question

Breast Cancer

answer

Cancer that forms in tissues of breast, usually the DUCTS and LOBULES. It occurs is BOTH men and women

question

Why is breast cancer rare in men?

answer

Males have less breast tissue

question

Ducts

answer

Tubes that carry milk to the nipple

question

Lobules

answer

Glands that make milk

question

Epidemiology/etiology

answer

235,000 cases and 40, 000 deaths *2,240 cases men

question

Incidence of breast cancer....

answer

Estimated incidence has been relatively stable since 2003, mortality has proportionally decreased

question

Genetics of breast cancer

answer

1. BRCA1/BRCA2 2. P53 3. HER2 *hereditary breast cancer represents 5-10% of all cases

question

BCRA1 and BCRA2

answer

1. Tumor suppressor genes 2. Relatively rare in the general population, estimated carrier frequency is 1:40 Jewish Ashkenazi women 3. More than 700 BRCA1 and 300 BRCA2 mutations identified- LOTSSS

question

P53

answer

1. Tumor suppressor gene 2. Associated with Li-Fraumeni syndrome of multiple hereditary cancers 3. Approximately 30% of breast cancers have mutation, inactivation, loss or down regulated expression of p53

question

HER2

answer

1. Encodes for human epidermal growth factor receptor 2 (protein) 2. Amplification/overexpression generally imparts a POORER prognosis 3. Used primarily to select patients who will benefit from anti-HER therapy

question

HER2 Testing

answer

Should be determined on every primary invasive breast cancer, recurrence and at presentation of metastatic disease: -immunohistochemistry (IHC)-->measures protein expression on cell surface, from 0-3+, subjective -in situ hybridization (ISH)-->identifies the prescience of gene amplification, reported as positive, equivocal or negative

question

Risk Factors for breast cancer

answer

1. Age 2. Reproductive History 3. Family History 4. Environment/Lifestyle

question

Age as a Risk Factor for Breast Cancer

answer

1. This is the number 1 risk 2. Large jump after 50 years old

question

Reproductive History as a Risk Factor for Breast Cancer

answer

1. The longer you are exposed to hormones the greater your risk 2. Endogneous estrogen exposure 3. Exogenous estrogen exposure-controversial

question

Endogenous estrogen exposure

answer

1. Early menarche (55) increases risk 3. Age of birth of first child > 30 or NO children increases risk

question

In regards to endogenous estrogen exposure what DECREASES risk?

answer

Early induced menopause before age 50 *tamoxifen and bilateral salpingo-oophorectomy

question

Exogenous estrogen exposure

answer

1. For oral contraceptives most clinicians feel that the benefits far outweigh the risks of developing breast cancer for most women 2. When the WHO released its study in 2001 about hormone replacement therapy, the practice declined rapidly, and breast cancer numbers dropped as well

question

Familial/Genetic Factors as a Risk Factor for breast cancer

answer

1. 1st and 2nd degree relatives impart an increased risk 2. Early onset breast cancer in a family member is suggestive of a hereditary predisposition 3. Overall risk is 1.5-3X greater if a woman has a mother or sister with breast cancer

question

Prior thoracic irradiation as a Risk Factor

answer

Chest radiation in anyway increases your incidence of breast cancer

question

Alcohol consumption as a Risk Factor

answer

Moderate amounts of alcohol (3-6 drinks per week) is associated with a 35-50% increase in the incidence of breast cancer

question

Diet as a Risk Factor

answer

Higher dietary fat intake has a correlation with breast cancer

question

Physical activity as a Risk Factor

answer

Lower risk with greater physical activity *even if you just start chemotherapy, getting active at any point helps

question

Body Mass Index as a Risk Factor

answer

Overweight or obese women have a higher risk of POST-menopausal breast cancer

question

Breast Density

answer

Mammographic measure of the amount of glandular (good-functional) tissue relative to fatty tissue in the breast *fatty tissue shows up as dense

question

Breast Cancer as a Risk Factor

answer

Women with more radio-dense breast tissue are at higher risk compared to women with more radiolucent breast tissue

question

Screening in Breast Cancer

answer

1. Breast Self Examination 2. Clinical Breast Examination 3. Mammography

question

Breast self examination

answer

-Generally NOT recommended with little data supporting a reduction in mortality when used alone -If done it should be done monthly the week after menses -Used in combination with other tests -May lead to high rates of unnecessary biopsies -ACS still endorses

question

Clinical breast examination

answer

- Qualified individual -May be most beneficial when combined with mammograms, not uniformly recommended -Recommended by the american cancer society to be done every 3 years for women 20-39 and annually for women > 40 yo

question

Mammography

answer

-Definite evidence that annual screening mammography reduces the mortality from breast cancer in women 50 yo or older -Solid evidence, use of MRI becoming more standard in higher risk patients -Data is lacking in women 75 yo or older -Not recommended in patients with a serious co-existing illness and life expectancy less than 5-10 years

question

Breast MRI

answer

American Cancer Society indicates that breast MRI is appropriate as a an adjunct to mammography in women with the following: -BRCA mutation -1st degree relative with a BRCA mutation but untested -Lifetime risk of 20-25% or greater as defined by the BRCAPRO model or other models LARGELY dependent on family history

question

3 bodies governing how to screen for breast cancer

answer

1. American Cancer Society 2. National Comprehensive Cancer Network* 3. United States Preventative Services Task Force **they all have differing recommendations on screening and definitions of high risk patients

question

High Risk for breast cancer?

answer

1. History of thoracic irradiaiton or mantle irradiation 1.7 % per Gail model 3. Lifetime risk of breast cancer > 20% based on models largely dependent on family history or genetic predispositions 4. Lobular carcinoma in situ (LCIS) 5. Prior history of breast cancer *risk reduction therapy might be indicated

question

What is the Gail model?

answer

-A mathematical tool used to determine the relative risk of developing breast cancer compared to a match aged control patient -Useful for white women with a limited family history to assist with decisions regarding cancer prevention -Many assumptions - not validated in other races - Use of age, number of 1st degree relative with invasive breast cancer, number of breast biopsies, nulliparity or age at first birth, atypical hyperplasia

question

Claus Model

answer

-Includes age, family history, age of onset of BC -Limitations; no account of ethnicity, male BC, ovarian cancer, personal medical/reproductive history

question

Normal Risk-Screening

answer

- Over 20: BSE - 25-39 : clinical breast exam by physician every 1-3 years - 40+: yearly mammogram and CBE

question

High Risk Screening

answer

1. BSE: all ages 2. CBE: all ages: every 6-12 months, if prior RT begin 8-10 years after RT or age 40, whichever comes first -Annual for women with prior RT less than 25 beginning 8-10 years after RT 3. Mammogram-annual w/ CBE 4. Breast MRI-annual w/ CBE for patietns with prior RT (age> 25) or for patients with lifetime risk of 20%

question

Options for risk reduction

answer

1. Bilateral total mastectomy +/- reconstruction 2.Bilateral salpingo-oophorectomy with peritoneal washings 3.Risk reduction agents -Pre-menopausal: tamoxifen or clinical trial -Post-menopausal - tamoxifen, raloxifene or exemestane clinical trial

question

Prevention or Risk Reduction Therapies

answer

1. Lifestyle modifications 2. Surgical Options- higher risk patients 3. Chemoprevention-only recommended in women > 35 years old

question

Lifestyle modifications for the prevention of breast cancer

answer

-No evidence that specific dietary components can effectively reduce breast cancer risk -Weight gain and obesity are risk factors for the development of POSTmenopausal breast cancer -Alcohol consumption even at moderate levels increase breast cancer -Exercise has been associated with a decreased risk of breast cancer

question

What are the two surgical options available for the prevention of breast cancer?

answer

1. Bilateral total mastectomy- removal of all (both) breast tissue 2. Bilateral salpingo-oophorectomy - decreases estrogen exposure

question

Bilateral total mastectomy for surgical prevention

answer

1. Lifetime risk in BRCA1/2 mutations carriers is about 56-84% 2. Bilateral risk reduction mastectomy (RRM) has DECREASED the risk of developing breast cancer by at least 90% in moderate-high risk women and in known BRCA 1/2 mutation carriers 3. Recommended for women at HIGH RISK (BRCA1/2, P53, PTEB mutations)

question

Bilateral salpingo-oophorectomy for surgical prevention

answer

1. Women with BRCA 1/2 are at increases risk for both breast and ovarian cancer-->so this will decrease risk of ovarian cancer as well 2. Effectiveness of procedure after completion of childbearing has been demonstrated in many studies-->80 % reduction in ovarian cancer and a 50% reduction in breast cancer 3. Unlike mastectomy this is ONLY for those with known or suspected BRCA 1/2 mutation

question

Chemoprevention agents

answer

1. Tamoxifen 2. Raloxifene 3. Aromatase Inhibitors

question

Tamoxifen

answer

1. Decreased incidence of invasive by 49% and noninvasive by 50% 2. May be given to healthy pre/post menopausal women > 35 who have a 1.7% 5 year risk of breast cancer as determined by the Gail model or who have had LCIS 3.-NSABP Trial

question

Tamoxifen-GC

answer

-20mg po qday x 5 years -Did see a decrease in bone fractures but an increase in: hotflashes, endometrial cancer in postmenopausal women, cataracts, and a SIGNIFICANT increase of pulmonary embolism w/ stroke

question

Raloxifene

answer

-Decreased incidence by 45-75%, similar to tamoxifen -Data is limited to POSTmenopausal women over 35 who have (Gail) or a history of LCIS -Star Trial

question

Raloxifene-GC

answer

-60 mg PO qday -When comparing ADRs, raloxifene has a lower incidence of thrombotic events, endometrial cancer and cataracts development -1st introduced for osteoporosis, so similar to tamoxifen the bone preserving effect is still there

question

Aromatase Inhibitors-Exemestane

answer

1. Reductions in contralateral breast cancer risk were seen in adjuvant trails with AI 2. Not FDA approved for prevention 3. No generics difficult to get covered by insurance 4. 42% reduction in contralateral breast cancers with anastrazole vs. tamoxifen

question

NCIC CTG MAP 3 Trial

answer

-Exemastane or placebo -Women who are >/= 35 years old with one of the following 1. Gail(1.66) 2. LCIS 3. Over 60 -Significant reduction of invasive breast cancer

question

Aromatase Inhibitors Exemestane GC

answer

Risk: -Arthritis- Joint/Muscle pain -Hot Flashes -Fatigue -Sweating -Insomnia -N/V

question

Clinical Presentation of Breast Cancer

answer

1. Hard, painless lump 2. Stabbing or aching pain may be first symptom-->sometimes 3. Less common nipple discharge, retraction or dimpling 4. Approximately 10% of patients will present with signs/symptoms of distant metastatic diseases->those who have ignored their lumps 5. About 80% of women first detect some abnormality themselves; detected via screening

question

The Lump

answer

-Solitary, unilateral, solid, hard, irregular, and nonmobile -Usually on one side of breast

question

Dimpling of nipple

answer

Peau d' orange (skin of orange)

question

Metastasis of the cancer

answer

About 50% of patients initially diagnosed with non-metastatic breast cancer will later develop metastases despite multimodality therapy, usually within 3-5 years following potentially curative therapy

question

Sites of metastases

answer

Most common are the: -Bone -Liver -Brain -Distant Lymph nodes -Skin

question

BRCA1

answer

By 70 years of age - the probability of developing breast cancer in women with BRCA1 mutation is 57% while ovarian cancer is 40%

question

BRCA 2

answer

By 70 years of age - the probability of developing breast cancer in women with BRCA2 is 49% and ovarian cancer is 18%

question

Pathophysiology of the breast

answer

-Composed of ducts, lobules, fatty tissue, other connective tissues and intramammary lymph nodes -Regional lymph nodes include axillary and internal mammary lymph node chains

question

What are the types of breast cancer?

answer

1. Ductal carcinoma in situ (DCIS) 2. Lobular carcinoma in situ (LCIS) 3. Invasive lobular carcinoma (IDC) 4. Others: tubular, mucinous, papilary, medullary

question

LCIS/DCIS

answer

-Not a premalignant lesion, risk factor for breast cancer -Both breasts are at equal risk

question

Invasive lobular carcinoma

answer

-Most common type of breast cancer (70%) -Worst prognosis of all types of breast cancer

question

Early Stage Breast Cancer

answer

-0,I- over 90 -IIA- 70-90 -IIB-50-70

question

Locally Advanced Breast Cancer

answer

-IIIA, B - 20-30

question

Advanced (Metastatic)

answer

-IV- 0-10

question

What are the prognostic factors?

answer

1. Stage at diagnosis 2. Response to primary therapy and stage of disease after primary therapy 3. Chemotherapy induced amenorrhea (premenopausal) 4. Estrogen/Progesterone receptor status 5. Histologic/nuclear grade 6. Proliferative markers 7. Lymphatic/vascular invasion 8. Ploidy 9. Diabetes/BMI 10. HER2

question

Response to primary therapy and stage of disease after primary therapy

answer

1. Primary resistance to systemic chemotherapy is a very POOR prognostic indicator 2. Pathological complete response is associated with a better relapse free survival compared to patients with a less than partial complete response

question

Chemotherapy induced amenorrhea

answer

1. May be an indicator of drug toxicity and therefore enhanced clinical benefit 2. Similar benefit regardless of remission status

question

Estrogen/Progesterone receptor status

answer

-ER positive tumors are generally less aggressive than ER negative tumors -Not an independent prognostic factor in the absence of endocrine therapy -predicts response to endocrine therapy

question

Histologic/nuclear grade

answer

Grade 1- well differentiated Grade 2- moderately differentiated Grade 3- poorly differentiated

question

Proliferative markers

answer

1. Faster growing, more aggressive but might be MORE responsive to chemotherapy *Ki-67 or mitotic index

question

Lymphatic/vascular invasion

answer

1. Indicative of spread to other structures within the breast 2. Generally an unfavorable prognostic factor

question

Ploidy

answer

Aneuploid tumors are a poor prognostic factor

question

Diabetes

answer

Associated with reduced survival in some studies

question

Obesity

answer

Associated with poorer outcome regardless of menopausal status

question

HER2 amplification/over expression

answer

1. More aggressive tumors regardless of patient status 2. Poor prognostic marker 3. Serves as a target for treatment with anti-HER2 therapy

Breast Cancer Part 1 – Flashcards

Unlock all answers in this set

Haven't found what you were looking for?

Search for samples, answers to your questions and flashcards