Breast Cancer Index (BCI) Registry

The purpose of the Breast Cancer Index (BCI) Registry study is to conduct a large scale, population-based prospective registry to evaluate long-term clinical outcome, clinical impact, medication adherence and quality of life in hormone receptor positive (HR+) early-stage breast cancer patients receiving BCI testing as part of routine clinical care to inform extended endocrine therapy.

The BCI Registry is designed as a large-scale data registry and biospecimen repository to evaluate the clinical outcome of hormone receptor positive (HR+) early-stage breast cancer patients completing primary adjuvant endocrine therapy and are considering extended endocrine treatment. The impact of BCI test results on extended endocrine therapy decision-making and clinical use patterns will be characterized. Extended endocrine therapy-specific medication adherence will be assessed annually. Primary tumor tissue will be collected for scientific research purposes including molecular profiling and for correlative studies. The sample size will consist of approximately 3,000 subjects across 30-50 sites in the United States.

The BCI registry will recruit patients with HR+ stage I to III breast cancer following an initial 4-7 years of adjuvant endocrine therapy that will have BCI testing performed as part of routine clinical care and meet the inclusion/exclusion criteria. After signing the informed consent form (ICF) during screening, physicians and patients will complete the pre-test Decision Impact Questionnaire. Upon ordering BCI by the treating physician, primary tumor tissue obtained from the patient during previous breast-conserving surgery or mastectomy will be requested by Biotheranostics to perform BCI testing at Biotheranostics' CLIA certified and CAP accredited clinical laboratory in San Diego, CA. Following BCI testing, the physician will share and discuss the BCI results with their patients and recommend to either stop or extend endocrine therapy for an additional 5 years. The impact of the BCI test results on extended endocrine therapy decision-making will be assessed using the post-test Decision Impact Questionnaire, which will be completed by both physicians and patients. In addition, medication adherence will be evaluated in patients that are recommended for or elect to continue treatment to complete 10 years of adjuvant endocrine therapy.

BCI reports both a prognostic and predictive result and has been shown to significantly stratify patients based on the risk of late distant recurrence as well as to predict the likelihood of benefit from endocrine therapy in multiple prospective-retrospective studies within randomized controlled trial cohorts. The BCI registry study will determine the long-term outcome and BCI test performance to add prospective validation for the prognostic and predictive capabilities of BCI. In this context, the impact of BCI test results on treatment decision-making and subsequently prescribed treatments will be characterized.

Analysis of BCI test performance with long-term outcome will be performed by Kaplan-Meier analysis with log-rank test to assess the statistical significance of the risk stratification by BCI risk groups. Cox proportional hazards regression will be used to derive the hazard ratios (HR) and the associated 95% confidence intervals for the comparison of BCI risk groups. Univariate and multivariate analysis adjusting for clinical factors such as age, tumor size, grade, and treatment background (adjuvant endocrine therapy and chemotherapy) will be conducted. Descriptive statistics will be used to evaluate the decision-impact and medication adherence scores of patients enrolled in the study.

Each participating site will maintain appropriate medical and research records for this trial, in compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional requirements for the protection of confidentiality of subjects. As part of participating in a Biotheranostics-sponsored study, each site will permit authorized representatives of the sponsor and regulatory agencies to examine clinical records for the purposes of quality assurance reviews, audits and evaluation of the study progress. The clinical trial manager will be in regular contact with the site research leader to check on progress and address any queries that they may have. Sites may be suspended from participating in the registry in the event of serious and persistent non-compliance with the protocol and/or Good Clinical Practice. Any major problems identified will be reported to the Trial Management Team and if necessary, the relevant regulatory bodies.

Eligibility Criteria:
Inclusion Criteria:

* Early stage (I, II or III) female breast cancer patients, who have completed 4-7 years of primary adjuvant endocrine therapy
* Patient was diagnosed with invasive breast carcinoma (ductal, lobular, or mixed ductal/lobular).
* The primary tumor was hormone receptor positive (HR+), i.e. estrogen receptor-positive and/or progesterone receptor-positive.
* The primary tumor was HER2 negative or positive and node-negative or node-positive with 1-3 positive lymph nodes.
* Subject has pre-treatment breast tumor tissue \[formalin fixed and paraffin embedded (FFPE)\] from a previous breast-conserving surgery, mastectomy or core needle biopsy available for testing by the Sponsor.

Exclusion Criteria:

* Patient has distant metastatic disease (M1).
* Patient was diagnosed with metaplastic breast cancer, carcinosarcoma, sarcoma, neuroendocrine carcinoma, adenoid cystic carcinoma, or phyllodes tumor.