Evaluating the Use of a Medication 'Switch' vs Guideline-directed Interventions for Relieving Side Effects of Aromatase Inhibitors Among Breast Cancer Patients

This is a two-arm, randomized-controlled trial with option for cross-over that compares the effectiveness of a 'switch' in hormonal therapy to guideline-directed intervention (GDI) for frontline management of side effects of aromatase inhibitors among breast cancer patients. Researchers plan to enroll post-menopausal patients with breast cancer who receive a first-time prescription for an aromatase inhibitor (AI). The anticipated enrollment is 124 participants to meet the goal of 62 evaluable participants.

Baseline symptom burden and quality of life will be assessed by validated surveys prior to starting AI. After starting AI, participants will be contacted at 2 weeks, and then every 4-weeks to screen for the development of bothersome side effects using a validated screening tool. The screening tool (FACIT GP5) is a single-item questionnaire that asks participants to respond to the following: "I am bothered by side effects of treatment," with answers ranging from 'Not at all' (score 0) to 'Very much' (score 4). Participants who score either a 3 or 4 on the FACIT GP5 will be considered to have a positive screening result. They will be randomized 1:1 to either receiving a different AI ('switch') or guideline-directed intervention (GDI). A 'GDI Book' was created for this study and will serve as a reference for selecting GDI treatment.

Participants who continue to have symptoms despite completing two lines of treatment within their assigned arm will be allowed to cross-over to the other treatment arm. Patients who are otherwise doing well in their treatment arm may stay in that treatment arm for the duration of the study. Cross-over is entirely optional.

Participants who do not develop side effects will continue to be monitored on study for up to 6 months. Participants with side effects that do not meet criteria for randomization (FACIT GP5 scores of 1 or 2) will receive standard of care at the discretion their treating provider.

Urine samples will be collected as a part of this study, to assess for adherence to endocrine therapy at the time of randomization, and at 3, 6 12 and 24 months after randomization. For participants that are not randomized, urine will be collected at 6, 12 and 24 months only. Urine samples will be collected during routine office visits when possible. Urine test results will remain anonymous (the treating provider will not know the results).

Inclusion criteria

• Histologic documentation of DCIS or invasive breast cancer by core needle or incisional biopsy.
• The DCIS or invasive cancer must be estrogen receptor alpha (ER)-positive
• The invasive cancer must be HER2-negative (IHC 0-1+, or with a FISH ratio of <1.8 if IHC is 2+ or if IHC has not been done)
• Clinical Stage I-III invasive breast cancer or DCIS
• Patients for whom adjuvant treatment with one of the following would be clinically indicated: letrozole, anastrozole, exemestane
• Patients who anticipate continuing with adjuvant endocrine therapy for a minimum of 2 years at the time of registration
• Women over 18 years of age who are post-menopausal, defined as last menstrual period >2 years prior to registration, or >1 year prior to registration with FSH and estradiol in post-menopausal range.
• Patients must meet the following clinical laboratory criteria:

• Absolute neutrophil count (ANC) >1,000/mm3 and platelet count > 75,000/mm3
• Total bilirubin <1.5 x the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN.
• Ability to give informed consent.

Exclusion criteria

• Prior endocrine therapy for any histologically-confirmed cancer or prevention of breast cancer in the last 10 years is not allowed.
• Any other adjuvant therapy for breast cancer. Exception: Bisphosphonate or denosumab treatment for metabolic bone issues are allowed.
• Patients who are prescribed tamoxifen as the first endocrine therapy rather than an aromatase inhibitor.
• Women who are pregnant or lactating.
• Prisoners.