Biomarker Monitoring for Breast Cancer Recurrence Risk

Overseen By Angela DeMichele, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Corticosteroids, Hydroxychloroquine

Disqualifiers: Uncontrolled diabetes, Cardiovascular risk, others

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

Compensation: Varies

Number of Visits: 2

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a single center, prospective cross-sectional study of women who have completed therapy for primary breast cancer within 5 years of diagnosis and are at increased risk for relapse. Patients will undergo screening bone marrow aspirate to test for presence of disseminated tumor cells (DTCs) Patients who harbor DTCs will be offered the opportunity for enrollment into a clinical trial of therapy targeting DTCs to prevent recurrence (separate protocols).

Will I have to stop taking my current medications?

The trial allows participants to continue taking adjuvant endocrine therapy and bone modifying agents as part of standard care. However, if you are taking tamoxifen and are DTC positive, you may need to stop it if your doctor agrees. Other medications, like certain anticoagulants, may need to be paused around the time of specific procedures.

Is olaparib (Lynparza) generally safe for humans?

Olaparib (Lynparza) has been studied for safety in various cancers, including ovarian and breast cancer. It is generally considered safe, but like all medications, it can have side effects, which may include nausea, fatigue, and anemia (low red blood cell count). ^{1 2 3 4 5}

How does the biomarker monitoring treatment for breast cancer recurrence risk differ from other treatments?

This treatment is unique because it uses a blood-based biomarker assay, like DiviTum TKa, to monitor and predict treatment response, potentially reducing the need for traditional disease monitoring and avoiding unnecessary treatments. It focuses on using circulating biomarkers to improve risk assessment and tailor treatments more effectively for breast cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Angela DeMichele, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

This trial is for women who finished breast cancer treatment within the last 5 years, have no signs of recurrence, and are at high risk of relapse. They must be willing to undergo bone marrow aspiration and blood tests, meet specific receptor criteria, and have good organ function. It's not for those with severe health issues, on other trials or certain medications, with cardiovascular risks or a history of lung disease.

Inclusion Criteria

I was diagnosed with invasive breast cancer in the last 5 years.

I finished my main cancer treatment at least 4 weeks ago.

My cancer has not returned after treatment.

Exclusion Criteria

Severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study

I have had lung inflammation or severe lung problems.

My diabetes is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Bone Marrow Aspirate

Patients undergo bone marrow aspirate to test for disseminated tumor cells (DTCs) by immunohistochemistry

1 day

1 visit (in-person)

Follow-up

Participants are monitored for the presence of disseminated tumor cells annually

5 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bone Marrow Aspirate
• Plasma/Buffy Coat
• Research Blood Collection
• Serum

Trial Overview The study involves collecting blood samples from participants to check for disseminated tumor cells (DTCs) in the bone marrow. Women found to have DTCs may join further trials targeting these cells to prevent cancer recurrence.

How Is the Trial Designed?

Group I: Screening Bone Marrow Aspirate Experimental Treatment 1 Intervention

All patients will undergo screening bone marrow aspirate to test for disseminated tumor cells (DTCs) by immunohistochemistry. The bone marrow sample is also used for other research tests.

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Published Research Related to This Trial

The OPINION study is evaluating the safety and efficacy of olaparib as a maintenance therapy for women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer who do not have BRCA mutations, involving patients who have undergone at least two prior lines of platinum-based chemotherapy.

The primary goal of the study is to assess progression-free survival, which will help determine how effective olaparib is in delaying cancer progression in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Poveda, AM., Davidson, R., Blakeley, C., et al.[2020]

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 is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

The combination of olaparib and carboplatin is tolerable for patients with sporadic triple negative breast cancer (TNBC), showing a modest overall response rate of 22% in a study of 28 women, with one complete response lasting over 69 months.

The most common side effects included neutropenia and thrombocytopenia, indicating that while the treatment is manageable, careful monitoring for these adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer. Lee, JM., Hays, JL., Chiou, VL., et al.[2019]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

The DiviTum TKa assay can significantly reduce the need for traditional monitoring methods in hormone receptor positive metastatic breast cancer, leading to cost savings of approximately $128,400 over three years by decreasing the number of imaging tests and biomarker assessments.

Incorporating DiviTum TKa into treatment plans may also result in additional savings of about $465,600 by avoiding ineffective therapies, suggesting that the assay not only helps in monitoring but also in making more cost-effective treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budget impact analysis of the DiviTum TKa assay in postmenopausal women with hormone receptor positive metastatic breast cancer. Carlson, JJ., Guzauskas, GF., Dann, RA., et al.[2022]

This study suggests that liquid biopsy read-outs, including chemokines and microRNAs, could be effective biomarkers for identifying early luminal breast cancer patients at risk of metastasis, addressing the current limitations of molecular diagnostic tests.

By analyzing baseline plasma and serum samples, these biomarkers could enhance existing prognostic factors, leading to better risk stratification and more personalized treatment options for patients with early luminal breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer. Lambrechts, Y., Garg, AD., Floris, G., et al.[2023]

In a study of 44 patients with metastatic breast cancer treated with nab-paclitaxel, the expression levels of the SPARC protein in tumor tissues and serum did not show a clear association with treatment outcomes.

The findings suggest that SPARC expression is not a predictive biomarker for the efficacy of nab-paclitaxel in this patient population, indicating that other factors may influence treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of nab-paclitaxel does not seem to be associated with SPARC expression in metastatic breast cancer. Schneeweiss, A., Seitz, J., Smetanay, K., et al.[2015]

In a study of 312 breast cancer patients, the presence of CD49f+ tumor cells was linked to a significantly increased risk of disease recurrence, indicating its potential as a prognostic biomarker.

Breast tumors with CD49f+ cells were associated with markedly decreased disease-free survival, suggesting that testing for this biomarker could enhance treatment planning and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer. Ye, F., Zhong, X., Qiu, Y., et al.[2020]

The StemPrintER Risk Score (SPRS) outperformed the Oncotype DX Recurrence Score (RS) in predicting the risk of distant recurrence in a study of 776 postmenopausal ER+/HER2- breast cancer patients, showing better prognostic performance over a ten-year follow-up period.

SPRS provided more valuable prognostic information than RS when combined with clinical treatment scores, suggesting it could help identify high-risk patients who may need more aggressive treatment while allowing low-risk patients to avoid unnecessary chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of StemPrintER with Oncotype DX Recurrence Score for predicting risk of breast cancer distant recurrence after endocrine therapy. Pece, S., Sestak, I., Montani, F., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]

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

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. [2020]

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

Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer. [2019]

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

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

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

Budget impact analysis of the DiviTum TKa assay in postmenopausal women with hormone receptor positive metastatic breast cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of nab-paclitaxel does not seem to be associated with SPARC expression in metastatic breast cancer. [2015]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

CD49f Can Act as a Biomarker for Local or Distant Recurrence in Breast Cancer. [2020]

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

Comparison of StemPrintER with Oncotype DX Recurrence Score for predicting risk of breast cancer distant recurrence after endocrine therapy. [2022]