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