis w/ contrast
Given LFT’s and alk phos within normal limits and absence of abdominal pain per ROS, no indication for CT abdomen/pelvis w/ contrast
Given ROS negative for bone pain and alkaline phosphatase within normal limits, no indication for bone scan
Stage IIIA or higher OR inflammatory:
Cross sectional imaging (CT C/A/P w/ contrast)
Bone scan (inpatient) vs. PET/CT (outpateint) (Preferred but limits of sensitivity as may miss very small mets)
Management of hormone receptor positive MBC in premenopausal woman
ovarian suppression + AI + CDK4/6 inhibitor
Contraindication to aromatase inhibitor
osteoporosis
contraindications to tamoxifen
- history of CVA
- fluoxetine use
Second line for hormone receptor positive MBC without PIK3CA
single-agent endocrine therapy, everolimus with endocrine therapy, or chemotherapy.
Evidence for tamoxifen for breast cancer chemoprevention
- reduces incidence of invasive breast cancer by 30%
- reduces fractures by 34%
- NO effect on mortality
Adjuvant for triple negative with residual disease
Capecitabine
T3 disease
Tumor greater than 5cm in greatest dimension
T4 disease
Tumor with extension to chest wall and or skin (ulceration or macroscopic skin nodules(
cN1 disease
Met to movable ipsilateral level I or II axillary lymph nodes
cN2 disease
Met to ipsilateral level I or II axillary lymph nodes that are clinically fixed or matted
cN3 disease
Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement; or in ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement.
pN1 disease
Micrometastases, or metastases in one to three axillary lymph nodes, and/or clinically negative internal mammary nodes with micro- or macrometastases detected by sentinel lymph node biopsy.
pN2 disease
Metastases in four to nine axillary lymph nodes, or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases.
pN3 disease
Metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; or in ipsilateral supraclavicular lymph nodes.
What are the luminal subtypes?
Histologic subtype associated with hormone receptor positive
Breast sarcoma subtype associated with radiation
Radiation-induced angiosarcoma
What is ovarian suppression?
Either GNRH agonist OR oophorectomy
Systemic therapy you can’t give in second and third trimester
HER-2 targeted drugs (oligohydramnios, pulmonary hypoplasia, skeletal abormalities, neonatal death)
CDK4-6 inhibitor that requires ECG monitoring
ribociclib
Second line preferred for metastatic triple negative
sacituzumab
ADH management
Surgical excision (exclude malignancy, excisional biopsy can diagnose DCIS or invasive carcinoma in around 30% of cases)
Management of locally advanced triple negative with pathCR
Surveillance (even including BRCA patients)
CDK4/6 inhibitor with highest rate of neutropenia + QTc prolongation
Palbociclib
Calcifications good or bad on imaging in breast?
bad
Role for PARP inhibitors in metastatic disease for BRCA mutant patients
second line
When are PARP inhibitors indicated adjuvantly
High risk (Node positive or T2 TNBC)
Drug used to treat hot flashes for breast cancer patients
oxybutynin
Adjuvant for HER2+, node negative
Taxol-trastuzumab
When is TCHP used for HER2+?
Larger tumors or Node positive
Firstline regimens for metastatic triple negative PDL1+
pembro + gem-carbo or taxane
BRCA mutation associated with male breast cancer
BRCA2 ,
IBC histologically
Clinical diagnosis based on skin findings. Still have tumor that is invasive ductal histology
NAC for inflammatory breast cancer
anthracycline and taxane based regimen
Screening interval and modality for high risk patients
annual mammogram + breast MRI
first line for metastatic HER2+
Trastuzumab + pertuzumab + taxane (docetaxel)
adjuvant for BRCA mutant TNBC with residual disease
Olaparib (NOT capecitabine)
Pathologic staging in hormone receptor includes
Oncotype
When continuation of endocrine therapy is needed to 10 years
high-risk, node positive disease
Management of papilloma
Surgical excision (commonly copresent with other premalignant features (ADH, DCIS) so need to cut out)
Adjuvant management of HER2 with path CR
continue trastuzumab with pertuzumab (Dual HER2 blockade) for total 1 year