in progress

Draft Research Plan

Screening for Breast Cancer

January 21, 2021

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

  1. What is the comparative effectiveness of different breast cancer screening strategies (e.g., by modality, interval, initiation age, use of supplemental imaging, or personalization based on risk factors) on breast cancer morbidity and breast cancer–specific or all-cause mortality?
    1. Does comparative effectiveness differ by population (e.g., by age, breast density, race/ethnicity, or family history)?
  2. What is the comparative effectiveness of different breast cancer screening strategies (e.g., by modality, interval, initiation age, use of supplemental imaging, or personalization based on risk factors) on the incidence of advanced breast cancer?
    1. Does comparative effectiveness differ by population (e.g., by age, breast density, race/ethnicity, or family history)?
  3. What are the comparative harms of different breast cancer screening strategies (e.g., by modality, interval, initiation age, use of supplemental imaging, or personalization based on risk factors)?
    1. Do the comparative harms vary by population (e.g., by age, breast density, race/ethnicity, or family history)?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. How do structural racism, social inequalities, unequal access to high-quality healthcare, and other factors contribute to disparities in breast cancer screening, diagnosis, treatment, and health outcomes? In particular, what may account for higher breast cancer mortality among Black women in the United States?
  2. How do new findings, analyses, or longer term followup from foundational effectiveness trials of mammography screening influence conclusions about the benefits and harms of screening mammography?
  3. What risk assessment tools are available for use in average-risk screening populations and how well do they perform, particularly to support decisions about screening in younger women?
  4. How do the personal preferences of younger and older women shape the ways in which they evaluate the potential harms and benefits of screening for breast cancer and decisions about whether to undergo screening?
  5. What are the accuracy and reproducibility of BI-RADS* determination of breast density?

*Breast Imaging-Reporting and Data System

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the evidence report. Criteria are overarching as well as specific to each of the key questions (KQs).

Category Include Exclude
Population Adult females History of breast cancer or high-risk breast lesions (DCIS, LCIS, ADH, ALH)

Clinically significant genetic markers or syndromes associated with high risk (e.g., BRCA1 or BRCA2 gene mutations, Li-Fraumeni syndrome, Cowden syndrome, hereditary diffuse gastric cancer, or other familial breast cancer syndromes)

Previous large doses of chest radiation (≥20 Gy) before age 30 years

Interventions Any mammography screening modality (i.e., film or digital mammography, digital breast tomosynthesis [3D mammography])

Screening strategy (e.g., screening interval, age to start or stop screening, personalized screening based on risk and other characteristics)

Any mammography screening modality plus supplemental screening (e.g., ultrasound, MRI)

Any mammography screening modality plus supplemental screening for a defined population (e.g., negative mammography, dense breasts, age group)
Breast imaging or clinical examinations conducted for diagnosis or surveillance

Screening strategies that do not include mammography

Comparisons Standard population-based screening with digital mammography Breast imaging or clinical examinations conducted for diagnosis or surveillance

Screening that does not include mammography

Outcomes KQ 1:
  • Breast cancer morbidity (e.g., adverse effects of treatment, physical/functional impairment)
  • Quality of life or subjective well-being
  • Breast cancer mortality
  • All-cause mortality

KQ 2:

  • Incidence of invasive breast cancer
  • Incidence of advanced breast cancer (e.g., study defined, metastatic breast cancer, stage of diagnosis based on BI-RADS)
  • Cancer subtypes defined by receptor status (e.g., ER/PR, HER2) that are associated with prognosis

KQ 3:

  • Interval cancers (false-negative results)
  • False-positive findings at screening and biopsy
  • Recall rate (need for further evaluation)
  • Overdiagnosis and overtreatment
  • Psychological harms (e.g., anxiety, depression)
  • Quality of life and subjective well-being
  • Radiation exposure
 
Timing KQs 1, 2: Followup from at least one round of screening (minimum 1 year), multiple rounds of screening, duration of followup

KQ 3:

  • Per round of screening
  • Over multiple rounds of screening
  • Lifetime
 
Setting Settings and populations of women applicable to U.S. primary care settings

Studies conducted in countries categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Programme)

 
Study Design KQs 1, 2:
  • Individual participant data meta-analyses
  • Randomized, controlled trials; controlled clinical trials

KQ 3: Above, plus cohort studies with contemporaneous controls, population-based nested case-control studies, and cross-sectional studies from included trials or large population-based studies

Narrative reviews, case reports, case series, editorials
Language English-language abstracts and articles (includes English-language abstracts of non–English-language papers)  

Abbreviations: ADH=atypical ductal hyperplasia; ALH=atypical lobular hyperplasia; BI-RADS=Breast Imaging-Reporting and Data System; BRCA=breast cancer gene; DCIS=ductal carcinoma in situ; ER/PR=estrogen receptor/progesterone receptor; LCIS=lobular carcinoma in situ; HER2=human epidermal growth factor receptor 2; MRI=magnetic resonance imaging.