scholarly journals A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Yu ◽  
Jiayi Wu ◽  
Ou Huang ◽  
Jianrong He ◽  
Li Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
External Validation ◽  
Clinicopathological Parameters ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Histologic Subtype ◽  
Her2 Breast Cancer ◽  
Significant Difference

Abstract Background The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS. Methods We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models. Results A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772–0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781–0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685–0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804–0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. Conclusions We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.

scholarly journals A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

2020 ◽  
Author(s):  
Jing Yu ◽  
Jiayi Wu ◽  
Ou Huang ◽  
Jianrong He ◽  
Li Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Recurrence Score ◽  
Clinicopathological Parameters ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Histologic Subtype ◽  
Her2 Breast Cancer

Abstract Background: The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients >50 years with RS >25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS.Methods: We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged >50 years. The primary outcome was high-risk RS (>25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method. We then assessed the nomogram in different subgroups of patients and compared it with several published models.Results: A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772-0.825) and optimism adjusted AUC was 0.794 (95% CI, 0.781-0.822). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes. The nomogram had better discriminate ability in patients who had tumors >2cm (AUC=0.847, 95% CI 0.804-0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al.Conclusions: We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.

Proliferation-based prediction for overall survival in locally advanced HER2(+) breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12007-e12007
Author(s):  
Manuel Pedregal ◽  
Federico Rojo ◽  
Cristina Carames Sanchez ◽  
Francisco Lobo ◽  
Yann Izarzugaza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Locally Advanced ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Ki67 Expression ◽  
Her2 Breast Cancer

e12007 Background: Breast cancer prognosis is influenced by several factors including Ki67 expression which may have a predictive role in luminal breast cancer patients. The aim of this study was to assess the value of Ki67 in breast cancers with positive hormonal receptors and HER2 overexpressed and to evaluate its impact on survival. Methods: Seventy eight consecutive patients diagnosed with locally advanced HER2 positive breast cancer who were treated with adjuvant therapy based on HER2 treatment were selected for this study (2004-2014). The adjuvant chemotherapy schemes were 44% TCH, 16% FEC, 11% AC/T and 29% other therapies. The median of followup was 68 months. Tumor proliferation was assessed immunohistochemically by Ki67 expression and calculated as percentage of stained tumor cells from this cohort previous to adjuvant chemotherapy administration and the results obtained were correlated with disease status and outcome. Results: High proliferation defined as a percentage > 15 of tumor cells was observed in 69% of the breast cancer patients cases. High proliferation significantly predicted longer overall survival (OS) (Log rank 0,012). At 10 years of follow-up, 93% of the patients with KI67 high expression were alive versus 43% of patients without overexpression. Multivariate analysis confirmed the clinical significance of Ki67 predicting OS for luminal HER2 breast cancer patients (p 0,04 y HR 9,6). Conclusions: High proliferation identifies a setting of luminal-B HER2+ subtype breast cancer patients with a significantly longer overall survival.

scholarly journals Liquid Biopsy: New Tool to Overcome CDKi Resistance Mechanism in Luminal Metastatic Breast Cancer

2021 ◽  
Author(s):  
Miriam González-Conde ◽  
Celso Yanez ◽  
Rafael López-López ◽  
Clotilde Costa
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Hormone Receptors ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

Association of primary prophylactic (PP) granulocyte-colony stimulating factor (G-CSF) use with chemotherapy dose modifications and relative dose intensity (RDI) among breast cancer patients receiving high-risk regimens for febrile neutropenia (FN).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 314-314
Author(s):  
Jaime Shaw ◽  
Jennifer Schenfeld ◽  
Akhila Balasubramanian ◽  
Renee Jaramillo ◽  
Darcie Sandschafer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Standard Dose ◽  
Dose Intensity ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Electronic Health Record Data ◽  
Nccn Guidelines ◽  
Significant Difference

314 Background: FN is a primary driver of chemotherapy modification and reduced RDI. Breast cancer patients often receive regimens with high risk ( > 20%) for FN. PP G-CSF use is recommended to decrease incidence of infection, as manifested by FN. Real-world evidence describing the association of G-CSF with reduced RDI in breast cancer patients is lacking. Methods: We retrospectively analyzed Flatiron Health Electronic Health Record data from 2011 to 2019 of adult female breast cancer patients initiating high-risk for FN chemotherapy regimens. PP G-CSF (pegfilgrastim, filgrastim, or biosimilars) use was assessed in the first and subsequent cycles of chemotherapy overall and by modality (on-body injector [OBI] vs. pre-filled syringe [PFS]). Standard dose was defined by NCCN guidelines. RDI was defined with respect to dose and timing of delivery: (delivered dose intensity/standard dose intensity)*100 and categorized as < 85% vs ≥85%. Characteristics were described by G-CSF use and adjusted relative risks (ARRs) were estimated for the association between G-CSF use and RDI, adjusting for age, serum hemoglobin, ECOG, HER2 status, and HR status. Results: There were 27,812 breast cancer patients included with a median age of 57 years. Most (90%) received PP-G-CSF. Four cycles of TC (docetaxel + cyclophosphamide) was the most common regimen prescribed (36%) and 82% of these patients received PP-G-CSF support in the first cycle, with OBI given more often than PFS (62% vs 38%). Second most common was dd AC-T Q1W (doxorubicin + cyclophosphamide followed by paclitaxel) and 98% of these patients received PP G-CSF (59% OBI vs 41% PFS). 80% of G-CSF users (vs 48% of those with no G-CSF) completed 4 or more cycles of chemotherapy (all regimens had ≥4 planned cycles). G-CSF users had a significant reduction in risk of RDI < 85% in Cycle 1 (ARR: 0.60; 95% confidence interval [CI]: 0.43 – 0.85) and Cycle 2 (ARR: 0.76; 95% CI: 0.59 – 0.97). At the overall chemotherapy course level, the risk of RDI < 85% was not significantly different by G-CSF use (ARR: 0.83; 95% CI: 0.63 - 1.08). There was no significant difference in risk of reduced RDI between OBI and PFS (ARR: 1.13; 95% CI: 0.94 - 1.35). Conclusions: This study revealed that 90% of breast cancer patients receiving high-risk for FN chemotherapy received PP-G-CSF support and completed more cycles than those who did not receive G-CSF. G-CSF users had lower risk of a reduced RDI in Cycles 1 and 2.

scholarly journals The concentration of matrix metalloproteinase 9 in the tumor and peritumoral tissue as prognostic marker in breast cancer patients

2019 ◽  
Vol 76 (5) ◽  
pp. 476-484 ◽  
Author(s):  
Danijela Cvetkovic ◽  
Bojan Milosevic ◽  
Aleksandar Cvetkovic ◽  
Srdjan Ninkovic ◽  
Jovana Jovankic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Significant Difference ◽  
Peritumoral Tissue

Background/Aim. Breast cancer is one of the most common malignancies among women all over the world. Tumor microenvironment represents one of the main regulators of tumorigenesis. We investigated the role of matrix metalloproteinases 9 (MMP-9) concentration in peritumoral tissue as a prognostic marker in the breast cancer patients. Methods. The ELISA test was used to determine a total MMP-9 concentration in carcinoma and peritumoral tissue sample in the patients with breast cancer. Comparison of MMP-9 protein expression with the clinicopathological parameters was evaluated. Results. Peritumoral tissue at 3 cm distance from the tumor produces more MMP-9 than the tumor itself. The ratio of concentrations of MMP-9 in the tumor and peritumoral tissue considerably changes in favor of peritumoral tissue with the increase of tumor size and the involvement of axillary lymph nodes. In N0 stage, the concentration ratio of MMP-9 in the tumor and peritumoral tissues was 1 : 1.44, but in the N2 stage, the ratio was 1 : 26.5. Conclusion. In patients with breast cancer even in an early stadium there is a change in MMP-9 concentration in peritumoral tissue. We can extract the group of patients at increased risk for the development of lymph node metastasis. A statistically significant difference between the concentrations of MMP-9 in the peritumoral tissue and cancer tissue exists only in case of metastatic disease not in MO stadium implying need for early detection of still unknown metastases in such patients.

Prediction of responsiveness to adjuvant anthracyclines in high-risk breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 597-597
Author(s):  
N. Brünner ◽  
B. Ejlertsen ◽  
M. Jensen ◽  
K. V. Nielsen ◽  
E. Balslev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Multivariate Regression Analysis ◽  
Invasive Disease ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Her 2 ◽  
Versus Treatment

597 Background: HER-2, TOP2A, and TIMP-1 have shown predictive properties regarding benefit from anthracyclines in patients with breast cancer. In the present study, TIMP-1 IHC was integrated with TOP2A FISH and HER-2 status in two separate profiles. Methods: The DBCG 89-D trial randomized 980 high-risk Danish breast cancer patients to nine series of CMF or CEF. CEF was superior to CMF in terms of DFS and OS (Ejlertsen et al, EJC 2007). HER-2 status and TOP2A copy number changes were determined as described previously (Knoop et al, J Clin Oncol. 2005). TMA s were constructed and analyzed centrally for TIMP-1 expression by IHC (± tumor cell immunoreactivity). TIMP-1 was combined with HER-2 into a joint HT marker (HT-non-responsive (HT-NR): HER-2 normal and TIMP-1 positive or HT-responsive (HT-R): HER-2 positive and/or TIMP-1 negative) and with TOP2A into a joint 2T marker (2T-NR: TOP2A normal and TIMP-1 positive or 2T-R: TOP2A abnormal and/or TIMP-1 negative). Relationships between IDFS, OS and the HT/2Tprofiles were analyzed using multivariate regression analysis. Results: Among patients with a HT-R profile CEF was superior to CMF in terms of both invasive disease-free survival (IDFS) (HR 0.62; 95% CI 0.45–0.86; p = 0.004) and overall survival (OS) (HR 0.63; 95% CI, 0.45–0.87; p = 0.005). In patients with a HT-NR profile, no significant differences between CEF and CMF were demonstrated for IDFS or OS. A significant HT profile (HT-R or HT-NR) versus treatment (CEF or CMF) interaction was detected by the Wald-test for both IDFS (p = 0.036) and OS (p = 0.047). An even more pronounced separation was observed regarding the 2T profile, and in patients with a 2T-R profile treatment with CEF was superior to CMF in terms of IDFS (HR 0.48; 95% CI 0.34–0.69; p < 0.001) and OS (HR 0.54; 95% CI, 0.38–0.77; p < 0.001). No significant difference was observed in patients with a 2T-NR profile. A highly significant 2T profile versus treatment interaction was detected for IDFS (p < 0.001) and OS (p = 0.004). Conclusions: Profiles created by joining TIMP-1 with either HER-2 status or TOP2A gene status seems advantageous compared to the use of a single marker. [Table: see text]

scholarly journals A Retrospective, Observational Study to Determine the Patient and Tumor Characteristics of HER2-Positive Breast Cancer Patients Treated at Five Main Public Cancer Centers in Malaysia

2020 ◽  
Vol 6 (01) ◽  
pp. 10-19
Author(s):  
Ros Suzanna Ahmad Bustamam ◽  
Yu Kong Leong ◽  
Flora Li Tze Chong ◽  
Florence Wong Yoke Fui ◽  
Yew-Teik Cheong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
High Risk ◽  
Cancer Patients ◽  
Lymph Node Involvement ◽  
Tumor Characteristics ◽  
Limited Information ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Node Involvement

Abstract Introduction Human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer is a high-risk subtype with poor prognosis. The incidence of HER2 expressing tumors is high in Malaysia; however, there is limited information on the characteristics of these tumors. Therefore, we sought to collect the patient and tumor characteristics of HER2+ breast cancer cases at five centers in Malaysia. Patients and Methods A retrospective review was conducted of the data from charts of patients diagnosed with HER2+ breast cancer between January 2014 and December 2015 at Hospital Kuala Lumpur, Institute Kanser Negara, Hospital Pulau Pinang, Hospital Besar Sarawak, and Hospital Likas in Malaysia. Results Of the 1,519 screened patient’ charts, 396 were included for the analysis. The average age of HER2+ breast cancer cases at diagnosis was 51.07 years. A high percentage of cases presented at an advanced stage (38.89 and 12.12% with stage 3 and 4, respectively). About 58.84% of patients were categorized as “high-risk,” with one or more lymph node involvement. Close to half (47.98%) of cases presented with T2 stage tumors, and infiltrating ductal carcinomas were reported in 85.35% of tumors. The most common immunohistochemical subtype was estrogen receptor (ER)+/progesterone receptor (PR)+/HER2+ (47.47%), followed by ER–/PR–/HER2+ (37.12%). Conclusion HER2 overexpressing tumors represent an aggressive subtype in Malaysia with large tumor size, high tumor grade, and lymph node involvement. Early diagnosis and management of these tumors may help improve the survival rates. Future studies should help elucidate the treatment patterns and outcomes in HER2+ breast cancer patients in Malaysia.

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