Assessing Breast Density's Value in Imaging - A Comparative Effectiveness Study (BCSC-ADVANCE)

• ClinicalTrials.gov Identifier: NCT02980848
• Recruitment Status: Recruiting
• First Posted: December 2, 2016
• Last Update Posted: October 9, 2020
• Sponsor: University of California, Davis
• Collaborators: Patient-Centered Outcomes Research Institute; University of California, San Francisco; Dartmouth College; Kaiser Permanente; University of Vermont; University of North Carolina; University of Illinois at Chicago; Advocate Health Care; Harvard Pilgrim Health Care; Albert Einstein College of Medicine; Erasmus Medical Center
• Information provided by (Responsible Party): University of California, Davis

Study Description

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.

Condition or disease	Intervention/treatment
Breast Cancer	Other: Screening digital mammography; Other: Screening digital breast tomosynthesis; Other: Screening breast magnetic resonance imaging; Other: Diagnostic mammography; Other: Pre-operative breast magnetic resonance imaging

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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 1212441 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 3 Years
• Official Title: Comparative Effectiveness of Breast Cancer Screening and Diagnostic Evaluation by Extent of Breast Density
• Study Start Date: September 2016
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
Screening group; Women without a history of breast cancer undergoing screening digital mammography, screening digital breast tomosynthesis, or screening breast magnetic resonance imaging.	Other: Screening digital mammography; Screening with digital mammography alone; Other: Screening digital breast tomosynthesis; Screening with digital mammography plus digital breast tomosynthesis; Other: Screening breast magnetic resonance imaging; Screening with digital mammography plus breast magnetic resonance imaging
Women with breast cancer; Women diagnosed with stage 0-III breast cancer undergoing pre-operative work-up with diagnostic mammography alone or diagnostic mammography plus pre-operative breast magnetic resonance imaging.	Other: Diagnostic mammography; Pre-operative diagnostic work-up with mammography alone; Other: Pre-operative breast magnetic resonance imaging; Pre-operative diagnostic work-up with mammography plus breast magnetic resonance imaging

Outcome Measures

Primary Outcome Measures :

1. Screening Benefits: Rate of early stage invasive cancer detection (Aim 1) [ Time Frame: Within one year after screen ]
   Number of stage I or IIA cancers diagnosed within 1 year of a positive screen divided by total number of screens
2. Screening Failures: Interval or advanced breast cancer rate (Aim 1) [ Time Frame: Within one year after screen ]

   Number of invasive cancer cases within 1 year of a negative screen divided by total number of screens

   Number of advanced cancers (stage IIB or higher) within 1 year of a screen divided by total number of screens

3. Screening Harms: Recall rate (Aim 1) [ Time Frame: Within one year after screen ]
   Number of positive screens divided by total number of screens
4. Screening Harms: False-positive (FP) recall rate (Aim 1) [ Time Frame: Within one year after screen ]
   Number of positive screens without a cancer diagnosed within 1 year divided by total number of screens
5. Screening Harms: FP biopsy recommendation rate (Aim 1) [ Time Frame: Within one year after screen ]
   Number of screens with a biopsy recommendation and no cancer diagnosed within 1 year divided by total number of screens
6. Screening Harms: Other consequences (Aim 1) [ Time Frame: Within one year after screen ]
   Number of DCIS diagnoses within 1 year of a positive screen divided by total number of screens, reported overall and by grade
7. Patient Reported Outcomes (Aim 1) [ Time Frame: Measured within one year post-screening ]
   Patient surveys targeted to determining outcomes of interest to patients
8. Rates of additional breast cancers detected (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of women with contralateral breast cancer diagnosed within 6 months of initial diagnosis over total number of women
9. 3-year rate of 2nd breast cancer events (Aim 2) [ Time Frame: 3 years after initial diagnosis ]
   Rate of 2nd breast cancers diagnosed within 3 years of follow-up (starting 6 months after initial diagnosis) calculated separately for ipsilateral and contralateral cancers
10. Patient Reported Outcomes (Aim 2) [ Time Frame: Measured 6-18 months post-diagnosis ]
    Patient surveys targeted to determining outcomes of interest to patients

Secondary Outcome Measures :

1. Performance Measures: Sensitivity (Aim 1) [ Time Frame: Within one year after screen ]
   Number of cancer cases within 1 year of positive screen divided by number of breast cancer cases
2. Performance Measures: Specificity (Aim 1) [ Time Frame: Within one year after screen ]
   Number of negative screens without cancer diagnosed within 1 year of screen divided by number of screens without breast cancer
3. Performance Measures: Positive predictive value (Aim 1) [ Time Frame: Within one year after screen ]
   Number of cancer cases within 1 year of positive screen divided by number of positive screens
4. Definitive surgery type (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Rates of unilateral mastectomy, or bilateral mastectomy, lumpectomy with reconstruction, lumpectomy without reconstruction
5. Negative predictive value of work-up with MRI (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of women with a negative pre-operative MRI and no additional cancers diagnosed within 6 months after initial diagnosis over the total number of women with a negative pre-operative MRI
6. Negative predictive value of work-up without MRI (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of women without a pre-operative MRI with no additional cancers diagnosed within 6 months after initial diagnosis over the total number of women without a pre-operative MRI
7. Core biopsy rates (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of core biopsies within 6 months of initial diagnosis over number of breast biopsies
8. Surgical biopsy rate (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of surgical biopsies within 6 months of initial diagnosis over number of breast biopsies
9. Benign biopsy rate (Aim 2) [ Time Frame: 6 months after initial diagnosis ]
   Number of initial benign biopsies over number of breast biopsies

Other Outcome Measures:

1. Modeled Long-Term Mortality Outcome: Breast cancers deaths averted (Aim 1) [ Time Frame: From date of first screening examination until the date of death from any cause, up to 100 years of age ]
   Breast cancers deaths averted estimated by the Cancer Intervention and Surveillance Modeling Network (CISNET) models
2. Modeled Long-Term Mortality Outcome: Life-years gained (Aim 1) [ Time Frame: From date of first screening examination until the date of death from any cause, up to 100 years of age ]
   Life-years gained estimated by the Cancer Intervention and Surveillance Modeling Network (CISNET) models
3. Modeled Long-Term Mortality Outcome: Overdiagnosis (Aim 1) [ Time Frame: From date of first screening examination until the date of death from any cause, up to 100 years of age ]
   Overdiagnosis estimated by the Cancer Intervention and Surveillance Modeling Network (CISNET) models

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• 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.

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.

Contacts and Locations

Contacts

Contact: Diana L Miglioretti, PhD; 530-752-7168; dmiglioretti@ucdavis.edu

Contact: Evan de Bie; 530-752-4726; emdebie@ucdavis.edu

Locations

United States, California

Sacramento Area Breast Imaging Registry; Recruiting

Davis, California, United States, 95616

Contact: Diana Miglioretti, PhD

San Francisco Mammography Registry; Recruiting

San Francisco, California, United States, 94143

Contact: Karla Kerlikowske, MD

United States, Illinois

Metro Chicago Breast Cancer Registry; Recruiting

Chicago, Illinois, United States, 60607

Contact: Garth Rauscher, PhD

United States, New Hampshire

New Hampshire Mammography Network; Recruiting

Lebanon, New Hampshire, United States, 03755

Contact: Anna Tosteson, ScD

United States, North Carolina

Carolina Mammography Registry; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Louise Henderson, PhD

United States, Vermont

Vermont Breast Cancer Surveillance System; Recruiting

Burlington, Vermont, United States, 05405

Contact: Brian Sprague, PhD

United States, Washington

Kaiser Permanente Washington Breast Cancer Surveillance Registry; Recruiting

Seattle, Washington, United States, 98101

Contact: Diana Buist, PhD

Sponsors and Collaborators

University of California, Davis

Patient-Centered Outcomes Research Institute

University of California, San Francisco

Dartmouth College

Kaiser Permanente

University of Vermont

University of North Carolina

University of Illinois at Chicago

Advocate Health Care

Harvard Pilgrim Health Care

Albert Einstein College of Medicine

Erasmus Medical Center

Investigators

• Principal Investigator: Diana L Miglioretti, PhD; University of California, Davis

More Information

Additional Information:

Breast Cancer Surveillance Consortium (BCSC) 

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02980848
• Other Study ID Numbers: 941466; PCS-1504-30370 ( Other Identifier: PCORI )
• First Posted: December 2, 2016
• Last Update Posted: October 9, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Please visit http://www.bcsc-research.org for information about requesting BCSC data.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, Davis:

digital mammography; digital breast tomosynthesis; breast magnetic resonance imaging; screening; breast density; breast imaging; pre-operative magnetic resonance imaging

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases