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Endocrine Therapy in Treating Patients With HER2 Negative, Low Risk Breast Cancer

Phase 4
Withdrawn
Conditions
HER2/Neu Negative
Invasive Breast Carcinoma
Postmenopausal
Stage 0 Breast Cancer
Stage IA Breast Cancer
Interventions
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Registration Number
NCT03238703
Lead Sponsor
Fred Hutchinson Cancer Center
Brief Summary

This pilot clinical trial studies how well endocrine therapy works in treating patients with HER2 negative, low risk breast cancer. Estrogen can cause the growth of breast cancer cells. Endocrine therapies such as aromatase inhibitors and selective estrogen receptor modulators may lessen the amount of estrogen made by the body.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the conversion rate from a standard low-toxicity approach to guideline-directed therapy which includes surgery +/- radiation therapy as a result of progression of disease or patient/provider choice.

II. To examine factors that might differ between those who convert from the low-toxicity approach to the guideline-directed therapy and those do not convert.

SECONDARY OBJECTIVES:

I. To measure the safety and clinical effectiveness of systemic endocrine therapy used in a prolonged neoadjuvant fashion.

II. To evaluate the impact of risk-stratified care in Quality-Adjusted Life Years (QALY) and QALY gains.

III. To estimate the cost savings of indefinitely delaying surgery and radiation in favor of systemic endocrine therapy alone.

OUTLINE:

Patients receive exemestane orally (PO) once daily (QD), anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Female
Target Recruitment
Not specified
Inclusion Criteria
  • Able to provide written informed consent

  • A diagnosis of invasive breast cancer, with or without an in situ component, that is:

    • Originally identified by screening mammography
    • Characterized by standard diagnostic mammography +/- breast ultrasound
    • Clinically node negative
    • Confirmed by breast magnetic resonance imaging (MRI) in a facility that maintains active American College of Radiology (ACR) accreditation to be of low clinical stage (=< 2 cm, node negative, unifocal invasive)
    • Estrogen receptor (ER) and progesterone receptor (PR) Allred scored, each > 5/8
    • Her2 negative using American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines
    • ki-67 proliferation scored, < 20%
    • Clinical Nottingham grade 1 or 2
    • Scored on the MammaPrint 70-gene breast cancer recurrence assay as low risk
  • Prior to the discovery of the breast cancer, clinically post-menopausal as defined as: i) one or more years from last menses; or ii) history of oophorectomy; or iii) follicle stimulating hormone (FSH) test result in the post-menopause reference range

  • Willing to accept oral endocrine therapy with a third generation aromatase inhibitor (AI) or selective estrogen receptor modifier (SERM)

  • Willing to undergo routine surveillance with breast ultrasound and/or mammography

Exclusion Criteria
  • Known contraindication to aromatase inhibitor or SERM therapy
  • Pregnant at time of or within prior year of diagnosis
  • Clinically detected or palpable disease prior to biopsy in either breast or ipsilateral axilla
  • Prior history of invasive breast cancer or ductal breast carcinoma in situ (DCIS)
  • Prior use of aromatase inhibitor therapy apart from assisted reproduction
  • Prior use of SERM
  • Unmanaged/uncontrolled mental health disorder
  • Life expectancy < 6 months (m) for any cause
  • Biopsy confirmed multifocal, multicentric, or contralateral disease that is invasive or non-invasive
  • DCIS with focal invasion

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (AI, SERM)Laboratory Biomarker AnalysisPatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)Quality-of-Life AssessmentPatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)Questionnaire AdministrationPatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)Tamoxifen CitratePatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)Toremifene CitratePatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)ExemestanePatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)AnastrozolePatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (AI, SERM)LetrozolePatients receive exemestane PO QD, anastrozole PO QD, letrozole PO QD, tamoxifen citrate PO QD, or toremifene citrate PO QD at the discretion of the treating physician. Treatment continues in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Conversion from oral endocrine therapy for any reason to guideline-directed therapyUp to 5 years

Includes clinical or radiographic progression, patient preference, endocrine therapy intolerance or toxicity, or death from any cause. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Secondary Outcome Measures
NameTimeMethod
Advanced imaging (if performed on any subset of patients)Up to 5 years

Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Effect of comorbidity severity interactionUp to 5 years

Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Effects emanating from tertiary careUp to 5 years

Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Effect of ageUp to 5 years

Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Cost-effectiveness and patient-centeredness outcomes defined as financial toxicity and solubility, quality of life (physical, mental, emotional changes) on endocrine therapy, and, access to support servicesUp to 5 years

Comparisons will be made to historical benchmarks for similar patients managed in a conventional locoregional manner for early-stage breast cancer. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Effect of type of endocrine therapy type (selective estrogen receptor modifier versus aromatase inhibitor)Up to 5 years

Will be compared to a concurrent group of patients managed in the conventional manner with upfront surgery +/- radiation therapy followed by systemic endocrine therapy. Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Progression of disease while on primary endocrine therapy, as measured objectively by routine diagnostic breast imaging (mammography and/or ultrasound)Up to 5 years

Descriptive statistics will be summarized among all patients and patients within each of the two groups (stay with oral therapy vs conversion due to any causes).

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium

🇺🇸

Seattle, Washington, United States

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