1 - Biology

11/9/2021

©AllinaHealthSystems 1

Cancer Biology, Pathology and Genetic Predisposition

Andrea Edwards, MS, CGCGenetic CounselorVirginia Piper Cancer InstituteAllina Health

November 9th, 2021

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Disclosure

I have no conflicts of interest in relation to this program or presentation.

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• Define cancer and associated terminology

• Review how cancer occurs and summarize cancer risk factors

• Recognize red flags of hereditary cancer syndromes and which patients should consider hereditary cancer genetic testing

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Objectives

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• Imhotep (2625 BCE)– Egyptian physician– “bulging mass in the breast”– Therapy: “there is none”

• Atossa (440 BCE)– Queen of Persia– Bleeding lump in breast– Greek slave removed the tumor

• Chiribaya tribe (700 CE)– Atacama desert in Peru– “Bulbous mass” in upper left arm

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History of Cancer

https://ceb.nlm.nih.gov/projects/ttp

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• Definition– “Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body”‐ National Cancer Institute

• Two main categories– Hematologic cancer

– Solid tumor cancer

• Not a single condition, but actually 100s of different diseases

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Cancer Background

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• According to the National Cancer Institute, the estimated number of new cancer cases in 2021 in the US will be 1,898,160 – #1 most common‐ breast cancer

– #2 most common‐ prostate cancer

– #3 most common‐ lung cancer

• Lifetime risk of cancer: 39.2% (based on 2016‐2018 SEER data)

•Median age of diagnosis: age 66

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Cancer Incidence

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• Tumor: a mass of tissue that results from abnormal cell growth and division– Benign‐ not cancerous, don’t spread to other areas of the body– Malignant‐ cancerous, cells will invade or spread to other areas of the body

• Carcinoma: cancer that begins in the skin or tissues that line internal organs• Sarcoma: cancer that begins in the bone or connective tissue • In situ: “in the original place”, no penetration of the basement membrane

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Cancer Terminology

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Cancer Pathology

http://www.gynecologycancer.org

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Cancer Grade

owise.uk/pathology‐report/

Increasing tumor aggressiveness

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• Stage 0 to IV– Stage 0: abnormal cells that haven’t spread (aka in situ)

– Stage I‐III: cancer that hasn’t spread beyond the site of the primary tumor or have only spread to nearby tissue

– Stage IV: cancer has spread to distant areas of the body

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Cancer Stage

onhealth.com/content/1/cancer_types_treatment

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Cell Biology Review

yourgenome.org 12

Cell Biology Review

civilsdaily.com

11/9/2021


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Cell Biology Review

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Cell Cycle Regulation

hep.ucl.ac.uk

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• DNA repair genes– Fix errors made during DNA replication– Inactivation leads to cancer development– Ex: MLH1, MSH2, MSH6, PMS2

• Tumor suppressor genes– Negatively regulate the growth of cells – Inactivation leads to cancer development– Ex: BRCA1/2

• Oncogenes– Play roles in cell cycle regulation– Activation leads to cancer development– Ex: RET

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Cell Cycle Regulation

labs.wsu.edu1616

Types of Gene Mutations

yourgenome.org

Translocation Point Mutation

Deletion Insertion/deletion

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Cancer: A Genetic Disease

dnascience.plos.org1818

Cancer Risk Factors

bioninja

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Cancer: Genetic, But Not Always Inherited

Medscape 2020


Sporadic Cancers

Hereditary Cancers

XX XX

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XX XX XX

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CancerousCell

CancerousCell

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Germline mutations Somatic mutations

• Occur initially in the egg or sperm • Occur in non‐germline cells (ex: breast, colon, lung, etc.)

• Are inherited • Not inherited

• Mutation is present in all cells of the body

• Mutation is only present in some cells in the body

• ~5‐10% of all cancers are hereditary • ~90‐95% of all cancers are sporadic

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Genetic Testing

Myriad Genetics

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Somatic Genetic Testing

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Hereditary Cancer Red Flags

Myriad Genetics

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Genetic testing criteria

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Family History Evaluation

Breast 75

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2727


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Bladder 65

Breast 70

Skin 59

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Breast 30Breast 37

Pancreatic 50

Breast 40

Ovarian 55

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Suspicious

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• Verbally reported family history • Revised family history based on pathology reports

Ovarian ca, dx 33d.65

Stomach cadx 55

Breast cadx 50d. 75

Breast atypiadx 50d. 75

Cervical ca, dx 33 d. 65

Bladder cadx 55

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Genetic Counseling Process

Referral placed by provider

Scheduling In person, virtual or phone visit

Patientcalled with results

Genetic testing ordered (if

indicated and patient consents)

No genetic testing (if not indicated or patient declines)

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• Risk assessment of personal and family history

• Education about basic genetics, inheritance, and hereditary cancer syndromes

• Explanation testing process and insurance coverage • Informed consent

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Genetic counseling appointment

• Interpretation of results based on personal and family history

• Screening and risk management recommendations

• Psychosocial support32

•Where?– Invitae, Ambry, Myriad, GeneDx, etc

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Genetic testing

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•What?– DNA sequencing and deletion/duplication analysis of genes related to inherited cancer syndromes

–Multi‐gene panels are commonly used to test for multiple genes at once

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Genetic testing

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•Why?– Guide screening and risk management recommendations for the patient and their relatives

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Genetic testing

Myriad Genetics

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Gene Based Screening Guidelines

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Genetic testing

Myriad Genetics

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• Types of results

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Genetic testing

Myriad Genetics 38

• Types of results

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Genetic Testing

Myriad Genetics

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Risk modeling

• IBIS risk model• Personal history (menarche, menopause, breast density, HRT, age at first child, etc)

• Family history• Genetic history

Myriad Genetics 40

• Genetic Information Nondiscrimination Act (GINA)

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Genetic testing

Myriad Genetics

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• Limitations and Risks– Unable to screen/prevent all cancers– Anxiety/distress– Insurance discrimination

– Possibility of unclear/unexpected results– Positive results with limited information

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Genetic testing

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Who?

23andMe, AncestryDNA, FamilyTreeDNA, etc.

What?

Tests for a selection of SNPs, including those related to inherited conditions, health risks, drug responses, and inherited traits

Why?

Can provide information in disease risk Patient curiosity

Limitations

Most risks are multifactorial MD not required to be involved Unexpected results (APOE‐4, 3‐site Jewish

BRCA1/2) Overly reassured by results (3‐site Jewish

BRCA1/2)

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Direct to Consumer Tests

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Genetics in Oncology Nursing

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• Genetic testing for hereditary cancer is a complex, ever evolving field• Be careful to clarify when asking a patient “have you had genetic testing?”• Identifying a hereditary cause for cancer in a family can aid prevention/screening for the patient and family members• Genetic counselors are here to help!

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Summary

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• [email protected]

• Allina Cancer Genetics: 612‐863‐0200

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Contact me

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1 - Biology