Final Research Plan

Breast Cancer: Screening

May 06, 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.

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Figure is an analytic framework that depicts the three Key Questions presented in the draft Research Plan. In general, the figure illustrates how breast cancer screening can reduce the incidence of advanced breast cancer, breast cancer morbidity and mortality, and all-cause mortality.

  1. What is the comparative effectiveness of different mammography-based 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 characteristics and risk markers (e.g., age, breast density, race/ethnicity, or family history)?
  2. What is the comparative effectiveness of different mammography-based 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 and progression to advanced breast cancer?
    1. Does comparative effectiveness differ by population characteristics and risk markers (e.g., age, breast density, race/ethnicity, or family history)?
  3. What are the comparative harms of different mammography-based 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 characteristics and risk markers (e.g., 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 racism, social inequalities, unequal access to high-quality healthcare, and other factors contribute to disparities in breast cancer incidence and outcomes? For example, 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 or women from racial/ethnic groups that are historically under-represented in research studies?
  4. How do the personal preferences of specific populations (including those that are under-represented in research) 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 harms of treatment associated with the detection of invasive breast cancer and ductal carcinoma in situ?

The 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 film or 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:

  • Detection and stage distribution of screen-detected invasive breast cancer
  • Detection of advanced cancer and stage distribution of any invasive breast cancer at time of screening and across followup, including interval cancers

Cancer subtypes will be defined by receptor status (e.g., ER/PR, HER2) since these are associated with prognosis

Advanced cancer definitions are not standardized and available outcomes will likely vary across studies (e.g., metastatic breast cancer, different stage and tumor size cutpoints)*

KQ 3:

  • False-positive and false-negative 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 two 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
  • Prospective cohort studies with contemporaneous comparison groups selected using unbiased criteria (e.g., screening modality used does not vary based on risk factor or marker)

KQ 3: All of the above, plus population-based nested case-control studies and cross-sectional studies from included trials or large population-based studies

 Narrative reviews, case reports, case series, and editorials

Observational studies using paired designs (i.e., within-person comparisons)
Language English-language abstracts and articles (includes English-language abstracts of non–English-language papers)  

* Where possible we will report outcomes for cancers diagnosed at American Joint Committee on Cancer (AJCC) stage IIA or higher.1

Abbreviations: ADH=atypical ductal hyperplasia; ALH=atypical lobular hyperplasia; 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.

The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) website from January 21, 2021, to February 18, 2021. Based on comments related to the scientific and conceptual scope of the review, the USPSTF revised the scope to require that effectiveness studies have data from at least two rounds of screening, include certain types of nonrandomized studies for the assessment of effectiveness, and include interval cancers as a benefit outcome rather than a harm. The USPSTF also clarified the proposed approach for including interval cancers and for defining advanced breast cancer. The USPSTF added a note to the Research Plan to explain that the evidence review would be accompanied by decision modeling. Additionally, the USPSTF revised the Contextual Question on racism and inequities in breast cancer mortality to be more specific, and replaced the contextual question on breast density assessment with a question on treatment harms, based on public feedback. The USPSTF made other minor changes to the text to clarify the scope and intention of the review. The USPSTF made no changes in response to comments that requested changes that are outside of the USPSTF scope, such as those related to the dissemination and implementation of screening to address underutilization.

  1. Kerlikowske K, Bissell MC, Sprague BL, et al. Advanced breast cancer definitions by staging system examined in the Breast Cancer Surveillance Consortium. J Natl Cancer Inst. 2020;djaa176.