Cancer GC Flashcards
Prevalence of BRCA1/2
1/400
BRCA 1 contributes…
20-40% to HBOC
BRCA 2 contributes…
10-30% to HBOC
Genomic mechanisms associated with BRCA 1 and 2
Maintains genomic integrity Damage repair regulated gene expression ubiquinates proteins chromatin remodeling cell cycle control
How is BRCA inherited
Autosomal dominant
reduced penetrance
transmission through males and females
maternal and paternal history are important
Features of HBOC
- Multiple family members affected across several generations
- BC under the age of 50
- Epithelial ovarian cancer at any age
- Male breast cancer
- Multiple primary cancer diagnoses (esp bilateral BC)
- Triple negative breast cancer under the age of 60 (estrogen/progesterone/her2neu)
Other cancer risk
Male BC prostate cancer pancreatic cancer melanoma colon endometrial
Risk for second breast cancer
up to 50% lifetime risk
ER/PR+
Selective estrogen receptor modulators: tamoxifan if pre-menopausal and Raloxifene if post-menopausal (can also use aromatase inhibitors)
Her-2/neu+
herceptin antibody
triple negative
ER/PR and her-2/neu receptor negative
very common in women with BRCA 1 mutations
BRCA 1
- likely to be triple negative
- higher risk for ovarian cancer (44%)
- male breast cancer
- slight risk for melanoma, pancreatic cancer and prostate cancer
BRCA 2
- likely to be ER/PR+
- risk for ovarian cancer (27%)
- high risk for melanoma, pancreatic cancer and prostate cancer
- risk for male breast cancer
Testing for BRCA 1 and 2
comprehensive= 85% detection, looks at 5 rearrangements
BART= additional rearrangements, only increases detection 3%
Single site is done if mutation is known
3 site is done for the most common AJ mutations
Claus
lifetime cancer risk assessment, if greater than 20% add MRI to the screen
strengths: includes age, mat and pat history, age of affected family members and ovarian cancer
limits: maximum of 2 primary or secondary relatives, cannot be male, only for unaffected probands, must have a family history, and cannot include other risk factors
Gail
5 year cancer risk assessment for tamoxifen or raloxifene prescription ( >1.6% risk)
Strengths: incorporates information other than the family history
Limits: can only include 2 1st degree relatives, no ages, no paternal, no ovarian cancer, only calculates risk for women >35 yo
Myriad
risk table
Strength: easy to use, readily available
limit: biased population, not exact (age or number of relatives), doesnt incorporate anything other than breast and ovarian
BRCAPro
Bayes
Limits: depends on current mutation frequency and penetrance data, assumes all affecteds are due to BRCA 1 and 2, does not use prostate or pancreatic cancer, computationally intensive
Couch and TC
Assess risk for unaffected to develop BC not for ovarian, captures pedigree and personal medical history
Cleveland Clinic for PTEN
risk calculation based on a questionare, score decides if patient should get testing for PTEN, a score of 3% or higher indicates
Lynch syndrome
Right sided, multiple tumors with MSI histology and immunohistochemical results indicating.
Amsterdam I
3 family members with colon cancer (where 1 is a first degree relative of the other 2)
2 generations affected
1 colon cancer diagnosed prior to age 50
Rule out FAP
Amsterdam II
Same as Amsterdam I, but the three family members can have any of the associated lynch cancers; endometrial, ovarian, gastric, small bowel, urothelial, CNS, pancreatic
Lynch genes
MSH2: MSH6 only binds to this protein, if MSH2 is mutated will not show on IHC (MSH2 can also be hypermethylated, studies can confirm, but are rare)
MSH6
PMS2
MLH1: PMS1 only binds here
EPCAM: will show loss if MSH2 is missing.
NCCN for Lynch
colonoscopy every 1-2 years starting 2-5 years before earliest onset
BSO and hysterectomy after reproduction
no strict screening for other associated cancers
FCCTX
Familial colon cancer without MMR, MSI or IHC, but meets amsterdam I
Guidlines for FCCTX
colonoscopy every 5 years starting 5-10 years prior to earliest diagnosis
FAP
classic or attenuated, due to mutations in the APC gene or the MYH gene. very high cancer risk. 100-70%
NCCN Guidelines for FAP
test, monitor, colonoscopy, colectomy and polypectomy, monitor with endoscopy every 6-12 months
Li Fraumini
Rare AD caused by mutation in tp53, 50% risk of cancer by age 35. Sarcoma, brain, breast, adrenocortical carcinoma, leukemia.
Cowden
AD, PTEN, breast, thyroid, endometrial, renal cell, melanoma, colorectal
Peutz-Jegher
AD, STK11, colon, breast, pancreas, stomach, ovaries and others.
high risk genes
BRCA1/2, CDH1, EPCAM, MLH1, MSH2, MSH6, PMS2, PTEN, TP53, STK11, APC
Moderate risk genes
ATM, PALB2, CHEK2
Newer genes
BRIP1, BMPR1A, NBN, BARD1, RAD51C, RAD51D, CDKN
Stages of grief
Denial Guilt Depression Anger Acceptance
indications for referral
suspected malformation syndrome (multiple, dysmorphic appearance, unusual birth marks or a single defect, idiopathic developmental, growth or cognitive delay),
second opinion
relatives have a known diagnosis
goals of the evaluation
establish a diagnosis provide accurate individualized counseling (include recurrence risk) estimate prognosis provide treatment formulate a care plan obtain appropriate tests initiate referrals as needed offer support (always)
defense mechanisms
denial intellectualization regression repression sublimation reaction formation
coping mechanisms
problem solving support seeking talking doing withdrawal
4 tenets of GC
the relationship is integral
patient autonomy is supported
patients are resilient
patient emotions make a difference
Self-psychology
the self is dependent on maintaining a relational context and having experiences that fortify the self
Self in relation
deemphasizes concepts of individuation and separation for ego formation (encourages self empathy)
Family systems theory
we are all part of a family system and our responses to information will be influenced by the system at play in our family of origin as well as the cultural context in which we were raised. therefore individuals are best understood through family dynamics
approaches to family therapy
- strategic
- structural
- multigenerational
family systems illness model (genetic)
considers the unique challenges that genomic conditions present especially in at risk and asymptomatic individuals
systematically based psychotheraputic model
includes the genogram
links individuals to interactional and intergenerational issues in the scope of a genetics issue
early intervention services
0-3
developmental delay
premature/low birth weight/ postnatal illness or surgery
at risk groups
receive: physical, cognitive, social/emotional, communication and self help services
must have family participation
includes: family teaching model, transdisciplinary model, transition planning
Part B
3-21
education based
-vision, hearing, gross and fine motor, speech and language, social/emotional.
diagnosis vs developmental delay
reevaluated every 5 years, includes transition
Families participate in goad identification
Preschool services
3- age of beginner
- must have significant delay
- physical or mental disability
- and need special education and related services
- uses and IEP for school and aid services
- wraparound available for children W/ DSM 5 diagnosis
