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ARE YOU AT RISK FOR
 BREAST CANCER?


    Jerrold S. Lozner, M.D.,
      MHA, FACS
      MHA FACS, ASBS
      November 10, 2011
Definition of Risk

• Understanding risk involves assessing the possibility of
  suffering harm or loss.
• A risk f
      i k factor i anything that increases your chances of
                 is    hi    h i                 h        f
  suffering harm or loss.
• We are going to analyze the factors that increase the risk
  for breast cancer and to evaluate the options that may
  mitigate that risk.
Breast Cancer Facts

• All women are at risk for breast cancer.
• Your breast cancer risk increases as you get older.
• Most women who develop breast cancer have no other risk
  factors.
• Although breast cancer is more common in women over
  the age of 40, younger women can also develop breast
  cancer.
• Breast cancer is 100 times more common in women than
  men.
Breast Cancer Facts

• One in eight women in the United States will be diagnosed
  with breast cancer in her lifetime.
• A
  Approximately 95% of all breast cancers in the United
          i     l        f ll b              i h U i d
  States occur in women over the age of 40.
• The five year survival rate for breast cancer when caught
  early before it spreads beyond the breast is 98%.
• An estimated 230,480 women and 2140 men will be
  diagnosed with invasive breast cancer in the United States
  di        d ihi       i b               i h     i dS
  in 2011. An estimated 39,520 women and 450 men will die
  from the disease in 2011.
Breast Cancer Facts

• There are 2.5 million breast cancer survivors in the United
  States today, the largest group of cancer survivors in the
  country.
  country
Risk Factors

• Being a woman
• Getting older
• Inherited mutations in the BRCA1 or BRCA2 breast
  cancer genes
• Previous biopsy that showed lobular carcinoma in situ
  (LCIS)
• Family history of breast cancer
• High breast density on mammogram
• Exposure to large amounts of radiation
Risk Factors

•   Personal history of breast or ovarian cancer
•   Starting menopause after age 55
•   Never having children
•   Having first child after age 35
•   Overweight after menopause
    O       i ht ft
•   More than one alcoholic drink each day
•   Postmenopausal use of estrogen/estrogen plus progestin
•   Current or recent use of birth control pills
Gender

The main reason women develop breast cancer 100 times
more frequently than men is because a woman’s breast
cells are constantly exposed to the growth-promoting
                                    growth promoting
effects of the female hormones estrogen and progesterone.
Aging

• About 1 out of 8 invasive breast cancers are found in
  women younger than 45, while about 2 of 3 breast cancers
  are found in women age 55 or older.
                                older
Family History of Breast Cancer

• Having one first-degree relative (mother, sister, or
  daughter) with breast cancer approximately doubles a
  woman s risk.
  woman’s risk Having 2 first degree relatives increases the
                            first-degree
  risk about 3-fold.
• The exact risk is not known but women with a family    y
  history of breast cancer in a father or a brother also have an
  increased risk of breast cancer.
• Less than 15% of women with breast cancer have a family
  member with the disease.
Personal History of Breast Cancer

• A woman with cancer in one breast has a 3 to 4 fold
  increased risk of developing a new cancer in the other
  breast or in another part of the same breast
                                        breast.
• This is different from a recurrence of the first cancer.
Race and Ethnicity

• Caucasian women are slightly more likely to develop
  breast cancer than are African-American women, but it is
  more common in African-American women under the age
                    African American
  of 45.
• Asian, Hispanic, and Native-American women have a
             p
  lower risk of developing breast cancer.
Dense Breast Tissue

• Women with denser breast tissue as seen on a
  mammogram have more glandular tissue and less fatty
  tissue,
  tissue and have a higher risk of breast cancer.
                                          cancer
• Dense breast tissue makes it more difficult for radiologists
  to spot problems on mammograms.
      p p                      g
Certain “Benign” Breast Conditions

• Some conditions found on breast biopsy are more closely
  linked to breast cancer risk than others.
Non-proliferative Lesions

• These conditions are not associated with overgrowth of
  breast tissue and do not seem to affect breast cancer risk.
• Fib
  Fibrocystic disease
             i di
• Mild hyperplasia
• Duct ectasia
• Simple fibroadenoma
• A single papilloma
       g p p
• Fat necrosis
• Mastitis
Proliferative Lesions Without Atypia

• These conditions show excessive growth of cells in the
  ducts or lobules of breast tissue and may increase risk 1.5
  to 2 times normal.
             normal
• Usual ductal hyperplasia
• Complex fibroadenoma
• Sclerosing adenosis
• Several papillomas
• Radial scar
Proliferative Lesions With Atypia

• In theses conditions, there is an overgrowth of cells with
  some of the cells no longer appearing normal. These may
  increase breast cancer risk 4 to 5 times higher than normal.
                                                       normal
• Atypical ductal hyperplasia (ADH)
• Atypical lobular hyperplasia (ALH)
Lobular Carcinoma in situ

• Cells that look like cancer cells grow in the lobules of the
  glands of the breast, but they do not grow through the wall
  of the lobules. It differs from DCIS in that it does not seem
         lobules
  to become an invasive cancer if not treated.
• However, women with LCIS have a 7 to 11 fold increased
  risk of developing invasive breast cancer in either breast.
Menstrual Periods

• Women who have had more menstrual cycles because they
  started menstruating at an early age (before age 12) and/or
  went through menopause at a later age (after age 55) have
  a slightly higher risk of breast cancer.
• The increased risk may be caused by a longer lifetime
                          y            y     g
  exposure to the hormones estrogen and progesterone.
Previous Chest Radiation

• Women who as children or young adults had radiation
  therapy to the chest area for another cancer such as
  Hodgkin s
  Hodgkin’s Disease or non Hodgkin lymphoma have a
                         non-Hodgkin
  significantly increased risk for breast cancer. If
  chemotherapy was also given, it may have stopped ovarian
  hormone production for some time, lowering the risk.
• Radiation treatment after age 40 does not seem to increase
  breast cancer risk
                 risk.
Having Children

• Women who have had no children or who had their first
  child after age 30 have a slightly higher breast cancer risk.
• H i many pregnancies and becoming pregnant at a
  Having                  i     db       i
  young age reduces breast cancer risk. Pregnancy reduces a
  woman’s total number of lifetime menstrual cycles, which
                                                 y
  may be the reason for this effect.
Recent Oral Contraceptive Use

• Women using birth control pills have a slightly greater risk
  of breast cancer than women who have never used them.
• W
  Women who stopped using birth control pills more than 10
             h        d i bi h           l ill        h
  years ago do not seem to have increased breast cancer risk.
Hormone Therapy After Menopause

• The Women’s Health Initiative found that those women
  taking a combination of estrogen and progestin increased
  their risk of developing breast cancer by 26% (and
  increased their risk for heart attack by 29% and stroke by
  42%).
• Among women who stopped taking HRT, rates of breast
  cancer significantly declined within one year.
• Women who stayed on HRT for 5 years doubled their
  annual risk for breast cancer.
Recommendation on HRT

• Women at high risk for breast cancer and those who have
  been diagnosed with breast cancer should avoid HRT.
• W
  Women at low risk for breast cancer can use HRT to
             l    i kf b
  control menopausal symptoms, but try for shortest possible
  duration and lowest possible dose.
                      p
• HRT does seem to reduce the risk of colorectal cancer and
  osteoporosis.
Breast Feeding

• Some studies suggest that breast feeding may slightly
  lower the risk of breast cancer especially if continued for
  1.5
  1 5 to 2 years. However this is not a common practice in
           years However,
  the US.
• The explanation may be that breast feeding reduces a
         p             y                      g
  woman’s total number of lifetime menstrual cycles.
Alcohol

• The use of alcohol is clearly linked to an increased risk of
  developing breast cancer, with a relationship to the amount
  consumed.
  consumed
• Those women who have 2 to 5 drinks per day have about
  1.5 times the risk of developing breast cancer as compared
                              p g                        p
  to non-drinkers.
• The American Cancer Society recommends that women
  have no more than one alcoholic drink per day.
                                               day
Being Overweight or Obese

• Being overweight has been found to increase breast cancer
  risk especially for women after menopause. After
  menopause when the ovaries stop making estrogen, most
                                            estrogen
  of a woman’s estrogen comes from fat tissue.
• The risk appears to be increased for women who gained
            pp                                     g
  weight as an adult but may not be increased in those who
  have been overweight since childhood.
Physical Activity

• Evidence is growing that physical activity in the form of
  exercise reduces breast cancer risk.
• R l recreational activity such as brisk walking lowered
  Regular         i l i i          h b i k lki l             d
  risk more than doing household chores.
• Physical activity throughout life was the most protective,
  but exercising after menopause was more productive than
  exercising only earlier in life.
• Recommendation: Exercise for at least 30 minutes 5 times
              d i           i f      l         i        i
  per week.
Breast Implants

• Breast implants do not increase breast cancer risk.
Which are the Major Risk Factors?

•   Mutation associated with hereditary cancer
•   Family history
•   First degree relative <50 years
•   Chest radiation <30 years
•   DCIS, LCIS, ADH,
    DCIS LCIS ADH ALH
•   Prior breast or ovarian cancer
•   Age
Which are the Minor Risk Factors?

•   Late or no childbirth
•   Early menarche
•   Late menopause
•   HRT
•   Postmenopausal obesity
    P t             l b it
•   Sedentary lifestyle
•   Alcohol
•   Smoking
Major Factors: Absolute Risk Per Year

•   BRCA ½                         2-3%
•   DCIS                           1-2%
•   LCIS                           1%
•   Atypia and Family History       1%
•   Atypia Alone
    At i Al                        0.5%
                                   0 5%
•   Prior Invasive Breast Cancer    0.75%
•   Age >60                         0 33%
                                    0.33%
Risk Reduction Options

• All Women           Lifestyle Changes      30-45%
• Atypia              Tamoxifen              86%
• High Gail Risk      Tamoxifen              49%




• SERM (Selective estrogen receptor modulator)
       (               g       p             )
Recommendations

•   Limit alcohol
•   Avoid long term estrogen therapy
•   Avoid adult weight gain
•   Exercise
•   Make healthy di t
    M k h lth dietary choices
                          h i
•   BSA versus BSE
•   Annual screening mammogram
•   Understand your risk
Modified Gail Risk Model
• This is a computer-based multivariate logistic regression
  model that uses:
• Age
• Race
• Age at menarche
• Age at first live birth or nulliparity
• Number of first degree relatives with breast cancer
• Number of previous breast biopsies
• Histology of the breast biopsies
To produce actuarial estimates of future breast cancer risk.
Breast Cancer Screening

• Normal Risk:

• Ages 20-40: Clinical breast exam every 1-3 years
              Breast awareness

  Age >40:     Annual clinical breast exam
               Annual mammogram
               Breast awareness
Breast Cancer Screening
             B    tC       S     i

• Increased Risk:
• Prior chest radiation therapy
• 5 year risk > 1.7 Gail Model
    y
• Lifetime risk > 20%
• Pedigree suggestive of genetic predisposition
• LCIS/ Atypical hyperplasia
• Prior history of breast cancer
Use Combination f
U C bi i of more frequent complete breast exam and
                           f            l b         d
  mammograms; Breast awareness; MRI; Risk reduction
  strategies; Genetic counseling
        g                       g
HEREDITARY BREAST AND OVARIAN CANCER:
WHAT WOMEN (AND MEN)
NEED TO KNOW



          Niecee Singer Schonberger, M.S., C.G.C.
                Certified Genetic Counselor




                          COMPILED BY BETH PESHKIN, MS, CGC
TOPICS FOR TODAY S DISCUSSION
           TODAY’S
What is genetic counseling and testing and who should consider it?
What information does genetic testing provide about cancer risks and what can be done
   to manage these risks?
What are the pros and cons of genetic testing?
What are the current areas of research and future directions?
WHAT IS GENETIC COUNSELING AND HOW CAN IT
HELP?
Genetic counseling is a discussion focused around risk
  assessment; options for medical management; and your
  perception of the potential benefits, risks, and
  limitations of genetic testing
                 g             g
Genetic counseling can help you make informed decisions
  about whether and what type of genetic testing may be
  useful and steps that may be taken p
                  p          y         protect yyour and
  your family’s health
Genetic counseling can help you develop and implement
  short and long term p
                 g     plans for what to do with
  information obtained from your risk assessment
WHAT IS GENETIC TESTING?
   Genetic testing refers to the assessment of inherited changes that result in increased
    susceptibility to cancer
   Alterations in several genes contribute to increased risk for breast cancer, the most
                                                                         cancer
    common of which are called BRCA1 and BRCA2
   These genes were identified in the mid 1990s and another major gene has not been
    found since. This is important because, depending on the setting, 30-80% of families
    with breast cancer will not harbor a mutation in these genes.
WHAT ROLE DO GENES PLAY IN THE DEVELOPMENT OF
BREAST AND OVARIAN CANCER?


                  15%-
                  20%

             5%-10%                         ~10%
  Breast Cancer                   Ovarian Cancer
                     Sporadic
                     Family
                      a y
                     clusters
                     Hereditary
BRCA1 AND BRCA2 ALTERATIONS IN THE
             ASHKENAZI JEWISH POPULATION
                       An estimated 1 in 40 Ashkenazi Jews
                         carries a BRCA1 or BRCA2 mut
                          (regardless of family history)
                                   BRCA1

                187delAG                       5385insC



• In non-Jewish individuals, only            BRCA2
about 1 i 400 will have a gene
  b t in        ill h
alteration                                   6174delT
• There are > 1,000 alterations in
each gene
     g
HOW DO YOU KNOW IF YOU MAY BE AT-RISK
FOR HEREDITARY BREAST CANCER?
YOUR FAMILY HISTORY IS KEY
 • Collect as much family history as you can, document it, share it with your
 relatives, and update it
 • Try to obtain medical records (pathology reports) or death certificates
 • This information can be used to provide a general (qualitative) and
 numerical estimate of your cancer risk and/or your chance of having a gene
 mutation
WHAT FEATURES ARE SUGGESTIVE OF
HEREDITARY BREAST/OVARIAN CANCER?
    Breast cancer diagnosed before age 50
    Breast cancer in 2 or more close relatives (same side of
     the family), especially if one was diagnosed before age 50
    Ovarian cancer, with or without a family history of breast
     cancer (even just one relative with this cancer i
             (      j t         l ti  ith thi        is
     significant)
    Breast and ovarian cancer in the same woman
    Breast cancer and relatives with prostate or pancreatic
     cancer
    Male breast cancer usually in conjunction with female
                   cancer,
     breast cancer in one or more close relatives
    Ashkenazi Jewish ancestry
The Family Pedigree:
            Initiate testing with a relative
                           g
            who has had breast or ovarian
Breast      cancer.
dx 61



                    70
   Breast
                    Breast        80    79
   dx 51
                    dx 49




              40   38
                   Breast
                   dx 37
BRCA1/2 ASSOCIATED CANCERS: LIFETIME RISKS


        Breast cancer 55%-85% (often early age at onset)
           Breast cancer, opposite breast: 40%-65%
            Ovarian cancer: 24%-44%

             • Risks for initial breast cancer and ovarian
             cancer are tend to be lower for women with
                           BRCA2 mutations
              • These are published risk ranges; risks in
                       clinical counseling vary
ADDITIONAL CANCER RISKS IN BRCA1/2 CARRIERS

    Cancers affecting men
              - prostate
              - breast (risk less than 10%)
    Other cancers (risk less than 10%)
              - pancreatic
              - stomach
              - melanoma
              - other sites to be determined
                 th    it t b d t       i d
REDUCING RISK: WHAT ARE THE OPTIONS?
    Surgery does not eliminate the risk of cancer
             - Risk reducing mastectomy: an option
             - Risk reducing ovary removal (oophorectomy) – significantly
       reduces the risk of ovarian cancer; also reduces breast
       cancer risk in premenopausal women: RECOMMENDED              BY AGE 40 OR
       AFTER CHILDBEARING

    A very significant implication of oophorectomy in young women is that it
       results in premature menopause. It can be challenging to effectively
       manage any associated symptoms.

    Increased surveillence

    Drugs may play a role in risk reduction. But other risks and benefits must be
       g
       considered.
           id d
            - Tamoxifen, Raloxifene, Aromatase Inhibitors?
            - Oral contraceptives
Insurance Issues
 Concern about genetic discrimination has been a persistent
 barrier to individuals’ seeking g
                               g genetic counseling and testing
                                                  g           g
 • There have been only a few documented cases of
 insurance discrimination based on genetic testing or genetic
 conditions
 • Most insurers will pay for cancer susceptibility testing,
 although risk th h ld and medical necessity may need t
   lth   h i k thresholds d       di l         it            d to
 be demonstrated
 • State laws may provide broader coverage than federal
 laws; GINA sets a minimum standard
GENETIC INFORMATION NONDISCRIMINATION
ACT OF 2008 WHAT GINA DOES
       2008:
   • Prohibits use of an individual’s genetic information in
   setting eligibility or premium or contribution amounts by
   group and individual health insurers.
   • Prohibits health insurers from requesting or requiring
   an individual to take a genetic test.
   • Prohibits use of an individual’s genetic information by
   employers in employment decisions such as hiringhiring,
   firing, job assignments, and promotions.
   • Prohibits e p oye s from requesting, requiring, o
       o b s employers o eques g, equ g, or
   purchasing genetic information about an individual
   employee or family member.
Potential Benefits of BRCA1/2 Testing

  • Identifies high-risk individuals
  • Id tifi noncarriers i f ili with a
    Identifies       i  in families ith
    known alteration
  • Informs medical decision-making
  • May relieve anxiety and provide other
    psychological benefits
POTENTIAL RISKS AND LIMITATIONS OF BRCA1/2
TESTING
   Testing does not detect all mutations and may not rule
      out hereditary risk
   Women who test negative f an alteration in their family
                                for                       f
      still have a risk of developing cancer
   Efficacy of some interventions not well established
            y
   May result in mild distress or anxiety; survivor guilt
   May elicit concerns about insurance discrimination
Concluding Thoughts
 • The choice to be tested is a personal one and
 should be made after genetic counseling and
 careful consideration of the potential implications
 for yourself and your family. Take time to think
 about these issues.
 • Genetic testing can be a life altering, powerful
 experience. No two people respond the same way
 to the information. Sometimes the reaction is not
        information
 what people anticipate.
 • We are more than what’s in our genes. Genetic
                      what s
 testing won’t provide all the answers, but it may
 provide important, if not life saving, pieces of
 information.
 information
Are you at risk for breast cancer ?

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Are you at risk for breast cancer ?

  • 1. ARE YOU AT RISK FOR BREAST CANCER? Jerrold S. Lozner, M.D., MHA, FACS MHA FACS, ASBS November 10, 2011
  • 2. Definition of Risk • Understanding risk involves assessing the possibility of suffering harm or loss. • A risk f i k factor i anything that increases your chances of is hi h i h f suffering harm or loss. • We are going to analyze the factors that increase the risk for breast cancer and to evaluate the options that may mitigate that risk.
  • 3. Breast Cancer Facts • All women are at risk for breast cancer. • Your breast cancer risk increases as you get older. • Most women who develop breast cancer have no other risk factors. • Although breast cancer is more common in women over the age of 40, younger women can also develop breast cancer. • Breast cancer is 100 times more common in women than men.
  • 4. Breast Cancer Facts • One in eight women in the United States will be diagnosed with breast cancer in her lifetime. • A Approximately 95% of all breast cancers in the United i l f ll b i h U i d States occur in women over the age of 40. • The five year survival rate for breast cancer when caught early before it spreads beyond the breast is 98%. • An estimated 230,480 women and 2140 men will be diagnosed with invasive breast cancer in the United States di d ihi i b i h i dS in 2011. An estimated 39,520 women and 450 men will die from the disease in 2011.
  • 5. Breast Cancer Facts • There are 2.5 million breast cancer survivors in the United States today, the largest group of cancer survivors in the country. country
  • 6. Risk Factors • Being a woman • Getting older • Inherited mutations in the BRCA1 or BRCA2 breast cancer genes • Previous biopsy that showed lobular carcinoma in situ (LCIS) • Family history of breast cancer • High breast density on mammogram • Exposure to large amounts of radiation
  • 7. Risk Factors • Personal history of breast or ovarian cancer • Starting menopause after age 55 • Never having children • Having first child after age 35 • Overweight after menopause O i ht ft • More than one alcoholic drink each day • Postmenopausal use of estrogen/estrogen plus progestin • Current or recent use of birth control pills
  • 8. Gender The main reason women develop breast cancer 100 times more frequently than men is because a woman’s breast cells are constantly exposed to the growth-promoting growth promoting effects of the female hormones estrogen and progesterone.
  • 9. Aging • About 1 out of 8 invasive breast cancers are found in women younger than 45, while about 2 of 3 breast cancers are found in women age 55 or older. older
  • 10. Family History of Breast Cancer • Having one first-degree relative (mother, sister, or daughter) with breast cancer approximately doubles a woman s risk. woman’s risk Having 2 first degree relatives increases the first-degree risk about 3-fold. • The exact risk is not known but women with a family y history of breast cancer in a father or a brother also have an increased risk of breast cancer. • Less than 15% of women with breast cancer have a family member with the disease.
  • 11. Personal History of Breast Cancer • A woman with cancer in one breast has a 3 to 4 fold increased risk of developing a new cancer in the other breast or in another part of the same breast breast. • This is different from a recurrence of the first cancer.
  • 12. Race and Ethnicity • Caucasian women are slightly more likely to develop breast cancer than are African-American women, but it is more common in African-American women under the age African American of 45. • Asian, Hispanic, and Native-American women have a p lower risk of developing breast cancer.
  • 13. Dense Breast Tissue • Women with denser breast tissue as seen on a mammogram have more glandular tissue and less fatty tissue, tissue and have a higher risk of breast cancer. cancer • Dense breast tissue makes it more difficult for radiologists to spot problems on mammograms. p p g
  • 14. Certain “Benign” Breast Conditions • Some conditions found on breast biopsy are more closely linked to breast cancer risk than others.
  • 15. Non-proliferative Lesions • These conditions are not associated with overgrowth of breast tissue and do not seem to affect breast cancer risk. • Fib Fibrocystic disease i di • Mild hyperplasia • Duct ectasia • Simple fibroadenoma • A single papilloma g p p • Fat necrosis • Mastitis
  • 16. Proliferative Lesions Without Atypia • These conditions show excessive growth of cells in the ducts or lobules of breast tissue and may increase risk 1.5 to 2 times normal. normal • Usual ductal hyperplasia • Complex fibroadenoma • Sclerosing adenosis • Several papillomas • Radial scar
  • 17. Proliferative Lesions With Atypia • In theses conditions, there is an overgrowth of cells with some of the cells no longer appearing normal. These may increase breast cancer risk 4 to 5 times higher than normal. normal • Atypical ductal hyperplasia (ADH) • Atypical lobular hyperplasia (ALH)
  • 18. Lobular Carcinoma in situ • Cells that look like cancer cells grow in the lobules of the glands of the breast, but they do not grow through the wall of the lobules. It differs from DCIS in that it does not seem lobules to become an invasive cancer if not treated. • However, women with LCIS have a 7 to 11 fold increased risk of developing invasive breast cancer in either breast.
  • 19. Menstrual Periods • Women who have had more menstrual cycles because they started menstruating at an early age (before age 12) and/or went through menopause at a later age (after age 55) have a slightly higher risk of breast cancer. • The increased risk may be caused by a longer lifetime y y g exposure to the hormones estrogen and progesterone.
  • 20. Previous Chest Radiation • Women who as children or young adults had radiation therapy to the chest area for another cancer such as Hodgkin s Hodgkin’s Disease or non Hodgkin lymphoma have a non-Hodgkin significantly increased risk for breast cancer. If chemotherapy was also given, it may have stopped ovarian hormone production for some time, lowering the risk. • Radiation treatment after age 40 does not seem to increase breast cancer risk risk.
  • 21. Having Children • Women who have had no children or who had their first child after age 30 have a slightly higher breast cancer risk. • H i many pregnancies and becoming pregnant at a Having i db i young age reduces breast cancer risk. Pregnancy reduces a woman’s total number of lifetime menstrual cycles, which y may be the reason for this effect.
  • 22. Recent Oral Contraceptive Use • Women using birth control pills have a slightly greater risk of breast cancer than women who have never used them. • W Women who stopped using birth control pills more than 10 h d i bi h l ill h years ago do not seem to have increased breast cancer risk.
  • 23. Hormone Therapy After Menopause • The Women’s Health Initiative found that those women taking a combination of estrogen and progestin increased their risk of developing breast cancer by 26% (and increased their risk for heart attack by 29% and stroke by 42%). • Among women who stopped taking HRT, rates of breast cancer significantly declined within one year. • Women who stayed on HRT for 5 years doubled their annual risk for breast cancer.
  • 24. Recommendation on HRT • Women at high risk for breast cancer and those who have been diagnosed with breast cancer should avoid HRT. • W Women at low risk for breast cancer can use HRT to l i kf b control menopausal symptoms, but try for shortest possible duration and lowest possible dose. p • HRT does seem to reduce the risk of colorectal cancer and osteoporosis.
  • 25. Breast Feeding • Some studies suggest that breast feeding may slightly lower the risk of breast cancer especially if continued for 1.5 1 5 to 2 years. However this is not a common practice in years However, the US. • The explanation may be that breast feeding reduces a p y g woman’s total number of lifetime menstrual cycles.
  • 26. Alcohol • The use of alcohol is clearly linked to an increased risk of developing breast cancer, with a relationship to the amount consumed. consumed • Those women who have 2 to 5 drinks per day have about 1.5 times the risk of developing breast cancer as compared p g p to non-drinkers. • The American Cancer Society recommends that women have no more than one alcoholic drink per day. day
  • 27. Being Overweight or Obese • Being overweight has been found to increase breast cancer risk especially for women after menopause. After menopause when the ovaries stop making estrogen, most estrogen of a woman’s estrogen comes from fat tissue. • The risk appears to be increased for women who gained pp g weight as an adult but may not be increased in those who have been overweight since childhood.
  • 28. Physical Activity • Evidence is growing that physical activity in the form of exercise reduces breast cancer risk. • R l recreational activity such as brisk walking lowered Regular i l i i h b i k lki l d risk more than doing household chores. • Physical activity throughout life was the most protective, but exercising after menopause was more productive than exercising only earlier in life. • Recommendation: Exercise for at least 30 minutes 5 times d i i f l i i per week.
  • 29. Breast Implants • Breast implants do not increase breast cancer risk.
  • 30. Which are the Major Risk Factors? • Mutation associated with hereditary cancer • Family history • First degree relative <50 years • Chest radiation <30 years • DCIS, LCIS, ADH, DCIS LCIS ADH ALH • Prior breast or ovarian cancer • Age
  • 31. Which are the Minor Risk Factors? • Late or no childbirth • Early menarche • Late menopause • HRT • Postmenopausal obesity P t l b it • Sedentary lifestyle • Alcohol • Smoking
  • 32. Major Factors: Absolute Risk Per Year • BRCA ½ 2-3% • DCIS 1-2% • LCIS 1% • Atypia and Family History 1% • Atypia Alone At i Al 0.5% 0 5% • Prior Invasive Breast Cancer 0.75% • Age >60 0 33% 0.33%
  • 33. Risk Reduction Options • All Women Lifestyle Changes 30-45% • Atypia Tamoxifen 86% • High Gail Risk Tamoxifen 49% • SERM (Selective estrogen receptor modulator) ( g p )
  • 34. Recommendations • Limit alcohol • Avoid long term estrogen therapy • Avoid adult weight gain • Exercise • Make healthy di t M k h lth dietary choices h i • BSA versus BSE • Annual screening mammogram • Understand your risk
  • 35. Modified Gail Risk Model • This is a computer-based multivariate logistic regression model that uses: • Age • Race • Age at menarche • Age at first live birth or nulliparity • Number of first degree relatives with breast cancer • Number of previous breast biopsies • Histology of the breast biopsies To produce actuarial estimates of future breast cancer risk.
  • 36. Breast Cancer Screening • Normal Risk: • Ages 20-40: Clinical breast exam every 1-3 years Breast awareness Age >40: Annual clinical breast exam Annual mammogram Breast awareness
  • 37. Breast Cancer Screening B tC S i • Increased Risk: • Prior chest radiation therapy • 5 year risk > 1.7 Gail Model y • Lifetime risk > 20% • Pedigree suggestive of genetic predisposition • LCIS/ Atypical hyperplasia • Prior history of breast cancer Use Combination f U C bi i of more frequent complete breast exam and f l b d mammograms; Breast awareness; MRI; Risk reduction strategies; Genetic counseling g g
  • 38. HEREDITARY BREAST AND OVARIAN CANCER: WHAT WOMEN (AND MEN) NEED TO KNOW Niecee Singer Schonberger, M.S., C.G.C. Certified Genetic Counselor COMPILED BY BETH PESHKIN, MS, CGC
  • 39. TOPICS FOR TODAY S DISCUSSION TODAY’S What is genetic counseling and testing and who should consider it? What information does genetic testing provide about cancer risks and what can be done to manage these risks? What are the pros and cons of genetic testing? What are the current areas of research and future directions?
  • 40. WHAT IS GENETIC COUNSELING AND HOW CAN IT HELP? Genetic counseling is a discussion focused around risk assessment; options for medical management; and your perception of the potential benefits, risks, and limitations of genetic testing g g Genetic counseling can help you make informed decisions about whether and what type of genetic testing may be useful and steps that may be taken p p y protect yyour and your family’s health Genetic counseling can help you develop and implement short and long term p g plans for what to do with information obtained from your risk assessment
  • 41. WHAT IS GENETIC TESTING?  Genetic testing refers to the assessment of inherited changes that result in increased susceptibility to cancer  Alterations in several genes contribute to increased risk for breast cancer, the most cancer common of which are called BRCA1 and BRCA2  These genes were identified in the mid 1990s and another major gene has not been found since. This is important because, depending on the setting, 30-80% of families with breast cancer will not harbor a mutation in these genes.
  • 42. WHAT ROLE DO GENES PLAY IN THE DEVELOPMENT OF BREAST AND OVARIAN CANCER? 15%- 20% 5%-10% ~10% Breast Cancer Ovarian Cancer Sporadic Family a y clusters Hereditary
  • 43. BRCA1 AND BRCA2 ALTERATIONS IN THE ASHKENAZI JEWISH POPULATION An estimated 1 in 40 Ashkenazi Jews carries a BRCA1 or BRCA2 mut (regardless of family history) BRCA1 187delAG 5385insC • In non-Jewish individuals, only BRCA2 about 1 i 400 will have a gene b t in ill h alteration 6174delT • There are > 1,000 alterations in each gene g
  • 44. HOW DO YOU KNOW IF YOU MAY BE AT-RISK FOR HEREDITARY BREAST CANCER? YOUR FAMILY HISTORY IS KEY • Collect as much family history as you can, document it, share it with your relatives, and update it • Try to obtain medical records (pathology reports) or death certificates • This information can be used to provide a general (qualitative) and numerical estimate of your cancer risk and/or your chance of having a gene mutation
  • 45. WHAT FEATURES ARE SUGGESTIVE OF HEREDITARY BREAST/OVARIAN CANCER?  Breast cancer diagnosed before age 50  Breast cancer in 2 or more close relatives (same side of the family), especially if one was diagnosed before age 50  Ovarian cancer, with or without a family history of breast cancer (even just one relative with this cancer i ( j t l ti ith thi is significant)  Breast and ovarian cancer in the same woman  Breast cancer and relatives with prostate or pancreatic cancer  Male breast cancer usually in conjunction with female cancer, breast cancer in one or more close relatives  Ashkenazi Jewish ancestry
  • 46. The Family Pedigree: Initiate testing with a relative g who has had breast or ovarian Breast cancer. dx 61 70 Breast Breast 80 79 dx 51 dx 49 40 38 Breast dx 37
  • 47. BRCA1/2 ASSOCIATED CANCERS: LIFETIME RISKS Breast cancer 55%-85% (often early age at onset) Breast cancer, opposite breast: 40%-65% Ovarian cancer: 24%-44% • Risks for initial breast cancer and ovarian cancer are tend to be lower for women with BRCA2 mutations • These are published risk ranges; risks in clinical counseling vary
  • 48. ADDITIONAL CANCER RISKS IN BRCA1/2 CARRIERS Cancers affecting men - prostate - breast (risk less than 10%) Other cancers (risk less than 10%) - pancreatic - stomach - melanoma - other sites to be determined th it t b d t i d
  • 49. REDUCING RISK: WHAT ARE THE OPTIONS? Surgery does not eliminate the risk of cancer - Risk reducing mastectomy: an option - Risk reducing ovary removal (oophorectomy) – significantly reduces the risk of ovarian cancer; also reduces breast cancer risk in premenopausal women: RECOMMENDED BY AGE 40 OR AFTER CHILDBEARING A very significant implication of oophorectomy in young women is that it results in premature menopause. It can be challenging to effectively manage any associated symptoms. Increased surveillence Drugs may play a role in risk reduction. But other risks and benefits must be g considered. id d - Tamoxifen, Raloxifene, Aromatase Inhibitors? - Oral contraceptives
  • 50. Insurance Issues Concern about genetic discrimination has been a persistent barrier to individuals’ seeking g g genetic counseling and testing g g • There have been only a few documented cases of insurance discrimination based on genetic testing or genetic conditions • Most insurers will pay for cancer susceptibility testing, although risk th h ld and medical necessity may need t lth h i k thresholds d di l it d to be demonstrated • State laws may provide broader coverage than federal laws; GINA sets a minimum standard
  • 51. GENETIC INFORMATION NONDISCRIMINATION ACT OF 2008 WHAT GINA DOES 2008: • Prohibits use of an individual’s genetic information in setting eligibility or premium or contribution amounts by group and individual health insurers. • Prohibits health insurers from requesting or requiring an individual to take a genetic test. • Prohibits use of an individual’s genetic information by employers in employment decisions such as hiringhiring, firing, job assignments, and promotions. • Prohibits e p oye s from requesting, requiring, o o b s employers o eques g, equ g, or purchasing genetic information about an individual employee or family member.
  • 52. Potential Benefits of BRCA1/2 Testing • Identifies high-risk individuals • Id tifi noncarriers i f ili with a Identifies i in families ith known alteration • Informs medical decision-making • May relieve anxiety and provide other psychological benefits
  • 53. POTENTIAL RISKS AND LIMITATIONS OF BRCA1/2 TESTING Testing does not detect all mutations and may not rule out hereditary risk Women who test negative f an alteration in their family for f still have a risk of developing cancer Efficacy of some interventions not well established y May result in mild distress or anxiety; survivor guilt May elicit concerns about insurance discrimination
  • 54. Concluding Thoughts • The choice to be tested is a personal one and should be made after genetic counseling and careful consideration of the potential implications for yourself and your family. Take time to think about these issues. • Genetic testing can be a life altering, powerful experience. No two people respond the same way to the information. Sometimes the reaction is not information what people anticipate. • We are more than what’s in our genes. Genetic what s testing won’t provide all the answers, but it may provide important, if not life saving, pieces of information. information