Summit Medical Group Senior Breast Surgeon Jerrold S. Lozner, MD, MHA, FACS and Genetic Counselor Nicee Singer Schonberger, MS, CGC, presented this lecture about current, state-of-the-art risk assessment tools, genetic counseling and high risk monitoring at our Berkeley Heights, NJ Campus

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
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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