Breast CancerPhase 2NCT03219476
Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Node-Negative Breast Cancer
A Phase 2 study testing Anastrozole, Letrozole and Exemestane in people with Breast Cancer and Invasive Breast Cancer, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Invasive Breast Cancer
- What is being tested?
- Anastrozole, Letrozole and Exemestane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2017to 20 Mar 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 19Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.
Read the 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.
- Conditions
- Breast Cancer, Invasive Breast Cancer
- Being tested
- Anastrozole, Letrozole, Exemestane, Tamoxifen
- Keywords
- aromatase inhibitor, breast cancer, estrogen receptor, progesterone receptor, endocrine-targeted therapy, Anti-estrogen therapy, HR+, HER2-negative, Neoadjuvant Treatment
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrozoleDrug
Also called Arimidex
1 mg once daily.
LetrozoleDrug
Also called Femara
2.5mg once daily.
ExemestaneDrug
Also called Aromasin
25 mg once daily.
TamoxifenDrug
Also called Soltamox
20 mg once daily.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At four weeks.
Secondary outcomes (2)
Number of Subjects Who Achieve Complete Radiographic Response.
This will be assessed by World Health Organization (WHO) criteria:
- Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy.
- Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy.
- No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated.
- Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).
Measured: At four weeks.
Number of Subjects Who Achieve a Partial Radiographic Response.
This will be assessed by World Health Organization (WHO) criteria:
- Complete Response (CR): The disappearance of all known disease, based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy.
- Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size), based on a comparison between the measurements at baseline and after four weeks of treatment with neoadjuvant therapy.
- No Change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of the lesion been demonstrated.
- Progressive Disease (PD): A 25% or greater increase in the total tumor size of the measurable lesions (calculated on the smallest diameter recorded over time).
Measured: At four weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start5 Feb 2017
- Primary completion4 Feb 2020
- Study completion20 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lubna Chaudhary, Medical College of Wisconsin
- Investigators
- Lubna Chaudhary, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219476
- Sponsor's protocol ID
- PRO30178
- Status last verified
- Apr 2025
- First submitted
- 12 Jul 2017
- Last updated
- 29 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37460683
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
- ClinicalTrials.gov ID
- NCT03219476
- Acronym / sponsor ID
- PRO30178
- Conditions
- Breast Cancer, Invasive Breast Cancer
- Keywords
- aromatase inhibitor, breast cancer, estrogen receptor, progesterone receptor, endocrine-targeted therapy, Anti-estrogen therapy, HR+, HER2-negative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 5 Feb 2017 (actual)
- Primary completion
- 4 Feb 2020 (actual)
- Study completion
- 20 Mar 2025 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 18 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant endocrine therapy treatment (physician's choice) | Experimental | Drug: Anastrozole, Drug: Letrozole, Drug: Exemestane, Drug: TamoxifenOnce 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnastrozoleAlso: Arimidex1 mg once daily. | Drug | Neoadjuvant endocrine therapy treatment (physician's choice) |
| LetrozoleAlso: Femara2.5mg once daily. | Drug | Neoadjuvant endocrine therapy treatment (physician's choice) |
| ExemestaneAlso: Aromasin25 mg once daily. | Drug | Neoadjuvant endocrine therapy treatment (physician's choice) |
| TamoxifenAlso: Soltamox20 mg once daily. | Drug | Neoadjuvant endocrine therapy treatment (physician's choice) |
Primary outcome
Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (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+ (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.
2 secondary outcomes
Number of Subjects Who Achieve Complete Radiographic Response.
Time frame: At four weeks.
Number of Subjects Who Achieve a Partial Radiographic Response.
Time frame: At four weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37460683Chaudhary 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lubna Chaudhary principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anastrozole, Letrozole and Exemestane in people with Breast Cancer and Invasive Breast Cancer, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy. (time frame: At four weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03219476, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.