Hereditary Breast Cancer Risk JUNE MIKKELSON, MS, CGC CERTIFIED GENETIC COUNSELOR CLINICAL GENETICS SERVICE, ROSWELL PARK
Hereditary Breast
Cancer Risk
JUNE MIKKELSON, MS, CGC
CERTIFIED GENETIC COUNSELOR
CLINICAL GENETICS SERVICE, ROSWELL PARK
Objectives
Identify genes/hereditary conditions associated with
breast cancer risk
Describe current testing options for hereditary
cancer (targeted vs. panel)
Describe the importance of genetic testing for
treatment planning and prevention of future cancer
risk.
Genetic Counseling
GC’s are Master’s level trained medical providers specializing in hereditary disorders
National certification; state level licensure in some areas
Cancer genetics is a subspecialty
Typical consultations take ~90 minutes
Obtain pertinent personal medical history information
Construct genetic pedigree (3-generation family tree)
Risk assessment
Counseling: differential diagnosis, testing options, limitations and benefits, screening/management options, and address legal, privacy, psychosocial issues
Family history - ASCO
Obtain family history of cancer/ precancerous conditions (3 generations)
1st - Parents, siblings, children
2nd - Grandparents, aunts/uncles, grandchildren, nieces/nephews
3rd - first cousins, great- grandparents, -aunts/ uncles
Document diagnosis, age of onset, current age/age of death
Clarify diagnoses (ex. Cervical vs. uterine vs. ovarian cancer)
Update at least yearly
Identifying Patients (NCCN)
Personal diagnosis
Breast cancer <45
TNBC <60
Male breast cancer
Bilateral (first diagnosis under age 50)
Malignant phyllodes tumor
At any age PLUS family history:
breast, ovarian, pancreatic, prostate
Ancestry (Ashkenazi Jewish)
Individuals with multiple and/or rare cancers (ex. Sarcoma)
Identifying Patients
Best person to test in a family is an
affected individual with the most
significant history
Hereditary breast and ovarian
cancer syndrome - BRCA1/2
BRCA2
45-70% risk for female breast cancer
up to 60% risk for second primary
10-20% risk for ovarian cancer
Others
Male breast: up to 8%
Prostate: 17% for early onset
Pancreatic: up to 8%
Others
BRCA1
up to 50-87% risk for female breast cancer
up to 60% risk for second primary
~44% risk for ovarian cancer
Others
Male breast:1-2%
“elevated” risk for prostate and others
Breast Cancer
6/8/2015
+/- BRCA1 5385insC0:11
48
38 breast
38 breast
L breast stage2B, ER/PRR breast stage 1 ER/PR
chemo, radiation, mastectomyat 47, stage 4 metastatic
hormone tx. nowBRCA1 pos (5385insC)
BSO 2006nephrectomy x1
d/t angiomyolipoma (RPCI)
benign parthyroid tumor(removed)
+
0:12
50
40 breast
mastectomychemo/rad
BSO
BRCA1 pos (5385insC)
+
0:13
53
no genetic testing
0:16
55
reportedly BRCA1 neg.
-1:678
-1:8
d. 68 Parkinson's
34 breast
mastectomychemo/rad
TAH-BSO 30's
-2:5
d. 60's 60's leukemia
-1:1070's
-1:11
d. <1
-1:580's
40's colorectal
0:10
-1:4
3
-2:1 -2:2 -2:3
-1:750's
NHLlate 20's lymphoma
-2:6
d. 20's pnu
-2:4
-1:960
50's breast
-2:7
-1:1255
43 breast
mastectomychemo/rad
brain aneurysm @52
-1:1370's
50's breast
chemo/rad
-1:1450
45 breast
mastectomychemo/rad
0:14
2
0:15
d. 19
brain
0:17 0:18 0:19
4
0:20 0:21
BRCA1
Cancer risks
Breast
Ovarian
Others
Male breast
Prostate
? Colon, pancreatic, others
Management
Breast
MRI at age 25-29
Add mammogram at 30
Consider RR mastectomy
Ovaries
Consider TV-US/ CA-125
RR BSO age 35-40
Males
Consider PSA/DRE at 45
CBE at 35
BRCA1 continued
Management
Additional treatment option (clinical trial/ off label)
PARP inhibitors
Identify at risk relatives, etc.
Early detection
Prevention
Colon Cancer?
50 yo woman diagnosed
with colon cancer…
Not Lynch
6/8/2015
Portuguese, English/ No AJ
Clinical Genetics Service
Date Created: 9/7/12, jw
Updated: 09/12/12, 12/12/12 - AS
Scottish, other unk. ancestry/ No AJ
1:755
50 colorectal
rectal adenocarcinoma;nl. IHC/ inconclusive MSIbenign colon polyp 2012;
uterine fibroids;fibrocystic breast dis;one benign breast bx
nl. PTEN research test result
*
2:133
2:231
1:8
d. 30 car accident
1:1060
2:336
2:441
1:951
0:5
d. 89 MI/aneurysm? squamous cell ca
squamous cell caof hands/face/earsaortic aneurysm
0:6
d. 82 breast ca70's lymphoma
82 breast
Waldenstrom's dis in 70'sut/ovaries intact
no polyps
0:7
d. 91 ~80 prostate
possible sx. for cancerbrain aneurysm ~50's
1:1166
-1:3
d. 77 lung ca74 lung
hx smoking
-1:4
d. 85 breast ca~50's? breast
~50's-breast ca and"recurrence" approx 30y later
(double mastectomy);also possible hx of
uterine or other "female" cain ~40's??;
pt advised records destroyed
0:4
d. 80 cancer72 lung
non-small celllung ca;
hx smoking,agent orange exp
0:3
d. 50 heart attack
0:2
d. 70s aortic aneurysm
0:1
d. 20 cerebal palsy
0:0
d. 1 acidosis
1:5
2
1:61:3
2
1:1
2
1:2
2
-1:1
d. 65 aortic aneurysm
-1:2
d. 85 heart failure/surgery
1:4
d. 45 melanoma melanoma
1:12early 60's
1:13late 50's
Cancer site 1 = colorectal
Cancer site 1 = prostate
Cancer site 2 = breast
Cancer site 1 = lung
Cancer site 1 = lymphoma
Cancer site 1 = melanoma
Cancer site 1 = squamous cell ca
Cancer site 1 = breast
BRCA1!
6/8/2015
Portuguese, English/ No AJScottish, other unk. ancestry/ No AJ
+/- BRCA1 c.3331_3334delCAAG 1:757
50 colorectal58 breast58 breast
rectal adenocarcinoma;nl. IHC/ inconclusive MSIbenign colon polyp 2012;
uterine fibroids;fibrocystic breast dis;one benign breast bx
nl. PTEN research test resultLeft IDC triple pos
Right IDC triple negativeBRCA1 c.3331_3334delCAAG
*
2:133
2:231
1:8
d. 30 car accident
1:1063
2:336
2:441
1:954
54 breast
TNBCBRCA1/2 neg
-
0:5
d. 89 MI/aneurysm? squamous cell ca
squamous cell caof hands/face/earsaortic aneurysm
0:6
d. 82 breast ca70's lymphoma
82 breast
Waldenstrom's dis in 70'sut/ovaries intact
no polyps
0:7
d. 91 ~80 prostate
possible sx. for cancerbrain aneurysm ~50's
1:1166
-1:3
d. 77 lung ca74 lung
hx smoking
-1:4
d. 85 breast ca~50's? breast
~50's-breast ca and"recurrence" approx 30y later
(double mastectomy);also possible hx of
uterine or other "female" cain ~40's??;
pt advised records destroyed
0:4
d. 80 cancer72 lung
non-small celllung ca;
hx smoking,agent orange exp
0:3
d. 50 heart attack
0:2
d. 70s aortic aneurysm
0:1
d. 20 cerebal palsy
0:0
d. 1 acidosis
1:5
2
1:61:3
2
1:1
2
1:2
2
-1:1
d. 65 aortic aneurysm
-1:2
d. 85 heart failure/surgery
1:4
d. 45 melanoma melanoma
1:12early 60's
1:13late 50's
Prostate Cancer?
62 yo male accompanied wife to CGS
consult d/t her personal/family history
Shared his personal and family history of
prostate cancer
Scheduled an individual consult and pursued
testing
12/5/2016Clinical Genetics Service
Date Created: 04/27/16
Updated: 06/13/16
PolishPolish
1:7
60
48 brain
59 breast
44y, dx frontal tumor following seizure
48y, craniotomy d/t enlargement
dx oligo-astrocytoma
54y, MRI noted progression
craniotomy dx anaplastic astrocytoma
tx chemo/rad
59y, dx R invasive ductal ca
(ER/PR-,Her-2+)
tx mast/chemo
BRCAPlus-Expanded tstg negative
2:1
32
2:2
28
1:8
56
2:3 2:4
0:6
d. 53 MI/stroke
0:7
87
TAH d/t DUB
0:8
d. 80
0:9
d. 80 lupus
0:10
d. 70s hrt disease
0:12
d. 49
49 unknown cancer
0:12
d. 87 hrt disease
80s breast
0:13
d. 88 hrt disease
-1:3
d. 60 MI
-1:4
d. 70s hrt disease
0:0
d. 80 hrt disease
0:1
d. 60 hrt disease
0:2
d. 19 ruptured appendix
0:3
d. 70s hrt disease
0:4
d. 70s hrt disease
0:5
d. 80s hrt disease
-1:1
d. 80 MI
-1:2
d. 40s/50s
1:1
prostate
0:4
prostate
1:1
prostate
12/5/2016 Clinical Genetics Service
Date Created: 06/13/16
Updated: 07/19/16
*Medical Records Received
PolishPolish
1:5
62
52 prostate
gleason 7
tx radical prostatectomy
hx colon polyps
2:1
32
2:2
29
1:6
72
1:7
68
60 prostate
tx radical prostatectomy
now under eval for
metastases
1:8
57
0:3
d. 72
69 prostate
0:4
d. 94
2:3
35 testicular
2:4 2:5
0:5
d. heart disease
0:6
d. heart disease
0:7
d.
leukemia
0:8
d. 60s
0:9
d. Crohn's disease
0:10
d.
-1:3
d.
-1:4
d. 70s/80s
1:9
2
1:10
3
1:11 1:15
3
1:16
2
1:17 1:18
2
1:12
d. 50s
ovarian
1:14
d. 50s
ovarian
1:13
2:13
BRCA+
*
2:11
30s brain
2:12 2:14
30s breast
BRCA+
0:0
d. 50s/60s
0:1
d. 50s/60s
lung
smoker
0:2
d. 90s
-1:1
d. 70s
-1:2
d. 70s
2:6
3
2:7 2:8
4
2:9 2:10
d.
30s breast
2:15
40s testicular
2:16
d.
31 breast
2:17
d.
developmentally
disabled
possible hx brain tumor
1:1
2
1:2 1:3
2
1:4
2
BRCA2
Cancer Risks BRCA2
45-70% risk for female breast cancer
up to 60% risk for second primary
10-20% risk for ovarian cancer
Others
Male breast: up to 8%
Prostate: 17% for early onset
Pancreatic: up to 8%
Others
Management Additional treatment option
(clinical trial/ off label)
PARP inhibitors
Consideration of pancreatic cancer screening
Identification of at-risk family members
Early detection
Prevention
Family planning (Fanconi Anemia)
Young, multiple cancers
43 yo female
Breast cancer diagnosed at age 32 – treated in
community
Leiomyosarcoma diagnosed at age 40 – treated at Roswell Park!
Eventual referral from community to CGS
5/12/2016 Clinical Genetics Service
Date Created: 02/17/16 JM
Updated: 04/06/16 JM
* records received
French Canadian/ No AJGerman/ No AJ
1:543
32 breast40 sarcoma
R IDC (glycogen rich, clear cell carcinomafeatures) - ERpos, PR neg, HER2 pos
s/p R mastectomy (Lindfield)R calf cutaneuos
leiomyosarcoma - RPCI
*
2:314
2:412
1:445
1:639
0:368
0:467
CancerNext (32 genes,Ambry 2015)
pos. BRIP1 (p.R798*)
*
2:1
2
2:2 2:5
0:572
0:6 0:7 0:8 0:9 0:10
d. 58 acc.
0:12
TP53 neg
0:1347
-1:3
d. 52 MI
-1:2
d. 70 acc.
-1:4
d. 73 Alz.
-1:593
-1:1
0:260s
no info
0:0
d. EtOH
0:1
d. 70s
0:11
TP53 neg
1:17 1:18
2
1:1928
28 breast
TP53 pos.
1:3
d. teen acc.
1:1
N
1:2
N
1:7 1:8 1:9 1:10
CP
1:11
2
1:12 1:13
3
1:14
2
1:15
3
1:16 1:20
2
5/12/2016 Clinical Genetics Service
Date Created: 02/17/16 JM
Updated: 04/06/16 JM
* records received
French Canadian/ No AJGerman/ No AJ
1:543
32 breast40 sarcoma42 colorectal
R IDC (glycogen rich, clear cell carcinomafeatures) - ERpos, PR neg, HER2 pos
s/p R mastectomy (Lindfield)R calf cutaneuos
leiomyosarcoma - RPCIinv. moderately diff.
adenocarcinoma of transverse colonCancerNext (32 genes, Ambry 2016)
pos. TP53 - p.E298*APC VUS (p.T1445A)
*
2:314
2:412
1:445
1:639
0:368
0:467
CancerNext (32 genes,Ambry 2015)
pos. BRIP1 (p.R798*)
*
2:1
2
2:2 2:5
0:572
0:6 0:7 0:8 0:9 0:10
d. 58 acc.
0:12
TP53 neg
0:1347
-1:3
d. 52 MI
-1:2
d. 70 acc.
-1:4
d. 73 Alz.
-1:593
-1:1
0:260s
no info
0:0
d. EtOH
0:1
d. 70s
0:11
TP53 neg
1:17 1:18
2
1:1928
28 breast
TP53 pos.
1:3
d. teen acc.
1:1
N
1:2
N
1:7 1:8 1:9 1:10
CP
1:11
2
1:12 1:13
3
1:14
2
1:15
3
1:16 1:20
2
Cancer site 1 = breast
Cancer site 3 = colorectal
Li-Fraumeni syndrome
SBLA
Sarcoma
Breast/brain
Leukemia (acute)/ lymphoma
Adrenocortical carcinoma
Li-Fraumeni syndrome
Cancer risks >90% cancer risk by age 60
Risk for multiple malignancies
Almost every type of cancer has been reported
Malignancy risk in early life
Management FULL BODY and brain MRI
yearly (at time of dx.)
Breast MRI (age 20) and mammogram (age 30)
Colonoscopy (age 25 q2-5y)
Dermatologic exam (age 18)
Avoid radiation
Trials – blood work, others
Two adolescent sons – proactive management
Who to test?
50 yo female w/ history early-onset
breast cancer and mother with
ovarian cancer
BRCA1/2 negative (2010) – prior to
multigene panels
12/5/2016
Irish,Czech/ No AJ Irish, French/ No AJ
Clinical Genetics Service
Date Created: 12/08/09
Updated: 03/09/16, 04/12/16 JM
2:8
50
44 breast
L multifocal IDC
(ER/PR pos, Her-2 neg)
L mastectomy
BRCA1/2 neg (2009)
3:1
18
3:2
16
2:9
51
2:10
46
1:5
80
70 sarcoma
on calf;
tx leg amputation
(above the knee)
hx. colon polyps
no genetic testing
1:6
d. 64
59 ovarian
tx BSO, TAH, chemo
no genetic testing
1:7
70
0:2
d. mid 70's heart attack
cataracts
0:3
d. 80's 'older age'
1:0
82
1:4
d. 80
40s colorectal
thinks had another
cancer dx.
kidney rem'd in 60s
1:1
76
1:2
65
1:3
60
late 30's ovarian
0:0
d. 70's n/c
0:1
d. 80's n/c
3:4
15
3:3
16
3:5
19
3:6
16
3:7
14
3:8
9
2:11 2:122:4
3
2:52:2 2:3 2:6
2
2:72:1
3
12/5/2016
Irish,Czech/ No AJ Irish, French/ No AJ
Clinical Genetics Service
Date Created: 12/08/09
Updated: 03/09/16, 04/12/16 JM
* records rec'd
2:8
50
44 breast
L multifocal IDC
(ER/PR pos, Her-2 neg)
L mastectomy
BRCA1/2 neg (2009)
3:1
18
3:2
16
2:9
51
2:10
46
46 prostate
Gleason 7
sx, rad, now pill
hx. colon polyps
*
1:5
80
70 sarcoma
on calf;
tx leg amputation
(above the knee)
hx. colon polyps
no genetic testing
1:6
d. 64
59 ovarian
tx BSO, TAH, chemo
no genetic testing
1:7
70
0:2
d. mid 70's heart attack
cataracts
0:3
d. 80's 'older age'
1:0
82
1:4
d. 80
40s colorectal
thinks had another
cancer dx.
kidney rem'd in 60s
1:1
76
1:2
65
1:3
60
late 30's ovarian
0:0
d. 70's n/c
0:1
d. 80's n/c
3:4
15
3:3
16
3:5
19
3:6
16
3:7
14
3:8
9
2:11 2:122:4
3
2:52:2 2:3 2:6
2
2:72:1
3
12/5/2016
Irish,Czech/ No AJ Irish, French/ No AJ
Clinical Genetics Service
Date Created: 12/08/09
Updated: 03/09/16, 04/12/16 JM
* records rec'd
2:8
50
44 breast
L multifocal IDC
(ER/PR pos, Her-2 neg)
L mastectomy
BRCA1/2 neg (2009)
3:1
18
3:2
16
2:9
51
2:10
46
46 prostate
Gleason 7
sx, rad, now pill
hx. colon polyps
*
1:5
80
70 sarcoma
on calf;
tx leg amputation
(above the knee)
hx. colon polyps
no genetic testing
1:6
d. 64
59 ovarian
tx BSO, TAH, chemo
no genetic testing
1:7
70
0:2
d. mid 70's heart attack
cataracts
0:3
d. 80's 'older age'
1:0
82
1:4
d. 80
40s colorectal
thinks had another
cancer dx.
kidney rem'd in 60s
1:1
76
1:2
65
1:3
60
late 30's ovarian
0:0
d. 70's n/c
0:1
d. 80's n/c
3:4
15
3:3
16
3:5
19
3:6
16
3:7
14
3:8
9
2:11 2:122:4
3
2:52:2 2:3 2:6
2
2:72:1
3
MSH2 + MSH2 -
Lynch syndrome
Cancer risks Risk for breast cancer NOT
well defined!
Risks
Colon: up to 80%
Uterine: up to 60%
Ovarian: up to 24%
Others: stomach,
pancreatic, ureter, renal
pelvis, skin, brain
Management NO recommendations for
breast
Colonoscopy every 1-2
years starting at 25
Consider prophylactic TAH-
BSO
Other? – per fhx.
Personal and family history of
NOT cancer….
44 year old recently diagnosed with breast cancer
Personal history:
Astrocytoma
Freckling
CALs
Skin bumps
Fhx. mother diagnosed with a GIST, brother
diagnosed with glioblastoma
Neurofibromatosis type 1
www.google.com (images)
Neurofibromatosis type 1
Cancer Risks
Breast cancer
4x increased risk at <50
GISTs
Brain tumors/cancer
Optic nerve
Malignant peripheral nerve
sheath tumors
Management
Mammogram and MRI from
30-50
Annual PE with
developmental screen
Annual dermatologic exam
Annual ophthalmologic
Regular BP eval
Family History
56 yo female
Mother diagnosed with ovarian cancer; GYN
screening w/ CA-125 and TV-US yearly
Recent elevated CA-125 (165)
Referral to Roswell Park – negative CT
12/5/2016
German/ No AJItalian/ No AJ
1:8
56
CA-125, TV-US x10 yrs
recent elevated CA-125
1:9
55
42 breast
BRCA neg (2003)
0:6
d. 73
71 lung
smoker
MI @50
0:7
d. 48
45 ovarian
tx. Buffalo General Hosp.
smoker
0:5
1:6
67
TAH d/t fibroids
(unk. if ovaries rem'd)
1:7
57
-1:4
d. 70 mets
unknown cancer
thinks stomach primary
hx. ulcers
-1:5
d. 102
90 colorectal
benign breast
lump rem'd
0:4
d. 80 mets
65 breast
lung, brain mets
0:3
d. mid 60s mets
50s renal
lung, brain mets
thinks smoker
tx. at VA
0:0
3
0:1 0:2
late 70s
-1:2
d. late 60s
-1:3
d. 50 compl surgery
brain tumor
(unk. if malignant)
1:1
N
1:2
N
1:3
N
1:4
60s
1:5
60
50 breast
-1:1
ovarian
-2:1
ovarian
2:1 2:2 2:3
27
2:4
25
2:5 2:6
BRCA1 and BRCA2 positive
Cancer Risks
Quote highest risk
associated with each
BRCA1 and BRCA2 – not
additive
More common in those with
Ashkenazi Jewish ancestry
1 in 40 carrier frequency
Management
As both BRCA1 and BRCA2
pos
At risk relatives (sibs/kids)
50% risk for EACH BRCA1
and BRCA2
Multiple primaries
Personal history
Breast at 38
Thyroid at 54
Breast at 63 (opposite breast)
Family history
Multiple relatives with colon cancer
CHEK2 6/8/2015
--- EtOH/ drugs ---
+/- CHEK2 c.1263delT
Native America, unspecified
Caucasian/ No AJ German, Hungarian/ No AJ
1:6
66
38 breast
54 thyroid
63 breast
R breast mastectomy at 38
thyroidectomy d/t
microfocus of papillary carcinoma
L breast mastectomy 2012
TAH-BSO @ 34
col'y 12/2014 +1 polyp
positive for CHEK2 mutation
(c.1263delT), Ambry 2014
+
1:8
57
congenital blindness
lives in group home
2:4
47
copropoporhyria
breast lump (benign)
screened every 6 mo.
ut/ov intact
2:5
44
40's skin-unspecified
nl. mammog's
ut/ov intact
2:6
32
nl. mammog's
0:3
d. 75 sclerosis of liver
70 lung
0:4
d. 42
40 colorectal
0:7
d. 78
44 colorectal
had 2-3 surgeries,
colostomy
EtOH
(foster mother)
-1:3
d. 88 no cancer
-1:4
d. 80
79/80 colorectal
1:7
d. 3 wks.
1:9
65
EtOH
1:10
64
EtOH
1:11
d. 55 cirrhosus
EtOH
1:5
d. 67 mets
66 breast
bipolar
EtOH
?mastectomy
3:1
26
3:4
2
3:6
9 mo.
3:5
6
3:3
14
spina bifida
3:2
25
2:7
38
2:8
30
2:9 2:10 2:11 2:12
no info
2
0:5
2
0:2
1:12
72
69 colorectal
hx. colon polyps
EtOH
1:13
70
EtOH
1:3
early 70's
1:4
early 70's
0:8
d. 62
lung
smoker
0:9
d. 64
pancreas
worked at GM
smoker
EtOH
0:10
d. 80
79 prostate
0:11
75
some EtOH
0:12
d. 60's
lung
smoker
EtOH
0:6
d. 60 MI
EtOH
0:0
d. mid 70's
0:1
no info
n
2:1
n
2:2
n
2:13
6
1:14 1:15
3
1:16 1:17
d. 45 in sleep
developmental
disabilites
1:18 1:19 1:20
2
1:21 1:22
3
-1:1
d. <50 no info
-1:2
d. <50 no info
1:2
n
1:1
2:3
Cancer site 1 = skin-unspecified
Cancer site 1 = colorectal
Cancer site 1 = prostate
Cancer site 1 = lung
Cancer site 1 = pancreas
Cancer site 2 = thyroid
Cancer site 3 = breast
Cancer site 1 = breast
CHEK2
Cancer Risks Breast cancer
2-3x
Colon cancer
2x
Others
Uterine
Thyroid
Prostate
Melanoma
More!
Management Breast MRI in addition to
mammograms
Colonoscopy at age 40 and continue every 5 years
Other
Based on fhx.
Family history
51 yo female with metastatic breast cancer
First diagnosed with colon cancer 36
>80 polyps – clinically managed as FAP
Breast cancer diagnosed at 46 – just under 5
years later was found to have diffuse
metastatic disease
MAP
MUTYH Associated Polyposis
Cancer Risks Colon polyps
(<100)/cancer
Duodenal polyps/cancer (5%)
OTHERS – not well defined
Management Colonoscopy at 25-30; every
2-3y
Upper endoscopy at 30-35
Others – per fhx.
Autosomal Recessive
25% risk to siblings
Risk to children depends on partner’s status (1% carrier frequency)
Tumor testing
54 yo female w/ recent diagnosis of breast
cancer
Previous negative testing for familial BRCA1
mutation
Evaluation for myelodysplastic syndrome – had
Foundation One testing on blood sample
Somatic testing
Analysis of the genetic make up of
cancer cells
Reflect acquired (somatic) changes in
the cancer cells
MAY identify alterations that are
hereditary
12/5/2016
*Medical records received
Scottish, English/ No AJScottish, Irish, French/ No AJ
3:7
54
53 breast
L invasive breast ca.
(ER/PR pos, Her-2 pos)
BRCA1 site-specific neg.
44y - eval for myelodysplastic sx.
Foundation One (on BM bx.)
pos. PALB2 mut.
(MAF 49%)
confirmed on clinical testing
of blood sample
*
2:4
d. 63 heart attack
2:7
d. 87 old age
46 ovarian
60 breast
80 breast
BRCA1 pos
*
1:3
d. 78 pneumonia
1:4
d. 38
38 breast
tx radiation
3:8
58
BRCA1/2 neg
*
2:8
d. 87 hrt failure
2:9
d. 69 heart probs
60s prostate
2:11
d. 72
no info
2:10
d. 10 polio
3:12
d.
breast
no info
2:3
d. 80s heart probs
2:2
d. 98 heart probs
80s colorectal
2:1
d. 70s heat probs
2:0
d. 60s
colorectal
1:1
d. 40s accident
1:2
d. 92 CHF
3:1 3:2
70's
unknown cancer
thinks colon primary
3:3
3
3:4 3:5 3:6 3:9
2
3:10
2
3:11
2
1:5
d. 50s/60s heart
1:6
d.
stomach
1:7
d.
renal
1:8
d.
colorectal
4:3 4:4
2
4:1 4:2
PALB2
Cancer Risks
Breast
2-4x
Pancreatic
“elevated”
?Prostate, Ovarian
Management
Breast MRI and
mammogram
Pancreatic screenings in
the presence of a fhx.
Others – per fhx.
Somatic testing
64 yo male
Prostate cancer
Metastatic gallbladder cancer at 63
Tumor testing – BRCA2 pos.
BRCA2 & PMS2!
BRCA2 and PMS2
Cancer Risks BRCA2
Breast/ovarian
Prostate
Lynch
Colon, Uterine,
Ovarian, Pancreatic,
Renal, Prostate, ?breast
Management
BRCA2
Lynch
Children at 50% risk for
each condition!
Treatment
Olaparib
Keytruda
Tumor testing - cautions
refer based on personal/ family history and
separately based on result
germline mutations may be revealed or
masked by testing tumor
blood sample = germline testing
Genotype: Phenotype
Multiple genes – all cause higher breast cancer
risk
May or may not be associated with other health/
cancer risks
Same genetic change in different individuals =
different outcomes
NOT 100% risk to develop cancer!
Value
Surgical decision making
Risk reducing surgeries/
enhanced screenings
Targeted therapies!