What are the two genes associated with inherited cases of breast cancer called?

ANSWER : BRCA1 and BRCA2

how do BRCA1 and BRCA2 function normally? abnormally?

ANSWER : -when functioning normally, these 2 genes act as tumor suppressor genes. This means that 

they help repair DNA damage and prevent cancer cell formation

what % of all breast cancers are associated with BRCA1 and BRCA2 mutations?

ANSWER : about 5-10%

what is the avg US woman’s chance of developing breast cancer? how does this stat change if the 

woman has a BRCA gene mutation?

ANSWER : It is estimated that an average woman in the US has a *12%* chance of developing breast 

cancer in her lifetime. This risk increases to up to *85%* if the woman has a mutated BRCA1 or BRCA2 

gene

sporadic cancer

ANSWER : occurs by chance… people with this type typically don’t have relatives with this type

familial cancer

ANSWER : caused by a combination of genetic and environmental factors

hereditary cancer

ANSWER : an altered gene is passed down in the family from parent to child

what are some signs of a BRCA2 mutation?

ANSWER : -both males and females are affected, and there’s no sign of ovarian cancer

How many nucleotides does BRCA2 contain? How many mutations? What do these mutations do to the 

DNA? What will happen to the protein produced by this gene?

ANSWER : -the BRCA2 gene contains more than 80,000 nucleotides and is larger than the average gene

Marker Analysis

ANSWER : technique where the gene mutation is analyzed using a genetic marker instead of directly 

analyzing the gene itself

genetic markers

ANSWER : -short sequence of DNA associated with a particular gene or trait with a known location on a 

chromosome

the genetic markers used in marker analysis are…

ANSWER : short DNA sequences called short tandem repeats

names for short tandem repeats

ANSWER : STRs; microsatellites

An STR is…

ANSWER : a region of DNA composed of a short sequence of nucleotides repeated many times.

do different ppl have different # of STRs?? what does this mean???

ANSWER : Yes: the number of repeated sequences in a given STR varies from person to person.

how can we use STRs to distinguish ppl?

ANSWER : Most STRs occur in gene *introns* (non-coding regions of DNA) so the variation in the number 

of repeats does not usually affect gene function, but we can use STRs to differentiate between different 

alleles.

relationship between the gene of interest and the genetic marker

ANSWER : because pieces of DNA that are near each other on a chromosome tend to be inherited 

together, an STR that is located on chromosome 13 next to the known BRCA2 mutation can be used as 

the genetic marker for this case

how will this genetic marker testing work? (starting with collecting samples)

ANSWER : 1. DNA is extracted from each family member 2. The region of DNA containing the STR which 

is going to be used as the genetic marker for this mutation is amplified using PCR 3. The amplified DNA 

will then be run on a gel using gel electrophoresis —because different alleles have a different number of 

repeats present in the STR, gel electrophoresis will separate different alleles based on the # of repeats 

present 4. the more repeats present in the STR, the longer the DNA fragment will be

what is loaded in the first well of the gel?

ANSWER : DNA size markers (a set of DNA fragments of known molecular sizes). They can be used as a 

standard to determine the sizes of unknown fragments

to construct a standard curve, you need to…

ANSWER : plot the relative mobility value (Rf) for each standard marker versus their molecular size in 

base pairs on a semi-logarithmic graph

Rf is BASICALLY

ANSWER : how fast the DNA moves

women who have an abnormal BRCA1 or BRCA2 gene have…

ANSWER : a 50-80% risk of breast cancer by the age of 70. Lifetime risk of ovarian cancer is also 

increased

nutrition (preventative measures of cancer)

ANSWER : overweight women are thought to be at higher risk for breast cancer because the extra fat 

cells make estrogen, which can cause extra breast cell growth. Also, eating without pesticides may 

protect against unhealthy cell changes associated with pesticide use in animal studies

physical activity (preventative measures of cancer)

ANSWER : exercise consumes and contains blood sugar and limits blood levels of insulin growth factor, a 

hormone that can affect how breast cells grow and behave

hormonal or anti-estrogen therapy (preventative measures of cancer)

ANSWER : estrogen makes hormone-receptor-positive breast cancers grow. So reducing the amount of 

estrogen or blocking its action can reduce the risk of early-stage hormone-receptor-positive breast 

cancers coming back after surgery

prophylactic surgeries

ANSWER : surgery that removes one or both breast to reduce the risk of developing breast cancer by 

90-95% *in those that have a BRCA mutation)

What is the harm associated with breast cancer screening?

ANSWER : Risk for false-positive findings

How does screening possibly cause harm?

ANSWER : Screening leads to identification of a breast cancer that would not have caused clinical 

consequences in a women’s lifetime had it not been detected

All pts with dx of breast cancer, regardless of stage, require what?

ANSWER : Some sort of local therapy; surgery with or without radiation therapy & often systemic 

therapy

Is it possible to distinguish biologically insignificant cancers from those that will proceed to grow, 

metastasize & lead to pt’s death?

ANSWER : No, not possible

What is the most common cause for hereditary breast & ovarian cancers?

ANSWER : Presence of germline mutations in tumor suppressor genes & breast cancer type 1 & 2 

susceptibility genes (BRCA 1 & 2)

What is the criteria for genetic risk evaluation for breast cancer and/or ovarian cancer?

ANSWER : Known mutation in family of a gene

What is considered first degree relative?

ANSWER : Siblings Parents Children

What is considered second degree relative?

ANSWER : Half-siblings Grandparents Aunts Uncles Grandchildren Nieces Nephews

What is considered third degree relative?

ANSWER : First cousins Great-grandparents Great-grandchildren

These features indicated increased likelihood of having what type of mutation:

ANSWER : BRCA mutations

What is the percentage of risk for breast cancer for BRCA1- associated cancers?

ANSWER : 50-85%

What is the percentage of risk for secondary primary breast cancer for BRCA1- associated cancers?

ANSWER : 40-60%

What is the percentage of risk for ovarian cancer for BRCA1- associated cancers?

ANSWER : 15-45%

What can BRCA 1 also increase risk of?

ANSWER : Prostate & colon cancers

What factors put a person at a higher risk for breast cancer?

ANSWER : Hx of chest radiation

Menarche at what age puts person at higher risk for breast cancer?

ANSWER : Menarche before age 12 yrs

True or false: current use of combination menopausal hormone therapy increase risk for breast cancer

ANSWER : TRUE

True or false: Moderate alcohol use compared with abstention increases risk for breast cancer

ANSWER : TRUE

Which resource omits breast density as risk factor?

ANSWER : NCI Breast Cancer Risk Assessment Tool

True or false: NCI Breast Cancer Risk Assessment Tool is more accurate for women with markedly positive 

family hx & women over 70 years

ANSWER : False, less accurate

What does Breast Cancer Surveillance Consortium focus importance on?

ANSWER : Breast density & age

For whom is the Ontario Family History Assessment Tool, Manchester Scoring System, Referral Screening 

Tool, Pedigree Assessment Tool, & Family History Screen 7 useful for?

ANSWER : Women with family hx of breast cancer

True or false: Many women who develop breast cancer do not fall into a clear high-risk group

ANSWER : TRUE

True or false: No low-risk groups, other than young age, have been identified in which screening can 

clearly be omitted

ANSWER : TRUE

By what percentage does screening reduce breast cancer mortality?

ANSWER : 15-20%

Screening causes reduction in breast cancer mortality smaller magnitude & less statistically significant for 

which age group of women?

ANSWER : 40-59

Reduction is highly significant with screening in which age group of women?

ANSWER : 60-69

Reduction has not been shown to be significant in which age group of women with screening?

ANSWER : 70-74

True or false: screening has shown to reduce all-cause mortality

ANSWER : FALSE

What are the harmful effects of false positive results?

ANSWER : Unnecessary follow-up tests & biopsies

What are the harmful effects of overdiagnosis?

ANSWER : Cancer that would never have progressed to clinical importance in absence of screening

What is another harm of screening?

ANSWER : Radiation exposure- small risk

Initiating screening at age 40 averts how many breast cancer deaths?

ANSWER : 1 per 1000 deaths in women among ages 45-49

What percentage of breast cancer deaths were attributed to dx at age >74?

ANSWER : 0.26

How often should screening occur until remaining life expectancy is about 10 years?

ANSWER : Biennial- estimated to reduce breast cancer deaths & harms for women in their 70s

Benefit of screening is low among women greater than what age?

ANSWER : 80

What are the risk factors for women aged 40-49; more than 2 fold increased risk?

ANSWER : 1st degree relative with breast ca Age of 1st degree relative with breast ca <40-50 Prior benign 

breast biopsy result 2nd degree relative with breast cancer Breast density BI-RADS category 3

What are the risk factors for women aged 40-49; 1.5- 2.0 fold increased risk?

ANSWER : Prior benign breast biopsy result

What are the risk factors for women aged 40-49; 1.0-1.5 fold increased risk?

ANSWER : Current oral contraceptive use

Who is annual screening recommended for?

ANSWER : Women with higher risk of breast cancer

Does sensitivity & specificity of digital mammography increase or decrease with age?

ANSWER : Increases

Does sensitivity & specificity of digital mammography increase or decrease with increasing breast 

density?

ANSWER : Decreases

Does 3-D mammography (tomosynthesis & digital mammography) improve or reduce sensitivity & 

specificity?

ANSWER : Improve

Is contrast-enhanced MRI more or less sensitive/specific than mammography?

ANSWER : More sensitive but less specific

What screening method is best for average risk women?

ANSWER : Mammogram

What screening method is best for increased breast cancer risk?

ANSWER : Tomosynthesis

What screening method is expensive & has lack of evidence for effectiveness in average-risk women bc of excessive false positives?

ANSWER : MRI

What screening method has no evidence that it improves results over mammography screening for 

average-risk women?

ANSWER : Ultrasonography

Does instructing average risk women to do breast self-exam improve mortality?

ANSWER : No, causes excess benign biopsies

What can be added to mammography for high risk patients?

ANSWER : Breast MRI

What should be considered when making a decision about screening?

ANSWER : Woman’s values

What is appropriate for women with extremely dense breasts & those with 1-2 first degree family 

members with breast cancer?

ANSWER : Annual screening & digital breast tomosynthesis

Who should the MRIs be reserved for?

ANSWER : Women who are very high risk

What is the role of genetic counseling?

ANSWER : Reduces worry about breast cancer & increases the accuracy of risk perception

Who should be offered genetic counseling & testing?

ANSWER : Women with ≥1 family members with BRCA1 / BRCA2 mutation

What are the options for prevention in eligible women?

ANSWER : Healthy lifestyle

What type of healthy behaviors can reduce breast cancer risk?

ANSWER : Physical activity reduces breast cancer risk about 12%

For women with hereditary breast cancer mutations, what is an effective alternative to 

chemoprophylaxis?

ANSWER : Prophylactic bilateral mastectomy

What do selective estrogen receptor modulators (SERMS) ex. Tamoxifen, Raloxifene- do?

ANSWER : Stimulate some estrogen receptors while blocking others

What do aromatase inhibitors (AIs) ex. Anastrazole, exemestane- do?

ANSWER : Inhibit the enzyme aromatase, which converts androgens to estrogens

What are the harms of SERMs?

ANSWER : Tamoxifen: endometrial cancer and VTE (RR 2.0) for women ≥50 yrs

What are the harms of AIs?

ANSWER : Anastrozole: musculoskeletal side effects, hypertension, vaginal dryness, vasomotor 

symptoms

Tamoxifen or raloxifene: women more likely to remain sexually active & to have less difficulty with sexual 

interest and enjoyment

ANSWER : Tamoxifen

Tamoxifen or raloxifene: reduced risk for uterine cancer & slightly lower risk for VTE

ANSWER : Raloxifene

What is the mainstay of screening for breast cancer?

ANSWER : Mammography

What does mammography do?

ANSWER : Measure changes in the movement of protons in fat & water with the application of changing 

magnetic fields

What contrast agent needs to be administered for mammography?

ANSWER : Gadolinium

What are the two most important mammography indicators of breast cancers?

ANSWER : Masses Microcalcifications

What are microcalcifications?

ANSWER : Tiny flecks of calcium – like grains of salt – in the soft tissue of the breast that can sometimes 

indicate an early cancer

What type of appearance do malignant masses have?

ANSWER : Spiculated appearance

What type of tissue may hide tumors?

ANSWER : Fibroglandular tissue

The breasts of which women contain more glands & ligaments resulting in dense breast tissue?

ANSWER : Younger women

With age, breast tissue becomes more what?

ANSWER : Fatty & has fewer glands