Breast Cancer Screening Recommendations: What’s All The Fuss?

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Breast Cancer Screening Recommendations Whats
All The Fuss?

• Mary S. Davey, M.D.

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• Breast cancer- the scope of the problem and who
  is at risk
• Breast cancer screening options- what is
  available and what is on the horizon
• Breast cancer screening recommendations- how to
  make sense of them

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The Headlines

• Shocking and unconscionable
• Incredibly flawed
• Will have deadly effects for women
• Countless American women will die needlessly
• Deliberate decisions to trade womens lives for
  money
• November 17th, 2009 United States Preventative
  Services Task Force (USPSTF) new breast screening
  guidelines were released

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U.S. Breast Cancer FactsAmerican Cancer Society
2010

• 207,090 new cases of invasive breast cancer
• 28 of all cancer diagnoses in women
• 54,010 cases of in situ breast cancer
• 39,840 estimated breast cancer deaths
• 15 of cancer deaths in women

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Nebraska Breast Cancer FactsAmerican Cancer
Society 2010

• 1160 women will be diagnosed with invasive breast
  cancer this year
• 210 women will die from breast cancer this year

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Breast Cancer Incidence Trendshttp//seer.cancer.
gov/statfacts/html/breast.html

• 1980-1987 increased 4/year
• 1987-1994 constant
• 1995-1998 increased 1.6/year
• increased screening, use of hormone replacement
  therapy (HRT), increased obesity rates, delayed
  childbearing
• 1999-2006 decreased 2/year
• Reduced use of HRT
• Drop in mammography utilization

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Breast Cancer Deaths http//seer.cancer.gov/statfa
cts/html/breast.html

• 1975-1990 increased 0.4/year
• 1990-1995 decreased 1.8/year
• 1995-1998 decreased 3.3/year
• 1999-2006 decreased 1.9/year
• Decline larger in women under age 50 years
• Decrease likely due to earlier detection,
  improved treatment and decreased incidence

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• Lifetime probability of developing invasive
  breast cancer is 12 (1 in 8)
• Every womans risk is different

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Breast Cancer Risk Factors

• Relative risk gt4.0
• Female
• Increasing age
• Known genetic risk factors
• Two or more first degree relatives with
  premenopausal breast cancer
• Radiation therapy to chest between 10 and 30
  years of age
• Personal history invasive breast cancer or ductal
  carcinoma in-situ (DCIS)
• History of biopsy showing atypical ductal
  hyperplasia or lobular neoplasia
• High breast density

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Age

• Risk of developing cancer in next 10 years
• 30 year old 1 in 250 (0.40)
• 40 year old 1 in 68 (1.47)
• 50 year old 1 in 35 (2.84)
• 60 year old 1 in 27 (3.67)

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Genetic risk factors

• 5 to 10 of breast cancer patients have a
  hereditary form of the disease
• Genetic mutations BRCA-1 and BRCA-2
• Lifetime breast cancer risk 36 to 85
• Other disorders with increased risk
• Ataxia-telangectasia (ATM), Li-Fraumeni (p53 and
  CHEK2), Cowden syndrome (PTEN), Hereditary
  diffuse gastric cancer syndrome (CDH1)

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Breast Density

• The amount of fibroglandular parenchyma on a
  mammogram
• Mammogram reports describe density
• The breast is almost entirely fat
• There are scattered fibroglandular densities
• The breast tissue is heterogeneously dense. This
  may lower the sensitivity of mammography
• The breast tissue is extremely dense, which could
  obscure a lesion on mammography

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Almost Entirely Fat
RCC
LCC
RMLO
LMLO
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Scattered Fibroglandular Densities
RCC
LCC
RMLO
LMLO
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Heterogeneously Dense
RCC
LCC
RMLO
LMLO
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Extremely Dense
RMLO
LMLO
RCC
LCC
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Breast Density

• Breast cancer and breast parenchyma are both
  white
• Fat is nearly black
• The greater amount of fat, the easier it is to
  recognize a cancer
• Heterogeneously dense and extremely dense breasts
  can obscure a cancer, even a large cancer

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Cancer in Fatty Breasts
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Cancer in Dense Breasts
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Breast Density

• Cannot be predicted based on physical exam
• Unrelated to breast size or consistency
• More common in younger women, during breast
  feeding, women using hormone replacement therapy
• 60 of women under 50, 40 of women in their 50s
  and 25 of women in their 60s have
  radiographically dense breasts

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Breast Density

• Sensitivity and specificity reduced
• Sensitivity 33 to 81
• False positives increased
• Breast density is a significant independent risk
  factor for breast cancer
• 4-5x relative risk
• Connecticut law mandates patient notification and
  ultrasound evaluation

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Breast Cancer Risk Factors

• Relative risk 2.1 to 4
• One first degree relative with breast cancer
• High bone density

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Breast Cancer Risk Factors

• Relative risk 1.1-2.0
• Early menarche
• Late menopause
• Late first pregnancy
• Nulliparity
• Never breastfed
• Hormone replacement therapy
• Obesity (postmenopausal)

• Personal history endometrial, ovarian or colon
  cancer
• Alcohol consumption
• Race
• Physical inactivity
• History of biopsy showing hyperplasia without
  atypia

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Breast Cancer Prognosis

• Breast cancer is a progressive disease
• Early arrest of the disease improves survival
• Prognosis related to extent of disease
• Localized-98 five year survival
• Regional-84
• Distant-23
• http//seer.cancer.gov/publications/survival/surv_
  breast.pdf

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Breast Cancer Prognosis

• Larger cancers more likely to metastasize
• lt1 cm- 10 spread to lymph node
• 2cm- 35
• 3 cm- 50
• Median size of cancer found mammographically is
  1-1.5cm
• Median size of cancer found at clinical breast
  exam 2-2.5 cm

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Breast Cancer Screening

• Goal of screening is to reduce mortality
• detect cancer early when treatment is more
  effective and has fewer morbidities

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Early Detection

• Breast imaging
• Mammography
• Ultrasound
• MRI

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Mammography

• Mammography is the best screening tool available
• Good sensitivity (90) in fatty breasts
• 80-90 sensitivity on average
• Inexpensive
• Widely available

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Mammography

• Mammography is the only screening test which has
  been shown to reduce deaths due to breast cancer
• 20-40 mortality reduction for women in the
  screened groups vs. control groups

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Digital Mammography

• Improved breast cancer detection over analog
  (film-screen) mammography for
• Women with dense breasts
• Women under 50
• Premenopausal women
• Lower radiation dose
• No increase in false positive rate
• Expensive

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Breast Ultrasound

• Diagnostic test for evaluation of mammographic
  and palpable abnormalities
• Can differentiate cystic from solid
• Characterize solid masses
• Evaluate the axilla for metastatic disease
• First exam for patients less than age 30

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Breast Ultrasound

• Screening ultrasound
• No radiation, no compression
• 28 increase cancer detection over mammography
  alone
• Not ready for widespread use
• Low specificity, higher cost, lack of
  availability
• Low sensitivity for calcifications of DCIS

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Breast Ultrasound
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Breast Ultrasound
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Breast MRI

• Excellent tissue differentiation
• High sensitivity for breast cancer
• Not limited by breast density
• No ionizing radiation

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Breast MRI Applications

• Implant evaluation
• Inconclusive mammography/ultrasound
• Cancer staging
• Response to chemotherapy
• Search for occult primary neoplasm
• Cancer screening

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MRI Breast Screening

• Sensitivity for screening young high-risk women
  better than mammography
• 71-100 with MRI vs. 20-50 for mammography
• Detects 56 more cancers than mammography and
  ultrasound combined

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Cancer in Dense Breasts
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MRI Breast Cancer Screening

• Why not everyone?
• Expense
• Invasive procedure
• Contraindicated in some patients
• Lack of expertise and MRI availability
• Low specificity results in excess biopsies and
  additional follow-up

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Further Breast Imaging

• Breast scintigraphy
• Digital tomosynthesis
• Positron emission mammography (PEM)
• Computed Tomography (CT)
• Thermography, infrared imaging

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Breast Scintigraphy

• Molecular breast imaging, breast specific gamma
  imaging, nuclear medicine breast imaging
• Injection of radionuclide Tc99 Sestamibi
• Radionuclide is taken up by cancers
• Improved cancer detection in dense breasts

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Breast Scintigraphy
AP Photo/The Mayo Clinic
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Breast Scintigraphy

• High whole body radiation dose precludes use in
  screening
• Dose may be reduced in future
• Problem solving tool
• For uncertain clinical findings, mammogram, or
  ultrasound
• For patients who cannot undergo MRI

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Digital Tomosynthesis

• 11 mammographic images
• Reduced callbacks, increased cancer detection
• Increased radiation dose, expense make widespread
  adoption unlikely

Mitka M, New Screening Methods Offer Hope for
More Accurate Breast Cancer Detection,JAMA.2008
299 397-398. (Photo credit Breast Imaging
Division/Massachusetts General Hospital)
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Positron Emission Mammography

• Injection of fluorodeoxyglucose (FDG)
• Cancers take up FDG
• High specificity but lower sensitivity than MRI
• High radiation dose and expense preclude use in
  routine screening
• Assess extent of disease, response to treatment,
  evaluation for recurrence

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Breast Computed Tomography

• Good resolution
• Improved patient comfort over mammography
• Higher radiation dose, expense and lack of
  availability makes widespread use unlikely

• Lindfors KK, et al, Dedicated breast CT initial
  clinical experience. Radiology 2008246(3)725733
  .

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Breast Cancer Screening Recommendations

• American Cancer Society (ACS)
• United States Preventative Services Task Force
  (USPSTF)

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Screening Guidelines ACS

• Women at average risk
• Ages 20 to 39
• clinical breast examination at least every three
  years
• Age 40 and over
• annual screening mammography and clinical breast
  exam
• Breast self-exam (BSE) is an option for women
  starting in their 20s
• Elderly women
• continue screening as long as woman is in
  reasonably good health and would be a candidate
  for cancer treatment

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Screening Guidelines ACS

• Women at high (gt20 lifetime) risk
• Annual mammogram and MRI beginning at 30
• Women at moderate (15-20 lifetime) risk
• Discuss with clinician the benefits and
  limitations of adding MRI to yearly screening
• Yearly MRI is not recommended for women with
  lifetime risk less than 15

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Screening Guidelines ACS High Risk Patients

• Known BRCA1 or BRCA2 mutation
• First degree relative with BRCA1 or 2 and no
  testing themselves
• Radiation therapy to the chest between the ages
  of 10 and 30 yrs
• Have Li-Fraumeni, Cowden, or hereditary diffuse
  gastric syndromes, or a first degree relative
  with one of these syndromes
• Risk assessment toolsgt 20 lifetime

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Screening Guidelines ACS Moderately Increased Risk

• Personal history of breast cancer, DCIS, lobular
  neoplasia, atypical ductal hyperplasia
• Have dense breasts at mammography
• Risk assessment tools 15-20 lifetime

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Risk assessment tools

• Gail model
• http//www.cancer.gov/bcrisktool/
• Cancer risk assessment software
• http//www4.utsouthwestern.edu/breasthealth/cagene
  /default.asp
• http//www.hughesriskapps.net/
• Creighton Hereditary Cancer Prevention Clinic
• http//medschool.creighton.edu/medicine/centers/hc
  c/index.php
• csnyder_at_creighton.edu, [phone]

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USPSTF Breast Cancer Screening Recommendations

• Against screening mammography before age 50
• Decision to screen earlier is individual one
• Biennial screening mammography for women between
  the ages of 50 and 74
• Insufficient evidence for screening women 75
  years and older
• Against teaching breast self-examination
• Insufficient evidence for clinical breast exam
• Insufficient evidence for digital mammography or
  MRI instead of film mammography for screening

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USPSTF Recommendations

• No screening for women 40-49 years
• Benefit of mortality reduction considered too
  small compared to harms of screening
• Biennial screening
• Benefit of mortality reduction consider too small
  compared to harms of screening
• Recommendations based on metaanalyses of
  randomized controlled trials (RCT) and on
  computer generated models

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USPSTF Analysis

• Based on review of RCTs
• Screening mammography mortality reductions were
• 15 for women in their 40s
• 14 for women in their 50s
• 32 for women in their 60s

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In Rebuttal

• The mortality benefit is likely underestimated by
  the USPSTF studies
• The harms of screening are decreasing and are not
  as detrimental as estimated by the USPSTF
• There is no other effective screening tool for
  detection of early curable breast cancer

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Mammography RCTs

• Benefits of screening underestimated
• Only 61-89 of women invited to be screened
  actually participated (noncompliance)
• Women in the control group often sought screening
  on their own (contamination)
• Often used poor quality or single view exams
• Subgroup analysis on 40-49 year old women
  performed when studies not designed for this

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Harms of Screening Mammography

• Additional interventions
• Anxiety
• False sense of security
• Radiation Exposure
• Overdiagnosis of cancer

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Harms of ScreeningAdditional Intervention

• For every 1000 mammograms
• 80-100 women (8-10) asked to return for addition
  evaluation
• 45-65 told that there is nothing of concern
• 20 are asked to return in 6 months
• Probably benign (lt2 prob of malignancy)
• 15 (1-2) recommended to have a biopsy
• 2 to 5 will have cancer
• 10-13 have benign biopsy

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Harms of ScreeningAdditional Intervention

• Need for additional evaluation inherent
• Vast majority of false-positive studies resolved
  with mammogram or ultrasound
• Harm of biopsies greatly reduced by image guided
  needle biopsy
• Ultrasound guided , stereotactic or MRI guided
• Surgical biopsy for diagnosis rarely needed
• Needle biopsy is an outpatient procedure that in
  most cases is nearly painless

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Harm of ScreeningAnxiety

• Psychological distress
• Lessen degree of distress
• Patient education
• Same day screening results for patients with
  history of breast cancer and those with elevated
  anxiety
• Rapid recall of abnormal mammograms, additional
  imaging and biopsy

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Harms of Screening False Sense of Security

• Mammograms miss some cancers
• One in five cancers not seen at mammography
• Normal mammogram does not exclude cancer
• Negative mammogram should not deter further
  work-up of a clinically worrisome finding
• Patient education is key

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Harms of Screening Radiation Exposure

• Ionizing radiation can cause cancer
• The risk of radiation induced breast cancer is
  much less than benefit of mammography
• Annual screening from 40-50 years results in 36.5
  lives saved per life lost

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Harms of Screening -Overdiagnosis

• Diagnosis of cancers that would not become
  clinically apparent in a patients lifetime
• Undiagnosed cancer at autopsy
• Invasive breast cancer 1.3
• Ductal carcinoma in situ 8.9
• Biopsy, surgery, radiation, and chemotherapy have
  psychological and physical effects

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Harms of Screening Mammography-Overdiagnosis

• Treatment is in the realm of surgical, radiation
  and medical oncology communities
• Understanding of tumor biology is improving
• Breast cancer assays
• Research evaluating treatment protocols for DCIS

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What age to begin screening?
http//breastscreening.cancer.gov/data/performance
/screening/2009/rate_age.html
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USPSTF Findings

• Number needed to invite to screen to prevent one
  death
• Ages 40-49 1904
• Ages 50-59 1339
• Ages 60-69 377
• The mortality reduction is equivalent in the
  40-49 and 50-59 age groups

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USPSTF Findings

• USPSTF computer models showed
• Mortality reduction starting screening at 40
• Starting screening at 40 is more cost-effective
  in terms of life-years saved than extending
  screening past age 69 years.

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Women 40-49

• 1 in 69 diagnosed with invasive cancer
• 14,000 women 40-49 diagnosed with breast cancer
  each year
• 18 of breast cancer deaths in patients diagnosed
  in their 40s
• 1/3 of years of life lost to breast cancer occur
  among women diagnosed in their 40s
• Most women diagnosed with breast cancer in their
  40s have no known significant risk factors

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Annual vs. Biennial screening

• USPSTF models suggest biennial screening has 81
  of the mortality reduction of annual screening
• Annual screening especially important in women
  aged 40-49 years
• Cancers more aggressive in younger women
• Annual screening saves the most lives

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Breast Cancer Mortality

• Since 1990 US breast cancer mortality has
  declined 2/year
• 30 reduction in mortality
• Likely due to early detection and improved cancer
  treatment

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• Benefits of annual screening mammography
  beginning at age 40 outweigh the harms
• Screening mammography reduces mortality
• Current mammography technology and image guided
  needle biopsy have reduced harm from false
  positives
• Improved understanding of cancer biology reducing
  harm from overdiagnosis
• For now mammography is our best method for
  detecting small curable cancers