Test Description

BCI is a multi-gene quantitative RT-PCR assay that provides two outputs based on unique gene signatures: BCI Prognostic and BCI Predictive. BCI Prognostic provides information regarding a patient’s individualized risk for distant recurrence, while BCI Predictive provides prediction of likelihood of benefit from extended (>5 years) endocrine therapy.1-3

BCI Prognostic was developed from the combination of two gene expression-based biomarkers: 1) the HOXB13:IL17BR ratio (H/I), which is associated with tumor responsiveness to endocrine therapy in breast cancer;5-7 and 2) Molecular Grade Index (MGI), which consists of the average expression of five cell cycle-associated genes (BUB1B, CENPA, NEK2, RACGAP1 and RRM2) and provides quantitative and objective molecular assessment of tumor grade and proliferative status.8 BCI Predictive is an endocrine response biomarker based on the HoxB13/IL17BR ratio (H/I).3,5-7

Methodology

BCI is a real-time RT-PCR assay that measures the expression of H/I, MGI and four normalization genes. RNA is extracted from macrodissected formalin-fixed paraffin embedded tumor samples, converted to cDNA by reverse transcribing the extracted RNA, and quantitative PCR is performed using TaqmanTM technology. The BCI Prognostic Score is calculated by combining these values into a continuous index.1 Results are presented as a score ranging from 0 to 10 and are categorized into levels of risk: for risk of late (post-5 year) distant recurrence, Low risk = BCI < 5.0825 and High risk = BCI ≥ 5.0825; for risk of overall (0-10 year) distant recurrence, Low risk = BCI <5.0825, Intermediate risk =≥5.0825 to 6.5025, and High risk = BCI >6.5025. BCI Predictive (H/I) is reported as either High or Low, determined by a previously validated cut-point.6

Clinical Evidence

BCI Prognostic: BCI Prognostic provides an individualized estimate for a patient’s risk for distant recurrence in the late (5-10 years post-diagnosis) and overall (0-10 years post-diagnosis) timeframes.1,2 The BCI risk of distant recurrence is generated based on analysis of gene expression from the submitted tumor sample. The corresponding individualized risks of recurrence are calculated based on the relationship between BCI score and breast cancer recurrence in a population ER+, node-negative patients treated with adjuvant tamoxifen in a validation study using the prospective randomized Stockholm clinical trial.1 The risk of distant recurrence increases continuously with increasing BCI score. For both timeframes (late and overall), patient risk is also reported as a risk category based on pre-specified cut points. In clinical studies, the BCI Intermediate risk had a statistically similar risk of late (5-10 year) recurrence as the BCI High risk group;1,2 thus risk categories for risk of late recurrence are reported as Low or High risk only. BCI Prognostic has been validated in 3 independent cohorts.1,2 Note that Risk of Recurrence is based on analysis of BCI Prognostic in the Stockholm clinical study1 and applies only to LN- patients. LN+ patients should be considered at high risk of recurrence.2

BCI Predictive: BCI Predictive provides a prediction of likelihood of benefit from extended (>5 years) endocrine therapy.3 Patient results for this test are categorized as either High or Low Likelihood of Benefit. The ability of BCI to predict likelihood of benefit from extended (post-5 year) endocrine therapy was validated in the NCIC CTG MA.17 trial.3,4 Patients categorized as High BCI Predictive were more likely to benefit from extended endocrine therapy and had a statistically significant decrease in cancer recurrence (absolute benefit of 16.5%; p=0.007). Patients categorized as Low BCI Predictive had no statistically significant decrease in cancer recurrence when treated with extended endocrine therapy (p=0.35).

Intended Uses and Limitations

The Breast Cancer Index (BCI) Risk of Recurrence & Extended Endocrine Benefit Test is intended for use in patients diagnosed with estrogen receptor-positive (ER+), lymph node-negative (LN-) or lymph node positive (LN+; with 1-3 positive nodes) early-stage, invasive breast cancer, who are distant recurrence-free. BCI provides: 1) a quantitative assessment of the likelihood of both late (post-5 years) and overall (0-10 year) distant recurrence following an initial 5 years of endocrine therapy (LN- patients) or 5 years of endocrine therapy plus adjuvant chemotherapy (LN+ patients), and 2) prediction of likelihood of benefit from extended (>5 year) endocrine therapy. BCI results are adjunctive to the ordering physician’s workup; treatment decisions require correlation with all other clinical findings.

This test was developed and its performance characteristics determined by Biotheranostics, Inc. lt has not been cleared or approved by the U.S. Food and Drug Administration. This test is used for clinical purposes. lt should not be regarded as investigational or for research. How this information is used to guide patient care is the responsibility of the physician. Biotheranostics is certified under the Clinical Laboratory lmprovement Amendments of 1988 to perform high complexity clinical laboratory testing.

References
  1. Zhang Y, et al. Clin Cancer Res. 2013;19:4196-205.
  2. Sgroi DC, et al. Lancet Oncol. 2013;14:1067-76.
  3. Sgroi D, et al. J Natl Cancer Inst. 2013;105:1036-42.
  4. Goss PE, et al. N Engl J Med. 2003;349:1793-802.
  5. Ma XJ, et al. Cancer Cell 2004; 5:607‐16.
  6. Ma XJ, et al. J Clin Oncol 2006; 24:4611‐9.
  7. Wang Z, et al. Clin Cancer Res 2007; 13:6327‐34.
  8. Ma XJ, et, al. Clin Cancer Res 2008; 14:2601‐8
Breast Cancer Index Intended Use and Limitations

The Breast Cancer Index (BCI) Risk of Recurrence & Extended Endocrine Benefit Test is intended for use in patients diagnosed with estrogen receptor-positive (ER+), lymph node-negative (LN-) or lymph node positive (LN+; with 1-3 positive nodes) early-stage, invasive breast cancer, who are distant recurrence-free. BCI provides: 1) a quantitative assessment of the likelihood of both late (post-5 years) and overall (0-10 year) distant recurrence following an initial 5 years of endocrine therapy (LN- patients) or 5 years of endocrine therapy plus adjuvant chemotherapy (LN+ patients), and 2) prediction of likelihood of benefit from extended (>5 year) endocrine therapy. BCI results are adjunctive to the ordering physician’s workup; treatment decisions require correlation with all other clinical findings.

This test was developed and its performance characteristics determined by Biotheranostics, Inc. lt has not been cleared or approved by the U.S. Food and Drug Administration. This test is used for clinical purposes. lt should not be regarded as investigational or for research. How this information is used to guide patient care is the responsibility of the physician. Biotheranostics is certified under the Clinical Laboratory lmprovement Amendments of 1988 to perform high complexity clinical laboratory testing.