Clinical trial NCT02980848: Assessing Breast Density's Value in Imaging - A Comparative Effectiveness Study
Official title: Comparative Effectiveness of Breast Cancer Screening and Diagnostic Evaluation by Extent of Breast Density
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Keywords: digital mammography
digital breast tomosynthesis
breast magnetic resonance imaging
screening
breast density
breast imaging
pre-operative magnetic resonance imaging
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: University of California, San Francisco
name: Dartmouth College
name: Kaiser Permanente
name: University of Vermont
name: University of North Carolina
name: University of Illinois at Chicago
name: Wake Forest University Health Sciences
name: Harvard Pilgrim Health Care
name: Albert Einstein College of Medicine
name: Erasmus Medical Center
First posted: 2016-12-02
Enrollment: 1341172
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will include women age 40-79 undergoing screening mammography (Aim 1) and women age ≥18 with a first breast cancer diagnosis (Aim 2). We will include women in the BCSC cohort with mammography from 2005-2017. BCSC participants are identified from seven BCSC breast imaging registries. The BCSC prospectively collects data during routine clinical practice through voluntary partnerships with radiology facilities. Women enter the BCSC cohort when they receive a breast-imaging exam at a participating facility.

Brief summary: This Breast Cancer Surveillance Consortium (BCSC) ADVANCE study is a large, observational pragmatic comparative effectiveness research study using high-quality, prospectively collected data from BCSC registries to generate evidence on how breast density should be integrated into decision making around breast cancer screening and preoperative diagnostic work-up. We will augment existing BCSC registry infrastructure with additional prospective data collection and collection of patient reported outcomes (PROs), CISNET modeling of long-term screening outcomes, and qualitative data from focus groups with women represented in two aims.

Detailed description: Aim 1: Compare the effectiveness of breast cancer screening using digital mammography alone versus digital mammography plus supplemental screening (digital breast tomosynthesis or MRI) by extent of breast density.

Sub aim 1: Evaluate whether the performance of tomosynthesis improves with years of experience, and whether any "learning curve" depends on radiologist specialty (i.e., breast imaging specialist vs. general radiologist).

Aim 2: Compare the effectiveness of preoperative MRI versus no MRI by extent of breast density among women with an initial, pathologically confirmed diagnosis of DCIS or invasive breast cancer.

Covid-19 Enhancement Aim and Hypotheses:

Develop patient-focused messaging content through focus groups that radiology facilities can use when scheduling appointments to inform women of the safety to schedule or postpone breast screening or diagnostic services.

Eligibility criteria: Aim 1 Clinical Outcomes

Inclusion criteria:

* Women aged 40-79 undergoing screening mammography from 2010-2017 for comparisons with tomosynthesis and 2005-2017 for comparison with breast MRI at a facility that participates in one of six BCSC breast imaging registries
* Digital mammography exams performed for screening and performed with or without supplemental screening with digital breast tomosynthesis from 2010-2017 or breast MRI from 2005-2017, at a facility that participates in one of seven BCSC breast imaging registries, and in women who meet inclusion criteria.

Exclusion criteria:

* Exams performed on women with a history of breast cancer, mastectomy, or breast augmentation.
* Unilateral mammograms and mammograms performed within 9 months of a prior mammogram to avoid classifying diagnostic exams as screening
* Exams without complete cancer capture during the follow-up period

Aim 1 Patient Reported Outcomes

Inclusion criteria:

* Women aged 40-74 years undergoing screening mammography, with or without supplemental screening with digital breast tomosynthesis or breast MRI, at selected BCSC facilities
* Women within 12 months of a digital screening mammogram with known breast density and no known breast cancer diagnosis
* For MRI subgroup, we will include women with a screening MRI within the prior 24 months
* Within strata defined by BCSC registry, breast density subgroup (dense vs. not dense), and race/ethnicity, women with supplemental screening with digital breast tomosynthesis or breast MRI will be matched to women without supplemental screening

Aim 1 Focus Groups

Inclusion criteria:

* Women age 40-74 years undergoing screening mammography, with or without supplemental screening (defined as digital breast tomosynthesis or breast MRI)
* Women within 12 months post-most recent screening examination with known dense breasts from most recent screening mammogram and no known breast cancer diagnosis
* Women who are able to speak English and can travel to a nearby location for a discussion

Subaim 1

Inclusion criteria:

* Radiologists interpreting digital mammography and/or tomosynthesis for at least one year from 2010-2017 at a facility that participates in the BCSC
* Digital mammography exams and digital breast tomosynthesis performed for screening and evaluated by a radiologist meeting inclusion criteria from 2010-2017

Exclusion criteria:

* Exams performed on women with a history of breast cancer, mastectomy, or breast augmentation
* Unilateral mammograms and mammograms performed within 9 months of a prior mammogram to avoid classifying diagnostic exams as screening
* Exams without complete cancer capture during one year following the screening mammogram

Aim 2 Clinical Outcomes

Inclusion criteria:

* Women at least 18 years of age with a first breast cancer diagnosis (DCIS or invasive) from 2005-2017 for whom there was a mammogram performed within the year prior to breast cancer diagnosis at one of the participating BCSC registry facilities
* Women for whom we have pathologically-confirmed breast cancer (DCIS or invasive) with a pathology or biopsy record related to the incident cancer diagnosis in the BCSC data
* MRI and mammography examinations performed for pre-operative work-up from 2005-2017 at one of the participating BCSC registry facilities in women meeting eligibility criteria

Aim 2 Patient Reported Outcomes

Inclusion criteria:

* Women at least 18 years of age with a first pathology-confirmed breast cancer diagnosis (DCIS or stage I-III invasive) within 6-18 months
* Known breast density at the time of breast cancer diagnosis

Aim 2 Focus Groups

Inclusion criteria:

* Women age ≥18 with a first breast cancer diagnosis (DCIS or stage I-III invasive cancer) within 1-5 years and after completion of active breast cancer treatment who have undergone mammography or MRI pre-operatively.
* Women who are able to speak English and can travel to a nearby location for a discussion

COVID-19 Enhancement Focus Groups

Inclusion criteria:

* Women age 18-74 who were due for breast imaging services during the COVID pandemic and have either canceled their appointment, delayed their appointment, or kept their appointment
* Women who are able to speak English and can attend calls virtually through Zoom or over the phone
* In addition, for focus groups with women who have prior breast cancer:

  1. First breast cancer diagnosis (DCIS or stage I-III invasive cancer) within 1-3 years prior to March, 2020.
  2. Completed active cancer treatment (ongoing endocrine and Herceptin therapy acceptable)
  3. No evidence of a second breast cancer event in cancer registry or pathology data before recruitment.

Primary outcomes:
measure: Screening Benefits: Rate of early stage invasive cancer detection (Aim 1)
timeFrame: Within one year after screen
measure: Screening Failures: Interval or advanced breast cancer rate (Aim 1)
timeFrame: Within one year after screen
measure: Screening Harms: Recall rate (Aim 1)
timeFrame: Within one year after screen
measure: Screening Harms: False-positive (FP) recall rate (Aim 1)
timeFrame: Within one year after screen
measure: Screening Harms: FP biopsy recommendation rate (Aim 1)
timeFrame: Within one year after screen
measure: Screening Harms: Other consequences (Aim 1)
timeFrame: Within one year after screen
measure: Patient Reported Outcomes (Aim 1)
timeFrame: Measured within one year post-screening
measure: Rates of additional breast cancers detected (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: 3-year rate of 2nd breast cancer events (Aim 2)
timeFrame: 3 years after initial diagnosis
measure: Patient Reported Outcomes (Aim 2)
timeFrame: Measured 6-18 months post-diagnosis
Secondary outcomes:
measure: Performance Measures: Sensitivity (Aim 1)
timeFrame: Within one year after screen
measure: Performance Measures: Specificity (Aim 1)
timeFrame: Within one year after screen
measure: Performance Measures: Positive predictive value (Aim 1)
timeFrame: Within one year after screen
measure: Definitive surgery type (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: Negative predictive value of work-up with MRI (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: Negative predictive value of work-up without MRI (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: Core biopsy rates (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: Surgical biopsy rate (Aim 2)
timeFrame: 6 months after initial diagnosis
measure: Benign biopsy rate (Aim 2)
timeFrame: 6 months after initial diagnosis
Other outcomes:
measure: Modeled Long-Term Mortality Outcome: Breast cancers deaths averted (Aim 1)
timeFrame: From date of first screening examination until the date of death from any cause, up to 100 years of age
measure: Modeled Long-Term Mortality Outcome: Life-years gained (Aim 1)
timeFrame: From date of first screening examination until the date of death from any cause, up to 100 years of age
measure: Modeled Long-Term Mortality Outcome: Overdiagnosis (Aim 1)
timeFrame: From date of first screening examination until the date of death from any cause, up to 100 years of age
Locations:
city: Davis
country: United States
facility: Sacramento Area Breast Imaging Registry
state: California
city: San Francisco
country: United States
facility: San Francisco Mammography Registry
state: California
city: Chicago
country: United States
facility: Metro Chicago Breast Cancer Registry
state: Illinois
city: Lebanon
country: United States
facility: New Hampshire Mammography Network
state: New Hampshire
city: Chapel Hill
country: United States
facility: Carolina Mammography Registry
state: North Carolina
city: Burlington
country: United States
facility: Vermont Breast Cancer Surveillance System
state: Vermont
city: Seattle
country: United States
facility: Kaiser Permanente Washington Breast Cancer Surveillance Registry
state: Washington
Study officials:
affiliation: University of California, Davis
name: Diana L Miglioretti, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tosteson ANA, Schifferdecker KE, Smith RE, Wernli KJ, Zhao W, Kaplan CP, Buist DSM, Henderson LM, Sprague BL, Onega T, Budesky J, Jackson-Nefertiti G, Johnson D, Miglioretti DL, Kerlikowske K. Women's Breast Cancer Screening Confidence by Screening Modality and Breast Density: A Breast Cancer Surveillance Consortium Survey Study. J Womens Health (Larchmt). 2022 Nov;31(11):1547-1556. doi: 10.1089/jwh.2021.0649.
citation: Onega T, Zhu W, Kerlikowske K, Miglioretti DL, Lee CI, Henderson LM, Tosteson ANA, Wernli KJ, diFlorio R, Weaver DL, Buist DSM. Preoperative MRI in breast cancer: effect of breast density on biopsy rate and yield. Breast Cancer Res Treat. 2022 Jan;191(1):177-190. doi: 10.1007/s10549-021-06418-x. Epub 2021 Oct 22.