Decision Support Systems (DSS) & Established

Risk Factors for Breast Cancer

Data Structure and Sources

SCH

EGC

ID

EHIF

EHIS

HOS

Personal ID code

Estonian Health Information System

Estonian Health Insurance Fund

Estonian Genome Center

Hospital Information Systems

School Medicine System

Data coding systems:

ATC: The Anatomical Therapeutic Chemical (ATC) Classification System is used for the classification of active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties.

LOINC: Logical Observation Identifiers Names and Codes (LOINC) is a database and universal standard for identifying medical laboratory observations.

ICD-10: ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization (WHO).

CDA: Clinical Document Architecture. Scen

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Invitation to Join

Regular ScreeningSelection & Sequencing Pilot Users Selection GP Receives Notification

Counselling and Personalised Plan

Privacy and Sharing

Informed Consent

Setting privacy levels and sharing principles.

Invitation to join the patient portal and gain more insight into genetic and life style related risks

Regular screenings. Notifications for involved parties.

Genes are sequenced during the personalised medicine pilot programme.

Anna is chosen as one of the subjects who’s genes will be sequenced in 2016 as part of the personalised medicine pilot.

Secure log-in. Updating terms of service. Confirming being informed of genetic risks.

• Anna decides to share her disease risk index (calculated using genetic risks, lifestyle data and medical history) with first-degree relatives and her GP.

• She restricts other clinical specialists to only see the last 5 years of her medical history data. During future clinical visits permissions for viewing older medical records, lifestyle and gene risk data must be granted individually every time.

Adding Fenotype Data

Databases

Risk Index Sharing Risk Data Notifications Booking an Appointment

Sharing risk data with relatives for genetic risk assessment and preventive screening selection.

Receives yearly notifications for upcoming screening appointments in her patient portal.

Can conveniently book medical appointments and see steering guidelines for next steps.

Adding additional data sources and fill in questionnaires to complete her risk assessment and health profile.

Connects her health profile to the various data sources. Every time a new data source is connected, data sharing options (limited/full access to first-degree relatives, GP, family nurse, clinical specialists) appear.

Sees a summary of risk assessment of various diseases. Sees relatively high risk of developing breast cancer and a high genetic risk of diabetes type II. Directed to counselling.

Reviews the results of genetic sequencing. Compiles a family disease tree and validates the data inserted by the patient.

Goes to genetic counselling.

Multi-risk assessment. Sees DS suggestions for personalised risk score and clinical screening plan. Assigns a yearly MRI screening plan with lifestyle suggestions. Explains potential disease risk and shows the screening plan in her patient portal.

• Estonian National Health Information System (ENHIS)

• Prescription Centre• Hospitals who have joined the pilot for more

detailed information regarding procedures• Laboratories

• Life habits• Family history• Medical history

Patient portal:• Suggestions for further steps: Based on your

genetic test you might have a higher risk of developing breast cancer. Please book a visit for attending genetic counselling.

Professional EHR:• High risk patient is added to the genetic

counselling and screening list, process DS.

Anna has two daughters who haven’t yet gone through genetic disease risk assessment. Anna informs her daughters. Anna shares her genetic risk data with them, daughters are listed in EHR as higher risk citizens.

Patient portal:• Notification: Anna receives notification to

share her health risk data with her relatives.

Patient portal• Notification: Yearly screening approaching.

Please book GP visit for MRI scans.

Estonian Genome Center (EGC)

Estonian Genome Center (EGC), GP, family nurse,

genetic councellor, oncologist

Anna Tamm, 42 Genetic breast cancer risk

Ten years ago Anna donated her tissue sample to the Estonian Genome Centre population-based biobank signing the broad informed consent for the usage of

her genome data for scientific purposes.

Genetic CouncellorGP

Prevention and early detection on the basis of germline cancer hereditary susceptibility testing with personalised preventive strategies

Digital decision support for genetic risk evaluation: NCCN Guidelines Version 1.2015 Breast and/or Ovarian Cancer Genetic Assessment

Criteria for further genetic risk evaluation: • An individual with a cancer diagnosis meeting any of the following:• A known mutation in a cancer susceptibility gene within the family • Early-age-onset breast cancer• Triple negative (ER-, PR-, HER2-) breast cancer ≤60 y • Two breast cancer primaries in a single individual• Breast cancer at any age, and: ≥1 close blood relative with breast cancer ≤50 y, or ≥1 close blood relative with invasive ovarian cancer at any age, or ≥2 close blood relatives with breast cancer and/or • pancreatic cancer at any age, • or from a population at increased risk.• Personal and/or family history of three or more of the following (especially if early

onset): pancreatic cancer, prostate cancer (Gleason score ≥7); sarcoma, adrenocortical carcinoma, brain tumors, endometrial cancer; thyroid cancer, kidney cancer, dermatologic manifestations and/or macrocephaly, hamartomatous polyps of gastrointestinal (GI) tract; diffuse gastric cancer (can include multiple primary cancer in same individual)

• Invasive ovarian cancer• Male breast cancer

Individual with or at risk for cancer

Risk assessment Informed consent:• Primary findings• Incidental findings• Plans for return of

results

Germline genetic testing (exome or WGS)

Cancer and noncancer risk management plan

Longitudinal follow-up

Cancer related findings:• Data analysis• Clinical interpretation• Genetic counselling• Disclosure

Incidental findings:• Data analysis• Clinical interpretation• Genetic counselling• Disclosure

Personal h

istory

Family

history

Exposu

re h

istory

Other disease risk assessment

Cancer risk assessment

Personalised cancer therapy on the basis of cancer tissue molecular profiling (+/- germline assessment)

Individual with or at risk for cancer

Tumor assessment Informed consent:• Tumor findings• Incidental findings• Plans for return of

results

Tumor genetic testing (exome or WGS)

Cancer and noncancer risk management plan

Somatic findings: • Possible implications

for therapy and/or prognosis.

Incidental germline findings:• Data analysis• Clinical interpretation• Genetic counselling• Disclosure

Germline assessment

Somatic genetic assessment

Schematic above: interpreted from Stadler, Schrader et al (2014). “Delivering precision medicine in oncology today and in future-the promise and challenges of personalised cancer medicine: a position paper by the European Society for Medical Oncology (ESMO).” Ann Oncol 25(9): 1673-1678.

Setup + Data Import Risk Assessment + Personalised Plan Clinical Visit + Personalised Treatment Plan Cancer Genetic CounsellingScenario A: PreventionPersonalised Prevention Plan for Genetic Breast Cancer Risk

Professional EHR Genetic Sequencing Results

Patient Portal PHR Risk Report

1 ye

ar

Disease Risk Index (patient

phenotype data + gene data +

family)

Notifications for data reviews

and patients requiring attention

Interpretation of genetic

sequencing results

Suggestions for clinical

procedures and diagnose

Patient steering guideline

(personalised screening plan)

Notifications for relatives with potential genetic

risk

Notifications for data reviews

and patients requiring attention

Näide geenianalüüsi kokkuvõttest:

MATERJAL: Märkus: 4ml VASTUSED: Pärilik rinna- ja munasarjavähk - BRCA1 geeni mutatsioonid 2.-11. eksonis (APEX) TEHTUD Pärilik rinna- ja munasarjavähk - BRCA1 geeni mutatsioonid 12.-24. eksonis (APEX) TEHTUD Pärilik rinna- ja munasarjavähk - BRCA2 geeni mutatsioonid 2.-14. eksonis (APEX) TEHTUD Pärilik rinna- ja munasarjavähk - BRCA2 geeni mutatsioonid 15.-27. eksonis, CHEK2, NBN ja RAD51 geenide mutatsioonid (APEX) TEHTUD Pärilik rinna- ja munasarjavähk - BRCA1, BRCA2, NBN, CHEK2, RAD51 geenide mutatsioonid (APEX) LEITI BRCA1 geenis heterosügootsena haigusseoseline mutatsioon 5382insC (HGVS tähisega NM_007294:c.5266_5267insC, p.Gln1756Profs74X). Mutatsioon 5382insC põhjustab BRCA1 valgus lugemisraami nihke ning enneaegse stoppkoodoni tekke 1829. positsioonis. Arvestades enneaegset stoppkoodonit tuleb mutatsiooni pidada suurel määral BRCA1 valgu funktsiooni kahjustavaks ehk kõrge vähiriskiga seotuks. 5382insC on üks kolmest kõige sagedasemast kliiniliselt olulisest ehk kõrge vähiriskiga seotud mutatsioonist BRCA1 ja BRCA2 geenides. Uuritud patsiendi kliiniline leid on seotud 5382insC mutatsiooniga BRCA1 geenis. Ehkki antud mutatsiooniga seotud täpsed haigestumisriskid ei ole teada, on BRCA1 geeni kõrge riskiga mutatsioonide esinemise korral kirjeldatud kuni 87% riski elu jooksul rinnavähki ning kuni 44% riski munasarjavähki haigestumiseks (Lancet 343:692-695, 1994). Patsiendile ja perekonnale on soovitav geneetiline ja onkoloogiline nõustamine. Patsiendi järglastel on 50% risk 5382insC mutatsiooni kandluseks. Soovitame sugulastele kaskaadskriiningut leitud mutatsiooni suhtes.

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EGC

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

EHIS

• Age (less than 50 vs. over 50) (relative risk 6.7): ID-code.

• Gender (female vs. male) (relative risk 100): ID-code.

• Race/Ethnicity: EGC.

• Age of menarche (less than 10) (relative risk 1.4 to 1.9): EGC. EHIS (narrative text).

• Age at first birth (more than 35) (relative risk 1.7): EGC. EHIS (narrative text).

• Nulliparity (relative risk 1.4): EGC. EHIS (narrative text).

• Age at menopause (more than 55) (relative risk 1.3): EGC. EHIS (narrative text).

• ADH, LCIS (relative risk 4.0 to 5.0): EGC (ICD10). EHIS (ICD10). EHIF (ICD10).

• First-degree relatives (relative risk 2.0 to 7.0): EGC.

• BRCA1/BRCA2 mutation (relative risk 10 to 30): EGC.

• P53 (Li-Fraumeni) (relative risk 1.5 to 6.0): EGC.

• Cowden syndrome (relative risk 2.0 to 4.0): EGC.

• Therapeutic radiation (relative risk 35): EHIS (narrative text). Hospital Information Systems (narrative text).

• Oral contraceptive pills (relative risk 0.9 to 1.0): EGC (ATC). EHIF (ATC).

• Estrogen replacement (more than 10 years) (relative risk 1.1): EGC (ATC). EHIF (ATC).

• Estrogen and progesterone (relative risk 1.4 to 3.0): EGC (ATC). EHIF (ATC).

• Obesity (BMI more than 30): EGC (numeric). EHIS has Height and Weight data in CDA documents presented in free text. Exception is the School Medicine Growth Notice where Height and Weight are in structured form.

• Exercise (more than 3 hours per week): EGC (coded questionaire). EHIS has behavioural data in CDA documents presented in free text, if any.

• Alcohol use (relative risk 1.1 to 2.2): EGC (coded questionaire). EHIS has behavioural data in CDA documents presented in free text, if any.

• Diet (relative risk 1.0): EGC (coded questionaire). EHIS has behavioural data in CDA documents presented in free text, if any.

• Mammographic density (relative risk 2.2 to 5.3)

• Number of first-degree relatives with breast cancer: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Number of second-degree relatives with breast cancer: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Number of third-degree relatives with breast cancer: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Age of onset of breast cancer in a relative: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Bilateral breast cancer in a relative: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Ovarian cancer in a relative: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

• Male breast cancer in a relative: EGC (coded questionaire). EHIS has genealogy data in CDA documents presented in free text, if any.

Established Risk Factors for Breast Cancer

EHIF

EHIF

SCH

EGC

EHISHOS

EHIF

EGC

EGC

EGC

EGC

EGCEHISEHIF

EGCEHIS

EGCEHIS

EGCEHIS

EGCEHIS

EGC

ID

ID

This developmental research project is commissioned by the Ministry of Social Affairs and carried out by the Tallinn University of Technology from March to June 2015. The project is supported by the European Union Structural Funds via the programme TerVE implemented by the Estonian Research Council.