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

NCT03219476 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO30178
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer; Invasive Breast Cancer

Keywords

aromatase inhibitor; breast cancer; estrogen receptor; progesterone receptor; endocrine-targeted therapy; Anti-estrogen therapy; HR+; HER2-negative; Neoadjuvant Treatment

Outcome Measures

Primary Outcomes (1)

• Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.

  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+ (up to 25% of cells stained), it's called "HER2 negative." If the score is 2+ (approximately 50% of cells stained), it's called "borderline." A score of 3+ (approximately 75% or more of cells stained) is called "HER2 positive." Upregulation means increased staining from a prior observation; Downregulation means decreased staining from a prior observation; and No Change means similar staining from a prior observation.

  At four weeks.

Secondary Outcomes (2)

• Number of Subjects Who Achieve Complete Radiographic Response.

  At four weeks.

• Number of Subjects Who Achieve a Partial Radiographic Response.

  At four weeks.

Study Arms (1)

Neoadjuvant endocrine therapy treatment (physician's choice)

EXPERIMENTAL

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; Drug: Letrozole; Drug: Exemestane; Drug: Tamoxifen

Interventions

Anastrozole DRUG

1 mg once daily.

Also known as: Arimidex

Neoadjuvant endocrine therapy treatment (physician's choice)

Letrozole DRUG

2.5mg once daily.

Also known as: Femara

Neoadjuvant endocrine therapy treatment (physician's choice)

Exemestane DRUG

25 mg once daily.

Also known as: Aromasin

Neoadjuvant endocrine therapy treatment (physician's choice)

Tamoxifen DRUG

20 mg once daily.

Also known as: Soltamox

Neoadjuvant endocrine therapy treatment (physician's choice)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Cis females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Chaudhary LN, Jorns JM, Sun Y, Cheng YC, Kamaraju S, Burfeind J, Gonyo MB, Kong AL, Patten C, Yen T, Cortina CS, Carson E, Johnson N, Bergom C, Tsaih SW, Banerjee A, Wang Y, Chervoneva I, Weil E, Chitambar CR, Rui H. Frequent upregulation of HER2 protein in hormone-receptor-positive HER2-negative breast cancer after short-term neoadjuvant endocrine therapy. Breast Cancer Res Treat. 2023 Oct;201(3):387-396. doi: 10.1007/s10549-023-07038-3. Epub 2023 Jul 17.

  PMID: 37460683 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; Letrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Lubna Chaudhary
• Organization: Medical College of Wisconsin

lchaudhary@mcw.edu

414-805-4600

Study Officials

• Lubna Chaudhary

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 17, 2017
• Study Start: February 5, 2017
• Primary Completion: February 4, 2020
• Study Completion: March 20, 2025
• Last Updated: April 29, 2025
• Results First Posted: October 18, 2022

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)