Objectives

Demonstrate the incidence of breast cancer, facts and statistics

Review the risk factors of breast cancer and the tools of risk estimation

Outline the various current screening guidelines and related controversy

Discuss the available modalities for breast cancer screening ( indication, benefits, harms…)

Introduction Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death in women.

In the United States, breast cancer accounts for 29% of all cancers in women and is second only to lung cancer as a cause of cancer deaths

1 in 8 U.S. women (about 12%) will develop breast cancer over the course of her lifetime.Because of early detection, intervention, and postoperative treatment, breast cancer mortality has been decreasing.

Mammography for screening has largely contributed to early detection

Incidence

http://www.cancerresearchuk.org/cancer-info/cancerstats/world/incidence/

Incidence

Incidence

Incidence

Incidence

Incidence

Incidence

Incidence

Incidence: Year

Incidence: Age

Incidence: Race

Mortality

Mortality

Mortality

Percent of Deaths by Age GroupThe percent of breast cancer deaths is highest among women aged 55-64.

Median Age at death

68

Mortality

Risk Factors

RIS

K F

AC

TOR

S

Risk Factors

Risk Factors

Risk Factors Estimated Relative Risk

Advanced age >4

Family history• Family history of ovarian cancer in women < 50y >5• One first-degree relative >2•Two or more relatives (mother, sister) >2

Personal history•Breast cancer history 3-4•Positive BRCA1/BRCA2 mutation >4•Breast biopsy with atypical hyperplasia 4-5•Breast biopsy with LCIS or DCIS 8-10

Risk Factors

Con. Risk Factors Estimated Relative RiskReproductive history•Early age at menarche (< 12 y) 2•Late age of menopause 1.5-2•Late age of first pregnancy (>30 y)/Nulliparity 2•Use of combined estrogen/progesterone HRT 1.5-2•Current or recent use of oral contraceptives 1.25

Lifestyle factors•Adult weight gain 1.5-2•Sedentary lifestyle 1.3-1.5•Alcohol consumption 1.5

Risk Factors

BRCA1, BRCA2: genes produce tumor suppressor proteins that help repair damaged DNA and stabilize the cell’s genetic material.

When mutated, or altered, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

Specific inherited mutations  in BRCA1 and BRCA2 increase the risk of breast and ovarian cancers

Together, BRCA1 and BRCA2 mutations account for 20 to 25% of hereditary  breast cancers and 5 to 10% of all breast cancers.

Breast and ovarian cancers associated tend to develop at younger agesA harmful BRCA1 or BRCA2 mutation can be inherited from a person’s

mother or father.

Risk Factors

BRCA1 mutation increases the risk 55 to 65%, and BRCA2 45%

Genetic testing considered Breast cancer diagnosed before age 50 years Bilateral breast cancer Both breast and ovarian cancers in either the same woman or the same family Multiple breast cancers Male breast cancer Ashkenazi Jewish ethnicity

Management of positive genetic test: 1. Enhanced Screening; at younger ages, CBE, mammogram and MRI  2. Chemoprevention: Tamoxifen, Raloxifene 3. Prophylactic (Risk-reducing) Surgery. 

Risk Factors

Risk estimation models

Gail model Claus model BRCAPRO model Cuzick–Tyrer model BOADICEA model

Risk Factors

Risk Assessment Model (Gail)

Risk Factors

Risk Assessment Model

What is screening?

Test and exam used to find a disease like cancer in people who do not have any symptoms. i.e. early detection

Aiming at reduction of reduction of morbidity and mortality

What is screening?

What benefit to screening?

Early detection remains the primary defense available to patients in preventing the development of life-threatening breast cancer

For 50-74 year group, there is an intimated 30% reduction in mortality

For 40-49 year group, there is an intimated 17% reduction in mortality

Guidelines

Guidelines

Guidelines

Guidelines

Age 20+ Self-breast examination(optional) monthlyBreast clinical examination every 3 yrs

Age 40+ Mammography annually

High Risk mammography annually + 30 +MRI

Guidelines(controversy)

No requirement for clinicians to teach women how to perform BSE.

Insufficient current evidence to assess the additional benefits and harms of CBE beyond mammography in women 40 years or older

No requirement for routine screening mammography in women aged 40 to 49 years. the decision to start regular screening before 50 should be an individual one and take into account patient context, including the patient's values regarding specific benefits and harms

Biennial screening mammography for women between 50 -74 years

Stopping screening at age 74 as there is insufficient data to assess the benefits and harms in women > 75

November, 2009

Guidelines(controversy)

Guidelines(controversy)

Guidelines(controversy)

20-30% do not undergo screening

Screening Modalities

Breast Self-Examination (BSE)

Potential Benefits

Simple and non-invasive testWomen gain a sense of control over their healthBecome comfortable with their own breasts Some breast cancer has been detected with BSEIncreased awareness of breast changesLumps can be palpated with a BSE

Breast Self-Examination (BSE)

Potential Harms

Increased number of healthcare visitsTwice the number of benign breast biopsies Increased healthcare costsIncreased levels of cancer-related anxiety

No change in mortality from breast cancer with detection from BSE

Breast Self-Examination (BSE)

Breast Self-Examination (BSE)

Organizations that recommend BSE

   ACOG Recommends monthly BSE

   AMA Recommends BSE, no age specified

   Susan G. Komen Foundation Recommends monthly BSE

Organization that recommends against BSE

   Canadian Task Force for Preventive Healthcare

Organizations that recommend further discussion or indicate insufficient evidence

  ACS Starting at age 20, pros and cons of BSE should be reviewed; it is the individual's choice

   US PSTF Insufficient evidence to recommend for or against BSE

   NCI No specific recommendation

Clinical Breast Examination (CBE)

Clinical Breast Examination (CBE)

Benefits Not tested independentlyClinical trial support combining CBE with mammography to enhance screening sensitivity, particularly in younger women in whom mammography may be less effective and in women who receive mammograms every other year as opposed to annually.

Harms False-Positives additional testing and anxiety. False-Negatives potential false reassurance and delay in

cancer diagnosis. Of women with cancer, 17% to 43% have a negative CBE. Sensitivity is higher with longer duration and higher quality of the examination by trained personnel.

Mammography

48 million mammograms are performed each year in US

Special type of low-dose x-ray imaging used to create detailed images of the breast.

Currently it is the best available population-based method to detect breast cancer at an early stage, when treatment is most effective

Can demonstrate microcalcifications smaller than 100 µm.

Often reveals a lesion before it is palpable by clinical examination and, on average, 1-2 years before noted by self-examination

Mammography

Screening (asymptomatic)

Diagnostic (symptomatic)

Mammography

Mammography

Mammography

•

False-positive

Recalled examinations that does not lead to diagnosis of cancer.

Estimated average false-positive rate in US is 11%

Factors previous breast biopsiesfamily history of breast cancerestrogen useLack of a comparison mammogram(s).

False-negative

Sensitivity range from 70-90% false-negative 20%

Factors:

Mammographically occult cancer. Overlapping dense breast tissue Poor technique Reader variability

Mammography

Overdiagnosis

A cancer never become clinically apparent without screening before a patient’s death.

The median prevalence: an overview of 7 autopsy studies, occult invasive breast cancer 1.3% and of DCIS 8.9%

A “perfect” screening would identify 10% of women as having breast cancer, even though most of those cancers would probably not result in illness or death. Treatment would constitute overtreatment.

Currently, cancers that will cause illness and/or death cannot be confidently distinguished from those that will remain occult, so all cancers are treated.

Ultrasonography

Useful adjunct to mammography

Assist in suspicious lesion detected on mammography or physical examination

Useful in the guidance of biopsies and therapeutic procedures.

Originally, used as method of differentiating cystic from solid breast masses

Limitations as screening test: Failure to detect microcalcifications Poor specificity (34%)

Ultrasonography

Useful in detecting occult breast cancer in dense breasts.

Highly operator-dependent

Ultrasonography

somo-v Automated Breast Ultrasound System (ABUS) FDA approved, Sep. 2012

Breast cancer screening specifically in women with dense breast tissue

Indicated as an adjunct to mammo for women with a negative mammogram, no breast cancer symptoms and no previous breast intervention

Magnetic Resonance Imaging (MRI)

Explored in women at high risk and in younger women

MRI found to be highly sensitive (99% when combined with mammography and CBE)

An important adjunct screening tool for women BRCA1 or BRCA2 mutations, identifying cancers at earlier stages.

MRI has limited use as a screening tool: Cost. 10-fold higher cost than mammography Poor specificity (26%) false-positive reads

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI)

American Cancer Society MRI screening criteriaAnnual breast MRI screening in patients with the following risk factors:

BRCA mutationFirst-degree relative of BRCA carrier but untestedLifetime risk approximately 20-25% or greater, as defined by BRCAPRO or other risk modelsRadiation to chest when aged 10-30 years

Magnetic Resonance Imaging (MRI)

American Cancer Society MRI screening criteriaThe ACS found insufficient evidence to recommend for or against MRI screening in patients with the following risk factors:

Lifetime risk 15-20%LCIS or atypical lobular hyperplasia (ALH)Atypical ductal hyperplasia (ADH)Heterogeneously or extremely dense breast on mammographyPersonal history of breast cancer, including DCIS

The ACS does not recommend MRI in women <15% lifetime risk

For those with average risk, a combination of clinical breast examinations and yearly mammograms is recommended.

Conclusion

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death in women

Screening breast cancer has proven benefits in reducing mortality and this is independent of the benefits of improved therapy.

Various screening guidelines are currently being validated and followed by different medical organizations

Mammography remains the mainstay of screening, and in women at high risk, annual MRI is recommended

Understanding of the risks a benefits of a particular screening tool helps clinicians to make informed decision

• References• National Cancer Institute. Surveillance, Epidemiology, and End Results Program. SEER stat fact sheets: breast cancer.

http://seer.cancer.gov/statfacts/html/breast.html. • American Cancer Society. What are the key statistics about breast cancer? http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics. • National Cancer Institute. Breast cancer treatment (PDQ). General information about breast cancer.

http://www.cancer.gov/cancertopics/pdq/treatment/breast/Patient.• American Cancer Society. What are the risk factors for breast cancer? • http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/Page8#_483• http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-risk-factors. • National Cancer Institute. Breast cancer screening (PDQ).

http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional. • American Cancer Society. Breast cancer survival rates by stage. • http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-survival-by-stage. • http://www.medscape.org/viewarticle/583982• US Preventive Services Task Force. About the USPSTF.

http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/breast-cancer-screening. • The American Congress of Obstetricians and Gynecologists.  http://www.acog.org/About-ACOG/News-Room/News-Releases/2011/Annual-Mammograms• http://emedicine.medscape.com/article/1945498-overview• http://www.ncbi.nlm.nih.gov/books/NBK22311• http://www.haad.ae/simplycheck/tabid/131/Default.aspx• http://www.cancer.gov/bcrisktool/• http://www.slideshare.net/rajud521/breast-self-examination• http://seer.cancer.gov/statfacts/html/breast.html