in progress

Draft Research Plan

Breast Cancer: Medication to Reduce Risk

December 28, 2023

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.

Figure 1 is the analytic framework that depicts the two Key Questions to be addressed in the systematic review. The figure illustrates how medications to reduce the risk for primary cancer may reduce the incidence of breast cancer, breast cancer mortality, all-cause mortality, and affect quality of life (KQ1). Additionally, the figure indicates that the review will describe the approach used in studies to identify participants at increased risk of breast cancer (KQ1a), as well as harms associated with using the medication to reduce primary breast cancer risk (KQ3).

Abbreviation: DCIS=ductal carcinoma in situ.

1. What is the effectiveness of risk-reducing medications on primary invasive breast cancer, breast cancer mortality, all-cause mortality, and quality of life?
     1a.  How did the included trials identify and define participants as being at increased risk of primary breast cancer?
2. What are the harms of medications used to reduce primary breast cancer risk?

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

  1. What is the accuracy of different approaches for identifying individuals at increased risk of primary breast cancer, including clinical risk factors or prediction models?
  2. What are the perspectives and preferences of patients on breast cancer risk and the use of risk-reducing medications? 
  3. What are the current practices of primary care clinicians on breast cancer risk-reducing medications and what resources are needed to support patient-centered discussions?

To the extent possible, we plan to describe the participant characteristics of the included studies. Data on population characteristics will help us explore the degree to which the findings are broadly representative of the U.S. population eligible for the breast cancer risk-reducing medications. Participant characteristics will be described with respect to factors that can contribute to variability in intervention access and outcomes, including age, gender, race, ethnicity, cultural identity, socioeconomic status, insurance status, and geographic region. Specifically, as part of our effort to address health equity, we will search for and highlight evidence that could benefit individuals who historically have experienced increased risk of breast cancer mortality. This could include noting the effectiveness of risk-reducing medications for preventing triple negative breast cancer that is more prevalent among Black women and associated with higher breast cancer mortality. Additionally, the proposed Contextual Questions will include potential differences in the performance of breast cancer risk prediction models by race and ethnicity as well as patient and clinician factors that may be important to consider in the clinical setting to address health equity considerations.

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 Review. Criteria are overarching as well as specific to each of the Key Questions.

Category Include Exclude
Aim The use of medications to prevent primary breast cancer Use of medications for treatment or prevention of other outcomes (e.g., breast cancer reoccurrence, treatment of osteoporosis)
Populations Adult females without a preexisting or current invasive breast cancer diagnosis

Known carriers of pathogenic genetic variants that increase breast cancer risk

Females with previous nonmalignant breast biopsy results (e.g., atypical ductal hyperplasia)
Individuals with preexisting diagnosis of invasive breast cancer or DCIS; cisgender men
Interventions Medications to prevent primary breast cancer (tamoxifen, raloxifene, or aromatase inhibitors) Medications not used for prevention of primary breast cancer or unavailable in the United States
Comparisons Placebo, no treatment, or active comparator medication (tamoxifen, raloxifene, or aromatase inhibitors) Comparisons with other types of medications (e.g., aspirin)
Outcomes KQ 1 (Effectiveness): Incidence of primary invasive breast cancer (including tumor receptor status) and DCIS; breast cancer mortality; all-cause mortality; and quality of life

KQ 2 (Harms): Adverse quality of life and health outcomes

  • Fractures
  • Ophthalmologic disorders
  • Genitourinary outcomes
  • Thromboembolic events
  • Cardiovascular events
  • Risk of other cancers
  • Adverse outcomes related to quality of life
Noninvasive breast lesions other than DCIS
Setting Countries categorized as “Very High” on the 2021 Human Development Index, as defined by the United Nations Development Programme Countries not categorized as “Very High” on the Human Development Index
Study Design KQ 1: RCTs

KQ 2: RCTs, nonrandomized studies of interventions, or experiments with concurrent comparison groups

Cohort and case control studies conducted using data from cohort studies, registries, or medical record databases
Other study designs
Language English only Non-English publications
Study Quality Good- and fair-quality studies, according to design-specific criteria Poor-quality studies, according to design-specific criteria

Abbreviations: DCIS=ductal carcinoma in situ; KQ=key question; RCT=randomized, controlled trial.