Onc lec 3

How many women will develop breast cancer?

1 in 8

What percentage of breast cancer is familial?

5-10%
surveillance & more intensive screening may be appropriate at a younger age

What genetic alterations exist in cases of Breast cancer?

BRCA 1, BRCA 2, over expression of HER2

What is BRCA1 and BRCA2?

tumor suppressor genes; mutations are associated w/ increased risks of breast, ovarian, and prostate cancer

What is HER2?

oncogene associated w/ breast cancer hat results from increase in gene number not gene mutation (breast cells grow and divide in an uncontrolled manner)

often recur and are more aggressive and harder to cure

What type of gene alteration results in a breast cancer that often recur and is more aggressive?

HER2

How many women who develop breast cancer will have a BRCA1 or BRCA2 mutation?

only 5 to 10 out of 100

(most cases are not the resul

How many women who develop ovarian cancer will have a BRCA1 or BRCA2 mutation?

15 out of 100

(most cases are not the result of inherited mutation in BRCA)

What are the WHI findings on estrogen plus progestin?

resulted in inc risk of MI, CVA, blood clots, and breast cancer

dec risk of colorectal cancer

fewer fractures

no protection against cognitive impairment or dementia

What were the WHI findings on estrogen alone?

no change in MI risk

inc risk of CVA, blood clots, questionable breast cancer

dec risk of fractures

no effect on risk of colorectal cancer

What are the WHI findings on hormone replacement therapy (HRT)?

should not be taken to prevent CV disease

use the lowest dose possible for the shortest duration to achieve tx goals

can be used for relief of hot flashes and sx of vaginal atrophy

only for women at significant risk of osteoporosis

For average risk women, how often should women between the ages 45-54 get mammograms?

yearly

How often should women older than 55 get mammograms?

every 2 years

per the ACS for an average risk individual, when should a woman begin getting mammograms?

age 45 (their choice if they want to start between 40-44)

continue yearly until 54

What percentage of cancers does mammography fail to detect?

10-20%

According to ACS guidelines, how often should high risk patients who meet the criteria get an MRI and a mammogram to screen for breast cancer?

every year

What is the ACS criteria for high risk individuals to get a yearly MRI and mammogram for breast caner screening?

lifetime risk of breast cancer 20-25% or more

known BRCA1 or BRCA2 gene mutation

first degree relative w/ BRCA mutation

had radiation therapy to the chest b/t ages 10-30

have / have first degree relatives w/ lifraumeni syndrome, cowden syndrome, or Riley-ruvalcaba syndrome

What are the most common findings on a physical exam in a breast cancer patient?

single, non-tender, firm, immobile mass most commonly in the upper outer quadrant

What are PE findings in breast cancer patients that are less common?

nipple discharge or retraction, breast enlargement or shrinkage, peau d’orange, palable axillary or supraclavicular lymph nodes

When performing a PE, what finding is indicative of breast cancer and requires an immediate referral to surgical oncology?

peau d’orange (skin thickening or changes)

How do you dx breast cancer?

ultrasound and/or mammogram to confirm suspicious PE findings —> fine needle aspirate (FNA) or stereotactic core needle bx of nodule/mass (excisional bx preferred if possible)

What tumor markers are seen in breast cancer?

CA 15-3, CA 27-29, CEA

What should you do after any positive or suspicious findings on a mammogram?

surgical oncology referral

What is ductal carcinoma in situ (DCIS)?

noninvasive tumor in the breast ducts that can progress to invasive cancer

What is the most common type of invasive breast cancer?

infiltrating ductal carcinomas

How are invasive breast cancers classified?

opera, locally advanced, or metastatic

What do some Breast cancers rely on for growth?

estrogen (meaning they have receptors for estrogen)

Do ER positive breast cancers or ER negative breast cancers carry a better prognosis? why?

ER positive because they allow for target specific treatment

What is tamoxifen?

selective estrogen receptor modulator (SERM) that inhibits the growth of great cancer cells by competitive antagonism; taken as a 20mg pill QD

How is breast cancer staged?

TNM system

Ipsilateral axilla often staged w/ sentinel node bx to evaluate node involvement

What dictates the treatment and prognosis of breast cancer?

staging and molecular testing of tumor

When evaluating for biomarkers for breast cancer, what is ER?

estrogen-receptor; associated w/ more indolent course and treated w. hormone therapy (Tamoxifen)

When evaluating for biomarkers for breast cancer, what is PR?

progesterone-receptor

what is HER2 breast cancer treated with?

trastuzumab (Herceptin)

What is the “triple negative” in regard to breast cancer?

presence of ER, PR, and HER2 (worst kind of breast cancer)

worse survival, higher likelihood of metastatic disease, limited tx options

What are selective estrogen receptor modulators (SREM)?

breast cancer tx that blocks the effect of estrogen in the breast tissue; can be used to treat women pre and post menopause

ex: raloxifene (evista), tamoxifen (soltamox), toremifene (fareston)

What is an aromatasae inhibitor?

breast cancer tx that stops the production of estrogen; best for postmenopausal women

ex: exemastane (aromasin), anastrozole (amrimidex), letrozone (femara)

Which type hormone therapy drugs can be used before and after menopause?

SERM

What is the best type of hormonal therapy to start with for postmenopausal women?

aromatase inhibitors

What is associated with a higher risk of recurrence in breast cnacer?

larger tumor, with lymph node involvement or with more invasive behavior

What is the cure for metastatic breast cancer?

none- there is no known cure

What replaced cervical cancer as the leading cause of death from genital cancer?

ovarian cancer

How many women will get ovarian cancer by age 70?

1 in 72 (most commonly in women over 50)

What are risk factors associated with ovarian cancer?

family history, age, hereditary (BRCA1, BRCA2, lynch syndrome), nulliparity, hormonal therapy

What factors offer protection against ovarian cancer?

pregnancy, oral contraceptives containing both estrogen and progesterone x5 years, breast feeding x 1 year, tubal ligation, salpingo-oophorectomy, hysterectomy

Where does ovarian cancer usually remain?

abdominal cavity (metastasis to bone, lung or brain uncommon)

What is ovarian cancer frequently misdiagnosed as?

IBS, stress, depression

What is the clinical presentation of ovarian cancer?

abdominal fullness, bloating, wt loss, dec appetite, early satiety, vague abdominal discomfort, dysuria or urinary frequency, dyspareunia, low back pain

Who is at a high risk of ovarian cancer?

women w/ FHx ovarian/breast cancer

BRCA1 AND BRCA2 gene mutations

what is recommended for women who are high risk for ovarian cancer?

prophylactic oophorectomy or salpingo-oophorectomy b/t 35-40 and once childbearing is complete

How do you dx ovarian cancer?

tumor marker- Ca-125 (95% predictive of recurrence)

genetic testing- BRCA gene

transvaginal ultrasound

abdominal/pelvic CT scan

what is the tx for ovarian cancer?

surgery (TAH w/ BSO w/ omentectomy), chemotherapy, radiation

What accounts for 95% of testicular cancers?

germ cell tumors (GCT)

How does testicular cancer present?

nodule or painless swelling in 1 testicle noted incidentally ; dull ache or heavy sensation in lower abdomen or scrotum or perianal area

(10% have acute pain and 5% have gynecomastia)

What are risk factors for testicular cancer?

personal or fhx, infertility or subferitlity, HIV, hypospadias, extragonadal GCT

What reduces the likelihood of malignancy in testicular cancer?

cryptorchidism and orchiopexy

What precedes both seminomas and nonseminoma GCTs in adults?

premalignant condition GCNIS (germ cell neoplasia in situ)

In any man with a solid, firm mass w/in the testis, what must be the considered diagnosis until proven otherwise?

testicular cancer

Why do you NOT perform biopsies for testicular cancer/germ cell tumors?

may result in tumor seeding into scrotal sac or metastatic spread of tumor into inguinal nodes

(it can spread)

How do you dx testicular cancer?

scrotal ultrasound followed by CT scan of abdomen/pelvis/chest

measurement of serum tumor markers

radical inguinal orchiectomy

restroperitoneal lymph node dissection (RPLND)

What tumor markers are seen in testicular cancer?

alpha fetoprotein (AFP), beta-hCG, lactate dehydrogenase (LDH)

What staging system does testicular cancer use?

TNM

What should you perform BEFORE chemotherapy in men with clinically advanced testicular cancer?

radical orchiectomy (whenever possible)

How do seminomas differ from nonseminomas?

more likely to present w/ localized disease

rarely spread via blood stream to other areas

very sensitive to radiation therapy

usually not marked by inc serum to markers

indolent growth

How do nonseminomas (NSGCT) differ from seminomas?

spread via bloodstream to other areas

radiresistant

serum markers are elevated

What is the most common non-skin cancer in men AND the 2nd most common cause of cancer death in men?

prostate cancer

What is a man’s lifetime risk of prostate cancer?

1 in 7

How does prostate cancer usually present?

asymptomatic until obstructive voiding issues

What are risk factors for prostate cancer?

older age, fhx, inherited gene changes (BRCA1, BRCA2, lynch syndrome), african american race, high saturated fat diet

Describe the FHx risk factors associated w/ prostate cancer?

first degree - inc 2 fold

2 first degree - inc 9 fold

higher risk w/ affected brother than affected father

high risk if relatives were young at dx

What form of prostate cancer develops earlier (< age 50)?

hereditary

Per ACS, PCP should discuss the uncertanties, risks, and potential benefits associated w/ prostate screening, and the OFFER testing. What does this testing include?

PSA and DRE

When should discussion for prostate cancer screening take place for men with an average risk?

age 50 (and expected to live atleast 10 years)

When should discussion for prostate cancer screening take place for men with a high risk?

age 45 or 40

When should average risk men have a DRE and PSA?

54-69 (greatest benefit is in this age range)

When should high risk men have a DRE and PSA?

(african americans or those w/ FHX in first degree relative dx under age 65)

age 40-54

When is DRE and PSA testing NOT recommended?

over 70 or any man w/ less than 10-15 year life expectancy

What are the PSA reference ranges?

Balls said to just know that different age ranges have different target PSA levels and to not memorize the specific numbers

:-)

What is the tumor marker for prostate cancer?

PSA

What is the PSA level required for a dx of prostate cancer?

> 4.0 ng/ml

What level of increase per year in PSA requires a referral?

> 0.75 ng/ml

What not cancerous conditions raise PSA?

ejaculation w/in past 48 hours, bacterial prostatitis, acute urinary retention

Which test do you perform first- PSA or DRE? Why?

PSA bc there is a possibility of raising PSA if recent DRE

What is the gold standard for prostate cancer dx?

biopsy, 12-14 cores

How is prostate cancer graded?

gleason score- evaluate the 2 largest centers of disease

correlates w/ tumor volume, pathologic stage, and prognosis

How is prostate cancer staged?

TNM staging system

What is the tx for prostate cancer?

watchful waiting (not harmful w/ mild sx)

can consider bisphosphonate therapy for bone metastases

What are possible side effects of tx for prostate cancer?

incontinence and impotence

When is tx required for prostate cancer?

urethral and outflow obstruction, renal failure, recurrent UTI, hematuria, bladder stones

What is used for hormone therapy in prostate cancer?

leutinizing hormone releasing hormone (LHRH)

lower amount of testosterone is made by testicles and can cause a flare initially, but this can be prevented by giving anti-androgens a few weeks prior

What are possible preventative measures for prostate cancer?

yearly PSA & DRE, low fat diet, lycopene, increased soy diet, selenium, vitamin E

what accounts for 8—85% of all primary renal neoplasms?

RCC- renal cell carcinoma (originates in renal cell cortex)

What is the 2nd most common kidney cancer?

transitional cell carcinoma of the renal pelvis

What kidney cancer is common in children?

nephroblastoma (wilm’s tumor)

What rare form of RCC is seen in sickle cell?

renal medullary carcinoma

Who is RCC 50% more common in?

men

When does RCC predominantly occur?

6th-8th decade (64 is median age of dx)

What subtype of RCC accounts for 75-85% of tumors?

clear cell

What is the classic triad of sx for RCC?

flank pain, hematuria, and palpable abdominal renal mass

What are the most common sites of metastases with RCC?

lung, lymph nodes, bone, liver, brain