Page 1 Breast Cancer Screening USPSTF Grades Breast cancer is the - PDF document

The Breast Cancer Screening Controversy Disclosures • I have no conflicts of interest Asian Health Symposium 2019 Judith M.E. Walsh, MD, MPH Division of General Internal Medicine Women’s Health Center of Excellence University of California, San Francisco 1 2 Principles of screening USPSTF • Detection while patient is asymptomatic • Rigorous review of existing peer-reviewed – High sensitivity evidence • Early detection reduces the risk of death • Ratings reflect the strength of the from the cancer – randomized trials evidence on the benefits and harms of a • The number of false positives is preventive service acceptably low • No consideration of costs – High specificity – Reasonably high prevalence of disease • ACA: Must cover A or B ratings • Ideally few harms 3 4 Page 1

Breast Cancer Screening USPSTF Grades • Breast cancer is the most common cancer in Grade Evidence Recommendation women and the second leading cause of cancer A High certainty of substantial net benefit Provide B High certainty of moderate net benefit Provide death Moderate certainty of moderate/substantial net benefit • Screening mammography reduces breast C Moderate certainty that net benefit is small Selectively cancer mortality offer/provide D No net benefit or harms outweigh benefits Do not provide • Risk increases with age I Insufficient evidence regarding balance of benefits and harms • Pre-menopausal breast tissue is dense – Decreased sensitivity 5 6 Breast Cancer Screening Breast Cancer in Asian Women • Qingling is a 52 year old woman with • Overall incidence of breast cancer is no family history of breast cancer. lower in Asian women than in Her last mammogram showed “dense Caucasians breast tissue” and she was told to – Rates are increasing discuss next steps, with you, her • Breast density is higher in Asian PCP. women • You perform a clinical breast • Screening rates are lower in Asian examination, which is normal. women 7 8 Page 2

Breast Cancer Screening U.S. screening guidelines: no agreement Stopping Organization Starting age Frequency Comments age • What do you recommend to United States Qingling? Screening for age Preventive Services 40-49 = Grade C 50 74 Biennially Task Force – Breast ultrasound and recommendation (USPSTF) mammogram Annually, Continue screening As then as long as good American Cancer appropriate – Breast MRI and mammogram 45 biennially health, life Society (ACS) based on life once age expectancy > 10 expectancy – Digital breast tomosynthesis ≥ 55 years. American College As – Standard digital mammography Consider cessation of Obstetricians appropriate of screening at age 40 Annually and Gynecologists based on life 75. (ACOG) expectancy 9 10 USPSTF vs American Cancer Society Recommendations When to start USPSTF ACS • Age is the most important risk factor Age 2015 2015 for breast cancer 40-44 None (or biennial) None • Because of lower prevalence, 45-49 None (or biennial) Annual screening younger women leads to 50-54 Biennial Annual many more false positives 55-74 Biennial Biennial 75+ • Younger women have denser breasts Insufficient evidence Biennial if good health and for or against life expectancy ≥ 10 yrs – Mammography quality American Cancer Society Guidelines. JAMA 2015;314(15):1599-1614 11 12 Page 3

When to stop? Harms Of Screening • Over-diagnosis – Cancers diagnosed that never would cause symptoms: • What is the patient’s 10 year life patients receive all the costs and harms of treatment expectancy? – Estimates: 10% to 30% of invasive breast cancers plus much of DCIS • False positives • What are co-morbid conditions? – Anxiety – Additional tests including biopsies • Would woman want surgery, chemo, – One-third of total screening cost XRT? • Radiation exposure – One breast cancer for 3000 women screened annually for • E Prognosis Cancer Screening 10 years Jorgensen, BMJ, 2009 13 14 Screening has also led to large increase in Impact of mammographic screening in U.S. detection of ductal carcinoma in situ (DCIS) Figure 2. SEER9 Age-adjusted incidence rate of breast cancer by stage (1973-2005) Screening era 100 90 Localized 80 Incidence rate (per 100,000) 70 60 In situ Rate Localized Rate 50 Regional Rate Distant Rate 40 DCIS 30 20 10 Metastatic 0 1975 1980 1985 1990 1995 2000 2005 Year of diagnosis Li CEBP 2005 Welch NEJM 2013 Li CEBP 2005 15 16 Page 4

False-Positive Results and Breast Breast Cancer Deaths Randomized Trials, all ages Biopsies per 1000 women Age, years Deaths Averted Screening 95% Harms of One-Time Mammography Screening, 1,000 Women Over 10 confidence by age Years Interval Outcome 40-49 50-59 60-69 70-74 40 to 49 0.3 0 to 0.9 False-positive 121 93 81 70 50 to 59 0.8 0.2 to 1.7 mammogram (12%) (9%) (8%) (7%) 60 to 69 2.1 1.1 to 3.2 Breast 16 16 17 18 70 to 74 1.3 0 to 3.2 biopsies (1.6%) (1.6%) (1.7%) (1.8%) 75+ Unknown -- recommended Biopsies per 10 6 3 3 50 to 69 1.3 0.6 to 0.2 cancer diagnosed Bottom line: Greatest screening benefit in women aged 60-69; smaller, and possibly no, screening benefit in women aged 40-49 17 18 Estimated annual mammography Breast Density screening costs in the US • Relative amount of radio-opaque (white) Screening the 40 million women in the US elements to radiolucent (black) fat on the image. aged 50-74 costs $4.72 billion per year • Increased breast density can obscure detection of benign mass or cancer Screening the 22 million women in the US aged 40-49 costs an additional $1.32 • Radiographic finding billion per year – Does not correlate with physical exam • Associated with increased risk of breast cancer diagnosis but not increased risk of breast cancer mortality 2010 20 0 costs: O ’ Do Donohue et al An Ann Intern Med 20 2014; 4;160: 60:145 45-153 153 19 20 Page 5

State breast density legislation Breast Density • Requires notification of • A: almost entirely fatty women with heterogeneously dense or • B: Scattered areas of fibroglandular extremely dense breasts density • Exact wording specified by • C: Heterogeneously dense law: decreased sensitivity and increased risk for BC – May obscure small masses • No mandate for insurance • D: Extremely Dense coverage of supplemental – Lowers sensitivity of mammography screening in most states 21 22 Breast Screening Technologies Digital mammography • Standard of care • Compared with film mammography, higher • Digital Mammography sensitivity, same specificity in women < 50 years old, dense breasts • Digital Breast Tomosynthesis – Sensitivity 78% versus 51% film • Breast MRI – Specificity 90% • Worse in women 65 and older • Breast Ultrasound – Sensitivity 53% versus 69% film 23 24 Page 6

Digital Breast Tomosynthesis Mammography and Dense Breasts • Digital Breast Tomosynthesis (DBT) as a primary screening strategy • No evidence on screening techniques and mortality • Digital mammography is more sensitive than film for women with dense breasts • Is tomosynthesis preferred? – Not standard of care – Insurance coverage Yaffe Breast Cancer Research 2008 10:209 http://www.nydailynews.com/ 25 26 USPSTF: DBT Parked outside UCSF • Digital Breast Tomosynthesis (DBT) as a primary screening strategy – Benefit: Reduces recall rate and increases cancer detection rates compared to conventional mammography – Harm: twice as much radiation; unknown rate of over diagnosis. May increase biopsy rates • No evidence on mortality, morbidity, or QOL • “Insufficient evidence to fully assess benefits and harms” 27 28 Page 7

MRI Screening Supplemental screening: better outcomes? MRI Ultrasound (US) Tomosynthesis (DBT) • Does MRI have a role for screening in • Most sensitive • Well-tolerated • Similar cancer Advantages high risk women? • No radiation • Relatively detection rate, inexpensive fewer false – MRI is a very sensitive method of breast positives imaging and has been used as a diagnostic tool in women with breast cancer • High false • High false • Not as sensitive – Not influenced by breast density Limitations positive rate positive rate (low as MRI – Specificity is variable • Overdiagnosis • Limited evidence PPV) • IV contrast • Operator- – Expensive base (newer) • Claustrophobia • Limited dependent • Expensive availability USPSTF Grade I: January 2017 29 30 Bottom Line: Impact For Clinical Practice Breast Cancer Screening for All Women • MRI may be useful in screening high risk • 40-49 informed consent women – Digital if decide to screen: now standard • The effect of MRI screening on mortality is • 50-74 screen every 2 years not known • 75+ informed consent – not if life • MRI is not currently recommended for expectancy less than 10 years screening average risk women • Don ’ t promote SBE, promote breast • Ultrasound adds little to mammography awareness • Tomosynthesis is promising • BRCA risk equivalent: MRI 31 32 Page 8

Breast Cancer Screening Questions? For Asian Americans • Screening guidelines target all women • Screening rates are lower in Asian Americans than in other ethnic groups – Explore barriers to screening • Breast density is higher in Asian women Clinical significance unclear 33 34 Page 9