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Women Informed to Screen Depending on Measures of Risk (Wisdom Study)

Trial Status: Active

Most physicians still use a one-size-fits-all approach to breast screening in which all women, regardless of their personal history, family history or genetics (except BRCA carriers) are recommended to have annual mammograms starting at age 40. Mammograms benefit women by detecting cancers early when they are easier to treat, but they are not perfect. Recent news stories have discussed some of the potential harms: large numbers of positive results that cause stressful recalls for additional mammograms and biopsies. With the current screening approach, half of the women who undergo annual screening for ten years will have at least one false positive biopsy. Potentially more important are cancer diagnoses for growths that might never come to clinical attention if left alone (called "overdiagnosis"). This can lead to unnecessary treatment. Even more concerning is evidence that up to 20% of breast cancers detected today may fall into the category of "overdiagnosis." This study compares annual screening with a risk-based breast cancer screening schedule, based upon each woman's personal risk of breast cancer. The investigators have designed the study to be inclusive of all, so that even women who might be nervous about being randomly assigned to receive a particular type of care (a procedure that is typical in clinical studies) will still be able to participate by choosing the type of care they receive. For participants in the risk-based screening arm, each woman will receive a personal risk assessment that includes her family and medical history, breast density measurement and tests for genes (mutations and variations) linked to the development of breast cancer. Women who have the highest personal risk of developing breast cancer will receive more frequent screening, while women with a lower personal risk would receive less frequent screening. No woman will be screened less than is recommended by the USPSTF breast cancer screening guidelines. If this study is successful, women will gain a realistic understanding of their personal risk of breast cancer as well as strategies to reduce their risk, and fewer women will suffer from the anxiety of false positive mammograms and unnecessary biopsies. The investigators believe this study has the potential to transform breast cancer screening in America.

Inclusion Criteria

  • Female (biologically female at birth)
  • Age 40 years old to 74 years old

Exclusion Criteria

  • Prior breast cancer or DCIS diagnosis
  • Non-English or Spanish proficiency (Spanish added June 2019)

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: APPROVED
Contact: Rachael Bramlett Lancaster
Phone: 205-975-5972

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Antonia Petruse
Phone: 310-794-0367
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
Contact: Skye Stewart
Phone: 916-734-5772
San Diego
University of California San Diego
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE

Florida

Miami
Diagnostic Center for Women LLC
Status: ACTIVE
Contact: Michael Jonathan Plaza

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Louisiana

New Orleans
Louisiana State University Health Science Center
Status: ACTIVE
Contact: Agustin Abelardo Garcia

North Dakota

Fargo
Sanford Roger Maris Cancer Center
Status: APPROVED

South Dakota

Sioux Falls
Sanford Cancer Center Oncology Clinic
Status: ACTIVE

For almost 30 years, annual mammograms for women over 40 have been a cornerstone of the US

strategy to reduce mortality from breast cancer. A number of advances in the understanding of

breast cancer biology, and screening in general, have led to calls to revise and improve

national screening strategies (Esserman et al., 2014). In 2009, the US Preventive Services

Task Force (USPSTF) introduced changes to screening guidelines, recommending that annual

mammograms for all women 40-75 be replaced by biennial screening for women ages 50-75, and

that screening in the 40's should be individualized by taking patient context into account,

including the patient's values regarding specific benefits and harms. Despite being based on

a thorough review of the scientific literature, these recommendations continue to spark

debate and scientific opinion on the effectiveness of annual screening is greatly divided. On

one hand the radiology and obstetrics/gynecology community argues that annual mammograms

starting at 40 reduce the rate of interval cancers. On the other hand, primary care

physicians and other specialists believe that annual screening results in more

false-positives and unnecessary treatment and that a more targeted approach could result in

fewer false-positives and less over-diagnosis without increasing the number of interval

cancers. In fact it has been estimated that half of women will receive a false-positive

recall over 10 years of annual screening and that as many as 20% of all breast cancers might

be overdiagnosed. Since 2009 this debate has intensified, paralyzing the system and thwarting

any efforts to change or improve screening. The end result is that women are frustrated and

confused, and some have stopped screening altogether.

Despite a vastly improved understanding of breast cancer risk, the only criteria used to

establish a woman's screening recommendations is her age (and BRCA status if known), but

there are risk models available that incorporate personal and family history of breast

disease, endocrine exposures and breast density to assess breast cancer risk (Constantino, et

al., 1999; Parmigiani, et al., 1998; Tyrer, et al., 2004; Claus, et al., 2001; Ozanne, et

al., 2003). Most recently certain genetic mutations and common genetic variants (single

nucleotide polymorphisms or SNPs) have been confirmed predictors as well (Darabi, et al.,

2012). Therefore, advances in this understanding of breast cancer biology, risk assessment,

and imaging have enabled the creation of better tools and sufficient knowledge to replace the

one-size-fits-all approach to screening and to implement a new, personalized model; one that

provides recommendations on when to start, when to stop, and how often to screen that depend

upon well characterized measures of risk.

The investigators propose to test a transformational evidence-based approach to breast

screening that educates women about their actual risk, and tailors screening recommendations

to them as individuals. Within the Athena Breast Health Network, the study will compare

comprehensive, patient-centered risk-based screening to annual screening for women starting

at age 40. The comprehensive risk assessment is based on a widely accepted risk model, the

Breast Cancer Surveillance Consortium model, that includes endocrine exposures, family

history and breast density, with additional genomic risk factors that include rare and

uncommon major breast cancer susceptibility alleles as well as more common and recently

validated single nucleotide polymorphisms (SNPs) that can, cumulatively, contribute

significantly to a woman's individual risk. The study's personalized approach will recommend

an age to start and stop screening as well as a frequency based upon individual risk. Women

of highest risk will receive greater surveillance than those of lowest risk where the lower

bound is the USPSTF recommended guidelines. In this manner, the study will focus the most

effort on those most likely to develop the disease.

In close collaboration with patient advocates, the study has been designed as a 5-year,

preference-tolerant, 65,000 patient, randomized controlled trial of risk-based versus annual

screening. Individuals uncomfortable with the potential to be assigned to a particular arm in

the randomized cohort can participate in the self-assigned observational cohort, an example

of the pragmatic approach taken. Total accrual is anticipated to be 100,000 women across both

cohorts. A broad group of stakeholders have participated in crafting this approach, including

advocates, payers, the entire range of medical specialists and primary care providers and

researchers involved with breast cancer screening across the entire Athena Network,

technology partners, the Office of the President at the University of California, and

policy-making organizations.

The study hypothesizes that risk-based screening will be an improvement over annual screening

because it will be as safe, less morbid, enable more cancer prevention, less stressful and

more readily accepted by women as a result of an improved understanding of their personal

risk.

The Athena Breast Health Network was established across the 5 University of California

medical centers to develop a new, harmonized approach to breast cancer prevention, screening

and treatment. Athena is among the few centers in North America to use technology to

integrate risk assessment into breast screening. The investigators have developed a cadre of

"breast health specialists" who provide women with counseling and support around risk and

prevention. There are currently 100,000 registered Athena participants, with 30,000 new

patients per year and growing with the addition of Sanford Health, one of the largest rural

health networks in the country. The primary research mission of Athena is to address issues

requiring a population-based approach and translate solutions to clinical practice. Athena is

uniquely positioned to address the screening controversy and provide women with renewed

confidence in decisions about their breast health. Risk-based screening for breast cancer is

exactly the advanced, evidence-based approach to medicine described in the NIH and FDA's

"Path to Personalized Medicine". If these hypotheses prove to be correct, this study will be

able to establish a clear justification for its use, and provide a framework for widespread

implementation that will benefit women across the country.

Trial Phase Phase NA

Trial Type Screening

Lead Organization
UCSF Medical Center-Mount Zion

  • Primary ID PCS-1402-10749
  • Secondary IDs NCI-2018-00562, R01CA237533-01A1
  • Clinicaltrials.gov ID NCT02620852