Screening and prevention ofbreast cancer

Solveig HofvindCancer Registry of Norway/Oslo and Akershus University

College of Applied Sciences

ESMO Cape Town, February 10, 2017

DISCLOSURE OF INTEREST

• No conflicts of interest

Breast cancer burden

https://www.iarc.fr/en/media-centre/pr/2013/pdfs/pr223_E.pdfhttp://globocan.iarc.fr/ia/World/atlas.html

Most common cancer in women worldwide Nearly 1.7 million new cases diagnosed in 2012

12% of all new cancer cases 25% of all cancers in women

6.3 million women alive who are diagnosed with breast cancer

Leading cause of cancer death in the less developed countries

Since the 2008:>20% increase in incidence

>14% decrease in breast cancer death

Breast cancer burdenWestern Europe Norway South Africa

Incidence (2012) 90/100 000 73/100 000 41/100 000

Breast cancer mortality

16/100 000 12/100 000 17/100 000

http://globocan.iarc.fr/ia/World/atlas.html http://canceratlas.cancer.org/data/#?view=map&metric=Breast_Incid

Breast cancer burden

http://globocan.iarc.fr/ia/World/atlas.html

Incidence ASR Mortality ASR

5 years prevalence per 100 000

https://www.google.no/search?q=symptoms+control+and+rehabilitation&espv=2&biw=1067&bih=497&source=lnms&tbm=isch&sa=X&ved=0ahUKEwie17_Sh_bRAhVjM5oKHaNmCpYQ_AUIBigB#tbm=isch&q=symptoms+control+and+rehabilitation+breast+cancer&imgrc=LRUP0jKL_zHufM:

The cause of breast cancerUnknown

Trichopoulos, 2008

Prevention of the disease

Breast cancer

Risk factors

Non-modifiable

Reproductive

Modifiable

Secondaryprevention- identification and

treatment of premalignant or

subclinical tumors

Primaryprevention

-preventing theonset of the disease

Tertiaryprevention- symptoms control and rehabilitation

Screening - definition

Health screening: Screening refers to a test or exam

done to find a condition before symptoms begin.

Screening tests may help find diseases or conditions

early, when they are easier to treat. Last, 1981

There is no universally accepted definition of medical screening. Wald, J Med Screen, 2008

The activity contains three elements:

Process of selection with the purpose of identifying those who are at a sufficiently high risk of a specific disorder to warrant further investigation or sometimes direct preventive action.

Systematically offered to an asymptomatic population who have not sought medical. Normally initiated by medical authorities and not by a patient's request.

Its purpose is to benefit the individuals being screened.

Screening – definition cont.

Wilson and Jungner, WHO, 19681. The condition sought should be an important health problem.

2. There should be an accepted treatment for patients with recognized disease.

3. Facilities for diagnosis and treatment should be available.

4. There should be a recognizable latent or early symptomatic stage.

5. There should be a suitable test or examination.

6. The test should be acceptable to the population.

7. The natural history of the condition, including development from latent to declared disease, should be adequately understood.

8. There should be an agreed policy on whom to treat as patients.

9. The cost of case-finding (including diagnosis and treatment of patients

diagnosed) should be economically balanced in relation to possible

expenditure on medical care as a whole.

10.Case-finding should be a continuing process and not a “once and for

all” project.Wilson & Junger, 1968

Yes or no?

More points needed?

Norway:11. The benefits should outweigh the harms

12. Personal and legal aspects should be ensured

13. The screening program should be acceptable from an ethical point of view

14. Information about the screening program should be evidence based and facilitate an informed choice about participation

15. The screening program should satisfy requirements related to cost effectiveness

16. A plan for administration, quality assurance and evaluation should be available

Yes or no?

The goal of mammography/breast cancer screening: Reduce mortality from the disease

by detecting the cancers in an early stage

IARC handbook in Breast Cancer Screening, 2002

Clinical breast examination: No effect on breast cancer mortality

Organized mammographic screening: Breast cancer death among invited versus non-invited: max 25% reduction

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breast-cancer-screening

2009

https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breast-cancer-screening

2009

Broeders et al. J Med Screen 2012

European service screening programs

38-48% reduction in breast cancer mortality among screened versus not screened

25-31% reduction in breast cancer mortality among invited versus not invited

Broeders et al. J Med Screen 2012

October 2012

UK Independent panel - mortality

UK Independent Panel, Lancet 2012

Effect of screening with mammography in reducing mortalityfrom breast cancer for women aged 50-69 years

Sufficent evidence

Effect of screening with mammography in reducing mortalityfrom breast cancer for women aged 45-49 years

Limited evidence

Effect of screening with mammography in reducing mortalityfrom breast cancer for women aged 40-44 years

Limited evidence

Effect of screening with mammography in reducing mortalityfrom breast cancer for women aged 70-74 years

Sufficient evidence

Clinical breast examination

Reduces breast cancer mortality - Inadequate evidence

Shifts the stage distribution of tumors detected toward a lower stage - Sufficient evidence

Breast self-examinationReduces breast-cancer mortality when taughtInadequate evidenceReduces the rate of interval cancer when taughtInadequate evidenceReduces breast-cancer mortality when practiced competently and regularlyInadequate evidence

http://ecibc.jrc.ec.europa.eu/recommendations/list/3

For asymptomatic women aged 40-44 with an average risk of breast cancer, the ECIBC’sguidelines Development Group (GDG) suggests not implementing mammographyscreening over no mammography screening, in the context of an organised screening programme (conditional recommendation, moderate certainty in the evidence).

For asymptomatic women aged 45-49 with an average risk of breast cancer, the ECIBC’sguidelines Development Group (GDG) suggests mammography screening over nomammography screening, in the context of an organised screening programme(conditional recommendation, moderate crtainty in the evidence)

For asymptomatic women aged 50-69 with an average risk of breast cancer, the ECIBC’sguidelines Development Group (GDG) recommends mammography screening over nomammography screening, in the context of an organised screening programme (strongrecommendation, moderate certainty in the evidence).

For asymptomatic women aged 70-74 with an average risk of breast cancer, the ECIBC’sguidelines Development Group (GDG) suggests mammography screening over nomammography screening, in the context of an organised screening programme(conditional recommendation, moderate certainty in the evidence).

http://jamanetwork.com/journals/jama/fullarticle/2463262

http://jamanetwork.com/journals/jama/fullarticle/2463262

Informed choice

Mammography screening

Additional effects - benefits or harms?Interval breast cancer

Increased incidence of Ductal Carcinoma In Situ (DCIS)Increased breast awareness

Craniocaudal projection (CC)

Mediolaterale oblique projection (MLO)

LCC, FFDM LCC, DBT

Invasive ductal carcinoma, 10mm, Grade III + DCIS 27 mm, Grade III (from Prof Skaanes library)

LCC, FFDM LCC, Cone mag viewA

LCC, DBT

LCC, Cone mag viewB

Invasive ductal carcinoma, 4.5 mm, Grade II (from Prof Skaanes library)

Concern in Norway:

Are we detecting too much cancers?

Benefits versus harms

The goal of mammography/breast cancer screening: Reduce mortality from the disease

by detecting the cancers in an early stage

What is required to estimate breast cancer mortality as a result of screening?

10-15 years of follow up after screening/diagnosis

A large study population (power estimation)

A control group

Randomizedcontrolled

trial

Case controlstudies

Cohortstudies

1

32

11. The benefits should outweigh the harms

12. Personal and legal aspects should be ensured

13. The screening program should be acceptable from an ethical point of view

14. Information about the screening program should be evidence based and facilitate an informed choice about participation

15. The screening program should be cost effective

16. A plan for administration, quality assurance and evaluation should be available

Wilson and Jungner, WHO, 1968

+

Which resources are needed?

When screening mammography works• Organized screening programs

• Monitoring, quality assurance, evaluation, research

• Multidisciplinary team /close collaboration

• Secretary

• Radiographers

• Radiologists

• Pathologists

• Surgeons

• Oncologists

• Physicists

• Epidemiologists, statisticians

• Implementation of new technology based on sufficient evidence

• Individualization based on mammographic density and other risk factors?

http://ec.europa.eu/health/ph_projects/2002/cancer/fp_cancer_2002_ext_guid_01.pdf

http://www.cancercontrol.eu/

http://ecibc.jrc.ec.europa.eu/european-guidelines

http://www.breastcancer.org/symptoms/testing?gclid=Cj0KEQiAt9vEBRDQmPSow-q5gs8BEiQAaWSEDhX1cCh5fT8m4TwNBD0f56ZKdntOkHIVqUPAKNYtpw8aAnDP8P8HAQ

Early performance measures

Participation rate

Recall rate

Biopsy rate

Cancer detection rate

• Screen-detected

• Interval cancer

Histopathologic tumor characteristics

• Morphology

• Tumor size

• Grade

• Lyph node invlvements

• Hormonal receptors, Ki67, Her2

By- Age- Screening history- Breast density

The Norwegian Breast Cancer Screening Program

Start up: Pilot in four counties in 1996, nationwide coverage in 2005

Target group: About 600 000 women

Invitations: Personal letter, stated time and place for examination

Interval: Two years

Own cost: About 30 $

Screening: 23 stationary and 4 mobile units

Two views, independent double reading with consensus

Recall, diagnostics and treatment: 16 breast centers

Administration: Cancer Registry of Norway

Practical work: The breast centers

Quality assurance: Cancer Registry of Norway

Early performance measures in the NBCSP2006-2014

Average Range within thecounties

Participation (%) 75% (63% - 83%)

Recall (%)First attendanceSubsequent attendance

6.8%2.3%

(3.4% - 10.8%)(1.3% - 5.0%9

Screen-detected breast cancer(DCIS + invasive)

5.3/1000 4.0 – 6.6 /1000

Interval breast cancer (DCIS + invasive)

0.17/1000 0.13 – 0.22/1000

PPV-1 (breast cancer/recalls) 17% 10% - 25%

PPV-2 (breast cancer/biopsies) 45% 27% - 57%

Early performance measures in the NBCSP 2005-2011

Screen detectedbreast cancer

N=4835

Intervalbreast cancer

N=1633

Breast cancer detected outsidescrening n=1865

Tumor size<=20 mm20+mmNo information

82%18%6%

59%41%14%

74%26%10%

Grade 1+23No information

82%18%5%

65%35%6%

68%32%7%

Node involvementsLN+LN-No information

25%75%2%

56%44%7%

58%42%10%

J Med Screen, 2016

Crude breast cancer spesific survivalby detection mode and subtype

2005-2011

J Med Screen, 2016

28% reduction in breast cancer mortality among invited versus not invited37% reduction in breast cancer mortality among screened versus not screened

43% reduction in breast cancer mortality among screened versus not screened

Attendance rates in the NBCSPamong immigrants from African regions

Region First invitation Ever/never

Non-immigrants 76% 86%

All immigrants 53% 67%

Africa 39% 52%

Eastern Africa 34% 46%

Middle Africa 50% 60%

Northern Africa 38% 54%

Southern Africa 53% 68%

Western Africa 54% 66%

Country IRR first (unadjusted)

IRR first (adjusted)

IRR ever (unadjusted)

IRR ever (adjusted)

Non-immigrants 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref)

All immigrants 0.70 (0.69-0.70) 0.82 (0.81-0.82) 0.77 (0.77-0.78) 0.81 (0.81-0.82)

Africa 0.51 (0.49-0.53) 0.66 (0.63-0.68) 0.60 (0.58-0.62) 0.66 (0.63-0.68)

Somalia 0.22 (0.19-0.25) 0.30 (0.26-0.35) 0.31 (0.28-0.34) 0.30 (0.26-0.35)

Morocco 0.49 (0.45-0.55) 0.70 (0.64-0.78) 0.65 (0.61-0.70) 0.70 (0.63-0.77)

Eritrea 0.55 (0.49-0.61) 0.72 (0.65-0.80) 0.64 (0.60-0.70) 0.72 (0.65-0.80)

Ethiopia 0.61 (0.53-0.71) 0.68 (0.61-0.76)

South Africa 0.70 (0.61-0.81) 0.78 (0.70-0.87)

Kenya 0.63 (0.53-0.74) 0.79 (0.71-0.89)

Ghana 0.73 (0.62-0.85) 0.73 (0.64-0.83)

IRR for attendance in the NBCSPamong immigrants from African countries

Organized mammographic screening

• Reduces the mortality from breast cancer among invited and screened women

• The scope of overdiagnosis and overtreatment is unclear –

• False positive recalls and interval cancer are parts of a screening program

• Informed decision about participation

• Possibilities for quality assurance and evaluation