Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer

Vetter, Marcus; Landin, Julia; Szczerba, Barbara M.; Castro-Giner, Francesc; Gkountela, Sofia; Donato, Cinzia; Krol, Ilona; Scherrer, Ramona; Balmelli, Cathrin; Malinovska, Alexandra; Zippelius, Alfred; Kurzeder, Christian; Heinzelmann‐Schwarz, Viola; Weber, Walter; Rochlitz, Christoph; Aceto, Nicola

doi:10.1186/s13058-018-1067-y

Cited by 24 publications

(24 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At baseline, clusters were isolated in 50% of our patient cohort. This is slightly higher than recently reported by Vetter et al, who found 35% of their cohort had clusters present prior to treatment [26], using the Parsortix microfluidic device. Studies using the CellSearch™ system report cluster rates around 20% [27].…”

Section: Discussioncontrasting

confidence: 64%

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

O'Toole

Spillane

Huang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Detection and enumeration of Circulating Tumour Cells (CTCs) has been evaluated in many cancers such as breast cancer. However, the full prognostic and predictive power of CTCs for cancer cannot currently be harnessed, and the association between pathological complete response in patients receiving neoadjuvant chemotherapy for breast cancer and CTCs is still not clear. The aim of this study was to assess if CTCs could be used to predict pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: 26 patients were recruited, and blood samples taken pre- and post-neoadjuvant chemotherapy. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets clusters/microemboli. Counts were then correlated to the pathological response as measured by the Miller-Payne grading system. The associations between CTCs and clusters and pathological variables were evaluated with χ2 or ANOVA tests performed in the SPSS 24.0 statistics software. Results: 89% of the patients had invasive ductal carcinoma and 11% invasive lobular carcinoma. At baseline 85% of patients had CTCs present and only 4 patients were CTC negative. Median baseline CTC count was 7 (0-161) CTCs per 3mls of whole blood. Post chemotherapy, 58% of the patients had an increase in CTCs. This change in CTC count did not correlate with the Miller Payne grade of response to chemotherapy. No significant association was identified between the number of CTCs and clinical characteristics, including patient age, receptor status, tumour grade, disease type, lymph node metastasis, lymphovascular space invasion, radiological response or clinical or pathological stage. However, we did observe a correlation between pre-treatment CTC counts and body mass index, p<0.05. Conclusions: There was no correlation between the pre- and post-chemotherapy total number of CTCs/clusters and the Miller Payne grade. It is not enough to evaluate pathological response for neoadjuvant chemotherapy for breast cancer patients utilising CTCs identified by Giemsa staining alone. Additional characterisation is needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in breast cancer patients undergoing neoadjuvant chemotherapy.

show abstract

Section: Discussioncontrasting

confidence: 64%

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

O'Toole

Spillane

Huang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Otherwise, Vetter and colleagues 42 recently reported in a small size sample (n = 20) that some breast cancer patients turned negative during denosumab treatment.…”

Section: Discussionmentioning

confidence: 97%

“…Main methodological differences between the two studies prevent a direct comparison of the data, namely the criteria for defining a cell as CTC -EpCAM + CD45-in Vetter study vs. EpCAM + CK + DAPI + CD45-in our study-, and the procedure for CTC enumeration -manual vs. automated procedure, respectively. Moreover, Vetter www.nature.com/scientificreports www.nature.com/scientificreports/ and colleagues 42 did not describe the time-line schedule of blood draws subsequent the baseline one, hence we cannot compare time-matched CTC enumeration.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer

Pantano

Rossi

Iuliani

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Receptor-activator of nuclear-factor-κB-ligand (RANKL) and its receptor RANK have been recently identified as key players in breast cancer bone metastases. Since Circulating Tumor Cells (CTCs) are considered a crucial step of metastatic process, we explored RANK expression on CTCs in metastatic breast cancer (MBC), and the predictive value of RANK-positive CTCs in monitoring patients during treatment with denosumab (anti-RANKL antibody). To this purpose, we developed a novel CTC assay to quantify RANK-positive CTCs in forty-two bone MBC patients, candidates to denosumab treatment. Companion algorithms ΔAUC and Slope were developed, and correlated with time to first skeletal-related-events (SRE), time to bone metastasis progression and time to visceral metastasis progression. Twenty-seven patients had at least one CTC at baseline and, among these, nineteen (70%) had one or more RANK-positive CTCs. Notably, the baseline total CTCs, but not the RANK-positive, were associated with Time-to-first-SRE, Time-to-Bone-Metastasis-Progression and Time-to-Visceral-Metastasis-Progression. Conversely, during treatment monitoring, positive ΔAUC value, expression of RANK-positive CTCs persistence, correlated with longer Time-to-first-SRE (p = 0.0002) and Timeto-Bone-Metastasis-progression (p = 0.0012). Furthermore, the early increase at second day, in RANK-positive CTCs (Positive-Slope) was associated with delay in time-to-first-SRE (p = 0.0038) and time-to-Bone-Metastasis-progression (p = 0.0024). We demonstrate, for the first time, the expression of RANK on CTCs in MBC patients and that the persistence of RANK expression determines denosumab effectiveness. Receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK axis represents the main characterized therapeutic target to prevent bone metastasis in solid tumors 1. About 70% metastatic breast cancer (MBC) patients develops skeletal metastases often associated to skeletal related events (SREs) with a serious negative impact on patients' quality of life 2. Accumulating evidences suggest that RANKL/RANK signaling, not only influences bone microenvironment, mediating osteoclast activity and survival, but also promotes BC metastases 1,3. Indeed, RANK-RANKL blocking antibodies showed antitumor efficacy in bone MBC preclinical models both in preventive 4,5 and therapeutic settings 4,6,7. This antitumor effect could be either "indirect" through the inhibition of bone resorption that, in

show abstract

“…It would be beneficial to accumulate more knowledge in regard to the shedding process; does it occur constantly or in waves and what stimuli trigger it? For example, it was recently demonstrated that CTCs' presence correlates with low red blood cell count and that the treatment with the monoclonal antibody denosumab is associated with the absence of CTCs [22].…”

Section: Factors Affecting the Number Of Circulating Tumor Cells (Ctcmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

View full text Add to dashboard Cite

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.There are two main hypotheses describing cancer dissemination: linear progression, according to which, metastatic potential is gained gradually, and the whole process proceeds in steps and needs time, and parallel progression, according to which dissemination takes place early on, even before clinical manifestation of the tumor [6,7] (Figure 1). In the linear progression model, the evolving primary tumor gives rise to metastases due to increasingly aggressive and invasive phenotypes of the subclones of tumor cells. This model is in agreement with the postulated role of the epithelial-to-mesenchymal transition (EMT) in cancer and assumes active degradation of the stroma and migration into blood vessels by the motile, invasive single cells that broke loose from the epithelial monolayer. In contrast to that, parallel progression postulates intravasation by passive shedding, which may take place shortly after the angiogenic switch, occurring during the early, pre-invasive stage of tumor development [8,9].

show abstract

Denosumab treatment is associated with the absence of circulating tumor cells in patients with breast cancer

Cited by 24 publications

References 24 publications

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy

Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Contact Info

Product

Resources

About