hereditary breast cancer risk - cancer treatmenthereditary breast and ovarian cancer syndrome -...

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


~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


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


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


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


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


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



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



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




Updated: 03/09/16, 04/12/16 JM

* records rec'd

2:8

50

44 breast

L multifocal IDC


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


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




Updated: 03/09/16, 04/12/16 JM

* records rec'd

2:8

50

44 breast

L multifocal IDC


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


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 = prostate

Cancer site 1 = lung

Cancer site 1 = pancreas

Cancer site 2 = thyroid



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

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!

QUESTIONS?

June Mikkelson, MS, CGC

[email protected]

845-7634

mailto:[email protected]

hereditary breast cancer risk - cancer treatmenthereditary breast and ovarian cancer syndrome -...

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