22 - Breast Cancer Flashcards
What is the problem if a patient expresses HER2 genes?
amplification/overexpression generally imparts a poorer prognosis; chemotherapy sensitivity (such as with anthracyclines, this is controversial); endocrine therapy resistance (also controversial)
What increases risk of breast cancer?
- family Hx
- early age of menarche (before 12 yo)
- late age of natural menopause (>55 yo)
- women who don’t have kids before age 30
- diet and alcohol use
- exposure to radiation
-early induced menopause (before 50 yo) decreases risk
What is human breast tissue composed of?
- connective tissue and fat with an elaborate duct system
- abundant blood supply
- not fully developed until first pregnancy
Where does breast cancer most commonly spread to ?
-lung, bones, liver and brain most commonly
What type of surgery requires post operative radiation ?
Breast conserving surgery (lumpectomy)
What is TNM staging?
T = primary tumor (number based on size usually) N = regional lymph node involvement M = metastatic spread
What does stage 4 mean?
it has spread (in breast cancer that means most likely spread to lungs, skin, bones, liver, brain)
Number of lymph nodes affected is ____ related to disease recurrence
directly
What is a tumor grade?
- How aggressive the cancer is
- Look at level of cell differentiation by evaluating amount of tubule formation, nuclear size, and mitotic count
- Grade 1 = well differentiated (more favourable)
- Grade 2 = moderately differentiated
- Grade 3 = poorly differentiated (less favourable)
What is HER2-neu associated with?
increased tumor aggressiveness
What is the treatment for DCIS (ductal carcinoma in situ) ?
Stage 0 cancer
- Surgery (generally do not need axillary lymph node dissection)
- Radiation
- Tamoxifen
- Role of aromatase inhibitors not yet established
What is the Tx for stage 1 breast cancer?
- surgery
- radiation
- adjuvant chemo +/- endocrine therapy +/- biologic therapy
What is Tx for stage 2 and 3 breast cancer?
- surgery
- radiation
- systemic chemotherapy
- management is usually a combined approach of surgery followed by chemotherapy and then radiation to try to reduce the rate of local recurrence
- additionally, many patients will receive 1-2 cycles of neoadjuvant chemo to improve surgical resectability
- hormonal therapy in estrogen receptor positive patients is certainly of value as would be any therapy directed at Her-2ne over expression
If they have bone cancer, most will get a _______ prescribed to them
bisphosphonate
If they have spread to visceral organs (lung, liver), what do we consider for Tx ?
Most oncologists will consider systemic chemotherapy with an anthracycline based regimen or taxane based regimen
What is the Tx for brain or spinal cored metastases ?
usually radiation +/- corticosteroids
If a person has 3 cm invasive ductal cancer will Her2 neu positive, do they need adjuvant therapy ?
yes
What are some possible indications for radiation therapy ?
- breast conserving surgery
- mastectomy with positive margins
- lymph node positive disease
- large tumors
- neo-adjuvant indications
*may be used in metastatic disease to treat metastatic site (bone, brain)
Describe the Tx for early stage (stage 1-3) breast cancer ?
- surgery
- radiation
- chemotherapy
- endocrine therapy
Goals of Tx: long term remission or cure
*patients may receive all of the above or any combination depending on the cancer and patient specific factors
Describe the Tx for metastatic breast cancer (stage 4)
- Typically systemic therapy
- Palliative radiation
- Balance symptom relief with chemotherapy toxicities
- Exposure patient to what they have not been given before
Goals of Tx: Palliation
Most regimens in early breast cancer are combinations of two or more drugs and contain a _______, a ______ or both
an anthracycline, a taxane, or both
Doxorubicin:
______ antibiotic
anthracycline
Doxorubicin:
Lifetime cumulative dose of ?
500-550 mg/m2 - 21 day regimen
700 mg/m2 for weekly regimen
*usually administered in a 50 mg/m2 per dose
Doxorubicin:
Usually the first agent of choice for patients with ____ disease, unless patient has received an anthracycline in the adjuvant setting.
metastatic
Doxorubicin:
Most serious dose-limiting side effect is _______
cardiomyopathy
Doxorubicin:
What do we test before to prevent cardiomyopathy ?
baseline EF
want at least EF > 50%
if below 50%, then they need more MUGA scans
Doxorubicin:
Other side effects ?
- alopecia
- neutropenia
- n/v/d
- red urine
- vesicant (blistering)
- stomatitis (inflammation of mucous membranes)
Epirubicin:
Enantiomer of the molecule, ______
doxorubicin
Epirubicin:
What is the cumulative lifetime dose?
1000 mg/m2
Epirubicin:
used in ____ setting
adjuvant
Epirubicin:
SE ?
- alopecia
- neutropenia
- n/v/d
- mucositis
- pink urine
- vesicant
Paclitaxel:
possibility of developing _____ reactions and require premedications (histamine blockade & corticosteroids)
hypersensitivity
Paclitaxel:
used in the _____ setting
adjuvant
Paclitaxel:
SE
- hypersensitivity reactions
- neutropenia
- alopecia
- arthralgias/myalgias
- peripheral neuropathy
- diarrha
Paclitaxel:
What is the pre-treatment to avoid hypersensitivity rxn?
- dexamethasone
- ranitidine
- benadryl
*corticosteroid and then H2 and H1 blockade
Docetaxel:
Place in therapy?
2nd line metastatic Tx
Docetaxel:
What do we give it with?
dexamethasone bc docetaxel can cause fluid retention syndrome
Capecitabine:
metabolized to ___
FU
Capecitabine:
Can be delivered at ___
home
Capecitabine:
Side effects
- n/v/d
- hand foot syndrome
- fatigue
- hyperbilirubinemia
What 3 drugs can block HER2-neu?
- Trastuzumab
- Pertuzumab
- Lapatinib
Trastuzumab:
Used in _____ setting
metastatic
Lapatinib:
how do you take it
once daily on empty stomach
Trastuzumab:
Can contribute to ______
cardiomyopathy
*prob don’t give with doxorubicin lol
Trastuzumab:
other SE
- possibility of infusion related reaction with first dose - fever, chills, riggers, n/v, headache, cough
- myelosuppression - more so when in combo with chemotherapy
- diarrhea
- arthralgia, bone pain
List some 4th or 5th line agents
- Vinorelbine
- Gemcitabine
- Eribulin
Risks associated with anthracycline containing regimen?
- myelosuppression
- n/v/d
- cardiotoxicity
- stomatitis
- alopecia
Risks associated with taxane containing regimen?
- myelosuppression
- hypersensitivity reactions
- peripheral neuroapthy
- fluid retention
- arthralgia/myalgias
- skin/nail changes
- total body alopecia
Risks associated with trastuzumab containing regimens?
increased cardio toxicity
If they don’t have a taxane in adjuvant setting, what should they get in metastatic setting?
taxane
What is a type of hormonal therapy used in breast cancer?
aromatase inhibitors
List some aromatase inhibitors
- anastrozole
- letrozole
- exemestatne
MOA of aromatase inhibitors
inhibit adrenal steroids converting to estrogen
Who are aromatase inhibitors going to work in?
only going to work in post-menopausal women bc in pre-menopausal women 95% of estrogen comes from ovaries
so aromatase inhibitors will only prevent 5% of estrogen
SE of aromatase inhibitors
- myalgias/arthralgias
- headaches
- nausea
- vaginal dryness
- weight gain
- hot falshes
- bone fractures
Tamoxifen:
Place in therapy ?
agent of choice in the Tx of hormone receptor positive, premenopausal breast cancer
*still can be used in certain postmenopausal hormone receptor positive breast cancer patients
Tamoxifen:
Positive effects on ?
bone and lipid levels
Tamoxifen:
Describe MOA
SERM (selective estrogen receptor modulator)
- antagonist effect in breast - inhibits ER
- agonist effect in bones, lipids, endometrium
- standard dose is 20mg PO daily
- not given concurrently with chemo
- may antagonist benefit of chemo - better outcomes when given sequentially
- can further increase VTE risk
Tamoxifen:
SE
- hot flashes
- n/v
- vaginal bleeding/discharge
- increased incidence of cataracts
- endometrial changes? cancer
- thromboembolic events (DVT or PE)
List some bisphosphonates
- Pamidronate
- Zoledronic acid
- Clodronate
- Denosumab
When is hormonal therapy of value?
if they have an estrogen receptor/progesterone receptor positive cancer
What are our options for hormonal therapy ?
- aromatase inhibitors (for post-menopausal women)
- tamoxifen
How do we treat premenopausal breast cancer?
- Tamoxifen 20mg orally once a day for 5 years remains the Tx of choice
- Risk vs benefit begins to change after 5 years
How do we treat post menopausal cancer in metastatic setting?
- Tamoxifen remains a choice for patients
- All 3 of the aromatase inhibitors have been shown to be effective either after progression on tamoxifen or as first-line
How do we treat post menopausal cancer in adjuvant setting?
- Tamoxifen still remains a choice for patients
- Anastrozole has been studied vs tamoxifen as first line therapy
- Showed that anastrozole is superior to tamoxifen
- Letrozole is superior to tamoxifen
*after 5 years we can start them on letrozole, but we don’t know how long they should be on letrozole for?
If they have thromboembolic events, what do we avoid?
tamoxifen
If they have family Hx of osteoporosis, what do we avoid?
aromatase inhibitor
If they have previous MI, what do we avoid?
aromatase inhibitors
What about if they have fibromyalgia?
keep in mind the drugs that have SE of arthralgias and myalgia (taxanes and trastuzumab)
