question

def of breast cancer

answer

neoplastic proliferation of breast cells

question

classifications of breast tumors

answer

ductal-pathways for milk and lobular-where milk is produced

question

types of ductal tumors

answer

ductal carcinoma in situ (DCIS), infiltrating ductal, subtypes include medullary, tubular, mucinous, papillary, adenocystic, carcinosarcoma

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ductal tumor percentages

answer

15% of all breast cancers, 85% of all noninvasive breast cancers

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ductal carcinoma in situ (DCIS) is considered a __ lesion

answer

premalignant

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how long does it take DCIS tumors to become invasive

answer

15 year period 30-60% of them

question

two types of lobular tumors

answer

lobular carcinoma in situ (LCIS) and infiltrating lobular

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when is lobular carcinoma in situ found

answer

found incidentally during an evaluation of an abnormal mammogram - found in 1.6% of breast biopsies

question

90% of LCIS occurs in

answer

postmenopausal women highest incidence age 44-46

question

lobular carcinoma in situ is not considered a __

answer

premalignant lesion, BUT indicates significantly increased risk for developing breast cancer

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breast cancer is usually __ carcinoma

answer

ductal

question

how many women will develop invasive breast cancer

answer

1 in 8

question

chances of BC in men

answer

1 in 1,000 not rare

question

how many women will die each year from BC

answer

~40,000

question

half of all cases of BC occur in women ___

answer

older than 65

question

BC is major cause of death for women ages

answer

35-54 (most aggressive cancer occurs here)

question

risk factors of BC

answer

age, family history, genetics, reproductive and hormonal, environmental, proliferative breast disease, past history of BC, gail model

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approx __ of BC cases are hereditary

answer

10%

question

how can you get BC genetically

answer

hereditary and sporadic

question

types of hereditary BC

answer

mutation of BRCA1 (most important), mutation of BRCA 2 gene, and li fraumeni syndrome

question

types of tumor suppressor genes

answer

Mutation of BRCA1 and 2

question

BRCA1: highly penetrant germ line BRCA mutations are rare and carried by __ of individuals in most population

answer

0.5%

question

mutation of BRCA1 gene in ashkenazi jews

answer

2.5% carrier rate

question

BRCA 1 occurs in approx _ in _ women in the US

answer

1 in 100

question

BRCA1 gene can be inherited from

answer

either parent

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multiple gene polymorphisms have been described in BRCA1 located on

answer

the long arm of chromosome 17

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BRCA1 confers a ____ lifetime risk for BC

answer

40%-85%

question

BRCA1 confers a ___ lifetime risk for ovarian cancer

answer

15%-40%

question

BRCA1 increase the risk of a second BC to __% at 5 years

answer

20%

question

BRCA2 is located on

answer

chromosome 13

question

BRCA2 confers a __to__ lifetime risk for BC

answer

25-90%

question

BRCA2 confers a _to_ risk for ovarian cancer

answer

10-20%

question

BRCA2 confers a __% lifetime risk for male BC

answer

6%

question

BRCA2 has a __fold over general population

answer

100

question

BRCA2 is associated with increased risk for

answer

pancreatic cancer

question

if you are a man with BRCA2 gene, your statistics ..

answer

jumped a lot (for BC or pancreatic cancer?)

question

li fraumeni syndrome is a gremline deletion of

answer

p53

question

p53 is an important

answer

tumor supressor gene

question

li fraumeni syndrome risk for BC

answer

56% by age 44 and 90% lifetime risk

question

li fraumeni syndrome confers increased risk for

answer

brain, lung, and adrenal tumors as well as sarcomas and leukemias

question

genetic sporadic BC occurs in _% of cases

answer

90% -- it just happens, majority

question

mutations in sporadic BC

answer

HER2/nu (ERBB2), MYC, CPY7, and CCND1 and tumor supressor genes p53, RB1, and CDKN2

question

acquired homozygous mutations for __ and __ are rare in sporadic tumors

answer

BRCA1 and 2

question

__ of tumor suppressor genes and protooncogenes have been implicated in the genetics of sporadic BC

answer

hypermethylation

question

reproductive and hormonal risk factor

answer

inc risk due to inc estrogen exposure to breast tissue..the less time you are exposed to estrogen the better

question

how period and menopause relate to bc

answer

if you start period late and go into menopause early you have less of a chance of BC early menarche (less than 12) late menopause (after 55)

question

in reproductive and hormonal BC you have high levels of

answer

serum estradiol

question

*** check this-hormone replacement therapy with conjugated equine estrogen and medroxyprogesterone acetate pose

answer

no inc risk

question

reproductive and hormonal risks: inc risk due to prolonged time of __ tissue vulerability

answer

lob 1

question

what inc risks due to prolonged time of lob 1 tissue vulnerability

answer

late first pregnancy (after 30) and no breast feeding

question

reproductive and hormonal factors that have no effect on risk of BC

answer

termination of pregnancy and oral contraceptives

question

reproductive and hormonal: these decrease risk

answer

pregnancy (changes lob1 tissues) and breast feeding.. they are both protective

question

description of environmental BC

answer

incidence cannot be fully explained by genetic and reproductive and hormonal risks but direct links to environmental toxins have been difficult to prove

question

obesity/high fat diet environmental risk factor

answer

inc BMI associated with 2 fold inc in BC-inc estrogen production by adipocytes

question

environmental risk factors of BC

answer

obesity, smoking, alcohol (2 drinks per day), radiation, antibiotics

question

proliferative breast disease includes

answer

fibrocysts or fibrocystic breast disease

question

proliferative breast disease affects _ women in the US

answer

1.2 million

question

___ is a step along the continuum from normal breast tissue to carcinoma in situ and inc risk of BC fourfold

answer

atypical hyperplasia in proliferative breast disease

question

independent risk factor of proliferative breast disease

answer

inc mammography density

question

nearly half of women will develop carcinoma in situ in

answer

contralateral breast tissue, with 1% per year developing invasive carcinoma

question

can be used to estimate overall BC risk

answer

gail model or cuzick and claus model

question

pathophysiology of BC

answer

cellular and tissue changes

question

cellular and tissue changes (pathophysiology): mammary cancer originates in areas of the breast called

answer

lob 1

question

lob 1 are

answer

undifferentiated terminal structures of the mammary gland

question

cellular and tissue changes: lob 1 contains many

answer

undifferentiated cells with high proliferation rates (ready to change into anything!)

question

lob 1 are particularly sensitive to

answer

carcinogens

question

pathophysiology cellular and tissue changes: lob 1 is present in greatest amounts between

answer

the onset of menarche and the first pregnancy, most vulnerable time for mutagenesis

question

after pregnancy and breast feeding, lob 1 matures to lob 2 or 3 which is more

answer

differentiated and less vulnerable to mutagenesis

question

pathophysiology cellular and tissue changes: progressive tissue changes include

answer

atypical hyperplasia followed by carcinoma in situ (CIS) followed by invasive carcinoma

question

progressive tissue changes are characterized by

answer

increasing numbers of mutations leading to invasion and metastasis (leaving the site of origin and going to another place)

question

progressive tissue changes are influenced by

answer

cell adhesion molecules and metric metalloproteinases and cathepsins

question

parathyroid related hormone produced by tumor cells facilitates

answer

bone metastasis - so breast cancer goes to bone

question

tumor cells secrete angiogenesis factors, allowing for

answer

increased primary tumor size and access to blood vessels for metastasis

question

2 extracellular and tissue changes

answer

immune evasion and multidrug resistance

question

2 growth factors

answer

estrogen and epidermal growth factor (EGF)

question

estrogen is a growth factor for breast cell proliferation and is required for

answer

normal breast cell function

question

must have estrogen exposure for

answer

breast cell development

question

estrogen receptors

answer

cytosol proteins present in normal breast cells and on many cancer cells of primary breast tumors and their metastases

question

in cancer cells that have estrogen receptors present, estrogen stimulations of these receptor's results in

answer

inc cell proliferation

question

why do estrogen receptor cells slow the growth rate

answer

bc they are normal cells

question

drugs that block estrogen receptors in the breast

answer

tamoxifen

question

less normal, more aggressive, and unresponsive to tamoxifen therapy

answer

cancers cells that do not have estrogen receptors

question

best kind of breast cancer

answer

estrogen receptor type

question

epidermal growth factor binds to HER receptors (HER2/neu) and leads to

answer

increased mitosis and resistance to tamoxifen

question

increased HER/neu expression is present on 20-30% of

answer

breast tumors

question

blocks HER2/neu receptors

answer

trastuzumab (hercpetin)

question

patient presentation: history

answer

medical hx of breast disease, reproductive hx (age of onset of menses, # of pregnancies, age of 1st pregnancy, age of onset of menopause), history of hormone use, family hx of bc, alcohol consumption, smoking hx, diet

question

patient presentation: symptoms

answer

breast and axillary symptoms (mass, pain in breast, nipple discharge (bloody) or retraction (sunken inward), skin changes (looks like the outside of an orange), arm swelling in pits), symptoms of metastasis (headache, seizure, bone pain, dyspnea), fatigue, weight loss with no effort

question

patient presentation: examination

answer

breast mass (size, location, consistency, fixation to skin), skin changes (erythema, dimpling, edema), nipple changes (retraction, thickening, discharge), nodal status underneath, supraclavicular nodes)

question

differential diagnosis

answer

fibroadenoma, mastitis, metastasis from another primary tumor

question

keys to assessment

answer

screening for bc in the general public, screening for women who are at increased risk for bc, assessment once a breast mass is discovered

question

screening of women who are at increased risk for bc

answer

includes known BRCA mutation, women who are untested but have first degree relative with BRCA mutation, women with an approx 20-25% or greater lifetime risk of breast cancer based on specialized bc cancer risk estimation models

question

2007 ACS screening of women at inc risk of BC

answer

annual screening mammography and magnetic resonance imaging beginning at age 30 years; ovarian cancer surveillance with yearly transvaginal ultrasound and serum CA125

question

assessment once breast mass is discovered: further diagnostics

answer

mammography, ultrasound, MRI/PET

question

ultrasound differentiates

answer

cystic versus solid masses, helps to find palpable masses not seen on mammogram and can be used to guide biopsy

question

assessment once a breast mass is discovered: tissue diagnosis

answer

fine needle aspiration (95% accuracy with mammogram), core biopsy, excision biopsy (lumpectomy), ductal lavage-provides very early detection in high risk patients

question

assessing nodal status: sentinel node biopsy

answer

if the sentinel node is negative then it is highly likely that the rest of the axillary nodes are negative, thus it may eliminate the need for more extensive axillary biopsies, cytokeratin immunohistochemical staining can pick up micro metastases, further increasing the sensitivity of this procedure

question

assessment once a breast mass is discovered: assessing nodal status: axillary dissection

answer

if sentinel node is positive now recommend to stop and be sure to treat with both chemo and radiation

question

recent reports suggest that testing for circulating and disseminated tumor cells may be useful in determining

answer

prognosis in advanced breast cancer

question

chest radiograph and bone scan are indicated if symptomatic for

answer

metastases or if alkaline phosphatase is elevated

question

staging

answer

tumor, nodes, metastasis system; determines type of surgery and adjacent therapies

question

prevention of breast cancer

answer

smoking cessation, decrease alcohol intake, exercise and weightless, diet, selective estrogen receptor modulators, aromatase inhibitors, prophylactic mastectomy, oophorectomy

question

good diet

answer

decreased fats, increased omega 3, phytoestrogens and isoflavens

question

keys to management/prevention: selective estrogen receptor modulators

answer

tamoxifen-for primary prevention of bc in high risk patients; clearly reduces risk for bc but increases risk of endometrial cancer and thromboembolic disease

question

keys to management: aromatase inhibitors

answer

reduced the risk of developing breast cancer in the contralateral breast more effectively than tamoxifen

question

oophorectomy (ovary removal) can be used to reduce the risk of bc in high risk individuals by as much as

answer

50%

question

surgical management

answer

lumpectomy (just take lump out), modified radical mastectomy (take out whole or part of breast), total mastectomy, radical mastectomy

question

radiation

answer

local breast radiation after breast conserving surgery reduces the risk of local recurrence

question

keys to management: endocrine therapy (hormone manipulation) is used as adjacent therapy after surgery for both

answer

pre and post menopausal women with ER+ tumors

question

endocrine therapy increases survival and disease free survival and decreases the risk for

answer

disease in the contralateral breast

question

this type of endocrine therapy is used for 5 years avg

answer

SERMS (tamoxifen)

question

endocrine therapy that is safer and more effective than tamoxifen in postmenopausal women in most studies

answer

aromatase inhibitors block estrogen synthesis and have been found to be more effective and safer

question

chemotherapy

answer

adjunctive chemotherapy substantially improves long term, disease free survival in both premenopausal and postmenopausal women up to age 70 with node positive and node negative disease

question

key to management: trastuzumab (perception)

answer

monoclonal antibody to HER2/neu growth factor receptor

question

key to management: bisphosphonates reduce risk of

answer

skeletal metastases

question

key to management: targeted therapy for specific types of tumors based on

answer

molecular genetics is increasingly possible

question

key to management: tumor vaccines for...

answer

tumor associate antigens, metric metalloproteinase and cathepsin blockers, and antiangiogenic drugs are under investigation

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