Term
| cumulative lifetime risk of a women to get breast cancer is |
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Definition
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Term
| etiology of breast cancer |
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Definition
BRCA-1 and BRCA-2:
tumor suppressor genes
also associated with other cancers
more than 150 different mutations identified
p53:
tumor suppressor gene
mutations found in 50% of breast cancer
HER2:
Human Epidermal growth factor Receptor-2
ONCOGENE
over expressed in 25-40% of breast cancers
hormonal factors:
ER/PGR receptors |
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Term
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Definition
Ductal carcinoma in situ (DCIS):
precancerous
contained in cells lining duct
treated as cancer
Lobular carcinoma in situ (LCIS):
usually found incidentally on biopsy
do not show up on mammogram
unknown if progresses to cancer
risk factor for the development of cancer; not treated as cancer
invasvie ductal carcinoma (IDC):
70% of all breast cancer
worst prognosis
invasive lobular carcinoma (ILC):
10% of all breast cancers
others:
tubular, medullary, mucinous, inflammatory |
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Term
| breast cancer risk factors |
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Definition
HIGH RISK FACTORS (> 3 FOLD INCREASE):
age > 40
breast cancer in 2 or more 1st degree relatives (siblings, mother)
hyperplasia w/ atypia - irregular growing cells
LCIS (lobular carcinoma in situ)
Klinefelter's syndrome (men) - XXY
INTEREMEDIATE RISK FACTORS (RR 1.5-3):
mother with breast cancer before age 60
first live birth after age 25
used oral contraceptives > 4 years before pregnancy
ovarian cancer in one or more 1st degree relatives
menopause after the age of 55
EtOH greater than 3 drinks/day
MINOR RISK FACTORS (RR > 1-1.49):
mother with breast cancer after age 60
breast cancer in 2nd degree relative
early menarchy (before age 12)
obesity (10th percentile) AND age 50
postmenopausal estrogen replacement
EtOH 1-3 drinks/day |
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Term
| breast cancer presentation |
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Definition
painless lump is 1st sign in 90% of women
solitary, unilateral, irregular, nonmobile
other symptoms:
stabbing/aching pain
nipple discharge
nipple retraction
edema
redness/warmth |
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Term
| diagnosis of breast cancer |
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Definition
complete history and physical
mammography:
nothing suspicious (98% benign)
something of concern (20-30% cancerous)
clearly suspicious (75-90% cancerous)
biopsy:
send cytology and atypia
send for ER/PGR and HER2
bone scan - for more progressive breast cancer; common site of metastasis
labs
imaging |
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Term
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Definition
types of spread:
local spread
lymphatic spread
hematogenous spread
common sites of metastases:
skin
bone
liver
lung
brain |
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Term
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Definition
lymphagitic lung metastasis
liver metastases
rapidly growing tumor at any site
therapy:
chemotherapy and support
note: liver dysfunction can change choice of chemotherapy agents |
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Term
| complications of advanced breast cancer |
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Definition
hypoercalcemia
superior vena cava obstruction (SVC)
pleural effusion
pain
lymphedema |
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Term
| stage at breast cancer presentation |
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Definition
| 80% are diagnosed early in the disease = better survival rates |
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Term
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Definition
positive prognostic factors:
primary tumor size
number and extent of nodal involvement
response to primary therapy
ER/PGR positive - usually grow slower and are more responsive to therapy
histological grade
proliferative rate
HER2 negative - slower growing
other genetic mutations |
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Term
| breast cancer screening per ACS recommendations |
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Definition
mammogram:
women at least 40 years old should have yearly mammograms
clinical breast exam (CBE):
age 20-39 = every 3 years
at least 40 years old = yearly
self breast exam (SBE):
monthly starting at age 20 |
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Term
| prevention - risk assessment |
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Definition
use the modified Gail model for risk assessment (high risk > 1.7% in 5 years)
current age
age at menarche
age at first live birth
number of affected 1st degree relatives
number of breast biopsies
other high risk:
presence of atypical hyperplasia or LCIS
presence of defining genetic mutations |
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Term
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Definition
surgical:
prophylactic mastectomy (decrease risk by 90%)
oopherectomy before age 50 (decrease risk by 50%)
chemical:
tamoxifen 20 mg daily for 5 years
raloxifene 60 mg daily for 5 years |
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Term
| breast cancer prevention trail |
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Definition
in high risk women (>1.7% in 5 years)
tamoxifen decreased incidence of invasive breast cancer by 49% |
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Term
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Definition
surgical:
prophylactic mastectomy (decrease risk by 90%)
oopherectomy before age 50 (decrease risk by 50%)
chemical:
tamoxifen 20 mg daily for 5 years
raloxifene 60 mg daily for 5 years |
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Term
| breast cancer prevention trail |
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Definition
high risk women (>1.7% in 5 years)
tamoxifen decreased incidence of invasive breast cancer by 49%
study done is pre- and postmenopausal women |
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Term
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Definition
Originally approved in 1998 for the prevention of osteoporosis in postmenopausal women
MOA same as tamoxifen |
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Term
| multiple outcomes of raloxifene evaluation |
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Definition
study done on the general population (not just in high risk patients)
decreased risk of breast cancer
done in POST MENOPASUAL WOMEN only |
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Term
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Definition
postmenopausal women with an increased risk for the development of breast cancer
patients randomized to tamoxifen daily for 5 years or raloxifene daily for 5 years
for invasive breast cancer both were beneficial
for noninvasive breast cancer raloxifene was better; tamoxifen reduction was not statistically significant
however, at 8 year follow up the tamoxifen patients were doing better than the raloxifene patients |
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Term
| breast cancer prevention summary |
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Definition
surgical prophylaxis is one option: mastectomy and oopherectomy
pharmacologically:
tamoxifen and raloxifene are valid options
raloxifen does not have data in premenopausal women
most people will go the surgical route; no one uses SERMs for breast cancer prevention |
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Term
| breast cancer treatment - general principles |
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Definition
multimodality treatment approach
surgery with axillary lymph node dissection is the bases of therapy for non-advanced disease
patients who are ER/PGR positive should receive hormonal therapy
the goal is CURE in patients with stage III or better disease
almost everyone gets chemotherapy +/- trastuzumab (if the patient is HER2 +) |
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Term
| treatment of noninvasive carcinomas |
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Definition
LCIS (lobular carcinoma in situ):
CONSIDERED A HIGH RISK FOR CANCER
consider preventable measures (surgery, tamoxifen, roloxifene)
DCIS (dustal carcinoma in situ):
TREATED AS IF IT IS CANCER |
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Term
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Definition
2 types:
lumpectomy - only tumor and surrounding tissue removed
mastectomy - removes entire breast and surrounding tissue; usually just one side (unilateral); in advanced disease, both sides removed (bilateral)
if tumor is large (stage III), give chemotherapy first to shrink tumor, then do surgery |
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Term
| radiation after surgery if... |
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Definition
DEFINITE:
tumor > 5 cm
positive surgical margins
positive lymph nodes
lumpectomy
NONE:
mastectomy
AND
negative margins
AND
tumor < 5 cm
AND
no positive nodes |
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Term
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Definition
given in all patients
anthrcycline based chemotherapy is treatment of choice, but is controversial
role of taxanes is also controversial
if HER2 positive, add trastuzumab to chemo |
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Term
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Definition
given AFTER chemo and radiation
originally, tamoxifen was hormonal therapy of choice for all but metastatic disease
not aromatase inhibitors are considered to be preferred over tamoxifen
if started on tamoxifen you can switch to aromatase inhibitor
PREMENOPAUSAL WOMEN CANNOT TAKE AROMATASE INHIBITORS
hormonal therapy is causing any tumor that is left behind to stop growing; given AFTER chemotherapy b/c drugs won't work as well on cells that are not rapidly dividing |
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Term
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Definition
recurrences usually detected within 5-10 years
history and physical every 3-6 months for the first 3 years then every 6-12 months for 2 years, annually thereafter
monthly SBEs
yearly mammography and gynecologic exams (if you have breast cancer you have an increased risk of ovarian cancer) |
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Term
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Definition
treat with different chemotherapy agents, can use combination therapy
give trastuzumab if HER2 positive and haven't received trastuzumab before
chemo for recurrence should include anthracycline or taxane is haven't used before
if had hormonal therapy before, change agents |
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Term
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Definition
only used for ER/PGR positive
tamoxifen (SERM) for premenopausal women
AI for postmenopausal women
if stage I-III, use for 5 years, started after chemo
if stage IV, duration is undefined |
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Term
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Definition
selective estrogen receptor modulator (SERM)
should be started after chemotherapy is finished
given for 5 years
added benefits: prevent fractures? lower cholesterol?
ADRs: HOT FLASHES, N/V, menstrual irregularities, skin rash/dryness, headache, weight gain, THROMBOEMBOLIC EVENTS, ENDOMETRIAL CANCER (do not give to women with uterine hyperplasia), teratogen |
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Term
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Definition
anastrazole and letrozole are both non-steroidal, competitive binders of the aromatase enzyme
exemestane is a steroidal, non-competitive binder
letrozole has the most extensive data
exemestane has the least amount of data
ADRs: N/V, diarrhea, peripheral edema, HOT FLASHES, FRACTURES, fatigue, arthralgia |
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Term
| what if they were started on a tamoxifen and are now postmenopausal? |
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Definition
| if the patient is half way through tamoxifen, there is benefit to change to an AI |
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Term
| what if they are done with 5 years of tamoxifen and are now postmenopausal? |
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Definition
| if the patient has finished tamoxifen, there is benefit to follow with AI |
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Term
| chemotherapy - initial therapy |
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Definition
many various regiments have been evaluated
no clear "1st line" therapy
AC (doxorubicin + cyclophosphamide) is the historical front line chemo
role of antracyclines and taxanes are not clear |
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Term
| doxorubicin cardiotoxicity |
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Definition
maximum lifetime dose of doxorubicin is 500 mg/m^2
based on the parameter, not the total dose |
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Term
| AC major counseling points |
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Definition
every 3 week administration
ADRs:
quick - extravastation injury (people getting anthracycline should have a central IV acess), hypersensitivity
short term - red secretions, N/V, myelosuppression, alopecia
long term: cardiac toxicity, liver toxicity |
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Term
| body surface area calculation |
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Definition
BSA = SQRT((cm*kg)/3600)
2.54 cm = 1 in
2.2 lb = 1 kg |
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Term
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Definition
monoclonal antibody to the HER-2 receptor
duration:
1 year when used as upfront therapy
indefinite when used in patients with metastatic or relapsed disease
trastuzumab is started AFTER the anthracycline is completely finished
ADRS:
black box warning for hypersensitivity
black box warning for increased cardiotoxicity
DO NOT GIVE AT THE SAME TIME AS ANTHRACYCLINES (give after)
others - HA, N/V, diarrhea, peripheral edema |
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Term
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Definition
use chemotherapy again
if didn't get anthracycline, taxane, or trastuzumab (if HER-2 positive) the first time, give it in relapse
no evidence to support combination vs. monotherapy |
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Term
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Definition
1st line: anthracycline based regiments are still used 1st choice
2nd line: taxane based chemotherpy if haven't had before
there are many options for patients who should not get anthracyclines
trastuzumab should be used if patient is HER-2 positive
relapse disease has many options, no standards
bottom line: eventually, all patients should get an antrhacycline and taxane (unless cured) |
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