Pre-Operative Window of Adjuvant Endocrine Therapy to Inform RT Decisions in Older Women With Early-Stage Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This is a prospective multisite exploratory study for women ≥ 65 years of age with early stage estrogen receptor positive (ER+) breast cancer. These individuals will be treated with 3 months of pre-operative endocrine therapy (pre-ET) with assessment of tolerance to the endocrine therapy by patient reported outcome (PRO) measures (patient surveys).

Detailed Description
-----------------
This single arm pilot study evaluates the use of pre-operative endocrine therapy in women with early stage ER+ breast cancer who are 65 years or older and are scheduled to have breast conservation surgery (BCS). The purpose of this study is to see if tolerance of pre-operative endocrine therapy helps inform decisions on whether or not to omit radiation. Participants will be treated with the novel approach of 3 months of pre-operative endocrine therapy, so that the participants and providers will have some indication of tolerance prior to making a decision about radiation omission. Tolerance of the endocrine therapy will be assessed by patient reported outcome (PRO) measures during neoadjuvant and adjuvant endocrine therapy treatment periods. Breast cancer participants and their surgical oncologists will be asked their preference regarding radiation therapy before starting endocrine therapy and again pre-operatively. They will make a determination regarding radiation therapy as per standard care. The hypothesis is that knowledge of tolerance of endocrine therapy will influence the decision by the patient and the surgical oncologist whether or not to elect radiation omission.

Official Title
-----------------
Pre-Operative Window of Adjuvant Endocrine Therapy to Inform Radiation Therapy Decisions In Older Women With Early-Stage Breast Cancer

Conditions
-----------------
Breast Cancer Female

Intervention / Treatment
-----------------
* Drug: tamoxifen, letrozole, anastrozole, or exemestane
* Behavioral: Patient reported outcomes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (Summary): ECOG performance status 0-2 Diagnosed with anatomic stage I, ER positive, PR positive or negative, and HER2 non amplified invasive breast cancer and clinically negative nodes; any invasive breast cancer histologic subtype may be enrolled Tumor size ≤ 2 cm Patient has elected BCS as surgical choice Eligible to receive tamoxifen or an aromatase inhibitor Ability to take oral medication and be willing to adhere to the endocrine therapy for the 3 month period prior to BCS Exclusion Criteria (Summary): Prior or current use of endocrine therapy for breast cancer History of ipsilateral breast radiation Pregnancy or lactation Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Current or planned use of a strong CYP2D6 inhibitor (e.g. Fluoxetine, Paroxetine) and is not able to receive an endocrine therapy agent that does not use the CYP2D6 pathway

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Pilot, 1 arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-operative endocrine therapy<br>All participants enrolled to the study will receive 3 months of pre-operative endocrine therapy (e.g. tamoxifen or aromatase inhibitors (AIs) such as letrozole, anastrozole, or exemestane). The choice and dose of endocrine therapy will be at the discretion of the treating medical oncologist. | Drug: tamoxifen, letrozole, anastrozole, or exemestane<br>* choice and dose of neoadjuvant endocrine therapy at the discretion of the treating medical oncologist<br>* Other names: Endocrine therapy;Behavioral: Patient reported outcomes<br>* Questionnaire inquiries include the following: how cancer affects daily living beliefs about medicines and sensitivity to medicine symptoms adherence to endocrine therapy general health and well being depression and anxiety preference regarding radiation therapy<br>* Other names: surveys, questionnaires;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in participant preference for adjuvant radiation treatment | Change in participant response to question regarding preference for adjuvant radiation treatment | up to 6 months | 
| Change in surgeon preference for adjuvant radiation treatment | Change in surgical oncologist response to question regarding preference for adjuvant radiation treatment | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health related quality of life surveys as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | Health related quality of life will be assessed using the EORTC QLQ-C30 and QLQ-BR23. | Through 24 months after start of adjuvant treatment period | 
| General symptom burden as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | General symptom burden will be assessed using the Breast Cancer Prevention Trial Symptom Checklist. | Through 24 months after start of adjuvant treatment period | 
| Illness perception as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | Illness perception will be assessed using the Brief Illness Perception Questionnaire. | Through 24 months after start of adjuvant treatment period | 
| Beliefs about medicine as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | Beliefs about medicine will be assessed using the Beliefs about Medicines Questionnaire. | Through 24 months after start of adjuvant treatment period | 
| Perceived sensitivity to medicine as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | Perceived sensitivity to medicine will be assessed using the Perceived Sensitivity to Medicine Scale. | Through 24 months after start of adjuvant treatment period | 
| Breast cancer beliefs as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS | Breast cancer beliefs will be assessed using the UVA Breast Cancer Belief Survey, a novel series of questions regarding patient beliefs about breast cancer and breast cancer medications. | Through 24 months after start of adjuvant treatment period | 
| Treatment decision as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS. | Treatment decision will be assessed using the Treatment Decision Survey, a novel series of questions regarding why subjects decide to have or not to have radiation therapy, and why or why not to restart endocrine therapy. | up to 90 days after surgery, chemotherapy completion, or RT completion, whichever is later | 
| Perceptions related to medical choices as predictive measure for endocrine therapy adherence and to assess effect of pre-ET on decision outcomes for adjuvant therapy after BCS. | Subjects' perceptions related to their medical choices will be assessed using the Decisional Conflict Scale and the Decision Regret Scale. | Through 24 months after start of adjuvant treatment period | 
| Depression and anxiety as predictive measure for endocrine therapy adherence | Depression and anxiety will be assessed using the Center for Epidemiologic Studies Depression Scale Revised. | Through 24 months after start of adjuvant treatment period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, endocrine therapy, radiation, letrozole, anastrozole, exemestane, tamoxifen, survey, questionnaire, geriatric