TEST:

HER2DX

P=NA | N=NA | "MEDSIR...presenting the results of two sub-studies focused on biomarkers: transFal, focused on patients with HR+/HER2- advanced breast cancer and METSGain, centered on patients with early breast cancer....Notably, high expression of Ki67 and CDK6, along with elevated ctDNA density at baseline, were correlated with shorter progression-free survival and overall survival. These findings illuminate potential avenues for understanding and overcoming resistance to CDK4/6 inhibitors, marking a significant step forward in personalized cancer treatment....Notably, patients with high-risk scores at surgery and less molecular changes after anti-HER2 therapy were more likely to develop metastasis, further highlighting the potential of HER2DX tool developed by REVEAL GENOMICS S.L. in guiding treatment decisions for HER2+ early breast cancer patients."

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The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

These data suggest that HER2DX risk-score in RD provides additional information on the likelihood of developing distant recurrences. In RD, high expression of immune and luminal genes was associated with a reduced risk, while high expression of proliferation genes was associated with a higher risk. Molecular changes after anti-HER2 therapy were mainly observed in RD of pts that did not relapse.

In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinicopathological variables, including treatment regimen with or without trastuzumab.

"REVEAL GENOMICS, S.L...has announced the start of the DEFINITIVE study, led by FRCB-IDIBAPS, representing the first prospective trial for HER2DX. This landmark study will be pivotal in bolstering the clinical validations already acquired for HER2DX. The study seeks to secure the prospective validation for endorsement by clinical guidelines and ensure recognition and reimbursement across Europe."

Sponsored by CHUGAI PHARMACEUTICAL CO., LTD.

Sponsored by CHUGAI PHARMACEUTICAL CO., LTD.

Background: The PREDIX HER2 trial, compared six courses of docetaxel, trastuzumab, and pertuzumab (DTP) vs. trastuzumab emtansine (T-DM1) as neoadjuvant treatment for HER2-positive breast cancer (BC). This study demonstrates that antibody–drug conjugates and standard treatment harbor strikingly distinctive biomarkers across tumor ecosystem. Further external validation and integrated ML model comprising all unimodal models are ongoing.

Standardized HER2DX was evaluated centrally using RNA from baseline FFPE tumor biopsies from the WSG-ADAPT-TN study (NCT01815242), a multicenter phase II trial that randomized 336 patients with stage I–III early TNBC to 12-weeks of nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 d1,8 every 3 weeks (arm A) versus nab-paclitaxel 125 mg/m2 plus carboplatin AUC2 day 1,8 every 3 weeks (arm B). The HER2DX genomic test in TNBC provides valuable insights into the response and survival following neoadjuvant taxane-based chemotherapy in the absence of immunotherapy. The development of a tailored genomic assay for TNBC is currently in progress.

This study assessed the impact of HER2 heterogeneity on treatment response in stage II-III HER2+ breast cancer patients treated with neoadjuvant T-DM1 and pertuzumab. The HER2DX genomic assay demonstrates low variability within HER2+ breast cancer, supporting its reliability as a consistent tool for assessing prognosis, the probability of pCR and ERBB2 quantitative expression.

The inferior pCR rates among cases classified as ITH-HER2 translated into numerically inferior outcomes for both EFS and iDFS. The number of events is small; therefore, our results are exploratory. Selecting pts whose tumors lack ITH-HER2 can increase the chances of achieving RCB 0/I with neoadjuvant TDM1 + pertuzumab.

The integration of intrinsic molecular subtypes with stage or HER2DX risk-score predicts site-specific metastatic risk in HER2-positive BC, with potential implications for personalized surveillance and clinical trials aimed at preventing site-specific recurrence.

P2 | "In IgG-high tumors, the proportion of TLS+ tumors was 61.6% compared to 38.4% TLS-negative (p<0.001) Conclusions The B-cell/IGG signature is a GE pattern strongly associated with TLS across cancer types, even independently of TILs. This signature could serve as a valuable tool for precisely measuring TLS and predicting clinical outcomes and response to immunotherapy in cancer patients."

Patients (pts) with newly diagnosed stage I-IIIA HER2+ BC and PET evaluable lesions were randomized (1:4) to receive either docetaxel (T), carboplatin (C), and HP (group A) or HP ± endocrine therapy (ET) (group B). Conclusions HER2DX predicts pCR following neoadjuvant HP-based therapy (with or without chemotherapy) and identifies pts with a higher risk of recurrence. This assay might help individualize HP-based therapy in early HER2+ BC.

Methods Patients (pts) with stage I-III ERBB2+BC were treated with neoadjuvant pertuzumab+trastuzumab+paclitaxel (THP)x16w. Conclusions In early-stage ERBB2+ BC, a single dose of HP induces significant biological changes that may better predict pCR. At day 8, pts with high expression of HER2DX immune signature and immune-related genes have a higher probability of achieving a pCR following THP.

"REVEAL GENOMICS...announced the inclusion of its HER2DX test in the clinical guidelines for early-stage breast cancer prepared by the Spanish Society of Medical Oncology ( SEOM)."

P2 | N=377 | PHERGAIN (NCT03161353) | Sponsor: MedSIR | "REVEAL GENOMICS...announced another validation of HER2DX®, the world's first specialized genomic test for HER2+ breast cancer....MEDSIR´s PHERGAIN trial, the first results of which were published in the Lancet Oncology in 2021 and recently announced at ASCO Congress, randomized 356 patients with newly diagnosed HER2+ breast cancer to neoadjuvant systemic therapy with 6 cycles of multi-agent chemotherapy, trastuzumab, and pertuzumab (i.e., arm A) or 2 cycles of chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab (i.e., arm B)....The HER2DX® pCR-score was found to be significantly associated with pCR, regardless of the treatment regime, 18F-FDG-PET metabolic response, and hormone receptor status."

HER2DX pCR-score and risk-score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

"Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles. This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab."

"The results of this diagnostic/prognostic study suggest that the HER2DX pCR score assay could predict pCR following treatment with deescalated neoadjuvant paclitaxel with trastuzumab and pertuzumab in patients with early-stage ERBB2+ BC. The HER2DX pCR score might guide therapeutic decisions by identifying patients who are candidates for deescalated or escalated approaches."

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Methods Standardized HER2DX was evaluated centrally on baseline pre-treatment tumors from a prospective phase II clinical trial (NCT01796197), in which patients with HER2+ IBC were treated with neoadjuvant paclitaxel, trastuzumab and pertuzumab (THP) x 16 weeks. Conclusions HER2DX pCR-high designation may be less frequent in HER2+ IBC compared to HER2+ non-IBC. Lower mRNA expression of HER2 amplicon genes, and higher tumor burden at diagnosis, might explain the differences observed in the distribution of HER2DX scores and signatures between HER2+ IBC and non-IBC.

Within pts without a pCR (n=148), the HER2DX low-risk group had longer DFS than the high-risk (5-year 95.6% vs. 85.3%; HR=0.20, p=0.004), and it was significantly (HR=2.03; p=0.006) associated with DFS independently of hormone receptor and adjuvant T-DM1. Conclusions The HER2DX risk-score determined in baseline pre-treatment core-biopsies provides prognostic information beyond pCR status in patients with early-stage HER2+ breast cancer treated with neoadjuvant and adjuvant anti-HER2 treatment.

Among 56 evaluable pts treated with NAT, HER2DX pCR score was significantly associated with pCR (81% in pCR-medium/high and 32% in pCR-low; odds ratio=9.3, p=0.001), independently of the rest of variables. Conclusions In this first pilot and prospective study, HER2DX impacted clinical care in early-stage HER2+ BC.

Background In the APT and ATEMPT trials, adjuvant paclitaxel and trastuzumab (TH) and T-DM1 were found associated with excellent long-term outcomes for patients (pts) with small, node-negative HER2-positive breast cancer (HER2+ BC), respectively. The optimal cut-off (32) distinguished pts with low-risk (7-year RFI of 98.2%; 96.7%-99.6%) from high-risk disease (7-year RFI: 88.7%; 80.4%-97.8%) &lsqb;delta of 9.5%], including in multivariable analysis for RFI (HR: 6.87, 2.22-21.27, p<0.001) and iDFS (HR: 2.81, 1.26-6.23, p=0.01). Conclusions The HER2DX risk score is associated with the risk of recurrence among pts with small, node-negative HER2+ breast tumors treated with adjuvant TH or T-DM1.

Data from RNAseq and nCounter platforms were highly correlated in 30 analyzed RNA samples. Conclusions Analytical validation of HER2DX has proven it to be suitable for its intended purpose.

Finally, the mean ERBB2 mRNA expression (in log base 2) in HER2-low and HER2-0 disease was -1.86 and -2.72, respectively (1.8-fold difference). Conclusions The standardized HER2DX ERBB2 mRNA score predicts the clinical status of HER2 (positive, low and zero) in BC.

Conclusions Our findings highlight the heterogeneity of HER2-positive breast cancer. Spatial transcriptomics may help in refining gene expression signatures computed on bulk RNA, and these results open to further analyses aimed at better understanding the tumor microenvironment in this disease.

Similar results were obtained in other survival endpoints. Conclusions In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinical-pathological variables, including treatment regimen with or without trastuzumab.

All patients were treated with neoadjuvant trastuzumab (n=568) in combination with multi-agent chemotherapy (n=282), a single taxane (n=286), pertuzumab (n=264), lapatinib (n=103) or without a second anti-HER2 drug (n=201). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of type of treatment. Conclusions HER2DX might help identify patients with HER2-positive breast cancer who benefit from neoadjuvant dual HER2 blockade in combination with a single taxane.

Conclusions The 27-gene HER2DX genomic test predicts pCR following neoadjuvant THP in HER2+ BC. Updated data, including D8 HER2DX results, will be presented at the conference.

P2; Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population.

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In advanced HER2-positive (HER2+) breast cancer (BC), the new antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is more effective compared to trastuzumab emtansine (T-DM1). The HER2DX risk-score (P=.04) and the immunoglobulin (IGG) signature (P=.04) were significantly associated with OS since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ BC.

"REVEAL GENOMICS...announced positive results for HER2X® in a range of clinical scenarios, demonstrating the test’s reliability....The HER2DX pCR score predicted response to chemotherapy in combination with trastuzumab and pertuzumab in DAPHNe and GOM clinical trials....The results of 4 studies (APT, ATEMPT, DAPHNe and GOM) have been made public during the San Antonio Breast Cancer Symposium (SABCS), held from December 6 to 10 in San Antonio, Texas (USA)."