Biomarker-Guided Neoadjuvant Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Nusayba Bagegni, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Aromatase inhibitors

Disqualifiers: Inflammatory breast cancer, Metastatic disease, Bilateral breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 6 months

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for selecting breast cancer treatments using specific biomarkers (biological indicators). The aim is to determine if this approach can improve treatment outcomes for postmenopausal women with certain types of breast cancer, with a particular focus on Black patients. Participants may receive hormone therapy, such as Anastrozole (also known as Arimidex), chemotherapy, or a combination, depending on their cancer's characteristics. Those with ER-positive, HER2-negative breast cancer that can be surgically removed after treatment, and who have a tumor size of at least 2 cm, might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in breast cancer care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study used anastrozole to treat early-stage hormone receptor-positive breast cancer. Most patients tolerate it well, though some may experience joint and muscle pain, menopause-like symptoms, and mood changes such as depression.

Research has shown that combining anthracycline and/or taxane-based treatments can improve survival rates. However, these drugs may cause more intense side effects, including nausea, tiredness, and hair loss. While these side effects are common with chemotherapy, medical support can help manage them.

Both treatments have been safely used in many patients, but discussing any concerns with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a tailored approach to neoadjuvant therapy for breast cancer, which could lead to more personalized and effective treatments. Unlike the traditional one-size-fits-all method, this approach uses biomarkers like Ki67 and genetic tests such as Oncotype DX RS and PAM50 to guide treatment decisions. By distinguishing between low-risk, high-risk endocrine-sensitive, and high-risk endocrine-resistant groups, the trial aims to optimize therapy based on individual tumor characteristics. This could potentially improve outcomes while minimizing unnecessary side effects from more aggressive treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Studies have shown that anastrozole, which participants in this trial may receive, can significantly shrink tumors in breast cancer patients. One study found that tumor sizes decreased by up to 80.5% with anastrozole. This medication also effectively prevents breast cancer in women at high risk, reducing the chance of recurrence by 41% and lowering the risk of death by 34%.

In this trial, participants in the high-risk endocrine-resistant group will receive combination treatments with anthracycline and taxane. Research has supported these combinations for breast cancer, showing a 14% lower chance of recurrence compared to other therapies. Studies indicate that these combinations are strong options for reducing cancer spread before surgery. ^{3 6 7 8 9}

Who Is on the Research Team?

Nusayba Bagegni, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for postmenopausal women at least 18 years old with stage II/III ER-positive, HER2-negative breast cancer. Participants must have a tumor size ≥2 cm if lymph node negative, or any size with nodal involvement. They should be able to undergo MRI and tolerate neoadjuvant aromatase inhibitor therapy and chemotherapy.

Inclusion Criteria

My cancer is HER2 negative as confirmed by specific tests.

My breast cancer is ER-positive, HER2-negative, and aims for surgery after initial treatment.

I am fully active or can carry out light work.

Exclusion Criteria

Uncontrolled intercurrent illness that would limit compliance with study requirements

Any uncontrolled medical condition that in the opinion of the Investigator would pose a risk to participant safety or interfere with study participation or interpretation of individual participant results

My cancer has returned or spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant treatment with anastrozole for approximately 6 months, with risk category assessment and potential escalation to chemotherapy for high-risk endocrine-resistant group

6 months

Baseline MRI, Week 4 assessment, post-treatment MRI

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Combination anthracycline and/or taxane based treatment

Trial Overview The study tests a biomarker-driven approach using assays like VENTANA MIB-1 Ki67, Oncotype DX®, and PAM50 Prosigna to guide treatment selection in breast cancer patients. It compares the effectiveness of Anastrozole alone versus combined anthracycline/taxane treatments.

How Is the Trial Designed?

Group I: Low-risk group Experimental Treatment 4 Interventions

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw for research purposes at Week 4 (no breast tumor biopsy at this time point) and continue to receive 5 additional 28-day cycles of anastrozole. * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Group II: High-risk endocrine-sensitive group Experimental Treatment 4 Interventions

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 ≤10% (the high-risk endocrine-sensitive group) will continue to receive 5 additional 28-day cycles of anastrozole. * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Group III: High-risk endocrine-resistant group Experimental Treatment 4 Interventions

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 \>10% (the high-risk endocrine-resistant group) will receive escalated therapy with \~5-6 additional months of standard of care chemotherapy (combination anthracycline- and/or taxane-based at the discretion of their physician). * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Swim Across America

Collaborator

Trials

11

Recruited

410+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Swim Across America

Collaborator

Trials

8

Recruited

290+

Published Research Related to This Trial

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

Both neoadjuvant chemotherapy regimens, adriamycin and docetaxel (AD) and adriamycin, cyclophosphamide followed by paclitaxel (AC-T), showed similar effectiveness in treating locally advanced breast cancer, with overall response rates of 75.7% and 80.9% respectively.

However, the AC-T regimen was found to be more tolerable, as patients in the AD group experienced significantly higher rates of severe hematologic toxicities, including grade 3/4 neutropenia and neutropenic fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of neoadjuvant adriamycin and docetaxel versus adriamycin, cyclophosphamide followed by paclitaxel in patients with operable breast cancer. Hong, WS., Jeon, JY., Kang, SY., et al.[2021]

In a study of 26 postmenopausal women with hormone receptor-positive breast cancer, the combination of neoadjuvant chemotherapy and concurrent anastrozole resulted in a clinical complete response in 17.9% of patients and a clinical partial response in 57.1%.

The pathological complete response rate was 11.5%, indicating that the combined chemo-endocrine therapy was effective, but further research is needed to determine the specific contributions of the aromatase inhibitor versus the chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. Watanabe, N., Ootawa, Y., Kodama, K., et al.[2018]

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

In a study involving 668 postmenopausal women with advanced breast cancer, anastrozole was found to be as effective as tamoxifen, with similar median time to progression (8.2 months for anastrozole vs. 8.3 months for tamoxifen).

Anastrozole demonstrated a lower incidence of side effects, such as thromboembolic events (4.8% vs. 7.3%) and vaginal bleeding (1.2% vs. 2.4%), suggesting it may be a safer first-line treatment option for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. Bonneterre, J., Thürlimann, B., Robertson, JF., et al.[2022]

Anastrozole, a highly specific aromatase inhibitor, has emerged as a potentially better tolerated and more effective treatment for postmenopausal patients with hormone-sensitive breast cancer compared to tamoxifen, which has safety and tolerability issues.

The ongoing Arimidex, Tamoxifen, Alone or in Combination trial indicates that anastrozole is an effective and well-tolerated option for adjuvant endocrine treatment in early breast cancer, suggesting its potential role in chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anastrozole in adjuvant therapy for postmenopausal patients. Buzdar, AU.[2019]

In a study of 97 postmenopausal women with hormone receptor-positive breast cancer, neoadjuvant anastrozole showed a significantly higher histopathological response rate (35.4%) compared to tamoxifen (12.2%), indicating greater effectiveness in shrinking tumors before surgery.

The study also found that anastrozole led to more changes in estrogen and progesterone receptor status, with 5 out of 40 patients becoming ER-negative and 16 out of 17 becoming PgR-negative, suggesting a stronger impact on hormone receptor activity compared to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histopathological assessment of anastrozole and tamoxifen as preoperative (neoadjuvant) treatment in postmenopausal Japanese women with hormone receptor-positive breast cancer in the PROACT trial. Kurosumi, M., Takatsuka, Y., Watanabe, T., et al.[2022]

Anastrozole is more effective than tamoxifen in improving disease-free survival and reducing tumor recurrence in postmenopausal women with hormone receptor-positive early breast cancer, as shown in the ATAC trial with significant relative risk reductions of 17% and 19%.

Anastrozole has a better safety profile compared to tamoxifen, with lower rates of side effects such as vaginal bleeding, hot flushes, and thromboembolic events, while both treatments had similar impacts on patient quality of life during the first two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: in early breast cancer. Wellington, K., Faulds, DM.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10873072/

The effects of neoadjuvant anastrozole (Arimidex) on tumor ... The median reductions in tumor volumes as measured by ultrasound for those patients with a measurable 12-week assessment were 80.5 and 69.6% for anastrozole (1 ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext

Use of anastrozole for breast cancer prevention (IBIS-II) Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2000.18.22.3748

Anastrozole Versus Tamoxifen as First-Line Therapy for ... The data from this study show that anastrozole is at least as effective as tamoxifen as first-line therapy of advanced breast cancer in ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2104162

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... No between-group difference was noted for overall survival at 8 years (87.5% in the 2-year group and 87.3% in the 5-year group), with a hazard ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... The results of the Oxford meta-analyses3,4 have demonstrated significant reduction in both disease recurrence (41%) and breast cancer specific mortality (34%) ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/anastrozole-oral-route/description/drg-20061868

Anastrozole (oral route) - Side effects & dosage Anastrozole is used to treat early hormone receptor-positive breast cancer. It is also used for first-line treatment of hormone receptor-positive or hormone ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf

Arimidex (anastrozole) tablet label - accessdata.fda.gov For patients with advanced breast cancer, ARIMIDEX should be continued until tumor progression. ... There is, in this data, no indication that ARIMIDEX 10 mg is.

8. breastcancernow.org breastcancernow.org/about-breast-cancer/treatment/hormone-endocrine-therapy/side-effects-of-anastrozole-arimidex

Side effects of anastrozole (Arimidex) Common side effects of anastrozole include: Aching or pain in the joints and muscles; Menopausal symptoms; Low mood and depression; Difficulty sleeping ...

9. macmillan.org.uk macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/anastrozole

Anastrozole Anastrozole is a hormonal therapy drug. It is usually only used after you have been through menopause. It is used to: reduce the risk of early breast cancer ...