About this Webinar: This talk will explore breast screening for women 40-49. The benefits and harms for screening will be discussed, as well as what is unique about breast cancer in women in their 40s. In order to understand the controversy around current guidelines recommending against screening women 40-49, we will review the evidence upon which these guidelines are based, and their impact on breast cancer outcomes for these women.

1. Breast Screening for Women
40-49: Why the Controversy?
Anna N. Wilkinson, MSc., MD, CCFP, FCFP
Associate Professor, University of Ottawa
Family Physician, The Ottawa Academic Family Health Team
GP Oncologist, The Ottawa Hospital Cancer Centre
Program Director, PGY-3 FP-Oncology
Regional Cancer Primary Care Lead

2. Disclosures
• CFPC Grant for Breast Cancer Survivorship Tool/Oncology Briefs
• Regional Cancer Primary Care Lead- Stipend
• Consultant for Thrive Health
• Canadian Breast Cancer Network- Honoraria
• Thanks to Dr. Seely for use of some of the slides

3. Objectives
• Why screen for breast cancer?
• What is unique about breast cancer in women in 40s
• Why the controversy around breast cancer screening in women
40-49?
• What is the effect of current screening recommendations on
women in 40s?
• Should we screen women 40-49?

4. Breast Cancer
• 12.5% of Canadian women
will be diagnosed with breast
cancer in their lifetime
• 28,600 cases of breast
cancer in 2022 in Canada
• 5,500 Canadian women will
die from breast cancer
• 14% of all cancer deaths in
women in 2022
Cancer Today (iarc.fr) https://cancer.ca/en/cancer-information/cancer-types/breast/statistics

5. WHY SCREEN FOR BREAST CANCER?

6. Why Screen?
• Diagnosis at earlier stage
• Improved survival
• Decreased morbidity of treatments
• Treatment costs less
Benefits
• Anxiety
• False positives
• Overdiagnosis
Harms

7. Earlier
Stage
Interval ca or symptomatically detected
Screen detected

8. Two different 49 year old patients:
Screen detected vs symptomatic cancers

9. Improved Survival with Earlier Stage
100%
Stage 1
93%
Stage 2
72%
Stage 3
22%
Stage 4

10. Mortality from Breast Cancer
https://www150.statcan.gc.ca/n1/pub/82-003-x/2023009/article/00002-eng.pd
• Screening mammography began in 1980’s
• Breast cancer mortality has decreased by 49% since 1989

11. Increased Morbidity with Later
Stage Breast Cancer

12. Increased Cost with Treatment of Later
Stage Breast Cancer
• Cost to screen 1 women for
40’s ~$2600
• Costs increase exponentially
by stage
• Stage IV 11x more costly
than stage I
• Cost for one case of stage IV
>500K
HR+ HR+/HER2+ HER2+ TN
Breast Cancer Subtype
Stage IV
treatment 36x
cost of DCIS

13. Harms: False Positives
• Screening investigations can lead to further investigations
including:
– Imaging
– Biopsy
• Recalling women can cause anxiety and put them through
unnecessary investigations

14. Overdiagnosis
• “Overdiagnosis is the unnecessary treatment of cancer that would not
have caused harm in a woman’s lifetime, as well as physical and
psychological consequences from false positives.”
Wilkinson AN, Ellison LF, Billette JM, Seely JM. Journal of Clinical Oncology, August 4, 2023

15. Anxiety
• There can be elevated levels of anxiety associated with abnormal
mammograms
• Many women would prefer to experience transient anxiety with the
knowledge that cancer may be ruled out
• “Benevolent sexism”? There is not the same emphasis on anxiety with other
cancer screening.
• Anxiety is highly personal and must be a discussion with your patient

16. WHAT IS UNIQUE ABOUT BREAST CANCER IN
WOMEN IN 40S

17. Breast Cancer in the 40s
• Roughly 1 in 5 breast cancer
cases diagnosed in 40s
• Breast cancer is the 2nd leading
cause of death in women in 40s
• 27% of the life-years lost to
breast cancer are in 40s
• Median age at diagnosis of fatal
cancers is 49 years
18.5% of
screened
population

18. Oeffinger et al. JAMA 2015 https://jamanetwork.com/journals/jama/fullarticle/2463262

19. Breast Cancer Incidence in Younger Women is
increasing
30’s 40’s

20. Non-White Women are Diagnosed with Breast
Cancer at Younger Ages than White Women
• Non-white women have a peak age of
diagnosis of breast cancer < 50
• Mean age at diagnosis:
• white: 62
• non-white: ~55
• Mean age at death from breast cancer:
• 10 years earlier for non-white
women
Stapleton et al, 2018

21. Young
Women Have More
Aggressive Subtypes
of Breast Cancer
• More aggressive subtypes
(Triple Negative, Her2+ and
Luminal B/B-like) more
common in younger women
• Luminal A (least aggressive)
more common in women
older women

22. Age and Breast Density
• Younger women have
higher rates of dense
breast than older women
• Breast density:
– Increases the risk of breast
cancer
– Limits the ability of
mammograms to detect
breast cancer
Int J Cancer. 2104 Oct 1;135(7):1740-4

23. Limits cancer detection
Sensitivity of mammogram decreases to 50% in patients with extremely dense
breast tissue
A B C D

24. WHY THE CONTROVERSY AROUND SCREENING FOR
BREAST CANCER IN WOMEN 40-49?

25. History of Canadian Guidelines for Screening
Women 40-49
• 1979- Annual Mammogram for 50-59
• 1994- Annual Mammogram for 50-59, women 40-49 should not be
screened
• 1998- Mammogram for 50-59 every 1-2 years, women 40-49 should not be
screened
• 2001- Discuss screening risks/benefits at age 40 and decide on screening
• 2011- Mammogram 50-74 every 2-3 years, recommend against screening
women 40-49
• 2018- Mammogram 50-74 every 2-3 years, recommend against screening
women 40-49

26. 2018 Canadian Task Force Guideline Recommendations
• All decisions to undergo screening is conditional on the
relative value a woman places on possible benefits and harms from
screening.
• 40 to 49 years, we recommend not screening with mammography
(Conditional recommendation; low-certainty evidence)
– NNS (Number needed to screen) 1724
• 50 to 69 years, we recommend screening with mammography
every 2 to 3 years; (Conditional recommendation; very low
certainty evidence)
– NNS 50-59: 1333 ; NNS 60-69: 1087
• 70 to 74 years, we recommend screening with mammography
every 2 to 3 years; (Conditional recommendation; very low-
certainty evidence)
• NNS 645

27. Benefit of screening
depends on inputs
• Which type of evidence?
• False positives
• Breast cancer incidence
• Mortality benefit from
screening
• Overdiagnosis rate

28. Randomised Control Trial
vs Observational Trials

29. What evidence was used for 2018 Guidelines?
11 randomized control trials:
– New York, USA 1963
– Malmö I, Sweden 1976
– Malmö II, Sweden 1978
– Kopparberg, Sweden 1976
– Östergötland, Sweden 1978
– Edinburgh, Scotland 1978
– Canada CNBSS I 1980
– Canada CNBSS II 1980
– Stockholm, Sweden 1981
– Göteborg, Sweden 1982
– Finland 1987
Innovations in breast cancer treatment
 1984: Tamoxifen
 2004: Aromatase inhibitors
 2005: Trastuzumab (Hereceptin)
 2013: The 4 subtypes of breast cancer are defined
 2014: Sentinel lymph node biopsy
 2018: Genomic testing (Oncotype dx): allows 70% women
with early-stage ER+ BC to avoid chemotherapy
 2021: CDK4/6 inhibitors for metastatic ER+ BC, survival
increases to ~5years
 2022: CDK4/6 inhibitors approved for adjuvant treatment of
high risk ER+ BC
 2022: Antibody-drug conjugate (Enhertu) approved in
metastatic HER2+ BC
 2022: Hypofractionated radiation (5 fractions)
 2023: Immunotherapy used for high risk and metastatic
triple negative BC
• 30-60 years old, do not reflect
technological/treatment advances
or changes in population

30. CA Cancer J Clin 2002;52:68-
71
• Relative Rate of breast cancer
death from 8 RCTs
• Overall 24% reduction in death
• Canadian National Breast
Screening Study shows increased
risk of death with screening
Screening= benefit Screening= harm

31. CNBSS- A flawed study?
• Flawed design
– Palpable masses preferentially placed
in screening arm
– 58% and 49% had clinically palpable
cancers vs 15% in average population
– 16.4% advanced cancers in mammo vs
8.5% in usual care (p>0.003)
– Breast cancer mortality rate was 1.36x
higher in screening arm vs. usual care
• Poor quality mammograms

32. Coldman et al, 2014
Modern Observational Trials of Screened Populations
• Overall reduction in
mortality 49%
Screening= benefit Screening= harm

33. Mortality Benefit
• From 11 RCTs
– 15% reduction
• From Observational Trials
– 49% reduction

34. False Positives
• Important to distinguish between recalls for further imaging vs benign biopsy
• Imaging recall is not a false positive- it is a request for more information
• Numbers from BC program data:
Canadian Partnership Against Cancer. Breast Cancer Screening in Canada: Monitoring and Evaluation of Quality Indicators - Results Report, 2017. https://s22457.pcdn.co/wp-content/uploads/2019/01/Breast-Cancer-Screen-Quality-Indicators-Report-2012-EN.pdf
Recall
• ~15% of women are recalled for further
imaging on first screen
• ~7% of women recalled for further imaging
on subsequent screens
Biopsy
• 1.4% biopsy rate
• 0.36% are cancers
Compare with colon screening: 5% recall rate, 4.7% biopsy,
0.25% are cancers

35. Overdiagnosis
• Relevant for older women with co-morbidities, but less applicable
for younger women
• Literature: Overdiagnosis ranges from 0.1-33%, lower for younger
women
• Mortality due to breast cancer in women diagnosed with breast
cancer:

36. Canadian Task
Force on
Preventive Health
Care:
Overdiagnosis
• ”Women less than 50 years of age are at greater risk of these harms than older
women.”
• Estimates of overdiagnosis taken from CBNSS trial
Klarenbach et al., 2018
?

37. Benefit of
screening
depends
on inputs:
recall imaging

38. Benefit of
screening
depends
on inputs:
70 not 294
10 not 7
10 not 43
0.01 not 3
recall imaging
?5 not <1

39. WHAT IS THE EFFECT OF CURRENT SCREENING
RECOMMENDATIONS ON WOMEN IN 40S?

40. What happened when we stopped recommending
screening?
• 2011: Canadian Task Force recommended against screening
women 40-94
• Some provinces/territories continued to screen and some did
not

41. 0
10
20
30
40
50
60
2010 2011 2012 2013 2014 2015 2016 2017
INCIDENCE
RATE
(PER
100,000
FEMALES)
DIAGNOSIS YEAR
Stage-specific female breast cancer incidence rates, ages 40 to
49 years, Canada excluding Quebec, 2010 to 2017
Stage I Stage II Stage III Stage IV
Impact of Change in CTF guidelines in 2011
Wilkinson, A. N. et al. Curr Oncol 29, 5627-5643
• Increase later stage
disease at
diagnosis in 40s
and 50s
• 10.3% increase in
metastatic disease
in 50s

42. Across Canada, Women in 40s are
Diagnosed with Later Stage Breast Cancer
than Women in 50s

43. A Natural Experiment….
• Nova Scotia, British Columbia, Alberta, PEI and NWT
continued to offer annual screening with recall
• Data for all breast cancers diagnosed is collected for all
provinces/territories in the Canadian Cancer Registry (CCR)
• This allowed us to assess the impact of organised breast
screening programs on breast cancer outcomes
– i.e Stage and Mortality in Screener vs Comparators jurisdictions

44. 44.5
37.2
13.6
4.7
46.8
36.0
12.3
4.9
STAGE I STAGE II STAGE III STAGE IV
Proportion
of
cases
(%)
Stage at diagnosis
Comparators Screeners
Women 40-49 and 50-59 are diagnosed with
later stage breast cancer if no screening
program for 40s:
Curr. Oncol. 2022, 29, Wilkinson A,
…Seely JM
33.3
43.7
18.3
4.6
39.9 40.7
15.6
3.9
STAGE I STAGE II STAGE III STAGE IV
Proportion
of
cases
(%)
Stage at diagnosis
Comparators Screeners
p<0.001
p<0.001
p<0.001
p=0.001
p<0.001
p=0.003
p<0.001
p>0.05
40-49 50-59

45. Net Survival significantly greater for women
diagnosed with breast cancer if there is a
screening program for 40s

46. Provincial/territorial screening participation rates
correlate with stage and net survival
Wilkinson AN, Ellison LF, Billette JM, Seely JM. Journal of Clinical Oncology, 2023
40-49 % Screened
Rate/100,000
Stage 1
Stage 4

47. Provincial/territorial screening participation
rates correlate with net survival

48. There are more breast cancer cases in
women in 50s if they live in a jurisdiction
which did not screen in 40s

49. What We Know About Breast Cancer
in women in 40s
• Non-white women are at increased risk for diagnosis of
breast cancer younger than 50
• Dense breasts increase risk of breast cancer
• Women in 40s have more aggressive cancers
• Overdiagnosis is minimal in women in 40s
• Women in 40s who have access to screening are diagnosed
with earlier stage disease compared with those who do not
• Survival is significantly increased in women 40-49 who are
screened

50. What should we do for women 40-49?
• Guidelines currently under review by the Canadian
Task Force on Preventive Health
–Expected late fall 2023
–Evidence beyond RCTs will be considered
• Provinces and Territories continue to make their
own decisions around screening

51. What do I hope for?
• A recommendation for Women in their 40s to be screened
annually with mammography, if consistent with values and
preferences
– +/- supplemental screening if dense breasts
• Adoption by provinces and territories:
– Allows for organised programs with self-referral and reminders