TEST:

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

NCIC-CTG MA.5 and DBCG 89D are symmetrically designed randomized trials comparing adjuvant cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in high-risk breast cancer patients. The analysis provides evidence of the benefit from anthracycline in HER2-enriched subtype; for patients with discordance of HER2 subtype and clinical HER2 status, HER2-enriched subtype was predictive of anthracycline benefit whereas clinical HER2 positive status was not. Anthracycline-based adjuvant chemotherapy may safely be withheld for patients with a low ROR score while the benefit increases with increasing ROR score.

We focus on studies that directly compare these molecular tests and discuss how their strengths can be leveraged to improve clinical decision-making for early-stage HR+ breast cancers. Finally, we highlight remaining knowledge gaps and propose directions for future research.

Moreover, the implementation of Molecular Tumor Boards further enhances personalized treatment strategies, contributing to improved patient outcomes and survival rates. This review underscores the significance of tailored therapeutic approaches and highlights the dynamic evolution of breast cancer in clinical practice.

P2, N=324, Active, not recruiting, NRG Oncology | Trial completion date: Oct 2028 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

It is not an obvious biological entity but is nevertheless associated with potentially targetable molecular features, notably a high immune response and high FGFR4 expression. Strikingly, molecular features that define the HER2E subtype in luminal disease are also consistent in HER2-positive disease, including an epigenetic mechanism for high FGFR4 expression in breast cancer.

EZH2 and TOP2A were positively correlated with proliferation scores, while WNT11 and ITGB6 emerged as potential biomarkers independently associated with recurrence. These findings suggest novel biomarker candidates that could help overcome ET resistance, reduce recurrence, and improve outcomes in ER + BC.

P2, N=43, Not yet recruiting, Medical University of South Carolina

It is a simple, cost-effective tool that can aid in risk stratification and guide treatment strategies. Further validation in larger cohorts is recommended.

Treatment for breast DCIS ranges from active surveillance to mastectomy, often combined with adjuvant endocrine therapy. The work presented here based on a unique neoadjuvant trial provides direct information on hormone therapy responsiveness of this disease and further couples the biology of invasive breast cancer to its non-obligate precursor.

Our statistical analysis not only confirmed the reproducibility and accuracy of BCC, but also revealed similarities in prognostic characteristics between the HER2-low and Basal subtypes. Addressing this gap in breast cancer classification is clinically significant because it not only improves treatment stratification, but also uncovers novel molecular and immunohistochemical features associated with the HER2-low and HER2-high subtypes, thereby advancing our understanding of breast cancer heterogeneity and providing guidance in precision oncology.

High expression of LDHA was found to be associated with poor prognosis in BC. LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.

While multiple gene expression profiling tests are available, they classify patients differently and are not interchangeable; therefore, their application should be at the clinician's discretion during the decision-making process. It is essential that these tests are not the sole factor in determining the best treatment plan: other clinical considerations and patient preferences should also play a significant role in guiding treatment decisions.

Overall, PAM50 subtypes of breast cancer exhibit distinct immune microenvironments, both histologically and molecularly. These differences in immune properties should be considered when developing precise treatment strategies to achieve optimal therapeutic efficacy for patients.

P=N/A, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

P=N/A, N=95, Terminated, Chinese University of Hong Kong | Recruiting --> Terminated | N=400 --> 95; lack a funding and withdrawal of collaborator

This study provides an understanding of MTR values in pediatric cervical SC and their variations by sex, age, height, and weight, providing a baseline for comparisons in pediatric SC diseases.

P2, N=1100, Recruiting, SOLTI Breast Cancer Research Group | Trial completion date: Jul 2030 --> Dec 2031 | Trial primary completion date: Aug 2028 --> Oct 2029

All four tests have prognostic ability in LN+ patients. Evidence on predictive benefit is weaker, with equivocal evidence that Oncotype DX may predict chemotherapy benefit in LN+ post-menopausal patients. Use of Oncotype DX leads to fewer patients being recommended chemotherapy.

This study revealed that the two spinal cord enlargements exhibit different patterns and suggest significant differences in spinal cord morphometric values according to sex and ethnicity.

Within the basal subtype, the low-risk group had a statistically significantly higher spatial fraction of tumor-infiltrating lymphocytes (TILs) compared to the high-risk group (p = 0.0362). Our findings indicate that this subgroup with poor prognosis is driven by a distinct biological signature with high activation of hypoxia-related genes as well as a low number of TILs.

P3, N=27, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Jun 2025 --> Dec 2025

P2, N=311, Active, not recruiting, NRG Oncology | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=600, Not yet recruiting, Eastern Cooperative Oncology Group

The clinical behavior of HER2-enriched cancers is dominated by the underlying ER subtype. ER+/HER2-enriched cancers tend to have more indolent course and lesser chemotherapy sensitivity than their ER counterparts.

Preoperative treatment with elacestrant in early BC demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.

Finally, it was discovered that the phytosterol Schottenol inhibits breast cancer cell proliferation by downregulating MDH1 expression and enhances sensitivity to paclitaxel. These findings provide new insights into MDH1 as a therapeutic target and suggest Schottenol as a potential strategy to overcome breast cancer drug resistance.

P2, N=70, Recruiting, Criterium, Inc. | N=100 --> 70 | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027

This study confirms the independent prognostic value of PAM50 IS in HR+ /HER2- advanced BC treated with CDK4/6i and ET. Non-luminal subtypes exhibited the worst prognosis, underscoring the need for novel therapeutic strategies in this population.

P3, N=108508, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2030 --> Dec 2028

Our findings demonstrate that deep learning, trained to recognize genomic correlates in tissue morphology, can quantify and map subtype admixture in LumA breast cancer that has clinical significance. The low-cost and scalability of this method holds potential as a research tool for investigating ITH and perhaps improving the efficacy of precision oncology.

P2; Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P1; Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025

P3; Trial primary completion date: May 2028 --> Jun 2025

Interestingly, full-time employment was associated with improved breast cancer DFS. These findings highlight the importance of considering genetic ancestry beyond self-reported race and accounting for social determinants of health, in efforts to improve survival outcomes among Black women with breast cancer.

Given low rates of genomic testing uptake nationally, image-based methods may help identify ER+/HER2-patients who could benefit from testing.

P2; N=1065 --> 139 | Trial completion date: Mar 2029 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2027 --> Nov 2024; Serious concerns on the slow recruitment of the study that impacts the robustness of the scientific rationale and the study financial provision. It aims to assess carefully the situation and to evaluate the potential solutions to overcome the issues.

NACT was more effective in the molecular and dimensional tumor 'downstaging' than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.

Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies.

Our data provides comprehensive miRNA expression atlas in breast cancer subtypes and underscores the prognostic and therapeutic significance of numerous miRNAs, including hsa-miR-5683 in TNBC. The identified gene targets unravel the intricate regulatory network in TNBC progression, suggesting promising avenues for further research and targeted therapeutic interventions.

Similarly, PSC basal-luminal shows the basal neuroendocrine-like is much higher in Israeli cohort 27% vs 7.5% (p=0.004). Conclusions These preliminary results suggest that geographic variation of decipher genomic classifier risk score in patients with early prostate cancer may exist, and correlate with differences in transcriptomic profile, including androgen receptor activity, p53 mutation, pTEN tumor suppressor gene deletion, and basal-luminal biologic phenotype.

P1/2; Trial primary completion date: Aug 2026 --> Jun 2025

Implementing the Oncotype DX test for women with ER-positive and HER2-negative early breast cancer is of great value. Delayed implementation leads to increased costs, reduced quality of life, and life-years lost.