Download Case Studies for Module 2A - BRCA

A 40-year-old African-American woman comes in today for a full checkup. She is
feeling well and has not seen a doctor in several years because her job does not provide
health insurance. The only medication she takes is an oral contraceptive. She has no
chronic medical conditions, her 19 year old daughter is well, and her family history is
negative for any cancers or early heart disease.
Screening women age 50 is widely accepted. Multiple randomized controlled trials
have clearly demonstrated a significant decrease in mortality in women between the
ages of 50 and 70 who receive routine mammography screening. The benefit of routine
mammography screening in younger pre-menopausal women is less clear because the
results of multiple studies are conflicting. At younger ages, the incidence of breast
cancer is low and the sensitivity of mammography is decreased because the breast
tissue is more dense.
The National Institutes of Health (NIH) convened an expert panel in 1997 to review
the evidence for and against screening women ages 40-49. Mortality from breast
cancer and the risks and benefits of mammography were reviewed. A consensus
statement was not reached but the majority concluded that "the data currently
available do not warrant a universal recommendation for mammography for all
women in their 40s."
An alternative for women who are unable or unwilling to get regular mammogram
screening is a clinical breast examination (CBE) by a health care provider. A
competent annual clinical exam may diagnose breast cancers at a later stage but
possibly provide equal protection against mortality from breast cancer (9).
Organization
Recommendation
U.S. Preventive Services Task Force and American College of
Physicians
MMG every 1-2 years from age 40
American Medical Association
MMG every year from age 40
American Academy of Family Physicians (AAFP)
MMG every 1-2 years from age 50
American College of Obstetrician/Gynecologists (ACOG)
MMG every 1-2 years from age 40-49 and every year
age 50
American College of Radiology/ American Cancer Society
(ACR/ACS)
MMG every year from age 40
Canadian Task Force in Preventive Healthcare
MMG every 1-2 years from age 50
MMG = mammography
Breast cancer is uncommon in young women, affecting approximately 0.5% under the
age of 40.
You explain to her that the commonly quoted number of 1 in 8 women will get breast
cancer refers to lifetime risk (that is if a woman were to live to age 90). Also, the
majority of women who develop breast cancer will not die from it. It is more
appropriate to use age specific probabilities rather than lifetime probabilities when
counseling patients, as shown in the table below.
Recently, there has been a lot information in the media regarding the high risk of
breast cancer in women with the gene alterations, BRCA-1 and BRCA-2. They have a
much higher risk of developing breast cancer, but represent only 2-6 % of all women
with breast cancer. Hereditary cancer syndromes (including BRCA-1 and BRCA-2)
account for only 5-10 % of breast cancer in the US.
Incidence of Breast Cancer in all women and in
women with the BRCA-1 and BRCA-2 gene
mutations:
Age
All Women
BRCA-1/
BRCA-2Carriers
25
1 in 19,608
30
1 in 2,525
35
1 in 622
40
1 in 217
0.5%
16%
45
1 in 93
1.0%
42%
50
1 in 50
2.0%
59%
55
1 in 33
3.0%
72%
60
1 in 24
4.2%
77%
65
1 in 17
5.9%
80%
70
1 in 14
7.1%
82%
75
1 in 11
9.1%
84%
90 (lifetime) 1 in 8
12.0%
87%
NCI Surveillance Research Program
It is imperative to identify which women with a family history of breast cancer are at
moderate to high risk for hereditary breast cancer. The following algorithm
demonstrates when a women needs to be referred to a medical geneticist or familial
cancer clinic:
Ref: Warner E, et al. Hereditary breast cancer: Risk assessment of patients with a
family history of breast cancer. Canadian Family Physician 45: 105-112, 1999.
Oral contraceptive pills (OCPs) are associated with a very small increased risk of
breast cancer in current users and up to 10 years after discontinuing them.
A 1996 analysis of 54 studies showed current users have up to a 24% increased risk (6).
However, the absolute number of women diagnosed with breast cancer remains very
small because breast cancer is rare in young women. For example, among 10,000 30year-old women using OCPs, 5 will be diagnosed with breast cancer. By comparison, 4
women would be diagnosed with cancer in a similar group not taking OCPs.
A recent study has shown a 3 fold increase in breast cancer in women who took OCPs
prior to 1975 and who also had a strong family history of breast cancer (sister or
mother). But the OCP formulations prior to 1975 contained higher doses of estrogen
(75-150 mg) and have been discontinued (8). The study saw no increased risk in
women who took OCPs after 1975 and had a first degree relative with a history of
breast cancer.
US Breast Cancer
Incidence & Mortality
by Race/Ethnicity
1990-1997
Rate /
100,000
(National Cancer
Institute)
It is not clear why the overall incidence of breast cancer is highest in Caucasian
women and why the mortality from breast cancer is disproportionately higher for
African American women. We do know that African American women present with
more advanced disease than Caucasian women. So far, studies have been unable to
clarify the reasons for these trends.
Possible factors include:
 Socioeconomic variables such as lack of support systems and poor access to
health care services
 Cultural differences and racism which may decrease participation in screening,
diagnostic and treatment plans
 Genetic predisposition to more aggressive disease
Approximately 80 to 85 % of women diagnosed with breast cancer have no family
history of breast cancer.
Risk factors for breast cancer:
 Personal history of breast cancer
 Genetic alterations (e.g., BRCA1 and BRCA2)
 Older Age
 Family history of breast cancer (greater with first degree relatives, especially
pre-menopausal)
 Previous history of radiation therapy to the chest before age 30 (i.e.,
Hodgkin's)
 Race (higher in Caucasians and African-Americans)
Other factors include:
 History of breast biopsies
 First live birth after age 30
 Increased breast density
 Early menarche (before age 12)
 Late menopause (after age 55)
The following may play important roles in the development of breast cancer.
 Alcohol: Women who have two or more drinks per day are more likely to
develop breast cancer than those who do not drink. A small increase in breast
cancer was noted in women who have 1/2 to 1 drink each day in the Nurses'
Health Study.
 Sedentary lifestyle: The Nurses' Health Study showed that post-menopausal
women who have 1 hour of physical activity each week are 15-20% less likely
to develop breast cancer than women who are sedentary.
 Obesity: Increased weight and body mass index (BMI) are associated with a
higher risk of breast cancer in postmenopausal women
Yes there is the Gail model calculator that estimates an individual's risk for
developing invasive breast cancer in the next 5 years or over their lifetime. It is a
computer program developed by the National Cancer Institute based on data from
the Breast Cancer Detection and Demonstration Project.
It takes the following five risk factors into account:
 Current age (valid for women >35)
 Age at menarche
 Age of first live birth
 Number of first degree relatives with breast cancer
 Number of breast biopsies
Clinicians may use it to:
 Reassure women who overestimate their risk of breast cancer
 Identify women at high risk
 Modify options for breast cancer screening
Limitations:
It over predicts risk among premenopausal women and women with a strong family
history of breast cancer. Women who have a 1st, 2nd or 3rd degree relative with early
onset breast cancer should use the Claus Model calculator.
Risk assessment models are not appropriate for women with a family history suggestive
of an inherited cancer syndrome or in families in which BRCA1 or BRCA2 has been
identified.
The majority of cancers are in the upper outer quadrant of the breast near the axilla.
Only 5% are in the lower inner quadrant.
What should you do next?
A. Tell her it is probably benign and it's
unusual to have a cancer in that part of the
breast. Have her follow up for another
breast exam in 6 months.
B. Arrange for a diagnostic mammogram.
A diagnostic mammogram should be ordered. The
mass is most likely benign as 80% of breast masses
are noncancerous, but this cannot be assumed for
any individual who presents with an abnormal
exam. A diagnostic ultrasound should then be done
if the mammogram is normal.
She needs to be referred to a breast specialist for further evaluation. Remember, up to
25% of breast cancers will be missed by mammography in women in their 40s, while
perhaps 10% will be missed in 50-69 year olds.
Never be reassured by a normal mammogram when there is a palpable breast mass!
Practice guidelines for the diagnostic evaluation of abnormal breast findings have
been developed by the National Comprehensive Cancer Network (NCCN), a
consortium of 19 leading cancer centers in the US. These are not available
electronically, but can be obtained from the NCCN Web site.( http://www.nccn.org/)
It is imperative to work up a new breast abnormality with a diagnostic
mammogram even though she had a normal mammogram 6 months ago. Breast
cancer in younger women, particularly under the age of 40, is often more
agressive with higher mortality. This may be due to different hormone status or
different tumor biology in young women.
Cumulative probability of breast cancer
death 5 years after diagnosis
(Adapted from 13.)
Breast Cancer Online Resources
National Comprehensive Cancer Network (NCCN) Patient Guidelines
http://www.nccn.org/
American College of Obstetricians and Gynecologists
http://www.acog.org/
National Alliance of Breast Cancer Associations
http://www.nabco.org/
American Cancer Society's (ACS) Breast Cancer Resource Center
http://www.cancer.org/docroot/LRN/LRN_0.asp
CDC The National Breast and Cervical Cancer Early Detection Program
http://www.cdc.gov/cancer/nbccedp/index.htm
CancerNet
http://www.cancer.gov/cancer_information/cancer_type/breast
US Preventive Services Task Force: Screening for Breast Cancer
http://www.ahcpr.gov/clinic/uspstf/uspsbrca.htm