P183 Prognostic impact of discordance of biological markers between primary and metastatic breast cancer tissue from autopsy

Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case–control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04–0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13–0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77–7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.

Download Full-text

Evaluation of HER-2/neu in Serum and Tissue of Primary and Metastatic Breast Cancer Patients using an Automated Enzyme Immunoassay

The International Journal of Biological Markers ◽

10.1177/172460080101600406 ◽

2001 ◽

Vol 16 (4) ◽

pp. 255-261 ◽

Cited By ~ 24

Author(s):

R. Dittadi ◽

M. Zancan ◽

A. Perasole ◽

M. Gion

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Breast ◽

Normal Subjects ◽

Continuous Variable ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Breast Cancer Patients ◽

Her 2

Serum HER-2/neu concentrations were evaluated in 172 healthy subjects, 176 primary and 55 metastatic breast cancer patients, employing a new automated assay (Bayer Immuno 1™ serum HER-2/neu). Using 13 ng/mL as the cutoff, abnormal HER-2/neu serum levels were found in 8% (14/176) of primary and 50.9% (28/55) of metastatic breast cancer patients. Both in primary and metastatic breast cancer a significant relationship was found with the stage of the disease when serum HER-2/neu was considered as a categorized variable (p=0.0003 and p=0.02, respectively), but not when it was taken as a continuous variable (p=0.247 and p=0.146, respectively). Moreover, we evaluated the correlation between Immuno 1™ HER-2/neu and Oncogene Research Products ELISA assay in 53 normal subjects, 46 primary and 34 metastatic breast cancer patients. The correlation was relatively good (p<0.0001), although substantial differences could be found in single cases. The Immuno 1™ assay was also evaluated for the first time in breast cancer tissue. The method, which showed good performance both in terms of imprecision and linearity, was used to measure HER-2/neu protein in 140 cytosol samples from primary breast cancer tissue and in homogenates from 40 matched cases. The correlation between the two matrixes was very close (p<0.0001). By contrast, no correlation was found between serum and matched cytosol (p=0.101) or ho-mogenate samples (p=0.511).

Download Full-text

Circulating tumor DNA as a dynamic biomarker of response to palbociclib and fulvestrant in metastatic breast cancer patients

Breast Cancer Research ◽

10.1186/s13058-021-01411-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Lauren Darrigues ◽

Jean-Yves Pierga ◽

Alice Bernard-Tessier ◽

Ivan Bièche ◽

Amanda Bartolini Silveira ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Metastatic Breast Cancer ◽

Disease Progression ◽

Somatic Mutations ◽

Metastatic Breast ◽

Circulating Tumor Dna ◽

Prognostic Impact ◽

Radiological Evaluation ◽

Tumor Dna

Abstract Background Following the PALOMA-3 study results, the combination of palbociclib, a CDK4/6 inhibitor, with fulvestrant, a selective estrogen receptor degrader, has become a standard therapy in women with estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). Palbociclib has been shown to increase the progression-free survival (PFS) overall but no predictive biomarker of palbociclib efficacy has been validated so far. We thus evaluated whether early changes of circulating tumor DNA (ctDNA) levels are associated with palbociclib plus fulvestrant efficiency. Methods ER+ HER2− MBC patients were included in a prospective observational cohort before treatment initiation. Tumor response was assessed by radiological evaluation (RECIST v1.1) every 3 months. Plasma samples were collected before treatment (baseline), at day 15 (D15), at day 30 (D30), and at disease progression. We searched for somatic mutations from archived tumor tissues by targeted deep sequencing. For patients with somatic mutations identified, circulating tumor DNA (ctDNA) was tracked using digital droplet PCR. Ratios of ctDNA levels ([D15/baseline] and [D30/baseline]) were then correlated with prospectively registered patient characteristics and outcomes. Results Twenty-five of the 61 patients enrolled had a somatic mutation testable in plasma (NPIK3CA = 21, NTP53 = 2, NAKT1 = 2). At baseline, 84% of patients had detectable ctDNA levels but ctDNA levels had no prognostic impact on PFS (p = 0.10). Among those patients, ctDNA was still detected in 82% at D15 and 68% at D30. ctDNA clearance observed at day 30 was associated with longer PFS (HR = 7.2, 95% CI = 1.5–32.6, p = 0.004). On the contrary, a [D30/baseline] ctDNA ratio > 1 was associated with a shorter PFS (HR = 5.1, 95% CI = 1.4–18.3, p = 0.02) and all 5 patients with increased ctDNA levels at D30 showed disease progression after 3 months under palbociclib-fulvestrant. Finally, at the time of radiological tumor progression, ctDNA was detected in all patients tested. Conclusion Our study demonstrates that the efficiency of palbociclib and fulvestrant can be monitored by serial analyses of ctDNA before radiological evaluation and that early ctDNA variation is a prognostic factor of PFS.

Download Full-text

Synchronous and Metachronous Metastatic Breast Cancer, with Different Histology and Opposite Immunophenotype, Treated with Combination of Chemotherapy, Anti-Her2, and Endocrine Therapy: A Case Report

Case Reports in Oncology ◽

10.1159/000507433 ◽

2020 ◽

Vol 13 (2) ◽

pp. 544-549

Author(s):

Giacomina Megaro ◽

Luigi Rossi ◽

Serena Ceddia ◽

Marsela Sinjari ◽

Adele Mannino ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Case Report ◽

Disease Control ◽

Endocrine Therapy ◽

Biological Markers ◽

Metastatic Breast ◽

Control Therapy

In the case of our patient, the synergic action of endocrine therapy and chemotherapy plus dual anti-HER2 combination allowed a complete disease control. Therapy should be scheduled by considering the two cancers as individual entities. The approach to breast cancer is changing from being considered a singular disease to a multiform one, according to current research focused on biological markers such as HER2, ERs, and PRs, with important implications in clinical, prognostic, and therapeutic features.

Download Full-text

Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables

Scientific Reports ◽

10.1038/s41598-019-53606-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Alejandra Ivars Rubio ◽

Juan Carlos Yufera ◽

Pilar de la Morena ◽

Ana Fernández Sánchez ◽

Esther Navarro Manzano ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Breast Cancer ◽

Performance Status ◽

Univariate Analysis ◽

Metastatic Breast ◽

Prognostic Impact ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

AbstractThe prognostic impact of neutrophil-lymphocyte ratio (NLR) in metastatic breast cancer (MBC) has been previously evaluated in early and metastatic mixed breast cancer cohorts or without considering other relevant prognostic factors. Our aim was to determine whether NLR prognostic and predictive value in MBC was dependent on other clinical variables. We studied a consecutive retrospective cohort of patients with MBC from a single centre, with any type of first line systemic treatment. The association of NLR at diagnosis of metastasis with progression free survival (PFS) and overall survival (OS) was evaluated using Cox univariate and multivariate proportional hazard models. In the full cohort, that included 263 MBC patients, a higher than the median (>2.32) NLR was significantly associated with OS in the univariate analysis (HR 1.36, 95% CI 1.00–1.83), but the association was non-significant (HR 1.12, 95% CI 0.80–1.56) when other clinical covariates (performance status, stage at diagnosis, CNS involvement, visceral disease and visceral crisis) were included in the multivariate analysis. No significant association was observed for PFS. In conclusion, MBC patients with higher baseline NLR had worse overall survival, but the prognostic impact of NLR is likely derived from its association with other relevant clinical prognostic factors.

Download Full-text

P4-07-13: Prognostic Impact of Circulating Tumor Cells Assessed with the Cell Search Assay and Adna Test Breast in Metastatic Breast Cancer Patients – The DETECT Study.

10.1158/0008-5472.sabcs11-p4-07-13 ◽

2011 ◽

Author(s):

V Mueller ◽

S Riethdorf ◽

B Rack ◽

J Wolfgang ◽

PA Fasching ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

Prognostic Impact ◽

Breast Cancer Patients ◽

Cell Search

Download Full-text

Abstract P6-07-34: The prognostic impact of inositol polyphosphate 5-phosphatase PIPP (INPP5J) expression in breast cancer tissue

10.1158/1538-7445.sabcs16-p6-07-34 ◽

2017 ◽

Author(s):

N Kondo ◽

T-S Kim ◽

Y Wanifuchi ◽

Y Hato ◽

T Hisada ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Prognostic Impact ◽

Inositol Polyphosphate

Download Full-text

Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker

Cancers ◽

10.3390/cancers11091243 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1243 ◽

Cited By ~ 9

Author(s):

Giacomo Pelizzari ◽

Debora Basile ◽

Silvia Zago ◽

Camilla Lisanti ◽

Michele Bartoletti ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Lactate Dehydrogenase ◽

Prognostic Factor ◽

Metastatic Breast ◽

Prognostic Impact ◽

Line Treatment ◽

First Line ◽

Cox Regression Analysis ◽

First Line Treatment

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40–5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16–5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00–7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

Download Full-text

Direct Ex Vivo Observation of Homologous Recombination Defect Reversal After DNA-Damaging Chemotherapy in Patients With Metastatic Breast Cancer

JCO Precision Oncology ◽

10.1200/po.18.00268 ◽

2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Titia G. Meijer ◽

Nicole S. Verkaik ◽

Carolien H.M. van Deurzen ◽

Hendrikus-Jan Dubbink ◽

T. Dorine den Toom ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Homologous Recombination ◽

Ex Vivo ◽

Locally Advanced ◽

Metastatic Breast ◽

Cancer Tissue ◽

Predictive Tool ◽

Repair Capacity ◽

Biopsy Specimens

PURPOSE Biomarkers that predict response to poly (ADP-ribose) polymerase inhibitors (PARPis) are required to detect PARPi sensitivity beyond germline BRCA-mutated (gBRCAm) cancers and PARPi resistance among reverted gBRCAm cancers. Therefore, we previously developed the Repair Capacity (RECAP) test, a functional homologous recombination (HR) assay that exploits the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh primary breast cancer tissue. The aim of the current study was to validate the feasibility of this test on histologic biopsy specimens from metastatic breast cancer and to explore the utility of the RECAP test as a predictive tool for treatment with DNA-damaging agents, such as PARPis. METHODS Fresh tissue biopsies from easily accessible metastatic lesions from patients with locally advanced or metastatic breast cancer were irradiated with 5 Gy and cultured for 2 hours followed by detection of RAD51 foci presence (HR proficient) or absence (HR deficient [HRD]). HRD biopsy specimens as well as platinum/PARP-resistant specimens were subjected to BRCA1/2 sequencing. RESULTS RECAP had a success rate of 93% on biopsy specimens from metastatic breast cancer lesions (n = 44). Although HRD was detected in 13 (32%) of 41 specimens, only five showed a gBRCAm. In three patients with gBRCAm, post-treatment RECAP tests showed HR phenotype reversion after in vivo progressive disease on platinum and PARPi treatment, which was explained in one patient by a secondary BRCA1 mutation. CONCLUSION The RECAP test, which reflects real-time HR status regardless of BRCA mutations, is feasible in metastatic breast cancer biopsy specimens. Compared with gBRCA analysis, it may identify twice as many candidates for PARPi treatment.

Download Full-text