scholarly journals Improved risk estimation of locoregional recurrence, secondary contralateral tumors and distant metastases in early breast cancer: the INFLUENCE 2.0 model

2021 ◽  
Author(s):  
Vinzenz Völkel ◽  
Tom A. Hueting ◽  
Teresa Draeger ◽  
Marissa C. van Maaren ◽  
Linda de Munck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Clinical Decision Making ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Time Dependent ◽  
Individual Risk ◽  
Primary Tumors ◽  
Statistical Approaches

Abstract Purpose To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases (DM) using updated follow-up data and the best suitable statistical approaches. Methods Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (n = 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples. Results Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created. Conclusions INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.

scholarly journals Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jenny Stenström ◽  
Ingrid Hedenfalk ◽  
Catharina Hagerling
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Prognostic Factor ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Independent Prognostic Factor ◽  
Primary Tumors

Abstract Background Patients diagnosed with metastatic breast cancer have poor outcome with a median survival of approximately 2 years. While novel therapeutic options are urgently needed, the great majority of breast cancer research has focused on the primary tumor and less is known about metastatic breast cancer and the prognostic impact of the metastatic tumor microenvironment. Here we investigate the immune landscape in unique clinical material. We explore how the immune landscape changes with metastatic progression and elucidate the prognostic role of immune cells infiltrating primary tumors and corresponding lymph node and more importantly distant metastases. Methods Immunohistochemical staining was performed on human breast cancer tissue microarrays from primary tumors (n = 231), lymph node metastases (n = 129), and distant metastases (n = 43). Infiltration levels of T lymphocytes (CD3+), regulatory T lymphocytes (Tregs, FOXP3+), macrophages (CD68+), and neutrophils (NE+) were assessed in primary tumors. T lymphocytes and Tregs were further investigated in lymph node and distant metastases. Results T lymphocyte and Treg infiltration were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs in primary tumors correlated with proliferation (P = 0.007, P = 0.000) and estrogen receptor negativity (P = 0.046, P = 0.026). While both T lymphocyte and Treg infiltration had a negative correlation to luminal A subtype (P = 0.031, P = 0.000), only Treg infiltration correlated to luminal B (P = 0.034) and triple-negative subtype (P = 0.019). In primary tumors, infiltration of T lymphocytes was an independent prognostic factor for recurrence-free survival (HR = 1.77, CI = 1.01–3.13, P = 0.048), while Treg infiltration was an independent prognostic factor for breast cancer-specific survival (HR = 1.72, CI = 1.14–2.59, P = 0.01). Moreover, breast cancer patients with Treg infiltration in their distant metastases had poor post-recurrence survival (P = 0.039). Treg infiltration levels changed with metastatic tumor progression in 50% of the patients, but there was no significant trend toward neither lower nor higher infiltration. Conclusion Treg infiltration could have clinical applicability as a prognostic biomarker, deciphering metastatic breast cancer patients with worse prognosis, and accordingly, could be a suitable immunotherapeutic target for patients with metastatic breast cancer. Importantly, half of the patients had changes in Treg infiltration during the course of metastatic progression emphasizing the need to characterize the metastatic immune landscape.

Survival after locoregional recurrence in patients after breast cancer surgery.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 141-141
Author(s):  
T. Osako ◽  
R. Nishimura ◽  
Y. Okumura ◽  
R. Tashima ◽  
Y. Toyozumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Primary Tumor ◽  
Locoregional Recurrence ◽  
Distant Metastases ◽  
Breast Conserving Therapy ◽  
Breast Cancer Surgery ◽  
Systemic Metastasis

141 Background: The purpose of this study was to investigate factors for survival after locoregional recurrence in patients who underwent mastectomy or breast-conserving therapy (BCT) for primary breast cancer in our hospital. Methods: Out of 3,332 patients operated on from 1989 to 2008, 50 patients had chest wall recurrences after mastectomy (CWR), 40 patients had regional nodal recurrences (RNR), and 24 patients had ipsilateral breast tumor recurrences (IBTR) from 1997 to 2008. To investigate the prognostic factors for survival after locoregional recurrence, we conducted uni- and multivariate analyses of these cases. Results: The median follow-up time was 49.2 months. The 5-year survivals after recurrence of the patients with CWR, RNR and IBRT were 52%, 28%, and 68%, respectively. And the 10-year survivals were 15%, 0%, and 62%, respectively. Furthermore, the 5-year distant metastasis-free survivals were 24%, 13%, and 59%, respectively. In a multivariate analysis of the patients with CWR, type of recurrent nodules (diffuse/single, RR 21.0, p= 0.001), pT (T3 or 4 /T1, RR 11.4, p=0.01), pN (N3/N0, RR 15.5, p= 0.03), Ki67 of primary tumor (>50%/<20%, RR6.7, p=0.02) and ER of the primary tumor (+ / -, RR 2.6, p = 0.02) were independent prognostic factors. In a multivariate analysis of RNR, the method of first line salvage therapy (local /local + systemic, RR 16.1, p = 0.01) was only an independent prognostic factor. In the cases of IBTR, there were no independent prognostic factors for survival after recurrence. Conclusions: Although CWR developed distant metastases within 5 years, the survival depended upon the several biological factors. RNR developed distant metastases within a few years and provided poor prognosis. These suggested that RNR would be the first appearance of systemic metastasis not local disease. In contrast, IBTR provided better prognosis and a salvage treatment cured about 60% of the patients.

Association of a compact 13-gene VEGF signature with OS in E2100.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1027-1027 ◽  
Author(s):  
Scooter Willis ◽  
Kathy Miller ◽  
Brandon F Young ◽  
Charles M. Perou ◽  
Zhiyuan Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Predictive Biomarker ◽  
Phase Iii ◽  
Open Label ◽  
Primary Tumors ◽  
Regional Metastases ◽  
Poor Outcomes

1027 Background: E2100, an open-label, randomized, phase III trial, demonstrated a significant improvement in progression free survival and overall response rate with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer. Genentech completed additional clinical trials and submitted these data to the FDA. On 18 Nov, 2011, the FDA Commissioner revoked the agency’s approval of bevacizumab for the breast cancer indication because of the lack of evidence of an improvement in overall survival or a clinical benefit to patients sufficient to outweigh the risks. However, the Commissioner “encouraged Genentech to consider additional studies to identify if there are select subgroups of women who might benefit from this drug”. Hu et al. (BMC Medicine 2009) published a compact 13 gene VEGF-signature associated with distant metastases and poor outcomes. Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast/mesenchymal genes, and by the high expression of a 13 gene profile that included VEGF, ANGPTL4, ADM and the monocarboxylic acid transporter SLC16A3. Methods: We have investigated the VEGF signature in silico on Illumina DASL analysis of 122 FFPE samples remaining from E2100. Results: PFS benefit is seen for pacli + bev vs pacli in both treatment arms with the low VEGF signature (HR 0.45 95% CI .27-.77 p .009 n 67) and with the high VEGF signature (HR 0.57 95% CI .32-1.0 p .015 n 55). However, OS benefit is only seen for pacli + bev vs pacli in the high VEGF group (HR 0.56 95% CI .30-1.05 p .02 n 52) and not in patients with the low VEGF signature (HR 1.12 95% CI .66-1.90 p .81 n 67). Conclusions: Hence, this signature, which suggests that the response to hypoxia includes the ability to promote new blood and lymphatic vessel formation, shows great potential as a predictive biomarker of those patients to whom bevacizumab would convey an OS advantage benefit. We note with great caution that this exploratory analysis of trial subset is underpowered, hence, this compact VEGF signature is being pursued in other bevacizumab trial sets.

Symptomatic Metastases have Poorer Prognosis in Breast Cancer Patients Under Intensive Surveillance

2021 ◽  
Author(s):  
Sung Mi Jung ◽  
Jai Min Ryu ◽  
Byung Joo Chae ◽  
Jonghan Yu ◽  
Jeong Eon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Breast Cancer Patients ◽  
Asymptomatic Group ◽  
Symptomatic Group ◽  
Intensive Surveillance

Abstract Purpose The purpose of this study was to investigate risk factors for post-metastasis overall survival (PMOS), and to analyze the effect of early detection of distant metastases before symptoms occur on survival in breast cancer patients under intensive surveillance.Methods A total of 7,840 patients underwent surgery for breast cancer from January 2010 to December 2014 at Samsung Medical Center; of these, we retrospectively studied 316 metastatic breast cancer patients. The patients were divided into two groups based on method of metastases detection, routine surveillance without symptoms (asymptomatic group) or follow-up for new-onset symptoms (symptomatic group).Results Multivariate analysis of PMOS showed that the patients with multiple metastases had a 1.872 fold risk of PMOS (p = 0.011) compared to the patients with bone metastasis only. The hazard ratio for the symptomatic group was higher than that for the asymptomatic group (p < 0.001). When patients were stratified by tumor subtype, patients who were HR-positive and asymptomatic on diagnosis of distant metastasis had a better prognosis than those who were HR-positive and symptomatic on diagnosis. However, patients who were HER2-positive showed no significant survival difference between two groups.Conclusion Breast cancer patients who were diagnosed with distant metastasis after symptoms occurred had a poorer prognosis than patients who were diagnosed before symptoms had developed. It is important to follow up patients regularly for symptoms related to distant metastases. Our findings validate the need for intensive surveillance, suggesting reconsideration of the guidelines for metastases screening in breast cancer patients.

scholarly journals Serial Circulating Tumor DNA Identification Associated with the Efficacy and Prognosis of Neoadjuvant Chemotherapy in Breast Cancer

2021 ◽  
Author(s):  
Yidong Zhou ◽  
Yaping Xu ◽  
Changjun Wang ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Circulating Tumor Dna ◽  
College Hospital ◽  
Primary Tumors ◽  
Blood Samples ◽  
Tumor Dna

Abstract Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1,021-gene panel. Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, one versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904–290.9; p < 0.0001). Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient survival. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.Trial registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).

Phase Ib study of rebastinib plus antitubulin therapy with paclitaxel or eribulin in patients with metastatic breast cancer (MBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2611-TPS2611
Author(s):  
Jesus Del Santo Anampa Mesias ◽  
Maja H. Oktay ◽  
Xiaonan Xue ◽  
John Condeelis ◽  
Joseph A. Sparano
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Circulating Tumor Cell ◽  
Primary Objective ◽  
Primary Tumors ◽  
Phase Ib ◽  
Tie2 Receptor ◽  
Pharmacodynamic Biomarkers

TPS2611 Background: TMEM (Tumor Microenvironment of Metastasis) are microanatomic structures formed by a Mena-expressing tumor cell, Tie2-expressing macrophage, and endothelial cell in direct content, which serve as the primary portal for tumor cell intravasation into the circulation and subsequent metastasis. Paclitaxel (P) induces the formation of TMEM in the primary tumors of patients treated with neoadjuvant chemotherapy (NAC), and in the primary tumor and distant metastases in the PyMT/PDX models. Tumor cell intravasation is mediated by release of VEGF at TMEM sites from TMEM-associated Tie2HI/VEGFHI macrophages upon binding of the Tie2 receptor to angiopoietin. The Tie2 inhibitor rebastinib (R) inhibits intravasation at TMEM sites, reduces circulating tumor cell (CTC) burden, prevents distant metastases, and improves survival in breast cancer animal models when added to either P or eribulin (E). We hypothesize that the addition of R to antitubulin therapy in patients with HER2-negative MBC will prevent hematogenous dissemination and distant metastasis by inhibiting TMEM function, reduce CTC burden; and improve clinical outcomes. Methods: Primary objective of this phase Ib study (NCT02824575) is to evaluate safety and tolerability of R in two dose levels (DL) (50mg or 100mg PO BID) combined with IV P 80mg/m2 (day 1, 8 and 15) or E 1.4mg/m2 (day1 and 8) for four 21-day cycles. Key eligibility includes histologically confirmed HER2 negative MBC, ≤ 2 non-taxane chemotherapy regimens for R plus P arm or ≥ 2 chemotherapy regimens (including a taxane) for E plus R arm, ≥2 endocrine therapies ( including CDK4/6 inhibitor) for ER positive patients, ECOG PS 0 or 1; and normal organ and marrow function. Exclusion criteria include significant ocular or cardiac disease. Pharmacodynamic biomarkers to be measured during cycle 1-3 include CTCs, angiopoietin 1/2 levels and Tie-2 expressing monocytes. Tissue biopsy after two treatment cycles in 6 patients will be performed to evaluate TMEM score and function. With two DL of rebastinib, and 3-6 patients at each DL, it is anticipated that 6-12 patients will be required. This trial has enrolled two patients assigned to P arm combined with R 50mg BID. Clinical trial information: NCT02824575.

scholarly journals Receptor Conversion between Primary Tumors and Distant Metastases in 121 Cases of Metastatic Breast Cancer

2013 ◽  
Vol 04 (02) ◽  
pp. 102-107
Author(s):  
Chaoying Wang ◽  
Lijun Di ◽  
Kun Yan ◽  
Huiping Li ◽  
Guohong Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Distant Metastases ◽  
Primary Tumors ◽  
Receptor Conversion

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

Sign in / Sign up

Export Citation Format

Share Document