BREAST CANCER SCREENING

Screening Rationale

Detects clinically occult breast cancers

Pick-up rate

Detects ~8 breast Cancers per 1000 women screened for first time over 40.
- then 2-3 per 1000 for subsequent screening.
Mediolateral oblique (MLO) and craniocaudal (CO) views taken.
- radiation dose small; 100mrad or 0.1 cGy.

Evidence for screening efficacy
-
(endpoint death)

8 prospective RCTs conducted
- 7 at age 40+
- 1 at age 50+
- none screened beyond 74.
Nearly 500,000 women in total.

Meta-analysis in Lancet 2001 (October):
- only 2 of these trials was thought of suitable quality to include
- other 6 excluded
--> no significance reached in relative risk reduction
--> "screening not justified at any age".

US Preventive Service Task Force Review in 2002:
- 7 of the trials thought suitable quality.
- evaluated effectiveness of screening after 14 years of observation
- in all age groups, RR = 0.84 (CI=0.77-0.91)
- in women 50+, RR = 0.85 (CI 0.73-0.99)
- in women 40-49. RR = 0.85 (CI 0.73-0.99)
Thus NNT (screen) = 1224 for all ages to prevent one death
- or 838 for ages 50+
- of 1792 for ages 40-49.

Bottom line
Perhaps 1 life saved for every 1000 lives screened (some say 1-2 lives).

World Health Organization guidelines for a rational screening program (1968).
The condition should be an important health problem.
There should be a treatment for the condition.
Facilities for diagnosis and treatment should be available.
There should be a latent stage of the disease.
There should be a test or examination for the condition.
The test should be acceptable to the population.
The natural history of the disease should be adequately understood.
There should be an agreed policy on whom to treat.
The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole.
Case-finding should be a continuous process, not just a "once and for all" project.

Outline of evidence for guidelines

Should be offered annually to women 50+ on current evidence.
- now screen 50-74yo in Aus
- 40+ can turn up without a referral.
And ideally at least biennially to women aged 40-49
- screening interval depending on risk factors
Younger women with risk should be offered annual screening.
Mortality from breast cancer reduced 25% from 1990-2000, screening has contributed.
- decreased T-stage and increase in carcinoma in situ.

General Screening Recommendations (Australian Guidelines)
1. For women of average risk:
- regular 2 yearly mammography, between ages 50-69 (best evidence here due to breast density reduction after menopause; beyond 70 survival benefits become more marginal)
- but women aged 40-50 and 70+ are able to attend.
- mammography is not recommended for women younger than 40 years.
- if aged 40-49, women are encouraged to assess risks and benefits for themselves and balance these risks considering that screening is less effective.
- if aged 70+, encouraged to assess risks and benefits for themselves and balance these risks considering that screening is less effective.
- current participation rate for target age range is ~55% in Australia under BreastScreen Australia Program
- Mammography will pick up 90% of cancers "down to the size of a grain of rice"

2. Family History
- Individualised surveillance programs necessary
- Depends on age; e.g. regular self-surveillance, clinical exam, imaging with USS / mammography / MRI
- MRI now funded for screening in young at-risk.
General Aus. family history guideline:
Annual mammogram from age 40 if:
- One first degree relative with breast cancer before 50y
- One first degree relative with cancer in both breasts at any age
- Two or more first degree relatives with breast cancer at any age
Additional Notes from Cameron
--> Should begin annual screening 5-10 years (us. 10 years) before youngest age of diagnosis of breast cancer in a relative
--> if BRCA +ve, screen form age 25,  may need MRI.

3. High Risk Assessment
Models exist to strategy risk.
- high = >20% lifetime risk
- moderate = 15-20% lifetime risk
High risk: annual mammogram and ultrasound and 6 monthly examinations

Genetic causes of breast cancer include:
-BRCA 1 and 2 (90% of genetic CAs)
- p53
- PTEN (Cowden)
- Li Fraumeni
- others: HNPCC, Peutz-Jegher, Gorlin, androgen receptor gene
Tests for BRCA 1 and 2 are available
- expensive testing as must sequence a large gene with many mutations.
See breast cancer notes for management

Risk Categories

1. At or slightly above average risk
- no confirmed family hx
- one 1st or 2nd degree relative with breast Ca dx over 50
- two 1st or 2nd degree relatives dx with breast Ca at 50+ but on different sides of family
- one 2nd degree relative with breast Ca at any age
- covers 95% of population
- lifetime risk is 1:12

--> Mammogram from age 50y every 2y until 75 then “allowed to attend”


[2. Slightly above average risk]
1 first degree relative or 2nd degree before 50
- lifetime risk 1:10

-->Mammogram from age 50y every 2y until 70 then “allowed to attend”


3. Moderately increased risk
- 1 or 2 first degree relatives with breast Ca dx before the age of 50 (no high risk features)
- 2x 1st or 2nd degree relatives on same side of family with breast or ovarian Ca
- covers <4% of population
- lifetime risk 1:8

--> Begin screening 10y below first relative’s age or at 40

--> Yearly mammogram


4. High-risk
- 3x 1st or 2nd degree relatives on same side of family with breast or ovarian Ca
- 2 or more 1st or 2nd degree relatives on same side of family with breast or ovarian Ca and high risk features
--> ie. bilateral, age 40 or less, breast and ovary in one individual, male breast
- one 1st or 2nd degree with breast Ca at age45 or younger and 1-2 on same side with sarcoma 45 or less
- member of family with high risk breast cancer gene
- covers <1% of population
- lifetime risk 1:4

--> genetic testing

-->annual mammo and USS and 6m exam

--> young pt with high risk, best test is annual mri.

-->if test –ve and high risk, then still eligible for annual mri from any age; generally from age 30.

--> if test +ve also counsel for preventative mastectomy.



Screening Modalities

1. Self Examination
Recent updates have removed this from guidelines
No reduction in mortality from large RCTs
Cochrane review = no evidence for teaching or doing this.

2. Clinical Breast Exam
Key component; 10-20% of cancers are not visible on mammography
Beginning at age 20, should have clinical breast exam every 2-3 years, then annually after 40
Perform before mammography so that imaging can be correlated and biopsied, even if mammography normal.
6 monthly if high risk.

3. Mammography
Foundation of screening.
Two views: Craniocaudal Projection (CC) and MedioLateral Oblique (MLO)
- different from diagnostic mammography, whi h also includes additional view for palpable or screen-detected lesions.
- including spot compression, magnification views, exaggerated views or true lateral views
- as well as diagnostic ultrasound
Women with implants should have implant-displacement views, improves imaging of anterior part of each breast
- ie implant push back, and breast pulled forward over it, focusing on anterior breast.
Digital mammography now widely used; is equivalent.
- can use computer-assisted diagnosis; computer algorithm highlights possible areas of concern to radiologist.

4. BI-RADS Classification of Breast Imaging
Category
Assessment
Recommendation
0
Incomplete
Need additional imaging or prior studies for comparison
1
Negative
Resume routine screening mammography
2
Benign
Resume routine screening mammography
3
Probably Benign
Risk <2%; short term interval follow-up at 6m
4
Suspicious Abnormality
Immediate risk; biopsy
5
Highly Suggestive of Malignancy
Chance >95%; Treat appropriately
6
Known (proven) Malignancy
Treatment
Notes
Method of biopsy should be percutaneous core needle biopsy if possible
Pathologic and radiologic findings should then be correlated; if discordant evaluate further
BIRADS 5 with benign path should still be excised
- any lesion with discordant radiology and path should be excised.
Clinically suspicious lesions in patients with normal mammogram and ultrasound should also undergo biopsy.

Role of Other Imaging Tools

1. USS
Focused USS has an established screening role
- characterizes palpable or scree-detected lesions and directs biopsy.
1. All patients  with palpable abnormality and normal mammogram should have an uSS
2. Increasingly used to further characterise lesions on MRI
USS is best tool to detect cystic from solid.
USS malignancies appear:
- taller than wide
- irregular shape
- ill-defined margins
- posterior acoustic shadowing
- hypoechoigenicity
- increased vascularity.
Microcalcifications are not usually seen, but can evaluate area of mammographic calcification for a mass.
3. Role in Screening?
Increases detection at cost of increased benign biopsy.
Additional 1-7 cancers per 1000 women.
May improve detection of early breast cancer in the moderately increased risk group who do not currently meet criteria for MRI.

2. MRI
American Cancer Society guidelines for MRI use suggest annual MRI for:
1. Very high risk patients (Evidence-based)
- BRCA mutation
- Untested 1st degree relative of BRCA carrier
- Lifetime risk ~20-25% or greater
2. Recommended (Consensus opinion)
- chest radiation at age 10-30y
- Li-Fraumini
- Cowden and Bannayan-Riley-Ruvalcaba

3. Molecular Breast Imaging
Scintimammography (Tc99)
Promising and feasible testing tool, using two plates, may improve pick up beyond mammography.

4. High-Risk Screening
Online risk prediction tools can be used to quantify risk.

What about Men?
Men with known genetic risk mutation need screening (ie BRCA)
Monthly BSE, clinical exam, annual mammography