Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis

Poulakaki, Nikiforita; Makris, Georgios‐Marios; Παπανώτα, Αριστέα-Μαρία; Marineli, Filio; Marinelis, Alexandros; Battista, Marco-Johannes; Boehm, Daniel; Psyrri, Amanda; Sergentanis, Theodoros N.

doi:10.1016/j.clbc.2017.12.007

Cited by 24 publications

(23 citation statements)

References 55 publications

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“…We noted that in multivariate analysis tumour grade outperforms slightly proliferation-only-based Ki67 and is much more potent than the progesterone receptor itself. As the debate on the independent role of Ki67 has a long history, we do not extend this part of discussion here and direct the reader to numerous meta-analyses, reviews, and methodological papers [7,8,9,10,11,12,13]. Based on our data, we do not claim that tumour grade should be interpreted over Ki67 as a predictor of response and risk; we only stress the importance of grading as an ad- junct method of prognosis determination.…”

Section: Discussionmentioning

confidence: 86%

Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively

Jarząb¹,

Stobiecka²,

Badora-Rybicka³

et al. 2019

pjp

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Currently, breast cancer chemotherapy response can be predicted based on various parameters, with common reporting of tumour grade and Ki67 proliferation index. We analysed their association with pathological complete response (pCR) in a multivariate approach. The study was carried out in a group of 353 patients, treated by preoperative chemotherapy and prospectively observed. In selected patients, parallel to routing core needle biopsy assessment, gene expression profile of tumour was analysed by oligonucleotide microarrays. Tumour parameters associated with pCR in univariate analysis were: tumour grade, nuclear grade, mitotic index, Ki67, oestrogen and progesterone receptor (all p < 0.0001), and triple-negative status (p = 0.0032). The highest increase of pCR chance was observed in patients with high-grade tumours and with Ki67 ≥ 20%. In multivariate analysis, only tumour grade and oestrogen receptor status were predictive for pCR independently of other variables, with high grade increasing the odds of pCR 2.42 fold, and high ER decreasing the chance of pCR 0.41 fold. Tumour grading reflects important biological features of breast cancer and is not inferior to proliferation markers, including Ki67. It should be taken into account in decision-making for preoperative chemotherapy in parallel to breast cancer biologic subtypes, because grade 3 tumours exhibit a higher proportion of pCR.

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Section: Discussionmentioning

confidence: 86%

Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively

Jarząb¹,

Stobiecka²,

Badora-Rybicka³

et al. 2019

pjp

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“…S3D). Proliferative markers have demonstrated prognostic and predictive value in various clinical studies of DCIS progression risk (33)(34)(35).…”

Section: Spatial Genomics Reveals Characteristic Differences Between Dcis Clones With Different Fatesmentioning

confidence: 99%

Spatial genomics maps the structure, character and evolution of cancer clones

Lomakin

Svedlund

Strell

et al. 2021

Preprint

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Subclonality is a universal feature of cancers yet how clones grow, are spatially organised, differ phenotypically or influence clinical outcome is unclear. To address this, we developed base specific in situ sequencing (BaSISS). In fixed tissues, transcripts harbouring clone-defining mutations are detected, converted into quantitative clone maps and characterised through multi-layered data integration. Applied to 8 samples from key stages of breast cancer progression BaSISS localised 1.42 million genotype informative transcripts across 4.9cm2 of tissue. Microscopic clonal topographies are shaped by resident tissue architectures. Distinct transcriptional, histological and immunological features distinguish coexistent genetic clones. Spatial lineage tracing temporally orders clone features associated with the emergence of aggressive clinical traits. These results highlight the pivotal role of spatial genomics in deciphering the mechanisms underlying cancer progression.

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“…High proliferative index as assessed with Ki-67 has been shown to be predictive of local non-invasive [21,125], and any local [126,127], recurrence. A recent meta-analysis also found Ki-67 to be predictive of both invasive and noninvasive recurrence [126]. Phosphohistone-H3 (pHH3) has been suggested to be superior to Ki-67 in assessing mitotic activity for its high interobserver concordance and reduced time needed for interpretation [128].…”

Section: Immunohistochemistry Markersmentioning

confidence: 99%

Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies

Hanna

Parra‐Herran

et al. 2019

Modern Pathology

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Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductallobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/ or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.

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Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of the Breast: A Systematic Review and Meta-Analysis

Cited by 24 publications

References 55 publications

Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively

Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively

Spatial genomics maps the structure, character and evolution of cancer clones

Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies

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