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Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Node-Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03219476
Recruitment Status : Active, not recruiting
First Posted : July 17, 2017
Last Update Posted : September 22, 2021
Information provided by (Responsible Party):
Lubna Chaudhary, Medical College of Wisconsin

Brief Summary:
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.

Condition or disease Intervention/treatment Phase
Breast Cancer Invasive Breast Cancer Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Tamoxifen Phase 2

Detailed Description:

STUDY RATIONALE: Patients with hormone receptor (HR)+, HER2- node-negative breast cancers generally undergo surgical resection upfront, followed by adjuvant chemotherapy, if needed, in addition to adjuvant endocrine therapy. Because endocrine therapy is primarily delivered in the postoperative setting, the ability to assess the tumor response to this treatment modality is lost and very difficult to assess. This study offers the unique opportunity to assess the responsiveness of breast tumors to endocrine therapy while the tumors are still in vivo by treating patients with endocrine therapy before surgery and assessing molecular changes with treatment. By comparing pre- and post-treatment levels of molecular markers in individual tumors, the team expects to identify predictors of responsiveness to existing agents and identify new candidate therapeutic targets.

PRIMARY OBJECTIVE: The primary objective is to determine the frequency of increased HER family of receptor tyrosine kinases protein expression in tumors, following treatment with neoadjuvant endocrine therapy and their correlation with Ki-67 tumor responses. The team will measure cancer cell protein levels of growth factor receptors of the human epidermal growth factor receptor (HER) family before and after neoadjuvant endocrine therapy. The data will be used to inform a future randomized trial of combined endocrine and the most promising anti-HER targeted therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
Actual Study Start Date : February 5, 2017
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. Choice of endocrine therapy (aromatase inhibitors or tamoxifen) would be decided by medical oncologist, following a review of the patient's medical history and menstrual status. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
Drug: Anastrozole
1 mg once daily.
Other Name: Arimidex

Drug: Letrozole
2.5mg once daily.
Other Name: Femara

Drug: Exemestane
25 mg once daily.
Other Name: Aromasin

Drug: Tamoxifen
20 mg once daily.
Other Name: Soltamox

Primary Outcome Measures :
  1. Change in cancer cell protein levels of HER family members (HER1-4) following neoadjuvant endocrine therapy. [ Time Frame: At four weeks. ]
    ImmunoHistoChemistry (IHC) will be used. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it's called "HER2 negative." If the score is 2+, it's called "borderline." A score of 3+ is called "HER2 positive."

Secondary Outcome Measures :
  1. Number of subjects who achieve complete radiographic response. [ Time Frame: At four weeks. ]
    This will be assessed by World Health Organization (WHO) criteria.

  2. Number of subjects who achieve a partial radiographic response. [ Time Frame: At four weeks. ]
    This will be assessed by World Health Organization (WHO) criteria.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Cis females.
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female; age ≥18 years.
  • Pathologically proven diagnosis of invasive breast cancer, clinically stage I-II.
  • Clinically lymph node negative, confirmed by clinical exam and/or ultrasound imaging.
  • Estrogen- and/or progesterone-receptor-positive tumor, defined ≥1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
  • HER2/neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Pretreatment evaluations (minimum diagnostic workup) within 28 days prior to study
  • Qualify for anti-endocrine treatment (per medical oncologist).
  • Informed consent provided.
  • If history of contralateral breast cancer, patient completed all treatment two years prior
  • No treatment for this breast cancer or any malignancy within two years (except non-melanomatous skin cancer, carcinoma in situ of the cervix and contralateral breast cancer)
  • Using adequate methods of contraception; negative pregnancy test.
  • No strong CYP2D6 inhibitors.
  • Adequate organ function with baseline lab values.

    • Absolute neutrophil count (ANC) ≥ 1500/µL.
    • Hemoglobin (Hb) ≥ 9g/dL.
    • Platelet count ≥ 100,000/µL.
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
    • Serum bilirubin within ≤ 1.5 x ULN.

Exclusion Criteria:

  • American Joint Committee on Cancer (AJCC) clinical T4, N1-3 or M1, breast cancer.
  • Synchronous non-breast malignancy (exceptions include non-melanomatous skin cancer, carcinoma in situ of the cervix).
  • Purely noninvasive breast cancer (i.e., ductal carcinoma in situ, lobular carcinoma in situ).
  • Men with breast cancer.
  • Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent.
  • Pregnant or lactating women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03219476

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United States, Wisconsin
Froedtert Hospital
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
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Principal Investigator: Lubna Chaudhary Medical College of Wisconsin
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Responsible Party: Lubna Chaudhary, Associate Professor, Medical College of Wisconsin Identifier: NCT03219476    
Other Study ID Numbers: PRO30178
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Lubna Chaudhary, Medical College of Wisconsin:
aromatase inhibitor
breast cancer
estrogen receptor
progesterone receptor
endocrine-targeted therapy
Anti-estrogen therapy
Neoadjuvant Treatment
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents