Hereditary Cancer Program’s High-Risk

Clinic: Experience to Date

Melissa Laing, Nurse Practitioner

Mary McCullum, Nurse Educator

April 2012

Objectives

1. To review the clinic’s first (almost) 15 years of experience

with high-risk screening for women with confirmed BRCA1

or BRCA2 gene mutations

2. To discuss related clinical challenges

Background

• Provincial interdisciplinary Hereditary Cancer Program

• High-risk clinic established in 1997 at BCCA-Vancouver

• Eligibility criteria includes women who are:

• confirmed BRCA1/2 mutation carrier OR at 50% risk

for known family BRCA1/2 mutation

• not currently under the care of an oncologist

• able to attend appointments in Vancouver

• have not completed risk-reducing bilateral mastectomy

• Referred by their genetic counsellor

• Also provide breast screening for a small number of women

with other hereditary cancer syndromes

Results to March 31, 2012

Chart review and basic database to describe:

• clinic participants

• new cancers diagnosed

• method of detection

• risk-reducing surgeries completed

• ongoing follow-up

Clinic Participants

• 498 women in total have been assessed to date

• 250 women are currently followed by the high-risk clinic

– majority are BRCA1/2+

– other syndromes: • Ataxia Telangiectasia (n=3)

• Li-Fraumeni (n=2)

• Hereditary Diffuse Gastric Cancer (n=4)

• age 18-79 at initial consult

• majority from greater Vancouver area

Health

Region

%

popln

% clinic

pts

Fraser 35 33

Vancouver

Coastal

25 34

Vancouver

Island

17 17

Interior 16 13

Northern 7 1.5

Yukon <1 1.5

Clinic

participants

(n=485)

n

(%)

No. with

breast ca

No. with

ovarian ca

No. with other

cancer

> 1 cancer

diagnosis

Declined

carrier test

41

(8%)

0 0 0 0

BRCA1+ 243

(50%)

59

Unilat 50

Bilat 9

9 2 Hodgkins

1 endometrial

1* cervical and

colorectal *also had br ca

71

BRCA2+ 199

(41%)

48

DCIS 2

Unilat 43

Bilat 3

6*

*1 also had breast

cancer

1 scc H/N

1 rectal

1 lymphoma

1 cervical

1* endometrial*also had br ca

58

BRCA1 &

BRCA2+

2

(0.4%)

0 0 0 0

Total

BRCA1/2+

444

(92%)

107

(24%)

15

(3.4%)* includes 1 who also

had breast cancer

9

(2%)* includes 1 who also

had breast cancer

129

(29%)

Cancers diagnosed prior to participation in high risk clinic

Clinic Appointments

• Initial consultation with Nurse Practitioner and Nurse Educator

• Regular follow-up every 6 months or annually

• Clinical breast exam, imaging, referrals, decision support

• Discussion includes:

– High-risk breast screening

– Prophylactic mastectomy with breast reconstruction

– Ovarian cancer screening not recommended

– Bilateral salpingo-oophorectomy recommendation; effects of

surgical menopause

Breast Screening Guidelines

• Detailed clinical breast exam every 6 months starting at age 20

• Annual bilateral breast MRI from age 25-65

• Annual mammogram beginning at age 30

• Mammograms and MRIs alternate at 6 month intervals (ideally)

• Breast ultrasound if recommended by the radiologist

– eg. follow-up of abnormal finding, unable to tolerate MRI

• During pregnancy and lactation:

– clinical breast examination every 3 months

– MRI and mammogram are not recommended

– Breast ultrasound used to investigate abnormalities detected on breast

examination

– Regular MRI and mammogram resumes 3 months after completion of

breastfeeding

• Ovarian cancer screening methodologies (pelvic examination,

transvaginal ultrasound and CA-125) have limited sensitivity and

specificity and are therefore not recommended in British Columbia

• Oral contraceptive pills have been proven to reduce rates of

endometrial and ovarian cancer by 50% or more

• This benefit increases with duration of use and persists for up to 20

years after the oral contraceptives are stopped

• A protective effect, proportional to duration of use, was also

demonstrated for women with BRCA1/2 mutations

• The Society of Obstetricians and Gynecologists of Canada’s

position statement indicates that there is evidence that the use of

oral contraceptives in BRCA carriers does not increase their risk of

breast cancer above that related to their genetic risk

Ovarian Cancer

New Cancers Diagnosed

68 mutation carriers (15%) have had at least 1 new cancer dx

• 27 of those had a previous breast or ovarian cancer

• 5 had deferred carrier testing - proceeded after diagnosis

• 3 were diagnosed at their 1st clinic visit

• 5 have had 2 new diagnoses:

1) Bilateral breast ca (BRCA2+)

2) Invasive breast cancer + DCIS on contralateral

mastectomy (BRCA2+)

3) Bilateral DCIS (one detected on contralateral

mastectomy) (BRCA1+)

4) DCIS + peritoneal after BSO (BRCA1+)

5) 2nd breast cancer (multifocal) + ovarian cancer on BSO

(BRCA2+)

New Cancers Diagnosed n BRCA1+ BRCA2+

Invasive breast ca

#1 breast ca

#2 breast ca

#3 breast ca

38

26

11

1

22

15

7

0

16

11

4

1

DCIS 9 5 4

LCIS 1 1 0

Ovarian ca 7 4 3

Fallopian tube ca 2 1 1

Peritoneal ca (after PBSO) 3 1 2

Pancreatic ca 2 0 2

Malignant melanoma 3 2 1

Gastric cancer 1 0 1

Colorectal cancer 1 1 0

Lung cancer 1 1 0

TOTAL 68 38 30

Method of Cancer Detection

• Chart review for women with new breast or ovary cancer to identify

method by which an abnormality was initially reported

• Additional imaging required for confirmation in some cases

• Numbers too small to report by BRCA1/2 status

• 8 new cancers (breast or ovarian) diagnosed on pathology review at

time of prophylactic surgery

Detection Method Breast ca DCIS LCIS

Screening MRI 21 0 0

Screening mammo 8 7 0

Self-exam 6 0 1

Clinical exam 0 0 0

Screening ultrasound 2 (one while

lactating)

0 0

Prophylactic mastectomy 1 2 (contralateral) 0

New breast cancers

Detection

Method

Ovarian

cancer

Fallopian

tube cancer

Peritoneal cancer

after BSO

Screening

ultrasound

1 1 n/a

Symptomatic 3 0 3

Prophylactic

Surgery

3 1 0

New “ovarian” cancers

Risk-Reducing Mastectomy

• Reviewed with each woman who attends the clinic

• Reduces the probability of breast cancer by 90-95%

• Option of nipple-sparing mastectomy is reviewed with the

surgeon

• Breast reconstructive options are briefly reviewed

• Most choose reconstruction (but not all)

• After bilateral mastectomy, women are discharged to

their family physicians for routine examination of

reconstructed breasts and regional nodes; routine

imaging of reconstructed breasts is not recommended

Risk-Reducing BSO• Bilateral salpingo-oophorectomy

• Recommended to all BRCA1/2+ women between the ages of 35-40 and once childbearing is complete

• Reduces the probability of ovarian cancer by 85-95% and reduces the risk of breast cancer by approximately 50% when performed prior to menopause

• Small number of women have “actively declined” surgeries

• 2 women who declined carrier testing have completed BSO

• 3 women have completed salpingectomy alone (with plans to proceed with oophorectomy prior to age 40)

• The effects of surgical menopause, the impact on bone, heart and brain health, as well as hormone replacement therapy are reviewed with women pre-operatively; ongoing management of related concerns is provided

• Short-term HRT does not negate the protective effect of BSO on subsequent breast cancer risk

Surgery

Completed

Unaffected

(br/ov)

n = 324

Previous

br ca

n = 107** 1 with previous br + ov ca

Previous

ov ca

n = 15** 1 with previous br + ov ca

Bilateral

Mastectomy

(only)

25

(7%)

2 BM as tx

2 CPM

1 BM after GT

BSO (only)+/-

hysterectomy

101

(31%)

45

Excludes: 1 with previous ov ca

15 had BSO as

part of treatment

Includes: 1 with

previous br ca

Both BM

and BSO

57

(18%)

16 BM as br ca tx & BSO

20 CPM & BSO

11 BM & BSO after GT

1 BM and BSO

BSO: bilateral salpingo-oophorectomy; BPM: bilateral prophylactic mastectomy; CPM: contralateral

prophylactic mastectomy

Ongoing Follow-up & Discharge from Clinic

247 women (~50%) who attended at least one clinic appt are

not currently being followed:

• 45% discharged after risk-reducing surgeries complete

• 15% discharged to oncologist re new cancer

• 11% discharged to GP (e.g. older & ineligible for MRI)

• 9% lost to follow-up

• 7% moved out of province

• 7% deceased

• 6% declined further appointments

Clinical Challenges

• Breast screening as an emotional rollercoaster

• MRI access

– Priority booking system/waiting list

– Coordination with menstrual cycle

• Breast reconstruction

– Vancouver waiting list

– Other locations

• BSO decision-making

– Young and single/childless

– Surgical menopause

• “lost to follow-up”

– Recent letter to pt/MD

• Appts missed/cancelled on short notice

– Weather, travel, forgot

Future Directions

• Access to high-risk screening in each health region

• Enhanced data collection & analysis

• Research opportunities e.g.

– C Wilson project re outcomes of imaging

– Breast reconstruction waiting list

– Long-term follow-up (after risk-reducing surgeries)

– J Kwon project to model BSO vs salpingectomy

– Sexual health after BSO

– ? New ovarian screening methods

• Screening for other high-risk populations