Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

Hashmi, Atif Ali; Hashmi, Kashif Ali; Irfan, Muhammad; Khan, Saadia Mehmood; Edhi, Muhammad Muzzammil; Ali, Javaria; Hashmi, Shoaib Naiyar; Asif, Huda; Faridi, Naveen; Khan, Amir

doi:10.1186/s13104-019-4653-x

Cited by 63 publications

(50 citation statements)

References 20 publications

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“…In our study, tumors in denser breasts (BI-RADS c and d) were more often ER and PR positive compared to tumors in less dense breasts; thus, luminal-like BC was overrepresented in dense breasts. The majority of all tumors were highly proliferative regardless of MD, probably related to the indication of NACT [ 21 ]. Scientific inconsistency exists regarding the association between tumor receptor status and MD [ 22 ]; however, larger tumor size and positive lymph node status are suggested to be linked to high MD [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Skarping

Förnvik

Heide-Jørgensen

et al. 2020

Cancer Causes Control

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Purpose Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods A total of 495 BC patients receiving NACT in Sweden 2005–2019 were included, merged from two different cohorts. Cohort 1 was retrospectively collected (n = 295) and cohort 2 was prospectively collected (n = 200). Mammograms were scored for MD pre-NACT according to the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. The association between MD and accomplishing pCR post-NACT was analyzed using logistic regression models—for the whole cohort, stratified by menopausal status, and in different St. Gallen surrogate subtypes. Results In comparison to patients with low MD (BI-RADS a), the multivariable-adjusted odds ratio (OR) of accomplishing pCR following NACT was on a descending scale: 0.62 (95% confidence interval (CI) 0.24–1.57), 0.38 (95% CI 0.14–1.02), and 0.32 (95% CI 0.09–1.08) for BI-RADS b, c, and d, respectively. For premenopausal patients selectively, the corresponding point estimates were lower, although wider CIs: 0.31 (95% CI 0.06–1.62), 0.24 (95% CI 0.04–1.27), and 0.13 (95% CI 0.02–0.88). Subgroup analyses based on BC subtypes resulted in imprecise estimates, i.e., wide CIs. Conclusions It seemed as though patients with higher MD at baseline were less likely to reach pCR after NACT—a finding more pronounced in premenopausal women. Larger multicenter studies are needed to enable analyses and interpretation for different BC subtypes.

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Section: Discussionmentioning

confidence: 99%

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Skarping

Förnvik

Heide-Jørgensen

et al. 2020

Cancer Causes Control

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“…As glycolysis and tumor aggressiveness relates to high rates of proliferation (13,45), CBX2/7 protein (not CBX4/6/8) correlated significantly with protein levels of tumor proliferation marker Ki67 in TCGA breast tumors ( Fig. S2).…”

Section: Cbx2 and Cbx7 Are The Most Differentially Expressed Isoformsmentioning

confidence: 98%

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

Iqbal

Siddiqui

Rehman

et al. 2020

Preprint

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Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1 (cPRC1), play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N>3000 combined), we identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we determined that contrary effects of CBX2 and CBX7 on breast cancer metabolism were due to differential modulation of the mTORC1 signaling by two isoforms. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and down-regulated isoforms, respectively, in breast tumors compared to normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor aggressiveness. Genomic data showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to clinical drugs. In summary, this work identifies previously unknown antagonistic roles of CBX2 and CBX7 in breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer metabolism.Significance statementMetabolic reprogramming is a hallmark of cancer. Understanding how reprogramming of metabolism is regulated in cancer may reveal therapeutically relevant targets. Using integrative approach, we elucidate the hitherto unknown antagonistic roles of CBX2 and CBX7 in breast cancer metabolism. Highlighting the relevance of identified metabolic roles, we found that CBX2 and CBX7 (not other members) are the most differentially expressed isoforms in breast tumors (compared to normals) and the only isoforms which significantly correlate with breast cancer aggressiveness. Further, CBX2/7 predicted patient outcome and response to drugs used in breast cancer treatment, underscoring clinical significance of our study. In brief, this work unravels novel metabolic roles of CBX2/7 which may have implications in breast cancer treatment.

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“…1D). As glycolysis and tumor aggressiveness relates to high rates of proliferation [49,13] their gene expression ( Fig. S6A).…”

Section: Cbx2 and Cbx7 Are The Most Differentially Expressed Isoformsmentioning

confidence: 99%

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

et al. 2021

View full text Add to dashboard Cite

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins‐CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients ( N > 3000 combined), we performed pathway‐based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up‐ and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease‐specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA‐approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.

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Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

Cited by 63 publications

References 20 publications

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

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