Jennifer Ivanovich, MS

Washington University School of MedicineSt. Louis, MO

Start With Why by Simon Sinek

WHY

HOW

WHAT

The Golden Circle

WHYWe believe in challenging the status quo to bring about positive change for young adults with cancer.

HOWThe way we will bring about positive change is by our persistent pursuit of research, targeted education, support and advocacy with young survivors engaged as our most essential partners.

WHATWe build diverse approaches to reach young adults and lead clinical research focused on their aggressive disease.

Vision, Mission and Operations

Research

Advocacy Support

A B

A B

A B A B

A B

A B

Education

WHY

HOW

WHAT

History- 2001, Support and education program initiated

- 2005, Research program implemented

- 2011, CDC funding for support & education programming

- Needs assessment completed

Outreach- ~1,400 survivors in St. Louis region

- ~2,700 survivors throughout the United States engaged in our research program

Regional program with national outreach

Young Women’s Breast Cancer Program

Local Needs Assessment - Findings

• The majority of women currently engaged in our program have completed their primary cancer treatment.

• Minority young survivors and women with limited financial resources are not adequately represented.

• Young women wish to connect with other young survivors for peer support and information.

• Targeted support programming for women with metastatic breast cancer does not currently exist in St. Louis region.

• Young women desire targeted information that is easy to manage.

• Young survivors stated it was difficult to find targeted programs.

• There is a lack of support and education programming for young adults with cancer in St. Louis region.

YWBCP: Support programming

Cancer Care Continuum

End-of-lifePost treatment Survivorship

TreatmentDiagnosis

Risk Assessment

Prevention

DetectionCancer

recurrence / metastatic

disease

Peer Network

Monthly support / network group

YWBCP: Support programming

Cancer Care Continuum

End-of-lifePost treatment Survivorship

TreatmentDiagnosis

Risk Assessment

Prevention

DetectionCancer

recurrence / metastatic

disease

Monthly support / network group

Peer Network

Coach Program

Psychosocial support program

YWBCP: Educational activities

Cancer Care Continuum

End-of-lifePost treatment Survivorship

TreatmentDiagnosis

Risk Assessment

Prevention

DetectionCancer

recurrence / metastatic

disease

Guidance journal

Survivor Magazine

Educational Symposium

YWBCP: Educational activities

Cancer Care Continuum

End-of-lifePost treatment Survivorship

TreatmentDiagnosis

Risk Assessment

Prevention

DetectionCancer

recurrence / metastatic

disease

Together Magazine

Guidance journal

Educational Symposium

Genetics Navigation Tool

Survivorship Program

YWBCP: A different approach

Center of Creative ArtsEnriching lives and building community through the arts

Young survivor

art program

Barnes-Jewish Hospital

YWBCP: Research

Initial questions1. What are the as yet unidentified genetic factors that contribute to risk for

breast cancer, and in particular breast cancer at a young age? laboratory (molecular genetic) studies

2. How common is familial breast cancer in early-onset disease, and among those women with a positive family history, how many have BRCA1 or BRCA2 gene mutation?

family studies

3. How do we communicate clinical whole genome sequencing results to individuals and families?

communication studies

YWBCP: ResearchCriteria and study requirements- Diagnosed with invasive breast cancer < 40- Consent, blood specimen, medical records, and family cancer history

Enrollment status- 2,701 young survivors have asked to participate- 1,792 (66%) young survivors enrolled

- 37 years – average age at diagnosis- 1,607 parents, sisters enrolled

0100200300400500600700800

2005 2006 2007 2008 2009 2010 2011 2012

PROBANDS

YEAR

Number of probands enrolled by year

Love / Avon Army of Womenpartnership

YWBCP: Research

Racial background of young survivors

Caucasian (91%)

African-American (3.5%)

Hispanic / Latino (2.4%)

Asian (1.0%)

Other (2.1%)

Age at consent Number %< 30 95 5.330 - 34 283 15.835 - 40 552 30.840 - 44 460 25.745 - 49 160 8.950 - 60 159 8.960 - 70 73 4.1 13.470+ 8 0.4

Copy Number Variants Exome Sequencing

120 BRCA1 and BRCA2 negative probands and parents

(trios studied in Aim 1)

120 additional probands and parents

CNV technical validationNimbleGen custom 135K arrayQ-PCR

Refining CNV boundariesPCR–based analysis of de novo deletions

CNV candidates validated in addition to early-onset breast cancer cases (biologic validation)NibleGen custom 135K array

Data analysisdescriptive summary of CNVcompare total CNV “load” in cases and parentsdefine minimum CNV regionsdetailed annotation of all genes, miRNA, noncoding

RNAs in de novo CNV regions

CNV regions prioritized for further analysis

Goodfellow, Graubert, Ivanovich; Avon Foundation, NIH R01

€

120 BRCA1 and BRCA2 negative probands and parents

CNV discoveryNibleGen HD 2.1 array

Prioritize high confidence CNVs for follow-up studies• de novo variants• Recurrent “rare” variants involving coding sequences• CNVs that include genes known to be important in breast

biology/tumorigenesis

384 probands, BRCA1,2 negative and strong breast

cancer family history

Goodfellow, Mardis, Borecki, IvanovichWUSM Genome Center funding

YWBCP: Research – Molecular studies

YWBCP: Research – Family studies

Heritability

04-1009-120-001

Breast CA dx. 36

Adopted out of family

04-1009-374-001

2

65

Breast CAdx. 35

14

55 6065

22 2

38 4143 44 30, 35

15, 18 11, 13 18 15

67Prostate

CA dx. 67

67

2

55

35, 38 454340s 40s

61

d. 65Lung CAsmoker

d. 45Heart attack

d. 87 Heart

disease

d. 89Old age

04-1009-293-001

65

39Breast CA dx. 37

48

2

44 42 42

13, 10 12 15, 17

67Prostate

CA dx. 67

d. 77 Old ageHysterectomy dx. mid 30s

d. 67GI CA dx. 63

Breast Ca dx. 47Ovarian CA

dx. 70

Prostate CAdx. 60

Colon CA dx. 75

9

2

8, 13

2

8, 13

2

Only child

46 38, 45

2

74

04-1009-019-001

d. 85

d. Lung CA

d. Old Age

d. Lung CA

79 Basal Cell

Bladder CA

d. 45 Breast CA

Breast CA dx. 39

4

76 Breast CA dx. 46

Unilateral

32 2 21

1 2 3 1

45 36

11Cystic

Fibrosis

2.5Cystic

Fibrosis

9

Key Male Female Cancer DeceasedKey Male Female Cancer Deceased

0=Noninformative 1=Low risk 2=Elevated risk 3=Moderate risk

Figure 1: Representative pedigrees of family risk classification scheme

Male Female Cancer Deceased

Goodfellow, Ivanovich, departmental funding

YWBCP: Research – Communication studiesCommunicating sequencing results-NIH R01 funding anticipated to begin in June, 2012- Kaphingst, Dressler, Goodman, Ivanovich, Goodfellow, Biesecker

TECHNOLOGY

Rare, high penetrant alleles

Provider & public genetics

education

Common, low penetrant alleles

…Outcome &

communication research…

Clinical validation

studies…

Funding for education behavioral research

Information Access

…Cross discipline

training …

The Young Women’s Breast Cancer Program

Kim Selig, MSW -- Program Coordinator314-747-7156seligk@wudosis.wustl.edu

Jennifer Ivanovich, MS -- Program Director314-454-5076ivanovichj@wudosis.wustl.edu

Paul Goodfellow, PhD – Research Programgoodfellowp@wudosis.wustl.edu

Washington University School of MedicineBox 8100; Siteman Cancer Center660 S. Euclid AveSt. Louis, MO 63110