Breast Cancer, BRCA2 Gene

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Breast Cancer, BRCA2 Gene
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Breast Cancer

• Breast cancer specifically refers to a cancer
  that forms in tissues of the breast
• Usually in the ducts which are the tubes that
  carry milk to the nipple
• Or the lobules glands that make milk
• It occurs in both men and women
• Male breast cancer is rare

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Prevalence

• One in eight women in the US will develop Breast
  Cancer
• Male breast cancer 1 of the population
• Age and new occurrences per 1000 women
• 35-39 0.5
• 40-44 1.0
• 45-49 1.6
• 50-54 1.7
• 55-59 1.9

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Estimated Statistics for US in 2007 New Cases
Women (178,480) Men (2030) Deaths Women
(40,460) Men (450)
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Could you have it?

• Common Symptoms
• How the breast or nipple feels nipple
  tenderness, lump on the breast
• How the breast looks change in size or shape,
  scaly/red/swollen areas of the skin
• Nipple Discharge

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• Prognosis with Breast Cancer, it depends on the
  severity when detected. Earlier detection yields
  stronger survival rates
• Examples from the American Cancer Society below
• 100 of women survive breast cancer if it is
  detected before it starts to spread
• 88 of women survive breast cancer if it is
  detected while it is 2-5cm in diameter and has
  spread to axillary lymph nodes
• 56 of women survive breast cancer if it is
  detected after it has spread to axillary lymph
  nodes and to axillary tissues
• 49 of women survive breast cancer if it is
  detected after it has attached itself to the
  chest wall and chest lymph nodes
• 16 of women survive breast cancer if it is
  detected after it has spread to other parts of
  the body such as bone, lung or liver

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The Genetics of Breast Cancer

• BRCA1 and BRCA2 are both tumor suppressor genes
  and mutations lead to an increased risk of
  developing breast cancer
• BRCA1 and BRCA2 mutations account for 5-10 of
  breast cancer cases today
• With the mutation, a person is 3-7 times more
  likely to develop breast cancer

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Risks for developing Breast Cancer
Person without a mutated copy of BRCA2 gene
Person with a mutated copy of BRCA2 gene
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BRCA2 Breast Cancer 2, Early Onset

• Located on the long arm (q) of chromosome 13
• The protein is a DNA repair protein
• Works with RAD51
• Protein large, 20 exons
• Autosomal Dominant

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BRCA2 and Breast Cancer

• Over 800 mutations of the BRCA2 gene identified
• Lead to the production of an abnormally small,
  nonfunctional protein unable to repair damaged
  DNA or fix mutations occurring in other genes
• Mutations lead to cancer when the second
  (unmutated) copy of BRCA2 gene is lost
• Other cancers esp. prostate, but also ovarian
  pancreatic
• If two copies of the mutated BRCA2 gene inherited
  Fanconi anemia

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Getting Tested
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WHO?

• About 2.3 of individuals of Ashkenazi Jewish
  descent have a mutated or altered BRCA1 or
  BRCA2 gene.
• The most common BRCA2 mutation found in Ashkenazi
  Jews is the 6174delT mutation
• This mutation is thought to have a frequency of
  .3 among Ashkenazi Jewish

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WHO? cont.

• People with a close family member who is known to
  have the mutation (which can be inherited from
  either the mother or the father)
• People with a family member who got breast or
  ovarian cancer before the age of 50
• Those who have a male family member with breast
  cancer

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• Also, the frequency of this gene mutation is
  also higher in people of Norwegian, Dutch, and
  Icelandic origin

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What Does a Positive Result Mean?

• A person who has inherited a mutation on the
  BRCA2 gene has an increased RISK of getting
  certain types of cancer associated with the
  mutation
• It is impossible, however, to determine from this
  result whether or not the individual will
  actually get cancer
• A mutated BRCA2 gene produces protein that cannot
  carry out its normal function in helping to fix
  mutations, leading to a build up of mutated cells
  in the form of a Tumor

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What Does an Ambiguous Result Mean?

• Sometimes, it is not possible to tell whether
  certain alterations found during testing will
  increase the risk of getting cancers associated
  with the mutation. This is called an ambigious
  result.

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Why?

• People get tested so that they can make better,
  more informed decisions about what actions to
  take in the future
• For example, people who test positively may
  choose to get preventative treatments involving
  surgery and/or medication
• Some people testing positively choose to
  participate in medical research that could
  decrease their chances of getting cancer
• Different test results can also affect peoples
  decision about having children

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Problems With Getting Tested

• Most problems associated with getting tested are
  psychological, for example
• People cannot deal with their results emotionally
• If they test positive then they may become
  depressed
• If they test negative they may feel guilty for
  not having the mutation while other family
  members do
• Test results can affect peoples decisions
  regarding marriage and having children

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More Problems with Getting Tested

• Receiving genetic counseling before and after
  testing is very important
• Confidentiality of results is not guaranteed if
  they are placed in a patients medical records
• Insurance companies may find out and insurance
  prices could shoot up
• Positive results may lead to genetic
  discrimination by insurance companies and
  employers

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How?

• Testing for mutations or alterations in the BRCA2
  gene can be done through a simple blood test
• Some insurance policies cover testing while
  others do not
• 450 mutations have been identified in the BRCA2
  gene, but there are many more yet to be
  identified
• If a person has a mutation that has not yet been
  identified, his/her test result might be
  incorrect
• Most of these mutations involve insertions or
  deletions of base pairs

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Kaiser Permanente Criteria forBRCA1/2 Genetic
Testing

• Women with breast cancer plus one of the
  following
• B. Women with ovarian cancer plus one of the
  following
• C. Men with breast cancer plus one of the
  following
• D. Women or men without personal history of
  breast cancer, but with family history of breast
  and/or ovarian cancer plus one of the following

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Video of a Previvor
http//video.on.nytimes.com/?fr_story0aff7eb1147f
98a41e989541f3fc114c8e71dcd2
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Surgery

• Lumpectomy-tumor and surrounding tissue removed.
  
• Partial Mastectomy-cancer tissue is removed along
  with a portion of the surrounding breast tissue.
• Total Mastectomy-entire breast is removed.
• Modified Radical Mastectomy-entire breast, the
  lining over the chest muscles, many of the
  underarm lymph nodes are removed.
• Radical Mastectomy-entire breast, the underlying
  chest muscle, and all of the underarm lymph nodes
  are removed.

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Lumpectomy
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Radical Mastectomy
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Mastectomy with breast reconstruction
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Therapy

• Radiation therapy- X-rays can be used to shrink
  or kill the cancer cells at the tumor site.
• Hormone therapy- some types of breast cancer have
  receptors that are affected by different hormones.

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• Chemotherapy- Drugs are injected or taken orally
  to kill the cancer cells.
• Clinical treatment- experimental treatments are
  available for breast cancer.

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Side Effects

• Chemotherapy
• Nausea and vomiting
• Loss of appetite
• Loss of hair
• Mouth sores
• Increased susceptibility to infection
• Premature menopause
• Infertility

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• Radiation therapy
• Occasional fatigue
• Swelling and heaviness in the breast
• Skin changes similar to sunburn at the affected
  site
• Breasts can possibly become smaller and firmer
  after treatment
• Can contribute to swelling of the arm if underarm
  is irradiated after surgery.
• Hormone therapy
• Depends on the specific medication used and the
  individual patient
• A doctor should be consulted about the possible
  side effects before beginning treatment.

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Post-treatment therapy

• Doctors may refer their patients to support
  groups, councilors, or a psychologist for help in
  dealing with the aftermath of the disease and
  treatment.
• Breast reconstruction surgery
• Latissimus Dorsi flap a section of skin, fat,
  and latissimus dorsi muscle is transferred from
  the back to the breast area and shaped into a
  natural-looking breast.
• TRAM flap a section of skin, fat, and muscle is
  transferred from the lower half of the abdomen to
  the breast area and shaped into a natural-looking
  breast.
• Breast Implants

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Reconstructive Breast Implant Surgery
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Latissimus Dorsi Flap Breast Reconstruction
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TRAM Flap Breast Reconstruciton
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Breast Cancer Risk Calculator!

• http//www.cancer.gov/bcrisktool/

The room will split up into two halves. As we go
through the questions, choose the answers that
you think will maximize a persons risk of
getting breast cancer.