Dataset Information

A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.

ABSTRACT: Background: Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Methods: Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). Results: The F2P Score was established by integrating the clinical (age and tumor size) and genomic (ESR1, PGR, BCL2, CD68, GSTM1, and BAG1) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62-0.81) and BIC was 396.75 (95% CI, 252.37-541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87-4.61) or categorical (HR, 3.68; 95% CI, 1.70-8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. Conclusion: The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score.

SUBMITTER: Lin C

PROVIDER: S-EPMC7518385 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.

Lin Caijin C Wu Jiayi J Lin Lin L Fei Xiaochun X Chen Xiaosong X Huang Ou O He Jianrong J Chen Weiguo W Li Yafen Y Shen Kunwei K Zhu Li L

Frontiers in oncology 20200911

<b>Background:</b> Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). <b>Methods:</b> Patients with node-negative ER+/HER2- breast cancer and ...[more]

PMID: 33042787

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Project description:Background: Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2-]) is the most common molecular subtype of breast cancer (BC). Since the relationship between Luminal B (HER2-) BC and liver metastasis (LM) is poorly defined, this retrospective study aimed to develop an LM risk nomogram for patients with lymph node-related (N + Luminal B [HER2-]) BC. Methods: Data were obtained for patients initially diagnosed with BC from the Tianjin Medical University Cancer Institute and Hospital. There were 30,975 Chinese female patients with stage I-III BC and follow-up confirming 1217 subsequent patients with LM, and 427 patients with N + Luminal B (HER2-). The LM risk was assessed using Cox proportional hazards regression, histogram, Venn diagram, and Kaplan-Meier survival analysis, with further analysis for patients with N + Luminal B (HER2-) BC. A nomogram was established based on the N + Luminal B (HER2-) BC data, which was validated using calibration plots. Results: The median age of 427 patients with N + Luminal B (HER2-) liver metastasis of breast cancer (BCLM) was 49 years. The largest number of patients with BCLM was diagnosed between the second to the 6th year, the longest interval from initial BC diagnosis to subsequent LM was 145 months. The patients with LM as the first site of distant metastasis which is associated with better survival were analyzed by Kaplan-Meier. The nomogram was constructed for the risk of LM that included age, menstrual status, unilateral oophorectomy, pregnancy, hepatitis B antigen, region of residence, tumor size, lymph node, clavicular lymph nodes, progesterone receptor, and lymph vessel invasion. Conclusion: We described the clinicopathological characteristics of patients with stage I-III BC, and constructed a nomogram for calculating personalized LM probabilities for patients with N + Luminal B (HER2-), which could guide future prolonged or early extensive treatment decisions.

Project description:Background:Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER?<?1% have characteristics similar to those with 1%???ER?<?10%. We hypothesized that in patients with human epidermal growth factor 2 (HER2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy. Patients and methods:Patients with stage II or III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression. Results:A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR?=?0.99, 95% CI?=?0.986-0.994, P?<?0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER???10% tumors, but not those with 1%?ER?<?10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR?=?0.24, 95% CI?=?0.16-0.36, P?<?0.001) and overall survival (HR?=?0.32, 95% CI?=?0.2-0.5, P?<?0.001). Conclusion:Stage II or III HER2-negative primary breast cancer with ER?<?10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with?<10%, rather than?<1%, of ER and/or progesterone receptor expression.

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Dataset Information

A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.

Publications

A Novel Prognostic Scoring System Integrating Gene Expressions and Clinicopathological Characteristics to Predict Very Early Relapse in Node-Negative Estrogen Receptor-Positive/HER2-Negative Breast Cancer.

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