Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment

Pasha, Nida; Turner, Nicholas C.

doi:10.1038/s43018-021-00229-1

Cited by 83 publications

(58 citation statements)

References 178 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In comparison, the prediction of treatment response to neoadjuvant chemotherapy based on imaging and radiomics instead of invasive tissue sampling is a fairly new research focus. This new method for predicting treatment response comes with two positive effects: first, its non-invasive nature decreases potential risks associated with invasive procedures, and second, it attends to the intratumoral heterogeneity of breast cancer by enabling whole-tumor analysis (in contrast to focal biopsy), an important factor that has gained reasonable attention in past years [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer

Umutlu

Kirchner

Bruckmann

et al. 2022

Cancers

View full text Add to dashboard Cite

Background: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. Methods: A total of 73 female patients (mean age 49 years; range 27–77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2− group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2− receptor status.

show abstract

Section: Introductionmentioning

confidence: 99%

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer

Umutlu

Kirchner

Bruckmann

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Despite the breakthrough of antineoplastic medication, no effective and specific treatment for heterogeneous tumors has yet been applied (7). The rapid development of inter-tumor heterogeneity causes difficulty in clinical tumor treatment (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Tumor heterogeneity is an important feature of malignant tumor, manifesting as differences of genotype and phenotype between patients or malignant lesions of different organs in the same patient (inter-tumor heterogeneity) (5). Due to the different subtypes of tumor cells, which show various phenotypic characteristics, growth rates and invasion ability, the therapeutic sensitivity to anti-tumor treatment is diverse among various tumor lesions (6,7).…”

Section: Introductionmentioning

confidence: 99%

New classification for advanced breast cancer patients experiencing disease progression during salvage treatment: a single-center retrospective cohort study

Wen¹,

Ren²,

Li³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Attributed to inter-tumor heterogeneity, the therapeutic effect of salvage treatment is diverse and different malignant lesions might manifest various therapeutic responses among advanced breast cancer (ABC) patients. The present study aimed to explore the influence of the mode of lesion response on the subsequent treatment and to subclassify ABC patients for precise prognosis prediction.Methods: Based on the inclusion and exclusion criteria, ABC patients were retrospectively collected and followed up in the Guangdong Provincial Hospital of Chinese Medicine between 2018 and 2021.The treatment responses of all malignant lesions were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Testing subclassified models were constructed based on different assembly mode of progressed malignant lesions for further classification of ABC patients experiencing disease progression following first-line treatment. Multivariate survival analyses were performed to assess the second-line progression-free survival (PFS) of various subgroups and screen the suitable classification model. The most suitable model was utilized to classify enrolled ABC patients as a heterogeneous progression-disease (Heter-PD) group or homogeneous progression-disease (Hom-PD) group. Univariate analysis and multivariate Cox regression survival analyses were performed to assess the prognostic value of each variable.Results: A total of 70 ABC patients experiencing disease progression after first-line treatment were enrolled into the analyses and underwent median follow-up of 10.36 months. We constructed 3 testing models and Model C (Hom-PD was defined when all the target and non-target lesions were evaluated as progression, with or without new lesions) could further distinguish ABC patients with worse survival. The second-line progression-free survival (PFS) times were significantly different between two groups (11.04 vs.6.07 months, P=0.034). For ABC patients retaining partial medication after disease progression of first-line treatment, the Heter-PD group showed a tendency of better second-line PFS than the Hom-PD group (13.18 vs. 3.61 months, P=0.430).Conclusions: Based on the disease progression mode after first-line treatment, the classification model could classify ABC patients as Hom-PD and Heter-PD subgroups, which manifest distinct prognoses during the sequential treatment. For Heter-PD patients, retainment of partial medication might be a rational choice for second-line therapy.

show abstract

“…A tissue biopsy provides a snapshot of a tissue sample at a given time with only a small fraction of the suspected tumor extracted for a biopsy [3]. Subsequently, an even smaller fraction of tissue is analyzed, and therefore the tissue biopsy may not accurately portray intratumor spatial heterogeneity [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…With continued advances in cancer research [7][8][9], multiregion genetic analysis of consecutive tumors has shown that each tumor presents diverse, spatially distinct mutations with varied phenotypes within the same tumor [6]. Moreover, a single tumor biopsy sample With continued advances in cancer research [7][8][9], multiregion genetic analysis of consecutive tumors has shown that each tumor presents diverse, spatially distinct mutations with varied phenotypes within the same tumor [6]. Moreover, a single tumor biopsy sample may be inadequate to develop personalized medicine strategies due to the variations in tumor properties [10,11].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

et al. 2022

View full text Add to dashboard Cite

Advances in cancer research over the past half-century have clearly determined the molecular origins of the disease. Central to the use of molecular signatures for continued progress, including rapid, reliable, and early diagnosis is the use of biomarkers. Specifically, extracellular vesicles as biomarker cargo holders have generated significant interest. However, the isolation, purification, and subsequent analysis of these extracellular vesicles remain a challenge. Technological advances driven by microfluidics-enabled devices have made the challenges for isolation of extracellular vesicles an emerging area of research with significant possibilities for use in clinical settings enabling point-of-care diagnostics for cancer. In this article, we present a tutorial review of the existing microfluidic technologies for cancer diagnostics with a focus on extracellular vesicle isolation methods.

show abstract

Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment

Cited by 83 publications

References 178 publications

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer

New classification for advanced breast cancer patients experiencing disease progression during salvage treatment: a single-center retrospective cohort study

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

Contact Info

Product

Resources

About