Genetics

breast cancer

2nd most common cause of cancer related deaths

30

According to ACS 2018 recommendations, high risk patients should have a mammogram AND MRI yearly beginning at age _____.

40-44 45-54 55 and older 10 yr

According to the American Cancer Society (2018) recommendations for screening for women of average risk.... ◦ Age ______: option to start yearly mammograms ◦ Age ______: yearly mammograms ◦ Age ______: mammograms every other year or every year -- should be done while patients are in reasonable health and with another ____ year life expectancy.

no personal history no strong family history no genetic history no radiation to the chest prior to age 30

According to the American Cancer Society (2018), women of average risk is considered to be women with no ______, ______, ______, or ______

25-35

Annual mammogram beginning ages _____ if known family history of BRCA mutation

triple negative

BRCA 1 mutation is more likely to result in a ______ breast cancer

germline

BRCA mutations are considered ______ mutations: inherited and within all cells

tumor suppressor gene

BRCA mutations involve what gene?

20-25% 5-10% 15%

BRCA mutations make up... ◦ _____% hereditary breast cancer ◦ _____% of all breast cancer ◦ _____% of all ovarian cancer

90%

Bilateral mastectomy reduced risk in carriers by ____% in over a 6 year follow up

13%

Birth to death risk of breast cancer = ____%

2-3 years; endometrial and ovarian

For screening of HNPCC, it is recommended to have an upper endoscopy every ____ years and to undergo increased screening for _____ and _____ cancer

mismatch repair

HNPCC involves mutation in _____ genes

dominant

HNPCC is an autosomal _____ genetic disorder

right

HNPCC usually affects the [left/right] side of the colon

Breast Ultrasound

Helps determines if a lump is benign; uses high frequency sound waves; can tell if a lump is solid or cystic

HNPCC

Often other types of cancers in families with this genetic disorder...

Penetrance

Probability of someone with a deleterious mutation developing the disease; relative risk of developing disease

HNPCC

Rapid progression to cancer from polyps

1-2 yrs age 25 5 years

Relatives of those with HNPCC should have a colonoscopy every ____ yrs starting age ____ or ____ years younger than the youngest known affected family member

True

True or False: Yearly MRI screening is not recommended for women whose lifetime risk of breast cancer is less than 15%.

True: a biopsy is the true way to know if a lump/mass is cancerous or not

True or False: a mammogram alone cannot prove that an area of concern is breast cancer

True

True or False: genetic testing can focus on specific mutations as opposed to scanning whole gene

False; it occurs after a second mutation

True or False: hereditary breast cancer occurs after the initial mutation

True; it is the predisposition to cancer that is inherited

True or False: it is not actually the cancer that is inherited

False; not everyone with BRCA mutations will develop cancer, but will still pass BRCA mutation to offspring

True or False: those with the BRCA mutation that do not develop cancer will not pass on the gene to their offspring

Diagnostic mammogram - or used after an abnormal finding on a screening mammogram

Used to evaluate a breast problem or symptom

screening mammogram

Used to look for breast disease in those who appear to have no breast problems

cone compression view (mammography)

Used to make a small area of altered breast tissue easier to evaluate

40

Women age ____ & older should have a mammogram every year & should continue to do so for as long as they are in good health.

moderate; 15% to 20%

Women at ____ risk (____% lifetime risk) should talk with their doctors about the benefits & limitations of adding MRI screening to their yearly mammogram.

high; greater than 20%

Women at _____ risk (____% lifetime risk) should get an MRI & a mammogram every year.

20s & 30s; 3 yrs; 40

Women in their ____ should have a clinical breast exam (CBE) as part of a periodic (regular) health exam by a health professional preferably every ____ years. Starting at age ____, women should have a CBE by a health professional every year.

39% ; 11-17%

____% of women who inherit a harmful BRCA1 mutation & ____% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years

adenomatous

______ polyps may evolve into cancer

95%

a prophylactic bilateral oophorectomy reduces a persons risk by ____%

5 yrs

according to the American Cancer Society, CT colonography screening option is conducted every ____ yr(s)

45; 75-85

according to the American Cancer Society, colorectal screening should begin at age ____ and end at ages ____

5 yrs

according to the American Cancer Society, double contrast barium enema screening option is conducted every ____ yr(s)

1 yr

according to the American Cancer Society, fecal immunochemical test (FIT) screening option is conducted every ____ yr(s)

1 yr

according to the American Cancer Society, fecal occult blood test (FOBT) screening option is conducted every ____ yr(s)

5 yrs

according to the American Cancer Society, flexible sigmoidoscopy screening option is conducted every ____ yr(s)

3 yrs

according to the American Cancer Society, stool DNA test (sDNA) screening option is conducted every ____ yr(s)

Colonoscopy every 10 yrs

according to the American Cancer Society, the gold standard of colorectal cancer screening is _____

HNPCC (hereditary nonpolyposis colorectal cancer)

aka Lynch syndrome

colorectal cancer

any cancer from the cecum to the rectum; cells in the lining of the colon or rectum become malignant

Gardener Syndrome/Familial Colorectal Polyposis

bumps on bones of legs, arms, skull, and jaw; cysts in skin, teeth that don't emerge; freckles on inside lining of the eyes (severe form)

HNPCC

causes a 60-80% chance of developing colorectal cancer

FAP

causes a near 100% risk of colorectal cancer

Amsterdam Criteria II

criteria used for diagnosing HNPCC

APC-adenomatous polyposis coli tumor suppressor gene

familial adenomatous polyposis (FAP) involves a mutation in what gene?

autosomal dominant

familial adenomatous polyposis (FAP) is an autosomal _____ genetic disorder

breast cancer

most common cancer in women

Carcinoma insitu (CIS)

non-invasive & is the earliest form of breast cancer

5-10%

only ____% of breast and ovarian cancer are inherited

◦ Additional mutations ◦ Epigenetics ◦ Environmental factors (Smoking, Hormones, Chemicals)

penetrance is affected by what three factors?

55-65%

penetrance of BRCA 1 mutation is ______%

45-47%

penetrance of BRCA 2 mutation is ______%

three

there are how many rare syndromes associated with breast cancer?

perforation

there is a slight risk of _____ with colonoscopy

before menopause; bilateral; two

there is an increased risk of breast cancer if a person's 1st degree relative had breast cancer, especially if the cancer occurred _____, was _____, and/or if more than ____ 1st degree relatives

◦ Gender ◦ Age ◦ Positive family history

what are the 3 strongest risk factors for breast cancer?

· At least 3 relatives with a Lynch syndrome-related cancer · First degree relative · 2 successive generations · At least 1 diagnosed before age 50 · FAP excluded · Tumors verified through pathology

what are the 6 factors in the Amsterdam Criteria II for HNPCC?

◦ Does not detect all mutations ◦ Still risk of sporadic cancer ◦ Costs, emotional turmoil

what are the risks of BRCA screening?

· Genetic screening for children of patients: 10 yrs old · Yearly colonoscopy: 12 yrs old · Complete colectomy: by 20 yrs old if diagnosed

what are the three screening recommendations for those at risk for FAP?

· Transvaginal ultrasound · CA-125 serum level · Prophylactic bilateral oophorectomy

what are the three screening/management methods for ovarian cancer?

it enters the patient immediately into menopause

what is one consequence of a prophylactic bilateral oophorectomy?

it plays a role in base excision repair, so if mutated, it won't be able to fix errors that occur in DNA replication

what is significant about the MYH gene mutation of the APC gene involved in FAP?

Location

what is the main determinant of severity of FAP?

you cannot actually see the inside of the colon

what is the main problem with fecal screening tests such as FIT, sDNA, and FOBT?

NSAIDs, Vitamin C, red meat

what must a pt avoid 3 days prior to their fecal immunochemical test (FIT)?

stool DNA test (sDNA)

what type of colorectal cancer screening option is Cologuard?

Fine Needle Aspiration; Stereotactic Needle Biopsy

when a needle is used to remove fluid or a small amount of tissue from the breast done if lump cannot be palpated (US used to watch needle on screen as it moves into mass to take a sample)

founder effect

when specific mutations recur in generations of families (ex: Ashkenazi Jewish heritage)

36-85% 20-60%

with BRCA 1 mutation... · Lifetime risk for breast cancer: _____% · Lifetime risk for ovarian cancer: _____%

36-85% up to 27%

with BRCA 2 mutation... · Lifetime risk of breast cancer: _____% · Lifetime risk of ovarian cancer: _____%

2 polyps ; 1 cm

with adenomatous polyps, risk of colorectal cancer is increased if more than ____ polyps are found or if a polyp is greater than ____ cm