Screening Strategies for Breast Cancer Detection

Overseen By Ava A Mitra, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Vision less than 20/25, Neuromuscular disorders, Visual disorders

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

Compensation: Varies

Number of Visits: 100

70 Participants Needed

Trial Summary

What is the purpose of this trial?

Brief Summary A task like breast cancer screening (mammography) can be described as a "hybrid search" task. In basic visual search tasks, observers search for a target among distractors that are not the target. In hybrid search, observers search for two or more target types. In mammography, observers are searching for masses, calcifications ("calcs"), and some other signs of cancer like architectural distortion. In this experiment, the investigators have created a simulated version of mammography where non-expert (non-radiologist) observers can look for simulated masses and calcs. There are two types of stimuli, a 2D version (like an x-ray) and a 3D version (like the output of Digital Breast Tomosynthesis - DBT). The question that is being asked is whether it is better to ask about masses and calcs separately (first one, then the other) or to just let observers look for both at the same time.

Do I have to stop taking my current medications to join the trial?

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

Do I need to stop my current medications for this trial?

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

What data supports the idea that Screening Strategies for Breast Cancer Detection is an effective drug?

The available research shows that tamoxifen, a drug used in Screening Strategies for Breast Cancer Detection, has been effective in reducing the risk of breast cancer. Studies have shown that tamoxifen can decrease the incidence of breast cancer in women who are at high risk. Additionally, it has been found to increase bone density, which is a positive side effect. However, there are some concerns about potential side effects, such as bone loss in younger women and uterine issues in older women. Despite these risks, the benefits of tamoxifen in preventing breast cancer are considered to outweigh the potential downsides. Other drugs like raloxifene are also being studied for similar benefits, but tamoxifen remains a key option for prevention. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tamoxifen citrate (Nolvadex) for breast cancer prevention?

Research shows that Tamoxifen can reduce the risk of breast cancer and increase bone density. It is being studied in large trials to see if it can prevent breast cancer in healthy women, especially those with high-risk genes. ^{1 2 3 4 5}

What safety data exists for breast cancer screening methods?

The research provided does not directly address safety data for Tamoxifen citrate or Nolvadex, which are treatments rather than screening methods. However, it discusses the potential harms of breast cancer screening, such as overdiagnosis, which can lead to unnecessary treatment. Overdiagnosis rates vary widely, with estimates ranging from 0% to 50% depending on factors like age and screening methods. The benefits of mammography screening include a reduction in breast cancer-related deaths, but it also carries the risk of overdiagnosis, with recent estimates suggesting 31% overdiagnosis in the U.S. for women invited to biennial screening from age 50. The research emphasizes the importance of informing women about both the benefits and harms of screening. ^{6 7 8 9 10}

Is the drug used in the trial 'Screening Strategies for Breast Cancer Detection' promising?

Yes, the drug, low-dose tamoxifen, is promising because it can increase the sensitivity of mammograms, making it easier to detect breast cancer early. This means fewer cancers are missed during screenings, and it can help find smaller tumors, which are easier to treat. ^{5 11 12 13 14}

How does low-dose tamoxifen improve breast cancer screening?

Low-dose tamoxifen is unique because it reduces breast tissue density, which can improve the sensitivity of mammograms (breast X-rays) in detecting cancer, especially in women with dense breast tissue. This makes it different from other treatments that do not specifically target breast density to enhance cancer detection. ^{5 11 12 13 14}

Research Team

Jeremy M Wolfe, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for individuals over 18 years old with normal color vision and at least 20/25 corrected visual acuity. It's not suitable for those with a history of neuromuscular or visual disorders.

Inclusion Criteria

You must pass a color vision test called Ishihara.

I am over 18 years old.

Exclusion Criteria

Your vision, even with glasses or contacts, is worse than 20/25.

I have a history of muscle or eye disorders.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experimentation

Participants engage in hybrid search tasks using simulated mammography to identify masses and calcifications

1 year

Multiple sessions, each consisting of 100-400 trials

Follow-up

Participants are monitored for accuracy and response time in identifying simulated cancer cases

4 weeks

Treatment Details

Interventions

• Search for both together
• Search for one after the other
• Search only for calcifications
• Search only for masses

Trial Overview The study tests different methods of breast cancer screening in a simulated environment, comparing the effectiveness of searching only for masses or calcifications versus looking for both simultaneously or one after another.

Participant Groups

Group I: Mixed Trials Experimental Treatment 4 Interventions

There are four conditions in the experiment. All condition will be presented, randomly mixed in a single block of 400 trials (with breaks every 100 trials).

Group II: Blocked Trials Experimental Treatment 4 Interventions

There are four conditions in the experiment. Each condition will be presented in a separate block of 100 trials.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Tamoxifen, the first selective estrogen receptor modulator (SERM), has been shown to effectively reduce the risk of breast cancer and increase bone density, highlighting its dual benefits in cancer prevention and bone health.

Raloxifene is also being studied for its potential to prevent osteoporosis and reduce breast cancer risk, with ongoing research from the STAR trial expected to provide further insights within seven years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Antiestrogens to Prevent Breast Cancer. Jordan, VC.[2019]

Tamoxifen shows promise in preventing breast cancer development based on laboratory evidence and clinical trials, with a favorable safety profile that suggests it can be used in women without cancer.

While tamoxifen may have benefits for lipid metabolism and bone health, concerns about serious side effects like thromboembolism and the risk of developing a second cancer remain important considerations in ongoing prevention trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer chemoprevention. Tamoxifen: current issues and future prospective. Chlebowski, RT., Butler, J., Nelson, A., et al.[2019]

Tamoxifen is an effective treatment for steroid receptor positive breast cancer, but its success relies on the conversion to active metabolites, which are influenced by the CYP2D6 enzyme.

Genetic variations in CYP2D6 can significantly affect the efficacy of tamoxifen, especially in patients with poor or intermediate metabolizer variants, suggesting that personalized treatment strategies based on CYP2D6 genotyping could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of tamoxifen to enhance antitumour action for the treatment and prevention of breast cancer: the 'personalised' approach? Brauch, H., Jordan, VC.[2013]

In a study of 92 Turkish breast cancer patients, it was found that 77.1% had normal metabolism of tamoxifen, while 2.1% had poor metabolism, which is linked to significant endometrial hyperplasia, indicating that metabolic characteristics can influence the side effects of tamoxifen treatment.

The study revealed that poor metabolizers of tamoxifen (CYP2D6 *3/*4 and CYP2D6 *6/*6 genotypes) had a higher risk of developing endometrial thickening, suggesting that genetic testing for CYP2D6 polymorphisms could help predict treatment outcomes and side effects in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment. Günaldı, M., Erkisi, M., Afşar, CU., et al.[2022]

Tamoxifen is being evaluated in ongoing clinical trials involving over 24,000 healthy women to determine its effectiveness in preventing breast cancer, with results expected by the year 2000.

While tamoxifen may provide significant benefits in breast cancer prevention, it is associated with adverse effects such as transient bone loss in premenopausal women and potential uterine complications in postmenopausal women, leading to investigations of alternative drugs like raloxifene and toremifene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Status of antiestrogen breast cancer prevention trials. Powles, TJ.[2016]

In a study of 22,657 women, only about 47% of black and Hispanic women and 50% of white women reported having a recent mammogram, highlighting a significant gap in breast cancer screening utilization.

Key factors influencing breast cancer screening rates included having a routine examination in the past year, seeing a specialist, and having more than a high school education, indicating that targeted strategies are needed to improve screening among underrepresented groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of screening mammography and clinical breast examinations among black, Hispanic, and white women. Frazier, EL., Jiles, RB., Mayberry, R.[2022]

Automated information extraction from radiology reports for breast imaging is highly accurate, with recall, precision, and F-measure scores ranging from 0.8 to 1.0, indicating it can reliably identify key imaging findings.

The study analyzed 139,953 radiology reports and found varying prevalence rates of imaging findings, such as suspicious calcifications, which can help improve the understanding and effectiveness of breast cancer screening processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an Automated Information Extraction Tool for Imaging Data Elements to Populate a Breast Cancer Screening Registry. Lacson, R., Harris, K., Brawarsky, P., et al.[2018]

In a study of breast cancer screening in Helsinki, overdiagnosis estimates for breast carcinoma ranged from 5% to 7%, indicating a relatively low risk of misdiagnosis in women aged 50-59 who were invited for screening.

The study compared the incidence of breast cancer in invited cohorts with non-invited cohorts over a minimum follow-up of 14 years, providing robust estimates that align with other European studies on overdiagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki service study in Finland. Heinävaara, S., Sarkeala, T., Anttila, A.[2021]

Current efforts in breast imaging, such as the use of tomosynthesis and adjustments in screening protocols, aim to reduce the risks of overdiagnosis and overtreatment in mammography.

The emerging field of breast radiomics holds significant potential for minimizing overdiagnosis by identifying imaging biomarkers linked to tumor biology, which could help avoid unnecessary treatments for less aggressive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Can Advanced Imaging Be Used to Mitigate Potential Breast Cancer Overdiagnosis? Rahbar, H., McDonald, ES., Lee, JM., et al.[2022]

Mammography screening can reduce breast cancer-related deaths by approximately 15-25% in randomized trials, with more recent observational studies showing a reduction of 13-17%, translating to 2-3 lives saved per 1,000 women screened over 20 years.

However, the screening also leads to significant overdiagnosis, with an estimated 31% of cases being overdiagnosed, resulting in 15 women being overdiagnosed for every 1,000 women screened, highlighting the need for informed decision-making regarding screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and harms of mammography screening. Løberg, M., Lousdal, ML., Bretthauer, M., et al.[2022]

Low-dose tamoxifen exposure can potentially increase mammographic screening sensitivity, particularly in women with higher breast density, as modeled from data in the KARMA trial involving 517 diagnosed cancers.

A relative decrease in mammographic density of 20% or more due to tamoxifen could lead to a significant 24% reduction in interval cancers and a 4% reduction in the detection of larger tumors, highlighting its efficacy in improving cancer detection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women. Eriksson, M., Czene, K., Conant, EF., et al.[2021]

Tamoxifen treatment in a premenopausal woman for 5 years resulted in a decrease in mammographic breast tissue density, suggesting a potential therapeutic benefit from the drug.

After stopping tamoxifen, the woman's breast density returned to baseline, indicating that the changes in density may be reversible and highlighting the need for further research on the clinical implications of these density changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tamoxifen on breast tissue density in premenopausal breast cancer. Slanetz, PJ., Grandpre, LE., Yeh, ED., et al.[2019]

In a retrospective study of 52 breast cancer patients, there was no correlation found between tamoxifen use and breast density, suggesting that tamoxifen may not impact mammographic sensitivity as previously thought.

The study confirmed that breast density is inversely related to age and menopausal status, indicating that older and postmenopausal women tend to have lower breast density.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between mammographic breast density and tamoxifen in women with breast cancer. Tiersten, A., Ng, YY., Pile-Spellman, E., et al.[2016]

In a study involving 123 women with breast cancer and 942 controls, a 10% or greater reduction in mammographic breast density after 12-18 months of tamoxifen treatment was associated with a 63% reduction in breast cancer risk.

Women taking tamoxifen who did not achieve a 10% reduction in breast density showed no significant decrease in breast cancer risk, indicating that monitoring breast density changes can help identify those who will benefit most from tamoxifen as a preventive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. Cuzick, J., Warwick, J., Pinney, E., et al.[2022]

References

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

Targeted Antiestrogens to Prevent Breast Cancer. [2019]

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

Breast cancer chemoprevention. Tamoxifen: current issues and future prospective. [2019]

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

Targeting of tamoxifen to enhance antitumour action for the treatment and prevention of breast cancer: the 'personalised' approach? [2013]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment. [2022]

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

Status of antiestrogen breast cancer prevention trials. [2016]

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

Use of screening mammography and clinical breast examinations among black, Hispanic, and white women. [2022]

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

Evaluation of an Automated Information Extraction Tool for Imaging Data Elements to Populate a Breast Cancer Screening Registry. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki service study in Finland. [2021]

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

How Can Advanced Imaging Be Used to Mitigate Potential Breast Cancer Overdiagnosis? [2022]

10. England pubmed.ncbi.nlm.nih.gov

Benefits and harms of mammography screening. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women. [2021]

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

Effect of tamoxifen on breast tissue density in premenopausal breast cancer. [2019]

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

Relationship between mammographic breast density and tamoxifen in women with breast cancer. [2016]

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

Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. [2022]