Molecular subtype conversion in CTCs as indicator of treatment adequacy associated with metastasis-free survival in breast cancer

Grigoryeva, E. S.; Таширева, Л. А.; Alifanov, V.V.; Savelieva, O.E.; Вторушин, С. В.; Zavyalova, М. V.; Bragina, Olga; Garbukov, E. Yu.; Cherdyntseva, N.; Choinzonov, E. L.; Перельмутер, В. М.

doi:10.1038/s41598-022-25609-0

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…Grigoryeva et al. [ 25 ] observed changes in molecular subtypes in 90% of untreated breast cancer patients and 82% of those treated with neoadjuvant chemotherapy. Changes in molecular subtypes were more diverse in patients treated with neoadjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in the molecular interface of cancer cells during tumor growth and progression can be associated with many adverse effects, such as drug resistance, local recurrence, and metastatic spread. HR/HER-2 status and Ki-67 expression in tumor cells determine molecular subtype classification and treatment decisions in breast cancer patients [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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The relationship of changes in molecular subtypes with metastases and progression-free survival in breast cancer

Amansyah,

Prihantono,

Hamid

et al. 2024

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BACKGROUND: Molecular subtyping of breast cancer cells is increasingly being developed as an initial step in selecting therapy and predicting the prognosis of breast cancer patients. During breast cancer, the molecular subtype of cancer cells can change. This study aimed to analyze the relationship between changes in the intrinsic subtype of breast cancer with metastasis and progression-free survival in breast cancer patients. METHODS: This was a retrospective cohort study of patients diagnosed with breast cancer from 2016 to 2021. The molecular subtypes from the immunohistochemical examination results were recorded twice, and metastasis and progression-free survival (PFS) were recorded. The data were analyzed using the chi-square test and SPSS 26. RESULTS: Of the 44 patients, 19 (43.2%) experienced a change in molecular subtype, and 25 (56.8%) did not. No significant relationship existed between changes in molecular subtype and metastasis (p = 0.405). No significant relationship existed between changes in molecular subtype and PFS (p = 0.900). A significant relationship was found between changes in the molecular subtype and PFS in the patients with changes in the molecular subtype (p = 0.022). CONCLUSIONS: Changes in the intrinsic subtype were associated with PFS in breast cancer patients. Patients with an intrinsic subtype that changed to triple-negative showed worse PFS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The relationship of changes in molecular subtypes with metastases and progression-free survival in breast cancer

Amansyah,

Prihantono,

Hamid

et al. 2024

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“…In MBC, CD47 is expressed in most CTCs and is considered one of the markers identifying CTCs with tumor-initiating capacity. A recent report identified PD-L1-positive CTCs in patients with HR+/HER2−MBC [143].…”

Section: The Complex Interplay Between Immune Dynamics and Ctcs In Br...mentioning

confidence: 93%

“…Furthermore, Grigoryeva et al conducted pioneering research uncovering PD-L1 expression on CTCs in individuals diagnosed with HR+/HER2− BC. This discovery suggests a mechanism by which CTCs in this subtype may resist immune attacks [143].…”

Section: Immunological Dynamics Across Breast Cancer Subtypes: a Comp...mentioning

confidence: 93%

Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells

Kotsifaki,

Maroulaki,

Armakolas

2024

IJMS

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This review offers a comprehensive exploration of the intricate immunological landscape of breast cancer (BC), focusing on recent advances in diagnosis and prognosis through the analysis of circulating tumor cells (CTCs). Positioned within the broader context of BC research, it underscores the pivotal role of the immune system in shaping the disease’s progression. The primary objective of this investigation is to synthesize current knowledge on the immunological aspects of BC, with a particular emphasis on the diagnostic and prognostic potential offered by CTCs. This review adopts a thorough examination of the relevant literature, incorporating recent breakthroughs in the field. The methodology section succinctly outlines the approach, with a specific focus on CTC analysis and its implications for BC diagnosis and prognosis. Through this review, insights into the dynamic interplay between the immune system and BC are highlighted, with a specific emphasis on the role of CTCs in advancing diagnostic methodologies and refining prognostic assessments. Furthermore, this review presents objective and substantiated results, contributing to a deeper understanding of the immunological complexity in BC. In conclusion, this investigation underscores the significance of exploring the immunological profile of BC patients, providing valuable insights into novel advances in diagnosis and prognosis through the utilization of CTCs. The objective presentation of findings emphasizes the crucial role of the immune system in BC dynamics, thereby opening avenues for enhanced clinical management strategies.

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“…The sample processing and immunophenotyping was performed as described in our previous study 11 . Blood samples were collected to EDTA pre-coated 9 mL tubes, then incubated at 37 °C for 1.5 h. White blood cells were aspirated from thin white layer between plasma and red blood cells after their sedimentation.…”

Section: Methodsmentioning

confidence: 99%

EpCAM-CD24+ circulating cells associated with poor prognosis in breast cancer patients

Perelmuter,

Grigoryeva,

Savelieva

et al. 2024

Sci Rep

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Following the discovery of circulating tumor cells (CTCs) in the peripheral blood of cancer patients, CTCs were initially postulated to hold promise as a valuable prognostic tool through liquid biopsy. However, a decade and a half of accumulated data have revealed significant complexities in the investigation of CTCs. A challenging aspect lies in the reduced expression or complete loss of key epithelial markers during the epithelial-mesenchymal transition (EMT). This likely hampers the identification of a pathogenetically significant subset of CTCs. Nevertheless, there is a growing body of evidence regarding the prognostic value of such molecules as CD24 expressing in the primary breast tumor. Herewith, the exact relevance of CD24 expression on CTCs remains unclear. We used two epithelial markers (EpCAM and cytokeratin 7/8) to assess the count of CTCs in 57 breast cancer patients, both with (M0mts) and without metastasis (M0) during the follow-up period, as well as in M1 breast cancer patients. However, the investigation of these epithelial markers proved ineffective in identifying cell population expressing different combinations of EpCAM and cytokeratin 7/8 with prognostic significance for breast cancer metastases. Surprisingly, we found CD24+ circulating cells (CCs) in peripheral blood of breast cancer patients which have no epithelial markers (EpCAM and cytokeratin 7/8) but was strongly associated with distant metastasis. Namely, the count of CD45-EpCAM-CK7/8-CD24+ N-cadherin—CCs was elevated in both groups of patients, those with existing metastasis and those who developed metastases during the follow-up period. Simultaneously, an elevation in these cell counts beyond the established threshold of 218.3 cells per 1 mL of blood in patients prior to any treatment predicted a 12-fold risk of metastases, along with a threefold decrease in distant metastasis-free survival over a 90-month follow-up period. The origin of CD45-EpCAM-CK7/8-CD24+ N-cadherin—CCs remains unclear. In our opinion their existence can be explained by two most probable hypotheses. These cells could exhibit a terminal EMT phenotype, or it might be immature cells originating from the bone marrow. Nonetheless, if this hypothesis holds true, it's worth noting that the mentioned CCs do not align with any of the recognized stages of monocyte or neutrophil maturation, primarily due to the presence of CD45 expression in the myeloid cells. The results suggest the presence in the peripheral blood of patients with metastasis (both during the follow-up period and prior to inclusion in the study) of a cell population with a currently unspecified origin, possibly arising from both myeloid and tumor sources, as confirmed by the presence of aneuploidy.

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Molecular subtype conversion in CTCs as indicator of treatment adequacy associated with metastasis-free survival in breast cancer

Cited by 7 publications

References 26 publications

The relationship of changes in molecular subtypes with metastases and progression-free survival in breast cancer

The relationship of changes in molecular subtypes with metastases and progression-free survival in breast cancer

Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells

EpCAM-CD24+ circulating cells associated with poor prognosis in breast cancer patients

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