Density matters: breast cancer screening guidelines … · – Ltd evidence on patient-important...

Density matters: breast cancer screening guidelines November 23, 2019 Colin Mar BC Cancer Breast Screening

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Objectives

1. To appreciate the risks associated with breast density, in the context of other breast cancer risks

2. To understand the background and current means of breast density notification in British Columbia

3. To appreciate the potential benefits and limitations of supplemental ultrasound in screening

What is BD?

• Non-dense – Fatty – Fat – Black

• Dense

– Glandular, ducts

– Fibrous, CT – White

What is BD?

• Non-dense – Fatty – Fat – Black

• Dense

– Glandular, ducts

– Fibrous, CT – White

What is BD?

• Non-dense – Fatty – Fat – Black

• Dense

– Glandular, ducts

– Fibrous, CT – White

How is BD measured?

BD measurement: BIRADS

A B C D

BD measurement: complete BIRADS

A

The breasts are almost entirely fatty

B

There are scattered areas of fibroglandular density

C

The breasts are heterogeneously dense, which may obscure small masses

D

The breasts are extremely dense, which lowers the sensitivity of mammography

Why does it matter?

Rationale for notification

• Patient autonomy and right to knowledge re personal health – Increased understanding of breast cancer risk Optimized informed decision making re breast health

Challenges of notification

• Potential confusion and anxiety • BD assessment variability and reproducibility • Interpretability for the patient • Question of supplemental

– Implications for future study

Keating NL, Pace LE. New federal requirements to inform patients about breast density; will they help patients? JAMA 2019;doi: 10.1001/jama.2019.5919

Background: USA

• 2005 Connecticut BD legislation mandating supplemental US for dense breasts

• Followed by BD notification laws in 38 states • 2016 USPSTF: insufficient evidence to assess balance

of benefits/harms of supplemental • Feb/2019 federal BD inform law • Heterogeneous use of US and MR

Siu 2016

Background: International

• Australia does not recommend routine notification, or supplemental screening

• UK Nat Screening Committee completed systematic review and does not recommend sUS

BreastScreen Australia (2016). Breast Density and Screening: Position Statement.

Background: International

• International Agency for Research on Cancer – Inadequate evidence that sUS reduces mortality

or interval cancers • European Society of Breast Imaging

– 1st priority is digital mammo adoption to optimize sensitivity

International Agency for Research on Cancer (IARC). (2016)

Background: BC

Fall 2016 • Use of BD in BC Cancer Breast Screening

– Dense Breasts Canada – US activity – Cdn environment

• No federal legislation • 7/12 programs notifying PCP; 1 to Pt

• BD available to Pt/PCP upon Pt request

2016 2017 2018

Background BC

Spring 2017 • Commissioned an External Review

– Andy Coldman, PhD – Published literature – Key informants – BC program data 2011 – 2014

2016 2017 2018

Background: BC

Aug 2017 • Quebec

– supplemental US “can also be useful” for very dense breasts (BI-RADS d) + family Hx

– Rad recommendation and breast cancer risk assessment followed by patient discussion

2016 2017 2018

Background: BC

Spring 2018 • External Review recommendations

1. Develop a plan to communicate breast density • Involve participants and primary care providers • Use BC data to develop risk info for BC population • Messages BD in context of other recognized risk

factors 2. Continue with BI-RADS, and monitor 3. Supplemental not recommended

2016 2017 2018

Background: BC

Fall 2018 • Began BD notification to Pts and PCP • CTFPHC

– Ltd evidence on patient-important outcomes of sUS

Klarenbach, S. et al. (2018). Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer. Canadian Medical Association Journal, 190(49), E1441-E1451. DOI: 10.1503/cmaj.180463.

2016 2017 2018

Background: BC

Spring 2018 • External Review recommendations

1. Develop a plan to communicate breast density • Involve participants and primary care providers • Use BC data to develop risk info for BC population • Messages BD in context of other recognized risk

factors 2. Continue with BI-RADS, and monitor 3. Supplemental not recommended

2016 2017 2018

Markers of a successful screening test

• ↓Mortality • ↓Advanced cancers • ↑Sensitivity ↓Interval

cancers • ↑Cancer detection rate

• Abnormal call rate and false positives

• Overdiagnosis

RCT Data: J-START trial

• [M + CBE] vs [M + US + CBE] • 73K Japanese women 40-49 • 1st round only!

Ohuci et al. Lancet 2016

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

55% ↑cancer detection

Modality Abnormal call rate (%) PPV (%)

Mammo 6.6 4.8

US (after M-) 5.7 3.6

RCT Data: J-START trial

• Subsequent abstract: – Similar proportional increase across all densities

• Awaiting publication of 2nd round data

Ohuci et al. Lancet 2016 Ohuci et al. 2019

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

48% ↓Interval cancers

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

↑Screen detected cancers > ↓Interval cancers • Future mammo interval cancers • Future mammo detectable cancers • Overdiagnosis

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US, not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

Lower stage of US detected

RCT Data: J-START trial

Ohuci et al. Lancet 2016 Coldman 2018

Arm

Mode of Detection

TEST

Number of Cases

Stage 0 I II+

Intervention

Screen Detected

M or CBE 122* 45 (37%)

52 (43%)

25 (20%)

Screen Detected

US not M or CBE

59† 9 (15%)

39 (66%)

11 (19%)

Interval - 18 1 (6%)

8 (44%)

9 (50%)

TOTAL 199 55 (28%)

99 (50%)

45 (23%)

Control

Screen Detected

M or CBE 117 31 (26%)

48 (41%)

38 (32%)

Interval - 35 8 (23%)

17 (49%)

10 (29%)

TOTAL 152 39 (26%)

65 (43%)

48 (32%)

*1 case had missing stage and was omitted from this table †2 cases had missing stage and were omitted from this table

? ↓advanced interval cancers

Markers of a successful screening test

• ↓Mortality • ↓Advanced cancers • ↑Sensitivity ↓Interval

cancers • ↑Cancer detection rate

• Abnormal call rate and false positives

• Overdiagnosis

? ? ?

Background: BC

Spring 2018 • External Review recommendations

1. Develop a plan to communicate breast density • Involve participants and primary care providers • Use BC data to develop risk info for BC population • Messages BD in context of other recognized risk

factors 2. Continue with BI-RADS, and monitor 3. Supplemental not recommended

2016 2017 2018

Patient and Primary Care Engagement Committee Objectives and Representation

Pt/PCP Results Letters

Pt Brochure PCP Guide

3 Pt Reps

BC Divisions of Family Practice

BC Naturopathic Assoc

BC Cancer

Others Others • Dense Breasts Canada • Mammo technologist • BC Radiologic Society • First Nations Health

Authority • BC Ministry of Health

Focus Group Testing

• 250 random women 40-74 years – Geographic

– Various educational backgrounds

– Indigenous women

– ESL

• 14 Providers – Family Practice

– Radiology

– Mammography technologist

– Naturopathy

– Nurse Practitioner

BD Discussion Guide for Clinicians

• Can change; tending to decrease with age • Intro BI-RADS assessment of volume of dense tissue • “breast composition” = “breast density” • Intro masking/interval cancer and risk factor concepts • “dense breasts” = C/D vs spectrum: C vs D; B

Role of Mammography • Only means to know breast density • Continue regular mammo regardless of density • Proven mortality benefit, density aside • No screening test perfect, and density can mask • Any breast changes remain important, even if negative mammo

Updated Discussion Guide

“Understanding Breast Density as a Risk Factor” • Explain concept of Absolute Risk (“2y”) • Use 2 examples

“Additional Breast Cancer Risk Factors” • Overall risk is complex combination of: • Age, mutations, personal Hx, family Hx, Bx showing high risk lesion • Lifestyle choices: active, wt, EtOH, breastfeeding, hormone (“5+”) • Risk calculator links: NIH (-BD); BCSC (+BD)

“Relative Risk” explained

Updated Discussion Guide

Updated Discussion Guide “Supplemental Testing” (not “screening”) • Review purpose of screening: early cancer detection; not risk reduction • Insufficient evidence for recommendation of routine supplemental for dense • Does show additional cancer detection, including favourable stages • But unclear re overdiagnosis, proportion found at next screen, mortality • RCT for US ongoing, but need to discuss benefits vs limitations (FP, sensitivity) • Possible change in balance for density in combination with other risk factors

Objectives

1.To understand the background and current means of breast density notification in British Columbia

2.To appreciate the risks associated with breast density, in the context of other breast cancer risks

3.To appreciate the potential benefits and limitations of supplemental ultrasound in screening

Masking >> Carcinogenesis Must consider other risks, but relationship is unclear

False positives Uncertain benefit of additional cancers

Additional cancers ↓ Interval cancers

Acknowledgements

• Canadian Partnership Against Cancer

• Andy Coldman, PhD

• Javis Lui

References • Berg, W. A. et al. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast

cancer risk. JAMA 2012;307:1394–1404

• Berg WA, Mendelson EB. Technologist-performed Handheld Screening Breast US Imaging: How Is It Performed and What Are the Outcomes to Date? Radiology 2014;272:12-27

• BreastScreen Australia (2016). Breast Density and Screening: Position Statement.

• Brem, R. F. et al. Assessing improvement in detection of breast cancer with three-dimensional automated breast US in women with dense breast tissue: the SomoInsight Study. Radiology 2015;274:663–673

• Coldman A. Report on Breast Density. Vancouver, BC: BC Cancer 2018.

• International Agency for Research on Cancer (IARC). (2016). Breast Cancer Screening, Volume 15: IARC Handbooks for Cancer Prevention. Lyon, France

• Keating NL, Pace LE. New federal requirements to inform patients about breast density; will they help patients? JAMA 2019;doi: 10.1001/jama.2019.5919

• Ohuci N et al. Sensitivity and specifi city of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial . Lancet 2016; 387: 341–48

• Ohuchi N, Suzuki A, Harada Y, Zheng Y, Ishida T. Balance of mammography in conjunction with ultrasonography for breast cancer screening according to breast density: Japan Strategic Anti-cancer Randomized Trial, J-Start. International Cancer Screening Network Meeting, Rotterdam 2019.

• Rebolj M et al. Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis. British Journal of Cancer https://doi.org/10.1038/s41416-018-0080-3

• Sardanelli, F., Aase, H. S., Álvarez, M., Azavedo, E., Baarslag, H. J., Balleyguier, C., ... Forrai, G. (2017). Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Israel, Lithuania, Moldova, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Switzerland and Turkey. European Radiology, 27(7), 2737-2743. DOI: 10.1007/s00330-016-4612-z

• Saraiya et al. Breast density notification letter and websites: are they too “dense”? J Am Coll Radiol 2019;16:717-723

• Siu AL, on behalf of the U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164:279–296. doi: 10.7326/M15-2886.

• Wilczek, B., Wilczek, H. E., Rasouliyan, L. & Leifland, K. Adding 3D automated breast ultrasound to mammography screening in women with heterogeneously and extremely dense breasts: report from a hospital-based, high-volume, single-center breast cancer screening program. Eur. J. Radiol. 2016;85:1554–1563

BI-RADS A/B Results Letter

“no sign of breast cancer”

Symptoms + Normal screen

BI-RADS letter + paraphrase

• Do not have “dense breasts” • Refer to brochure

Encourage complete discussion of risk and modifiable factors

BI-RADS C/D Results Letter

“no sign of breast cancer”

Symptoms + Normal screen

• At least some dense tissue • Common and normal • Masking and Inc’d Risk • Refer to brochure

Encourage complete discussion of risk and modifiable factors

BI-RADS letter + paraphrase

Updated Patient Brochure

What is breast density? • Comparison of 2 tissue types • Normal, common

How do I know how much dense tissue I have? • Introduce BI-RADS assessment

BI-RADS composition categories • Had to paraphrase

Other important concepts • Based on mammo, not clinical • Can change, particularly with age

Why should I know my breast density? 1. Increased risk, but small impact on overall 2. Masking, so any symptoms still important

Graphic demonstration of density • Combined with masking demonstration

What you can do Are there additional screening tests available for those with dense breasts? • Evidence limitations precluding definitive

recommendation • Other tests may find additional cancers • Explain false positive risk

Updated Patient Brochure

Grade 6/7 reading level

Saraiya et al. Breast density notification letter and websites: are they too “dense”? J Am Coll Radiol 2019;16:717-723

Updated Patient Brochure

Updated Patient Brochure

“What you can do” continued:

• “If I have dense breasts, do I still need a mammogram?”

• “Besides getting regular mammograms, what else can I do? – “Be familiar with your breasts”

– “Understand your overall risk for breast cancer” (≠ “high” risk)

– “Make positive lifestyle choices” (5-plus)

“What else determines my risk for breast cancer?” – Age

– Personal Hx of breast cancer

– Family Hx of breast cancer

– Inherited gene mutations