TEST:

Breast Cancer Index®

"Four new studies regarding the Breast Cancer Index (BCI) test will be presented at the 2024 San Antonio Breast Cancer Symposium (SABCS). Among these studies, initial data will be premiered investigating the potential role of the BCI test to identify postmenopausal women with hormone-receptor positive (HR+), early-stage, node-negative disease who are at minimal risk of experiencing a distant recurrence. Full results will be shared during Poster Session 1 on December 11, 2024, at 12:30 p.m. CT [#P1-09-13]....Three additional investigational studies being presented at the SABCS conference related to the Breast Cancer Index test..."

Conclusions- We were able to confirm in this contemporary group the comparison findings of the 2016 TransATAC analysis that there can be a significant disparity between early recurrence risk as determined by the standard 30 or 70 gene expression profiles, and the BCI risk of late recurrence, as well as the potential benefit of longer term hormonal therapy in these patients. This suggests that the 11 gene BCI assay may be able to help patients decrease risk of late recurrences and avoid also unnecessary treatment related toxicity

The updates to the NCCN and ASCO Guidelines led to a significant increase in utilization of the BCI test at all City of Hope sites of practice. We anticipate that the Epic software enhancement will lead to further utilization of the BCI test.

Conclusions BCI (H/I) and BCI risk scores exhibited no correlation with BMI categories. BCI (H/I) consistently stratified patients into low- and high-likelihood for extended endocrine benefit independent of BMI categories, suggesting that BMI is not a reliable indicator for predicting recurrence risk or benefit from EET.

Performance of the adjusted BCI model was initially assessed in the tamoxifen-treated arm of the Stockholm trial (n=317) and then evaluated in a cohort from NCR (n=1247)... The current study demonstrates that an adjusted BCI minimal risk cut-point may identify postmenopausal women with HR+ N0 breast cancer, who are at sufficiently low risk of DR and thus unlikely to derive clinically meaningful benefit from adjuvant ET. These results support BCI as a biomarker to help guide the selection of HR+ breast cancer patients who could be spared from or consider shorter duration of adjuvant ET to avoid potentially serious side effects from these therapies.

In this cohort of high-risk BC patients who all had a DR event, BCI remained prognostic with lower BCI scores associated with longer TTDR. Initial findings from the genomic correlative analysis suggested an association of BCI with certain genomic features. Further analyses with additional samples are ongoing to substantiate these findings.

This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2- breast cancer patients.

Using a single electroencephalographic channel, attention classification accuracy ranges from 70% to 100% across all patients. The significance of this novel BCI paradigm lies in its ability to quantitatively measure selective tactile attention resources throughout the therapy session, introducing a top-down approach to classical sensory training interventions based on repeated neuromuscular electrical stimulation.

These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

This study demonstrates an increase in diagnostic activity in Australian general practice several months before LC and CRC diagnosis, indicating potential opportunities for earlier diagnosis. It identifies blood test abnormalities and distinct signatures that are early markers of LC and CRC. If combined with other pre-diagnostic information, these blood tests have potential to support GPs in prioritising patients for cancer investigation of different sites to expedite diagnosis.

We found a significant association between ODX and BCI predictive and prognostic scores. BCI predictive of extended ET benefit was associated with discordance with ODX RS. Higher predicted RR on ODX was associated with discordance with BCI predicted RR.

This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

Among these tests, Prosigna and EndoPredict® have at present been validated only on a prognostic level, while Oncotype Dx, MammaPrint, and BCI hold both a prognostic and predictive role. Oncologists and pathologists engaged in the management of EBC will find in this review a thorough comparison of available genomic assays, as well as strategies to optimize the utilization of the information derived from them.

HER2-low status is not a prognostic marker for Taiwanese breast cancer with trivial clinical and pathological differences compared to HER2-zero phenotype. Future studies are warranted to understand the biological and therapeutic relevance of this newly established taxonomy.

These findings indicate that social interaction can improve the neural synchronization between familiar partners with enhanced brain activations and brain-to-brain coupling. This study may provide a novel method for enhancing MI-based BCI performance in conjunction with neural synchronization between users.

Despite inclination towards cost-saving measures, Oncotype DX may be more useful to give prognosis in the early adjuvant period whereas BCI is more useful to evaluate late recurrence risk. Low or high Oncotype scores and tumor grade may not align with BCI findings. Considering the importance of managing toxicity against the risk of late recurrence, incorporating BCI testing can enhance EET recommendations, even for Stage I, node-negative, ER positive patients.

Results show no racial or ethnic differences in predicting the benefit of EET, strengthening BCI's universal applicability in diverse women with early-stage HR+ breast cancer. Patients with higher distant recurrence risk were predicted to benefit from EET. This suggests potential variations in tumor features or other factors affecting distant recurrence risk among racial groups.

BCI H/I and prognostic risk scores exhibited low concordance with RS risk categories. H/I consistently re-stratified RS risk categories into distinct H/I-Low and -High groups, further substantiating that prediction of CT benefit does not equate to prediction of EET benefit.

Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low risk patients are reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients' breast cancer risk is important.

This analysis in a large patient cohort of the BCI Registry confirms and extends previous findings on the significant decision-making impact of BCI on EET. Incorporating BCI into clinical practice resulted in changes in physician recommendations, increased physician confidence, improved patient satisfaction, and reduced patient concerns regarding the cost, drug safety, and benefit of EET.

"Hologic, Inc...today announced newly published study results revealing that use of the Breast Cancer Index (BCI) test led to physicians changing their long-term anti-estrogen treatment recommendations for 40% of patients with early-stage hormone receptor-positive (HR+) breast cancer. The results, which suggest that many women may be over- or undertreated without the incorporation of BCI, reflect real-world data from the largest prospective study assessing the impact of the BCI test on treatment decisions...Patients and physicians included in this study are participants in the BCI Registry Study....newly published findings reveal that when incorporated into routine clinical care, BCI has the potential to provide clinicians with greater confidence in their treatment recommendations, with 39% of providers saying they felt more confident in their recommendation for extended anti-estrogen therapy following BCI testing."

BCI(H/I)-High vs -Low did not show a statistically significant difference in ELT benefit for the primary endpoint (RFI). However, in time-dependent DR analysis, BCI (H/I)-High patients experienced statistically significant benefit from ELT after 4y, whereas (H/I)-Low patients did not. Because BCI (H/I) has been validated as a predictive marker of EET benefit in other trials, additional follow-up may enable further characterization of BCI's predictive ability.

The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients.

P=N/A; Recruiting --> Active, not recruiting

Of the 32 HER2-low tumors, 15/32 (47%) were BCI (H/I)-High (yes benefit) compared to 17/32 (53%) which were BCI (H/I)-Low (no benefit). Conclusions The prevalence of HER2 low tumors appears to be as high as 67% in reports to date. In this small series, the prevalence of HR+ HER2 low tumors was 29% (32/110).

The current BCI assay reports prognostic risk estimates based on tamoxifen-treated patients from the Stockholm (STO-3) cohort for node-negative (N0) patients, enrolled between 1976 through 1990 and a retrospective cohort from Massachusetts General Hospital (MGH) for patients with 1 to 3 positive nodes (N1), diagnosed between 1993 and 2007, of which approximately 50% were tamoxifen-treated... BCI prognostic validation in the TEAM trial enabled the characterization of DR risk that is more compatible with the current standard of care in the US, as postmenopausal patients were all treated with at least 2-3 years or 5 years of primary adjuvant endocrine therapy with an aromatase inhibitor. Results from the TEAM study provide a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients.

Conclusion BCI (H/I) consistently stratified CTS5 risk categories into separate BCI (H/I)-Low and BCI (H/I)-High groups, indicating that risk prognostication does not equate to prediction of benefit from EET. These results confirm previous findings in the IDEAL study demonstrating that CTS5 is not predictive of EET benefit and further substantiate the clinical utility of BCI as the only predictive biomarker for extended endocrine therapy benefit in patients with HR+ early-stage breast cancer.

A comprehensive and comparative analysis of mRNA expression levels and methylation patterns between TCGA breast cancer samples with high and low expression of HOXB13 revealed key signaling pathways and biological processes that may provide insights on the molecular mechanism of HOXB13 in the regulation of response to endocrine therapy in HR+ breast cancer.

The development and validation process of each tool was also briefly introduced. It is expected that the consensus will help guide and standardize the clinical use of multigene testing tools and further improve the level of precise treatment for EBC.

Evidence in the setting of predictive tests for extended endocrine therapy is sparse. Most relevant studies investigated the use of BCI, but these study populations were largely restricted to a single age, race, and ethnicity group. Future studies should evaluate a variety of biomarkers in diverse populations. Without sufficient evidence, physicians and patients face a difficult decision in balancing the benefits and risks of endocrine therapy extension.

Conclusions HER2-low status is not a prognostic marker for Taiwanese breast cancers while a slightly younger age of disease onset, less than half diagnosed with stage 0 and I, more ER and PR positivity and fewer grade III disease were observed for HER2-low phenotype compared with HER2-zero counterpart. These trivial differences distinguished HER2-low from HER2-zero spectrum among Taiwanese HER2-negative breast cancers.

Even after 5 years of adjuvant endocrine therapy, patients with hormone receptor-positive breast cancer have a significant risk for late recurrence, including distant metastases, that might be prevented with longer durations of endocrine therapy. However, the added toxicity and variable benefit derived from extended endocrine therapy make optimal patient selection crucial. Genomic assays are in development to risk-stratify patients for late recurrence and determine efficacy of extended endocrine therapy, with the aim to help guide extended endocrine therapy decisions for clinicians and individualize treatment strategies for patients.

In patients who continued ET after BCI testing, the rates of persistence to EET were high, particularly in patients with predicted high likelihood of benefit from EET. Use of EET is associated with increased use of DXA scans.

The establishment of criteria used to perform molecular tests in BC patients needs to be standardized, and the tests should be performed in specialized laboratories. Test centralization and reimbursement are fundamental to be able to compare the outcome of patients treated or not with chemotherapy in addition to hormone therapy to verify data from clinical randomized studies in a real-world setting.

Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy. >

Our findings highlight the utility of characterizing differences in BCI predictive and prognostic scores by race among breast cancer patients with early-stage HR+ tumors. Notably, Native Hawaiian women had 7.0 times increased odds of having a score predicting benefit of extended endocrine therapy compared to Caucasians. This result is salient given the high incidence of breast cancer among Native Hawaiians.

The TEAM pathology study consists of 3284 postmenopausal hormone positive breast cancer patients treated with either exemestane or tamoxifen followed by exemestane. Other clinico-pathologic tools such as Influence 2.0 and CTS-5 have good prognostic ability when compared to Oncotype Dx-trained results and RSClin. >

Conclusions This study emphasizes that most drugs are given at fixed dose and the gap in knowledge we have on the efficacy of the novel anti-cancer treatments and the use of GEP and MS according to patient adiposity. As the prevalence of obesity is increasing worldwide, the evaluation of body composition is needed to increase knowledge on optimal use of drugs in clinical practice.

However most of this data was generated with tamoxifen monotherapy during the first 5 years...This must be balanced against long term side effects of endocrine treatment, competing risks like the patients (biological) age and comorbidities and obviously the patients preferrence. For patients with intermediate risk 7 years appears to be the optimal duration and in those with high risk features endocrine therapy up to 10 years may be considered.

Design: In this cohort of 235 patients, >90% of patients were treated with Palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). Tumor evolution occurs on treatment with CDK4/6i; however, analyses of pretreatment biopsies can inform the duration of PFS. These data support discrete biological processes associated with sensitivity/resistance. Predictive algorithms could be developed to inform features of treatment decision which will require prospective validation which is ongoing.

These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.