Breast Cancer Flashcards
Epidemiology
- Most ___ malignancy in women in US
- 2nd most common cause of cancer related ___ in women
- Lifetime risk of developing breast cancer is 1 in __ women (risk increases with age)
- common
- death
- 8
T or F: increased HRT could contribute to the decreased in mortality based on results from the WHI study.
FALSE
- decreased HRT
decreased mortality is believed to be due to better treatments for both early and advanced breast cancer as well as screening
Risk Factors
More than 60% of patients will not have any risk factors
- increasing age
- Family history - relatives with disease increases risk
- Radiation
- ___ exposure endogenous - Early menarche late menopause
- Exogenous ___ OC/HRT
- alcohol - decreases hepatic ___ of estrogen
- Prior breast ___ with proliferative histology
- ___ or age > 30 years old before first birth
- Elevated BMI/Diet
- estrogen
- estrogen
- metabolism
- biopsies
- nulliparity
Genetics
Only ~ 5-10% of breast cancers are familial
Tumor Suppressor Genes
BRCA-1
- increased risk of ___ cancer (up to 40% lifetime risk) and ___ cancers (up to 60%)
- High prevalence of variants in Ashkenazi Jews
BRCA-2
- Greater risk for breast cancer (~50%), lower risk for ovarian (~20%)
- Greater incidence in male breast cancer
- ovarian
- breast
Types: Invasive Breast Cancer
Invasive carcinoma -invaded beyond the basement membrane of the duct or lobule
1. Invasive ___ carcinoma (IDC) – Most common accounting for 70% of all breast cancers
2. Invasive ___ carcinoma (ILC) – Second most common type ~ 15% of breast cancers
- ductal
- lobular
Types: Non-Invasive Breast Cancer
Ductal carcinoma in situ (DCIS) –
- Normal cells have undergone pre-malignant genetic transformation
- Typically seen as microcalcifications on a ___
Lobular carcinoma in situ (LCIS)
- Has not invaded beyond the ___ basement membrane
- Usually, an incidental finding on biopsy specimen obtained because of symptoms or mammographic findings consistent with benign lesions
- mammogram
- lobule
Types of Breast Cancer
Inflammatory:
- ___ form of breast cancer with rapid onset and poor prognosis
- The onset is typically days and weeks
- peau d’ ___
- delayed in diagnosis because most often thought of as cellulitis, so typically treated with multiple antibiotics before the diagnosis is made
- aggressive
- orange
FISH Testing
Can test for HER2 status in 2 different ways:
1. Immunohistochemistry (IHC): Detects ___ overexpression (1+, 2+, 3+)
2. Fluorescence In-Situ Hybridization (FISH): Detects gene ___ (if gene: chromosome copies are ≥ 2 considered positive)
- protein
- amplification
Oncotype DX
- Genetic test for expression of 21 genes which gives a recurrence score
- Can determine the likelihood that the breast cancer will ___ and whether the patient is likely to benefit from ___
Multi-gene assay validated for use in:
- ___ diagnosed breast cancer
- Stage __ or __
- Lymph node negative and positive (1-3 nodes)
- ER positive
- HER2 negative
- return
- chemo
- newly
- I, II
Oncotype DX: TAILORx
Low risk (< 26) = ___ therapy only
High risk (≥ 26) = ___ and
___ therapy
- the medium score group did not benefit from chemo (score of 16 to 25)
- women < ___ years of age and score of 16-25 did have a benefit from chemo
Demonstrates ~ 85% of people can be spared chemo
- hormone
- chemo, hormone
- 50
Natural History of Breast Cancer
T or F: Breast cancer can metastasize anywhere
T
- Malignant progression involves early changes in proliferation by systemic hormones
- Sites of metastasis: Bone, liver, lungs, brain, distant lymph nodes and/or skin
Adjuvant: ___ surgery
Neoadjuvant: ___ surgery
- after
- before
Stages I, II, and IIIA-C
- Goal is ___
- Lumpectomy + XRT
- Mastectomy + XRT
stage II and IIIA patients may have
___ chemo
- Most women will receive adjuvant therapy
Stage IV
- Treatment is ___
- primarily consists of chemo, hormonal therapy, +/- biologics, +/- immunotherapy
– radiation may be used to palliate symptoms
– Surgery only used for ___ relief
- cure
- neoadjuvant
- palliative
- symptomatic
T or F: radiation is an example of a neoadjuvant therapy
FALSE:
can only use XRT after surgery
Neoadjuvant therapy
Stage I, IIA, IIB, III disease
Goal: cure
- For patients with ___ tumors (> __ cm)
Benefits of neoadjuvant chemotherapy:
» 1. Allows less extensive ___
» 2. Allows you to see ___ to chemo while the tumor is still intact
- larger
- 1
- surgery
- response
Systemic Adjuvant Therapy
Adjuvant Hormonal Therapy
Surgical ablation:
– Oopherectomy: Removes the largest source of ___
Selective Estrogen Receptor Modulators (SERMs) - ___ (Nolvadex)
- Anti-estrogenic effects in breast but estrogenic properties in
other tissues (bones, lipids)
- Reduces risk of developing contralateral breast cancer
* Dosage: 20 mg daily
* Major toxicities – ___ , endometrial cancer and DVT (uncommon)
- estrogen
- tamoxifen
- hot flashes
Adjuvant Hormonal Therapy
LHRH Analogs
- ___ (Lupron): Monthly or Q 3 months
- ___ (Zoladex implant): Monthly or Q 3 months
- Flare: Initially causes increased release of ___ and ___
- Long-term, sustained exposure inhibits ___ production by the ovaries
- Estrogen and progesterone levels fall to ___ status after 2 - 4 weeks
- leuprolide
- goserelin
- FDH, LH
- estrogen
- post-menopausal
Aromatase Inhibitors (AI)
- Use only in ___ patients
- Will need to use ___ suppression if in a premenopausal woman
- Fewer adverse effects: No DVT/endometrial cancer, no protective effect on ___ (like tamoxifen)
- Osteoporosis, hot flashes, muscle aches, and pains
anastrozole, letrozole, exemestane
- used for ___ years and then reevaluated
- postmenopausal
- ovarian
- bone
- 5 years
T or F: Durations longer than 3 to 6 months of adjuvant chemotherapy improve survival
FALSE
- do not appear to improve survival
Most common chemotherapeutic agents: (8)
- doxorubicin
- epirubicin
- cyclophosphamide
- methotrexate
- fluorouracil
- carboplatin
- paclitaxel
- docetaxel
Chemotherapy Regimens
Standard chemotherapy consists of __ - __ cycles given every __ - __weeks
- 4-6
- 3-4
Adjuvant Chemotherapy Regimens
HER 2 negative disease (2)
Dose Dense ___→ ___ (NCCN preferred)
- ___ and ___
- repeat every ___ days
- must give ___
- followed by ___
___ (NCCN preferred)
- ___ and ___
- AC, Paclitaxel
- doxorubicin, cyclophosphamide
- 14
- growth factors
- paclitaxel
- TC
- docetaxel, cyclophosphamide
Dose Dense Anthracyclines
CALBG trial
- Evaluated dose density and sequential versus combination chemotherapy questions
- Group 4 = (every __ weeks plus ___ ) = Concurrent doxorubicin and cyclophosphamide x 4 followed by paclitaxel x 4
- Sequential therapy was found to be less ___
- Patients got same amount of chemo but in ___ time (hence, dose dense)
- 2, filgrastim
- toxic
- less
If cardiac problems, can consider ___ chemo regimen to avoid anthracyclines
TC
- docetaxel, cyclophosphamide
Adjuvant HER2 (+) Regimens
3 regimens
1. APT
2. TCH
3. TCH + ___
- APT = paclitaxel and trastuzumab
- TCH = docetaxel, carboplatin, trastuzumab
- TCH + pertuzumab
Duration of Therapy
HERA (Herceptin Adjuvant Trial)
- standard of care is to complete ___ year of adjuvant trastuzumab therapy
- Now with pertuzumab, will complete ___ year
of combined trastuzumab and pertuzumab
- one
- one
Residual Disease Therapy
Katherine Trial: HER2 (+), with residual
disease found on pathology after surgery
- Received ≥ 6 cycles of ___ (TDM-1) or trastuzumab IV every 3 weeks x 14 cycles
- ___ = Risk of recurrence or death was 50% lower compared to trastuzumab alone
- New standard of care
- If no residual disease, continue trastuzumab +/- pertuzumab x total of ___ year
- ado-trastuzumab emtansine
- TDM-1
- 1
TNBC: Triple Negative Breast Cancer: Standard of Care
Immunotherapy now is incorporated into chemo regimen for TNBC
- improved OS with addition of ___ to standard chemotherapy
- should be added into
chemo regimen and continued for __
- pembrolizumab
- 1
Adjuvant Chemotherapy Regimens
Triple negative disease (1)
___ + chemo
- ___ + ___ + Pembrolizumab - Repeat every 21 days x 4, then followed by:
- ___ + ___ + Pembrolizumab - Repeat every 21 days x 4, then followed by:
- Pembrolizumab to complete __ year of therapy
pembrolizumab
- paclitaxel, carboplatin
- doxorubicin, cyclophosphamide
- 1
Metastatic Disease
Goal of therapy is ___
- Median survival is ~ 3 years
- Bone and soft tissue metastases tend to have a better prognosis and respond to ___ therapy
- Symptomatic disease: ___
* ___(+) tumors tend to be more indolent
- palliation
- hormonal
- chemo
- ER/PR
How to Decide What to Give
Hormonal Therapy
- ER/PR+
- ___ disease free survival
- prior response to therapy
- ___ only disease
Chemo
- ER/PR - disease
- ___ disease free interval
- ___ progressing disease
- Disease ___ to hormonal
therapy
- long
- bone
- short
- rapidly
- refractive
HER2+ metastatic disease:
First line
___ + ___ + ___
trastuzumab
pertuzumab
docetaxel
___ is now considered 2nd line after failure of trastuzumab / pertuzumab and a taxane
- also now an option in
those with HER2 ___ disease
Fam-trastuzumab deruxtecan
- low
Triple Negative Breast Cancer (TNBC)
___ agents have shown benefit (2)
platinum
- carboplatin
- cisplatin
Triple Negative Breast Cancer (TNBC)
___ + chemotherapy is better than chemo alone in patients with a combined positive score of ≥ 10
- if no positivity, the platinum-based chemo is preferred
combined positive score: number of PD-L1 staining cells
pembrolizumab
Hormonal Therapy: Metastatic
Common to use sequential endocrine therapies in the metastatic setting
- If a patient responds to one endocrine therapy, it is ___ they will respond to another agent
- As the response time shortens with each line of therapy, it is likely that the patient will no longer respond to endocrine therapy and then
___ should be initiated
- likely
- chemo
Hormonal Therapy: Metastatic
1st Line
- ___ inhibitor + ___ inhibitor (abemaciclib, palbociclib, or ribociclib)
2nd Line
- ___ + CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) if not used before
- ___ + endocrine therapy (exemestane, Fulvestrant, or tamoxifen)
- aromatase, CDK4/6
- fulvestrant, everolimus
Breast Cancer Prevention Trials
Three agents have been studied in the
preventative setting
- tamoxifen
- raloxifene
- exemestane
Prevention
Tamoxifen and Raloxifene are effective
- both drugs reduce breast cancer by 50%
- Raloxifene did not reduce the risk of ___ or ___ like tamoxifen
- LCIS, DCIS
