Breast Cancer (2) Flashcards
What is the biggest risk factor for breast cancer?
Female gender
(note - males do get breast cancer, but it is rare and tends to be more invasive and aggressive in males)
Breast cancer risk factors
-weight, exercise (overweight = more adipose tissue and adipose tissue secretes estrogen, therefore, particularly greater risk in post-menopausal women)
-alcohol (limit to 1 drink for females, 2 for males)
-longer menstruation period… starting period before age 12, or getting menopause after age 55 (more periods = more exposure to estrogen)
motherhood:
-never having children/breastfeeding (having children decreases risk because you don’t get your period during pregnancy and breastfeeding - limits estrogen exposure)
-having children after age 35 (genetic damages occur to cells that the body cannot correct- linked to increase risk of breast cancer)
family history/genetics:
-Positive BRCA 1 or 2 gene
-relatives with breast cancer
How is breast cancer detected?
Breast self exams
-done monthly
-begins once you get your period
-look/feel the breast/nipple- look for changes, discharge
Breast imaging studies
-mammogram done annually
-begins at age 40-45
-mammography is done first, then if something is detected ultrasound for more evaluation, then MRI (or if dense breast tissue, start with MRI annually), then biopsy
Breast cancer susceptibility genes
BRCA 1 and BRCA 2
BRCA is a tumor suppressor gene (repair double stranded DNA breaks)
If “positive” (+) … means they inherited a mutation, if either gene is mutated, it will not suppress cancer growth
In general, the female risk of breast cancer is 12%, if BRCA positive it goes up to 70%
Certain ethnic groups are at higher risk for BRCA positive genes - Ashkenazi Jewish, non-Ashkenazi Jewish, Hispanic
What is “in situ” carcinoma
This is a in between stage- the cancer is just in the breast, has not spread yet
It is just in the breast (in the lobe or duct) - most patients will progress to invasive carcinoma, which will be able to spread
Molecular profiling of breast cancer (4 types of breast cancer)
Once patient is diagnosed, biopsied cells undergo genetic testing to see if they are hormone receptor (estrogen and progesterone) positive and HER2 positive - because this will determine the type of treatment used
Most common: Hormone receptor (+), HER2 (-)
-best prognosis
Hormone receptor (+), HER2 (+)
-10% of breast cancer
-HER2+ = more aggressive cancer
Hormone receptor (-), HER2 (+)
-5% of breast cancer
-HER2+ = more aggressive cancer
Hormone receptor (-), HER2 (-) … triple negative
-worst prognosis
-13% of breast cancer
-only treatment is traditional chemotherapy
ER+ vs PR+ cancer
Most (~70%) of cancers are estrogen receptor (ER) +
Progesterone receptor (PR) + tumors are also usually ER+
ER+/PR+ tumors are MORE responsive to antiestrogen therapy than ER+/PR- tumors
ER+/PR- are more common in women over 50 years old- worse prognosis because medications that block estrogen don’t work as well
HER2+ breast cancer
HER2 (human epithelial receptor) allows the tumor to grow at a more rapid rate - so HER2+ cancer is more aggressive and has a decreased survival and response to chemo rate and increased relapse and metastasis rate
Targeted therapy is used for these patients
All patients with new breast cancer diagnosis should be tested for this
Clinical presentation of breast cancer
Most of the time it presents as a painless mass
(so if you feel something and it hurts, that is actually a good indication that it is not cancer)
In some rarer cases there may be stabbing/aching pain
Nipple discharge and/or dimpling and/or retraction (changes from how it was before)
Common sites of breast cancer metastasis
Most common site = bone
Others:
Lungs and lymph nodes (close)
Liver (through blood, liver filters blood)
Brain (cannot use cooling caps!)
Available therapies for breast cancer (6)
- SERMs
- Aromatase Inhibitors (AIs)
- Traditional chemotherapy
- Monoclonal antibodies
- Cyclin dependent kinase inhibitors (CDK4/6)
- mTOR inhibitors
2 types of non-invasive breast cancers and management
Lobular Carcinoma in situ
-cancer of the lobes (the tubes that carry the milk)
-not as invasive as ductal
-observation + can use tamoxifen (gold standard) or AI to prevent invasive cancers
Ductal Carcinoma in situ
-cancer of the milk ducts (where milk is produced)
-more aggressive/more likely to become invasive than lobular
-requires lumpectomy (removal of lump) + breast radiation or total mastectomy + reconstruction + tamoxifen (or AI) (for 5 years)
General treatment approach for breast cancer
(neoadjuvant therapy if HER2+) –> surgery –> chemotherapy –> radiation
When is neoadjuvant therapy used for breast cancer?
If they are HER2+ (trastuzumab)
HER2+ neoadjuvant therapy
Before surgery - if HER2+ give trastuzumab
-this binds to the HER2 receptor and blocks growth signals
-HER2+ cancer is more aggressive, so we want to start with this agent to block tumor growth, then remove it (it can take a few weeks to get into surgery, so we don’t want to wait and let the tumor grow during that time)
given every 3 weeks for 4 neoadjuvant therapy cycles
When is a curative vs palliative approach taken?
Non-invasive and invasive breast cancer –> cure
Metastatic breast cancer (stage 4) –> palliation, prolong life, increase QOL, median survival is 3 years
Adjuvant therapy approach if ER(+)/PR(-), ER(-)/PR(+) ER(+)/PR(+) (hormone receptor +) AND HER2+
Trastuzumab + chemotherapy + endocrine therapy
Adjuvant therapy approach if ER(+)/PR(-), ER(-)/PR(+) ER(+)/PR(+) (hormone receptor +) AND HER2-
Chemotherapy + endocrine therapy
Adjuvant therapy approach if ER(-)/PR(-) (hormone receptor negative) and HER2 +
Trastuzumab + chemotherapy
(no endocrine therapy needed since no hormone receptors)
Adjuvant therapy approach if ER(-)/PR(-) (hormone receptor negative) and HER2 -
Just chemotherapy
(triple negative)
Which 2 classes of drugs are used for endocrine therapy?
Selective estrogen receptor modulators (SERMs)
-tamoxifen
-raloxifene
Aromatase Inhibitors (AIs)
-Anastrozole
-Letrozole
-Exemestane
When/for how long is endocrine adjuvant therapy given for?
Endocrine therapy is given after the completion of chemotherapy
For 5-10 years for patients with hormone sensitive cancers
(SERM or AI)
SERM use
Drugs: tamoxifen and raloxifene
Tamoxifen is used as endocrine adjuvant therapy for 5-10 years for patients with hormone sensitive cancers - given after chemotherapy is completed
Tamoxifen is the drug of choice for pre-menopausal women
Raloxifene is used as PROPHYLAXIS only (not treatment) in post-menopausal women with osteoporosis
SERM BBWs
Endometrial and uterine cancer
Thromboembolic events (DVT, PE)
SERM contraindications (3)
- Do not use with warfarin (DDI - tamoxifen increases warfarin concentrations)
- History of DVT/PE (BBW for thromboembolic events)
- Pregnancy/breastfeeding (teratogenic)
SERM ADRs and managements
Hot flashes / Night sweats
-can manage by given venlafaxine (note - this is the only SSRI that should be used, others will interact with tamoxifen because of CYP interactions)
Decreased bone density
-calcium/vitamin D supplementation
Decreased libido
Aromatase inhibitor use
Used for post menopausal women only for endocrine therapy for hormone sensitive breast cancer (after the completion of chemotherapy)
AIs don’t block ovarian estrogen production which is why they are not effective alone in pre-menopausal women
-tamoxifen is first line for pre-menopausal women, but if contraindication to tamoxifen, AIs can be used but ONLY IN COMBINATION WITH GnRH
AI contraindication (1)
Pregnancy
AI ADRs and management
High risk of osteoporosis
-calcium/vitamin D supplementation
-weight bearing activities
-DEXA screenings
Higher risk of CVD
Hot flashes/night sweats
Arthralgia/myalgia
What is the chemotherapy regimen for HER2 - breast cancer
Doxorubicin + cyclophosphamide (cycle 1) followed by/alternating with … paclitaxel (cycle 2)
note this is the general preferred regimen for patients without any contraindications based on conditions
What is the preferred chemotherapy regimen for HER2+ breast cancer?
Doxorubicin + cyclophosphamide (cycle 1) followed by/alternating with … paclitaxel + trastuzumab (cycle 2)
What is the alternative chemotherapy regimen for HER2+ breast cancer, when is this preferred?
For patients with cardiotoxicity (cannot use doxorubicin)…
Docetaxel + carboplatin + trastuzumab (cycle 1) followed by/alternating with … trastuzumab
What dosing approach is used for the chemo regimens?
Dose density - the cycles are shortened to 14 days
Which 2 classes of drugs are used to treat metestatic cancer?
CDK4/6 inhibitors
*Palbaciclib
*Abemaciclib
*Ribociclib
mTOR inhibitor
*Everolimus
CDK4/6 inhibitor ADRs/monitoring parameters
Interstitial lung disease
Neutropenia, anemia (monthly CBC)
N/V/D
Alopecia
Blurred vision
Risk of thromboembolic events
CDK4/6 inhibitor DDI
Avoid or reduce dose with CYP3A4 inhibitors or inducers
Risk reduction strategies
hese should be considered for patients who have a increased risk of breast cancer (family history or BRCA+) and 10 or more years life expectancy…
Bilateral total mastectomy (removing both breasts)
Bilateral salpingo-oohorectomy (removal of ovaries and fallopian tubes)
Pharmacotherapy based on menopause status…
-pre-menopause: tamoxifen
-post menopause: raloxifene (most likely), or AI, or tamoxifen
