Biomarker-Guided Neoadjuvant Therapy for Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Nusayba Bagegni, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study aims to utilize a novel biomarker-driven approach to guide neoadjuvant treatment selection. It is the hypothesis that this will improve clinical response for postmenopausal women with clinical stage II/III ER-positive, HER2-negative breast cancer and identify those who may not require neoadjuvant chemotherapy, with a primary focus on outcomes in Black patients.

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.

What data supports the effectiveness of the drug Anastrozole for breast cancer treatment?

Research shows that Anastrozole is more effective than Tamoxifen in improving disease-free survival and reducing the risk of tumor recurrence in postmenopausal women with early-stage breast cancer. It also has a better safety profile, with fewer side effects like vaginal bleeding and hot flushes. ^{1 2 3 4 5}

Is anastrozole generally safe for humans?

Anastrozole, also known as Arimidex, has been shown to be generally well-tolerated and safe for postmenopausal women with breast cancer, with fewer gynecologic side effects compared to tamoxifen. ^{1 4 6 7 8}

How is the drug Anastrozole combined with anthracycline and taxane different from other breast cancer treatments?

This treatment is unique because it combines Anastrozole, a drug that lowers estrogen levels, with chemotherapy drugs like anthracyclines and taxanes, which attack cancer cells directly. This combination targets hormone-sensitive breast cancer more effectively by using both hormonal and chemotherapy approaches, potentially improving outcomes compared to using these treatments separately. ^{3 4 5 9 10}

Research Team

Nusayba Bagegni, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Anastrozole (Hormone Therapy)
• Combination anthracycline and/or taxane based treatment (Chemotherapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

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+

Findings from Research

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 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 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]

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]

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]

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 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]

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]

References

1. England 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. [2022]

2. Germany 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. [2022]

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

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

4. United States 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. [2022]

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

Anastrozole: in early breast cancer. [2018]

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

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. [2018]

7. United States 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. [2022]

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

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

9. Japan pubmed.ncbi.nlm.nih.gov

Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. [2018]

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

Comparison of neoadjuvant adriamycin and docetaxel versus adriamycin, cyclophosphamide followed by paclitaxel in patients with operable breast cancer. [2021]