Lauren Schenck Genetic Counselor, LCGC

I have no financial relationships or conflicts of interest to disclose in relation to this presentation

Review of genetic counseling and cancer genetics

How common is inherited cancer? Red flags in a family history that should

prompt a genetics evaluation Overview of hereditary breast and ovarian

cancer (HBOC) and Lynch syndrome Update in genetic testing: panel tests

Assess personal and family history of cancer ◦ Is genetic testing appropriate in the family? ◦ Identify the most informative family member to test ◦ Determine and order the most appropriate genetic test(s)

Provide patient-oriented education about hereditary cancer syndromes and genetic testing

Interpret genetic test results, help patients and their

physicians understand and apply genetic test results to medical management decisions, and assist with patient’s psychosocial adjustment

Connect patients to supportive, informative and research-

related resources

Cancers diagnosed younger than average ◦ Breast cancer <50 yo ◦ Colon cancer <50 yo

Multiple family members with similar or related cancers ◦ Breast and ovarian ◦ Colon and uterine ◦ Melanoma and pancreatic

Rare cancers ◦ Male breast cancer ◦ Ovarian cancer ◦ Triple negative breast cancer (<60 yo)

People diagnosed with cancer more than once Multiple generations affected by related cancers AJ ancestry + breast and/or ovarian cancer

Hereditary breast and ovarian cancer (HBOC) Lynch syndrome

Genes: BRCA1, BRCA2 Most significant cancer risk: breast, ovarian Management: ◦ Females: high risk breast cancer screening OR mastectomy, BSO ◦ Males: PSA, breast awareness, consideration of mammograms

Breast cancer Gynecological cancer Cancer, unknown

Recommendations: ◦ Bilateral mastectomy or high risk surveillance

following breast cancer tx ◦ BSO ◦ Genetic testing for family members

Breast cancer Gynecological cancer Cancer, unknown

Also carries the BRCA1 mutation

Genes: MLH1, MLH2, MSH6, PMS2, EPCAM Most significant cancer risk: colon, uterine Management: Colonoscopy every 1-2 years,

consideration of hysterectomy and BSO (females)

1994-1995 Myriad patent on BRCA1 & BRCA2

2012 Ambry offers NGS, Without BRCA

2013 Supreme Court rules human genes cannot be patented

TODAY Many new labs and panels!

Which genetic testing

lab?

Most appropriate

test?

There are more than 50 well described cancer susceptibility syndromes, many of which can result from mutations in more than one gene

Benefits Limitations

Many genes analyzed ◦ Higher mutation

detection rate Often same cost as

single gene tests ◦ Generally cheaper than

multiple single gene tests One blood/saliva

sample

Unknown results Genes without

management guidelines

Benefits Limitations

Many genes analyzed ◦ Higher mutation

detection rate Often same cost as

single gene tests ◦ Generally cheaper than

multiple single gene tests One blood/saliva

sample

Unknown results Genes without

management guidelines

Breast cancer Intestinal adenocarcinoma Thyroid cancer Uterine cancer Pancreatic cancer Lung cancer

Studies suggest 2-4 fold increased risk of breast cancer in female carriers

Possible increased risks of pancreatic cancer Individuals with two ATM mutation have Ataxia

Telangiectasia (AT) ◦ Severe childhood onset condition involving

progressive ataxia often beginning at age 5yo or earlier, telangiectasia of the conjunctivae, immunodeficiency ◦ Cancer risks: leukemia, lymphoma ◦ Increased sensitivity to radiation

Recommendations: ◦ High risk breast cancer surveillance ◦ Genetic testing for family members

NOT a carrier of the ATM mutation

Presumably ATM mutation carrier

Benefits Limitations

Many genes analyzed ◦ Higher mutation

detection rate Often same cost as

single gene tests ◦ Generally cheaper than

multiple single gene tests One blood/saliva

sample

Unknown results Genes without

management guidelines

Important to assess personal and family history to determine:

Is a panel appropriate? Which genes?

68y female recently diagnosed with breast cancer

68y female recently diagnosed with breast cancer. Family history significant for early breast cancer, early colon cancer, and bile duct and intestinal cancer.

Benefits Limitations

Many genes analyzed ◦ Higher mutation

detection rate Often same cost as

single gene tests ◦ Generally cheaper than

multiple single gene tests One blood/saliva

sample

Unknown results Genes without

management guidelines

Breast cancer screening ◦ Oncology care team recommendations

Colon cancer screening ◦ Close blood relatives begin colon screening 5-10

years younger than earliest colon cancer diagnosis ◦ Continuation of colonoscopies at the intervals

recommended by gastroenterologist aware of personal and family history

Not all laboratories’ panels are created equal ◦ # of genes ◦ Sensitivity ◦ Portion of gene analyzed and how thorough ◦ Technology used for mutation confirmation ◦ Prices, billing policies, turnaround time, reporting ◦ VUS rates among labs ◦ Protocols for VUS reporting and reclassification

Not all laboratories’ panels are created equal ◦ # of genes ◦ Sensitivity ◦ Portion of gene analyzed and how thorough ◦ Technology used for mutation confirmation ◦ Prices, billing policies, turnaround time, reporting ◦ VUS rates among labs ◦ Protocols for VUS reporting and reclassification

Not all laboratories’ panels are created equal ◦ # of genes ◦ Sensitivity ◦ Portion of gene analyzed and how thorough ◦ Technology used for mutation confirmation ◦ Prices, billing policies, turnaround time, reporting ◦ VUS rates among labs ◦ Protocols for VUS reporting and reclassification

Comprehensive cancer risk assessment Personalized screening and management

recommendations Most appropriate and cost effective genetic

testing Supportive resources for your patients Saves you time!

http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

http://www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq#section/all

http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

http://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers http://jnci.oxfordjournals.org/content/97/11/813.short

http://www.mills-peninsula.org/cancer/services/genetic-counseling.html