The Interface Between Family History, Genomics and Chemoprevention in Performing Breast Cancer Risk

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The Interface Between Family History, Genomics
and Chemoprevention in Performing Breast Cancer
Risk Assessment

• Karen E. Lewis, MS, MM, CGC
• Priority Health
• Medical Policy and Technology Administrator

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Identification of at-risk individuals and families

• What are you going to ask?
• If you dont ask they may not tell
• Just because they tell does not make it true

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MCC Breast risk assessment tool for Primary care
providers has 3 questions to ask all women
annually

• Do you have a personal history of breast/ovarian
  cancer?
• Do you have a family history of breast/ovarian
  cancer?
• Do you have a history of breast biopsy?

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Personal History of Breast / ovarian Cancer

• 1 in 7 women will develop breast cancer in their
  lifetime
• The younger the age at the time of diagnosis the
  more your interest should be peaked (lt50 for
  breast CA)
• Verify the actual diagnosis (yes there are people
  who do not know what there specific diagnosis
  was)
• Refer to cancer genetics center for further
  evaluation

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Family history of Breast / Ovarian CA

• Genetic predisposition mutations to breast /
  ovarian cancer are equal opportunity players
• You must ask about cancers on both the maternal
  and paternal sides of the family
• The more cancers on any one side of the family
  the more interesting the family becomes
• Age still counts but so do non-breast and
  non-ovarian cancers
• Refer to cancer genetics center for further
  evaluation

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History of Breast Biopsy

• Personal history of atypical hyperplasia refer
  for further evaluation and/or Gail model
  assessment
• Those with LCIS or increased risk associated with
  Gail model (gt/ 1.7) should be referred for
  further discussion regarding chemoprevention and
  risk management strategies

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Autosomal Dominant Inheritance

• Each child has 50 chance of inheriting the
  mutation
• No skipped generations
• Equally transmitted by men and women

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Most Cancer Susceptibility Genes Are Dominant
With Incomplete Penetrance
Normal
Susceptible Carrier
Carrier, affected with cancer
Sporadic cancer

• Penetrance is often incomplete
• May appear to skip generations
• Individuals inherit altered cancer susceptibility
  gene, not cancer

ASCO
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Features Suggestive of BRCA1 or BRCA2 Mutations

• Multiple cases of early onset breast cancer
• Ovarian cancer (with family history of breast or
  ovarian cancer)
• Breast and ovarian cancer in the same woman
• Bilateral breast cancer
• Ashkenazi Jewish heritage
• Male breast cancer

ASCO
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BRCA1-Associated Cancers Lifetime Risk or
Penetrance
Breast cancer 55?85 (often early age at onset)
Second primary breast cancer 50
Ovarian cancer 20?40
Possible increased risk of other cancers (eg,
prostate, colon, endometrial)
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BRCA2-Associated Cancers Lifetime Risk
male breast cancer (6)
breast cancer (55?85) 2nd breast primary 50
ovarian cancer (up to 27) Ovarian cancer risk
after breast cancer 16
Increased risk of prostate (20-25, laryngeal,
and pancreatic cancers (magnitude unknown, but
probably lt5)
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Its not all about BRCA1 BRCA2

• Other rare genetic syndromes associated with
  increased risk and incidence of breast cancer
• These syndromes are the ones where the uncommon
  becomes common

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Causes of Hereditary Susceptibility to Breast
Cancer
Contribution to Hereditary Breast
Cancer 2040 1030 lt1 lt1 3070
Gene BRCA1 BRCA2 TP53 PTEN Undiscovered genes
ASCO
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Li-Fraumeni syndrome

• Associated genes P53 and CHEK2
• Li-Fraumeni syndrome (LFS) is a cancer
  predisposition syndrome associated with
• soft-tissue sarcoma
• breast cancer
• Leukemia
• Osteosarcoma
• Melanoma
• Colon CA
• Pancreatic CA
• CA of the adrenal cortex
• Brain CA
• Individuals with LFS are at increased risk for
  developing multiple primary cancers. Age-specific
  cancer risks have been calculated.

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PTEN Hamartoma Tumor Syndrome (PHTS)

• Complex group of syndromes associated with
  mutations in PTEN gene and have a variety of
  clinical manifestations (Cowden syndrome-CS,
  Bannayan-Ruvalcaba-Riley syndrome- BRRS, Proteus
  syndrome-PS)
• Major associated cancers include (seen most
  frequently in CS and BRRS)
• Breast
• Thyroid
• Endometrial

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And lets not forget our friend HNPCC

• Hereditary non-polyposis colon cancer (HNPCC) is
  characterized by an increased risk of colon
  cancer and other cancers that include cancers of
  the endometrium, ovary, stomach, small intestine,
  hepatobiliary tract, upper urinary tract, brain,
  and skin

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When to Suspect Hereditary Cancer Syndrome

• Cancer in 2 or more close relatives (on same
  side of family or lineage)
• Early age at diagnosis
• Multiple primary tumors
• Bilateral or multiple rare cancers
• Constellation of tumors consistent with specific
  cancer syndrome (eg, breast and ovary)
• Evidence of autosomal dominant transmission

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Genetic testing and insurance

• Its all good

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Do they pay for anything?

• Comprehensive research and review of
  tests/technology is performed. Resources may
  include, but are not limited to the following
• Scientific and medical literature
• State and federal regulatory agencies (e.g. Food
  and Drug Administration, Michigan Department of
  Community Health)
• Other federal agencies (e.g. National Institutes
  of Health, Centers for Disease Control and
  Prevention)
• Professional organizations (e.g. physician
  academies and associations)
• Managed care industry standards
• In-house experts and standing committees
• Technology assessment information services (e.g.
  HAYES)
• Participating providers
• Experts/specialists in the field

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Decisions of coverage for individual members,
policy formulation, or benefit design use the
following technology assessment criteria

• Evidence of clear therapeutic effectiveness when
  used in the general population, including
• Indications for use
• Subpopulations most likely to benefit
• Contraindications

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Assessment criteria cont

• Evidence of safety when used in the general
  population.
• Potential harms and long-term abnormal effects
  are known or understood
• Evidence that the medical community in general
  accepts the safety and effectiveness of the
  service outside of investigational settings.

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Assessment criteria cont

• Evidence of clinically meaningful outcomes.
• Clinical trials or meta-analyses must demonstrate
  consistent outcomes
• Outcomes must be outcomes that clinically matter
  (e.g. reduced morbidity)
• Outcomes must be better than or equal to existing
  treatment alternatives
• Evidence that clinically meaningful outcomes can
  be attained at a reasonable cost to the health
  care system

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Assessment criteria cont

• Service has been approved by the appropriate
  regulatory bodies, if necessary
• Priority Healths plan document (e.g. Certificate
  of Coverage, Summary Plan Document) language is
  consistent with the decision
• Legal/risk management issues are considered

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GENETIC COUNSELING, TESTING AND SCREENING
MEDICAL POLICY No. 91450-R2

• Hereditary Predisposition/Pre-symptomatic Genetic
  Testing Testing for the presence of hereditary
  predisposition in an at-risk individual may be
  done for conditions such as
• BRCA1/BRCA2
• Hereditary nonpolyposis colorectal cancer (HNPCC)
• Huntingtons Chorea
• Multiple Endocrine Neoplasia
• Myotonic Dystrophy
• Family history of genetic disorders (for example,
  a previous child with Duchennes Muscular
  Dystrophy)
• Priority Health will cover hereditary
  predisposition/pre-symptomatic genetic testing
  only when recommended by a Genetic Counselor.
• All genetic testing in Section 5.0 requires prior
  authorization by Priority Health, and must
  include documentation
• Of medical necessity
• That genetic counseling has been accomplished
• That informed consent has been obtained
• Obtaining specimens for these tests must be
  coordinated by the Genetic Counselors office.
• Genetic testing is not a covered benefit if the
  test results do not provide direct medical
  benefit to the member.

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GENETIC COUNSELING, TESTING AND SCREENING
MEDICAL POLICY No. 91450-R2

• Genetic testing of a non-member relative of a
  member may be a covered benefit if all of the
  criteria in 8.1 through 8.5 are met
• The test results are for the direct medical
  benefit of the member and testing the non-plan
  relative is the most cost effective method to
  obtain the medically necessary information for
  the member.
• The non-plan relatives insurance company has
  been billed and payment has been denied.
• Coverage is limited to the testing of five
  non-plan relatives as a lifetime benefit for a
  member.
• Testing of the non-member relative has been
  recommended by a genetics counselor and approved
  by Priority Health.
• All genetic testing must be processed through a
  Priority Health provider phlebotomist and
  laboratory, unless otherwise specified by the
  Genetics Counselor.

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Breast and Ovarian Cancer Screening by Molecular
Testing

• Three or more affected first or second degree
  relatives on same side of family, irrespective of
  age at diagnosis, or
• There are fewer then three relatives, but
• There are multiple primary or bilateral breast
  cancers in the patient or one family member, or
• A family member has been identified with a
  detectable mutation, or
• There are one or more cases of ovarian cancer at
  any age, AND one or more members on the same side
  of the family with breast
• cancer at any age, or
• There is breast cancer in a male patient, or in a
  male relative, or
• The patient is at increased risk for specific
  mutation(s) due to ethnic background (for
  instance Ashkenazi Jewish descent) AND
• has one or more relatives with breast cancer or
  ovarian cancer at any age, or
• The patient was diagnosed with breast cancer at
  45 years of age or less.

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PROPHYLACTIC CANCER RISK REDUCTION SURGERY
MEDICAL POLICY No. 91508-R1

• Prophylactic Cancer Risk Reduction Surgery
• Includes
• Prophylactic Mastectomy
• Prophylactic Oophorectomy
• Prophylactic Hysterectomy
• Prophylactic Thyroidectomy

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Breast MRI MEDICAL POLICYNo. 91488-R1

• Breast cancer screening
• Breast MRI is considered medically appropriate
  for women who meet either of the following
• With a known breast cancer gene mutation (e.g.
  BRCA1, BRCA2, PTEN), or
• With a high risk for breast cancer as determined
  by the GAIL model or similar evaluation based on
  family history.
• Both of the above require counseling from a
  certified genetic counselor or specialist, and

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What if a request is denied?

• Review to make sure you are highlighting the
  medical benefit to the member
• Use clear and concise language
• Ask to speak with the medical director
• Grievance and appeal process if necessary