Prediction of a Multi-Gene Assay (Oncotype DX and Mammaprint) Recurrence Risk Group Using Machine Learning in Estrogen Receptor-Positive, HER2-Negative Breast Cancer—The BRAIN Study
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SUBMITTER: Ji J
PROVIDER: S-EPMC10887075 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Altered expression of miRNAs has been observed in many types of cancer, including breast cancer, and shown to contribute to cancer growth, aggressiveness, and response to therapies. In this pilot study, we investigated the possible correlation of miRNAs with risk of recurrence of estrogen receptor positive, lymph node-negative mammary carcinomas as determined by the Oncotype DX® Breast Cancer assay. To accomplish this, we extracted RNA from a collection of breast carcinomas that had previously been analyzed by Oncotype DX®. Multiple Let-7 family members were negatively correlated with the recurrence score (RS), which is consistent with their tumor suppressor properties. Additional miRNAs were found to positively correlate with RS, including miR-377-5p, miR-633b, miR-548t and miR-3648. Pathway analysis of putative and validated targets suggests that these miRNAs may have a diverse range of functions that may contribute to tumor recurrence. Taken together, these findings provide evidence that a miRNA expression signature can be developed to aid existing methods to determine the risk of recurrence for women with estrogen receptor positive breast cancers treated with endocrine therapy.
| S-EPMC4696739 | biostudies-literature
Project description:INTRODUCTION:Hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers without lymph node metastasis have good prognosis. We compared the prognosis of hormone receptor-positive, HER2-negative, lymph node-negative cancers with Oncotype DX score ranges of 1 to 10 (1-10 group) and 11 to < 18 (11-18 group). PATIENTS AND METHODS:A total of 107 cases in the 1-10 group and 225 cases in the 11-18 group were reviewed. All patients received surgery. The use of chemotherapy, radiotherapy, and endocrine therapy, and overall survival (OS), disease-free survival (DFS), and distant metastasis were compared between groups. RESULTS:There were no statistical differences in the use of chemotherapy (5.05% vs. 6.05%, P = .724) or radiotherapy (52.53% vs. 59.07%, P = .276) between the 1-10 group and the 11-18 group, respectively. The median OS and DFS were 47 and 45 months, respectively, in the 1-10 group, and 49 and 48 months in the 11-18 group. No significant difference was seen in OS (P = .995), DFS (P = .148), or rates of metastasis (P = .998). The 11-18 group had more death events and distant metastasis (death, 5 events; recurrence, 2 events; metastasis, 2 events) than the 1-10 group (death, 0 events; recurrence, 4 events; metastasis, 0 events). The majority of recurrences seen in both groups were in young patients who failed to comply with their endocrine therapy regimen. CONCLUSION:Patients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients.
| S-EPMC6998376 | biostudies-literature
Project description:BackgroundThe effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18.Patients and methodsParticipants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR).ResultsA total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified.ConclusionsThe efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.
| S-EPMC11472226 | biostudies-literature
Project description:Oncotype DX (ODX), a 21-gene assay, predicts the recurrence risk in early breast cancer; however, it has high costs and long testing times. We aimed to identify clinicopathological factors that can predict the ODX risk group and serve as alternatives to the ODX test. This retrospective study included 547 estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and lymph node-negative breast cancer patients who underwent ODX testing. Based on the recurrence scores, three ODX risk categories (low: 0-15, intermediate: 16-25, and high: 26-100) were established in patients aged ≤50 years (n = 379), whereas two ODX risk categories (low: 0-25 and high: 26-100) were established in patients aged >50 years (n = 168). Factors selected for analysis included body mass index, menopausal status, type of surgery, and pathological and immunohistochemical features. The ODX risk groups showed significant association with histologic grade (p = 0.0002), progesterone receptor expression (p < 0.0001), Ki-67 (p < 0.0001), and p53 expression (p = 0.023) in patients aged ≤50 years. In patients aged >50 years, tumor size (p = 0.022), Ki-67 (p = 0.001), and p53 expression (p = 0.001) were significantly associated with the risk group. Certain clinicopathological factors can predict the ODX risk group and enable decision-making on adjuvant chemotherapy; these factors differ according to age.
| S-EPMC10527468 | biostudies-literature
Project description:BackgroundHER2 immunohistochemistry (IHC) reproducibility is suboptimal for HER-low cases (IHC 1+ or 2+).MethodsThe Yale cohort included 214 stages I-II estrogen receptor positive breast cancers with IHC scores 0, 1+, and 2+ and routine Oncotype DX Recurrence Score (RS) results. The Exact Sciences (ES) cohort included 9 57 624 patients who had an Oncotype DX RS assay that assigns HER2-negative, equivocal, or positive status based on HER2 mRNA levels.ResultsHER2 mRNA levels varied across IHC categories but with increasing medians of 9.10 (n = 89), 9.20 (n = 71), and 9.45 (n = 54) in IHC 0, 1+, and 2+, respectively. 22.4% of HER2-low (1+/2+) cancer had RS > 25. Over 98% of HER-low cancers were HER2-negative by Oncotype DX assignment.ConclusionsCancers with higher mRNA levels exist within IHC 0 and low categories, most of the HER2-low patients by IHC have low RS indicating no benefit from current adjuvant chemotherapies.
| S-EPMC10546821 | biostudies-literature
Project description:PurposeOncotype DX, a gene expression assay widely employed to aid decision making on adjuvant chemotherapy use in patients with primary oestrogen receptor-positive (ER+) breast cancer, produces a recurrence score (RS) related to distant disease recurrence (DR) risk (RS%). In node-negative patients, RS can be integrated with clinicopathological parameters to derive RS-pathology-clinical (RSPC) that improves prognostic accuracy.MethodsData were collected on patients having clinically indicated tests with an intermediate clinical risk of distant recurrence, and for whom the decision to prescribe chemotherapy remained unclear. Correlation between RS% and RSPC scores was examined. An agreement table was constructed using risk-categorised data. Association between RS%-derived categorical risk assignments and treatment recommendation was evaluated.ResultsData on 171 tests (168 patients) were available. Median DR risk by RS% was 11% (range 3-34%), by RSPC it was 15% (range 4-63%). Correlation between RS% and RSPC was 0.702 (p < 0.001). RS% classified 57.3% of cases as low-, 32.2% intermediate- and 10.5% high-risk for DR; by RSPC proportions were 33.9, 35.7, and 30.4%, respectively. The number of patients receiving chemotherapy recommendations was: 14/87 (16.1%) categorised as low-risk by RS%, 27/49 (55.1%) as intermediate-risk and 12/13 (92.3%) as high-risk. Of 149 patients recommended for endocrine treatment alone, 28 (18.8%) were categorised by RS% as low-risk but by RSPC as intermediate- or high-risk.ConclusionsIn this group of patients, RSPC assessed fewer patients as low-risk and more as high-risk than did RS%. The discordances between the scores indicate that RSPC estimates of risk should be considered when selecting patients for endocrine therapy alone.
| S-EPMC5847032 | biostudies-literature
Project description:Introduction: The GenesWell Breast Cancer Test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with early breast cancer. Here, we analyzed the concordance of the BCT score with the Oncotype DX recurrence score (RS) for risk stratification in Asian patients with pN0-N1, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: Formalin-fixed, paraffin-embedded breast cancer tissues previously analyzed using the Oncotype DX test were assessed using the GenesWell BCT test. The risk stratification by the two tests was then compared. Results: A total of 771 patients from five institutions in Korea were analyzed. According to the BCT score, 527 (68.4%) patients were classified as low risk, and 244 (31.6%) as high risk. Meanwhile, 134 (17.4%), 516 (66.9%), and 121 (15.7%) patients were categorized into the low-, intermediate-, and high-risk groups, respectively, according to the RS ranges used in the TAILORx. The BCT high-risk group was significantly associated with advanced lymph node status, whereas no association between RS risk groups and nodal status was observed. The concordance between the two risk stratification methods in the overall population was 71.9% when the RS low-risk, and intermediate-risk groups were combined into one group. However, poor concordance was observed in patients aged ≤50 years and in those with lymph node-positive breast cancer. Conclusions: The concordance between the BCT score and RS was low in women aged ≤50 years or with lymph node-positive breast cancer. Further studies are necessary to identify more accurate tests for predicting prognosis and chemotherapy benefit in this subpopulation.
| S-EPMC6670782 | biostudies-literature
Project description:Purpose To investigate relationships between computer-extracted breast magnetic resonance (MR) imaging phenotypes with multigene assays of MammaPrint, Oncotype DX, and PAM50 to assess the role of radiomics in evaluating the risk of breast cancer recurrence. Materials and Methods Analysis was conducted on an institutional review board-approved retrospective data set of 84 deidentified, multi-institutional breast MR examinations from the National Cancer Institute Cancer Imaging Archive, along with clinical, histopathologic, and genomic data from The Cancer Genome Atlas. The data set of biopsy-proven invasive breast cancers included 74 (88%) ductal, eight (10%) lobular, and two (2%) mixed cancers. Of these, 73 (87%) were estrogen receptor positive, 67 (80%) were progesterone receptor positive, and 19 (23%) were human epidermal growth factor receptor 2 positive. For each case, computerized radiomics of the MR images yielded computer-extracted tumor phenotypes of size, shape, margin morphology, enhancement texture, and kinetic assessment. Regression and receiver operating characteristic analysis were conducted to assess the predictive ability of the MR radiomics features relative to the multigene assay classifications. Results Multiple linear regression analyses demonstrated significant associations (R2 = 0.25-0.32, r = 0.5-0.56, P < .0001) between radiomics signatures and multigene assay recurrence scores. Important radiomics features included tumor size and enhancement texture, which indicated tumor heterogeneity. Use of radiomics in the task of distinguishing between good and poor prognosis yielded area under the receiver operating characteristic curve values of 0.88 (standard error, 0.05), 0.76 (standard error, 0.06), 0.68 (standard error, 0.08), and 0.55 (standard error, 0.09) for MammaPrint, Oncotype DX, PAM50 risk of relapse based on subtype, and PAM50 risk of relapse based on subtype and proliferation, respectively, with all but the latter showing statistical difference from chance. Conclusion Quantitative breast MR imaging radiomics shows promise for image-based phenotyping in assessing the risk of breast cancer recurrence. © RSNA, 2016 Online supplemental material is available for this article.
| S-EPMC5069147 | biostudies-literature
Project description:PURPOSE: To compare risk assignment by PAM50 Breast Cancer Intrinsic Classifier™ and Oncotype DX_Recurrence Score (RS) in the same population. METHODS: RNA was extracted from 151 estrogen receptor (ER)+ stage I-II breast cancers and gene expression profiled using PAM50 "intrinsic" subtyping test. RESULTS: One hundred eight cases had complete molecular information; 103 (95%) were classified as luminal A (n = 76) or luminal B (n = 27). Ninety-two percent (n = 98) had a low (n = 59) or intermediate (n = 39) RS. Among luminal A cancers, 70% had low (n = 53) and the remainder (n = 23) had an intermediate RS. Among luminal B cancers, nine were high (33%) and 13 were intermediate (48%) by the RS. Almost all cancers with a high RS were classified as luminal B (90%, n = 9). One high RS cancer was identified as basal-like and had low ER/ESR1 and low human epidermal growth factor receptor 2 (HER2) expression by quantitative polymerase chain reaction in both assays. The majority of low RS cases were luminal A (83%, n = 53). Importantly, half of the intermediate RS cancers were re-categorized as low risk luminal A subtype by PAM50. CONCLUSION: There is good agreement between the two assays for high (i.e., luminal B or RS > 31) and low (i.e., luminal B or RS < 18) prognostic risk assignment but PAM50 assigns more patients to the low risk category. About half of the intermediate RS group was reclassified as luminal A by PAM50.
| S-EPMC3336833 | biostudies-other
Project description:To evaluate the ability of a radiomics signature based on 3T dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to distinguish between low and non-low Oncotype DX (OD) risk groups in estrogen receptor (ER)-positive invasive breast cancers.Between May 2011 and March 2016, 67 women with ER-positive invasive breast cancer who performed preoperative 3T MRI and OD assay were included. We divided the patients into low (OD recurrence score [RS] <18) and non-low risk (RS ≥18) groups. Extracted radiomics features included 8 morphological, 76 histogram-based, and 72 higher-order texture features. A radiomics signature (Rad-score) was generated using the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate logistic regression analyses were performed to investigate the association between clinicopathologic factors, MRI findings, and the Rad-score with OD risk groups, and the areas under the receiver operating characteristic curves (AUC) were used to assess classification performance of the Rad-score.The Rad-score was constructed for each tumor by extracting 10 (6.3%) from 158 radiomics features. A higher Rad-score (odds ratio [OR], 65.209; P <.001), Ki-67 expression (OR, 17.462; P = .007), and high p53 (OR = 8.449; P = .077) were associated with non-low OD risk. The Rad-score classified low and non-low OD risk with an AUC of 0.759.The Rad-score showed the potential for discrimination between low and non-low OD risk groups in patients with ER-positive invasive breast cancers.
| S-EPMC6571434 | biostudies-literature