Risk-Based Screening for Breast Cancer

(WISDOM Trial)

Recruiting at 10 trial locations

Overseen By Laura van 't Veer, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Prior breast cancer, DCIS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

100000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is the treatment generally safe for humans?

Olaparib (Lynparza) has been studied for safety in various conditions, including breast and ovarian cancer. It has shown a manageable safety profile, meaning that while there are side effects, they are generally considered acceptable and can be managed with medical care. ^{1 2 3 4 5}

How is the drug Lynparza used in risk-based breast cancer screening different from other treatments?

Lynparza (also known as AZD-2281, MK-7339, KU0059436) is unique because it is part of a personalized breast cancer screening approach that uses individual risk factors, such as family history and genetic information, to tailor screening schedules. This contrasts with traditional screening methods that apply the same schedule to all women, regardless of their individual risk. ^{6 7 8 9 10}

Who Is on the Research Team?

Laura Esserman, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for women aged 40 to 74 who understand English or Spanish. It's open nationwide in the US and includes those who identify as female, capturing both sex at birth and gender identity. Women with a history of breast cancer, DCIS, or bilateral mastectomy can't join.

Inclusion Criteria

I identify as female and will provide my sex at birth and gender identity.

You live in one of these states: California, North Dakota, South Dakota, Iowa, Minnesota, Alabama, Louisiana, or Illinois, or you have health insurance from a participating plan.

Depending on funding for study services, recruitment will expand nationwide, therefore criteria (c) will not apply if funding allows. As of 2019, recruitment is available nationwide

Exclusion Criteria

I have had both breasts removed to prevent cancer.

I am unable to give consent by myself.

I have been diagnosed with breast cancer or DCIS before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Risk Assessment

Participants in the risk-based arm complete a health questionnaire, provide a saliva sample for genetic testing, and receive screening advice based on a comprehensive risk assessment.

4-8 weeks

1 visit (in-person) for sample collection, 1 visit (virtual) for results discussion

Screening Schedule

Participants receive personalized screening schedules based on their risk assessment, with high-risk individuals receiving more frequent screenings.

5 years

Follow-up

Participants are monitored for safety and effectiveness of the screening strategy, including rates of late-stage cancers and biopsy rates.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Risk-based Breast Cancer Screening Schedule

Trial Overview The study tests personalized breast cancer screening schedules based on individual risk against traditional annual screenings. Participants provide saliva for genetic testing, complete health questionnaires, and receive screening advice tailored to their comprehensive or basic risk assessment.

How Is the Trial Designed?

Group I: Risk-Based Arm Experimental Treatment 3 Interventions

Women in this arm will receive risk-based screening, where risk is calculated based on a model including personal history, family history, and genetic testing. All women in the risk-based arm complete a health questionnaire, provide a saliva sample for genetic testing, and receive screening advice based on a comprehensive risk assessment. Women in this arm will be tested for a panel of 9 genes related to breast cancer risk as well as a panel of SNPs, which can further modify risk. Women will be assigned a screening start date, screening stop date, and screening frequency.

Group II: Annual Arm Active Control 2 Interventions

Women in this arm will receive Athena standard of care mammography screening, including annual mammograms. They will complete a health questionnaire and receive screening advice based on a basic risk assessment.

Risk-based Breast Cancer Screening Schedule is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Ovarian cancer
• Breast cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer

Approved in United States as Lynparza for:

• Ovarian cancer
• Breast cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Robert Wood Johnson Foundation

Collaborator

Trials

161

Recruited

697,000+

Salesforce

Collaborator

Trials

2

Recruited

100,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Safeway Foundation

Collaborator

Trials

2

Recruited

100,000+

Color Genomics, Inc.

Industry Sponsor

Trials

1

Recruited

100,000+

Published Research Related to This Trial

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

In a Phase I study involving 28 Japanese patients with advanced solid tumors, olaparib tablets at doses of 200 and 300 mg twice daily were found to be tolerable, with no dose-limiting toxicities reported.

The most common side effects included nausea, decreased appetite, anemia, and constipation, but no confirmed antitumor responses were observed, leading to the selection of 300 mg bid as the recommended dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. Yonemori, K., Tamura, K., Kodaira, M., et al.[2022]

In a pilot study of 21 patients with localized HER2-negative, BRCA-mutated breast cancer, neoadjuvant treatment with niraparib showed a high tumor response rate of 90.5% after 2 cycles, indicating strong antitumor activity.

Among those who continued treatment for 2-6 cycles, 40% achieved a pathological complete response, and no new safety concerns were reported, suggesting that niraparib is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. Spring, LM., Han, H., Liu, MC., et al.[2022]

A model developed from the Karma cohort of 70,877 participants can effectively identify women at high risk for breast cancer by analyzing factors like mammographic density, microcalcifications, hormone replacement therapy use, and family history.

Women with high mammographic density and additional risk factors had a nearly ninefold increased risk of breast cancer, suggesting that individualized screening could lead to earlier detection and potentially better outcomes for high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical model for identifying the short-term risk of breast cancer. Eriksson, M., Czene, K., Pawitan, Y., et al.[2022]

Women with atypical ductal hyperplasia (ADH) have a 2.81 times higher risk of developing breast cancer, while those with atypical lobular hyperplasia (ALH) have a 4.14 times higher risk, based on data from the South Australian screening program.

The study highlights the importance of understanding these relative risk estimates for better clinical management and treatment decisions for women diagnosed with ADH and ALH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk profile of breast cancer following atypical hyperplasia detected through organized screening. Buckley, E., Sullivan, T., Farshid, G., et al.[2015]

In France, breast cancer screening is organized for women aged 50 to 74 with biennial mammograms, while those at high risk receive personalized screening based on specific medical histories.

A new risk-based screening approach is being tested, which uses algorithms that consider clinical factors, mammographic density, family history, and genomic data to tailor screening frequency according to individual breast cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Other approaches in breast cancer screening]. Veron, L., Wehrer, D., Caron, O., et al.[2022]

A comprehensive breast cancer screening program should incorporate risk assessment alongside clinical breast exams and mammography to effectively identify women at increased risk.

Women identified as high-risk should receive personalized screening schedules and prevention programs tailored to their specific risk levels, which can help detect tumors earlier when they are more treatable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive breast cancer screening. Programs now include individual risk assessment. Cardenas, K., Frisch, K.[2019]

Structured breast cancer screening programs in seven countries recommend starting routine mammography at either 40 or 50 years of age, typically biennially, highlighting a systematic approach to early detection.

Efficacy studies indicate clear benefits of screening for women aged 50 and older, while the evidence for younger women remains less definitive, suggesting a need for tailored screening guidelines based on age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periodic breast cancer screening in seven foreign countries. Shapiro, S.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the olaparib tablet formulation in Japanese patients with advanced solid tumours. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A clinical model for identifying the short-term risk of breast cancer. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Risk profile of breast cancer following atypical hyperplasia detected through organized screening. [2015]

8. France pubmed.ncbi.nlm.nih.gov

[Other approaches in breast cancer screening]. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Comprehensive breast cancer screening. Programs now include individual risk assessment. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Periodic breast cancer screening in seven foreign countries. [2019]