Prognostic impact of proliferation for resected early stage ‘pure’ invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation

Carbognin, Luisa; Sperduti, Isabella; Fabi, Alessandra; Dieci, Maria Vittoria; Kadrija, D.; Griguolo, Gaia; Pilotto, Sara; Guarneri, Valentina; Zampiva, Ilaria; Brunelli, Matteo; Orvieto, Enrico; Nortilli, Rolando; Fiorio, Elena; Parolin, Veronica; Manfrin, Erminia; Caliò, Anna; Nisticò, Cecilia; Pellini, Francesca; Scarpa, Aldo; Pollini, Giovanni Paolo; Conte, Pierfranco; Bria, Emilio

doi:10.1016/j.breast.2017.06.005

Cited by 18 publications

(21 citation statements)

References 21 publications

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“…Conversely (and similarly to our data) tumor histological grade did not result to be an independent prognostic factor for early-stage ILC in a different retrospective series [28]. With regard to the Ki67 role in the lobular histotype, we previously suggested that a very low cut-off of Ki67 (4%e5%) may be able to significantly discriminate the prognosis of patients with 'pure' ILC [2,29]. Our analysis does not represent a simple investigation of prognostic factors for ILC (as previously reported by different retrospective studies); the novelty of this study consists in the development and validation of a prognostic tool (consisting of the combination of reliable clinico-pathological factors with different prognostic weight according to the model's score assessment) easy to adopt in the clinical practice.…”

Section: Discussionsupporting

confidence: 86%

Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model

et al. 2020

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a b s t r a c tIntroduction: The clinico-pathological and molecular factors that drive the prognosis of invasive lobular breast carcinoma (ILC) are not entirely explored. In this regard, the development and validation of a prognostic model for ILC and the investigation of the distribution of molecular abnormalities (focusing on CDK4/6 alterations) according to prognosis were the aims of this study. Patients and methods: Two clinico-pathological multi-center data-sets of early-stage ILC patients (Training/Validation Set, TS/VS) were gathered. A 3-class model was developed according to the multivariate analysis for disease-free-survival (DFS) and externally validated. Mutational, copy number variation and transcriptomic analyses by targeted next generation sequencing (NGS) were performed (and validated with quantitative PCR) in an explorative cohort of patients with poor and good prognosis. Results: Data from overall 773 patients (TS/VS: 491/282) were gathered. The developed model significantly discriminated low/intermediate/high risk in the TS (10-years DFS: 76.3%/67.6%/39.8%, respectively, p<0.0001) and in the VS (p<0.0001). In the explorative cohort for molecular analysis (34 patients), CDK4 gain was present exclusively in the poor prognosis group (35.0%, p ¼ 0.03; OR 7.98, 95%CI 1.51e42.1, p ¼ 0.014). Moreover, CDK4 and 6 overexpression showed a trend toward an association with poor prognosis (OR 2.7, 95%CI 0.4e18.1, p ¼ 0.3; OR 3.29, 95%CI 0.56e19.25, p ¼ 0.18). Conclusions: A risk stratification model, able to accurately separate early-stage ILC patients' prognosis into different risk classes according to clinico-pathological variables, allowed to investigate potential biomarkers of prognosis with targeted NGS. CDK4 gain is suggested for future validation as a prognostic biomarker and a potential therapeutic opportunity in ILC patients.

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Section: Discussionsupporting

confidence: 86%

Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model

et al. 2020

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“…1 Clinicopathologic parameters associated with lobular BC and their prognostic implications are partly controversial. [19][20][21][22][23][24][25][26] In the current retrospective, exploratory subgroup analysis, we evaluated lobular BCs that were included in the PlanB trial, a large, prospective, multicenter phase 3 trial encompassing >2500 HR-positive/HER2-negative BCs. [30][31][32] Lobular BCs accounted for 14% of cases, as determined by central histology review.…”

Section: Discussionmentioning

confidence: 99%

“…Lobular BC was associated with low and intermediate RS (P < .001) ( Table 2). Low RS (range, 0-11), intermediate RS (range, [12][13][14][15][16][17][18][19][20][21][22][23][24][25], and high RS (range, 26-100) Oncotype DX categories were observed in 20%, 72%, and 8% lobular BCs, respectively. The prevalence of high RS results was 3-fold lower in lobular BC compared with nonlobular BC (8% vs 24%; P < .001).…”

Section: Lower Rs In Lobular Bcmentioning

confidence: 98%

Differential impact of prognostic parameters in hormone receptor–positive lobular breast cancer

Christgen

Gluz

Harbeck

et al. 2020

Cancer

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BACKGROUND: Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had hormone receptor-positive early BC (the West German Study Group PlanB trial). METHODS: BCs were centrally reviewed and classified as lobular (n = 353; 14%) or nonlobular (n = 2232; 86%). The median follow-up was 60 months. Five-year disease-free survival (DFS) estimates were obtained using the Kaplan-Meier method. Prognostic parameters were evaluated using Cox proportional hazard models. RESULTS: Lobular BC was associated with higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate RS. The prevalence of high RS (RS range, 26-100) was 3-fold lower in patients who had lobular BC compared with those who had nonlobular BC (8% vs 24%; P < .001). However, 5-year DFS estimates for lobular and nonlobular BC were similar (92.1% and 92.3%, respectively; P = .673). In multivariate analyses, prognostic parameters for DFS in lobular BC included grade 3 (hazard ratio, 5.06; 95% CI, 1.91-13.39) and a pathologic lymph node status (pN) of pN3 (

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“…The role and the detection of Ki67 could vary according to the breast cancer histology [18]. For this reason, we used three histologic types of breast cancers.…”

Section: Methodsmentioning

confidence: 99%

Relationship between the Ki67 index and its area based approximation in breast cancer

et al. 2018

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BackgroundThe Ki67 Index has been extensively studied as a prognostic biomarker in breast cancer. However, its clinical adoption is largely hampered by the lack of a standardized method to assess Ki67 that limits inter-laboratory reproducibility. It is important to standardize the computation of the Ki67 Index before it can be effectively used in clincial practice.MethodIn this study, we develop a systematic approach towards standardization of the Ki67 Index. We first create the ground truth consisting of tumor positive and tumor negative nuclei by registering adjacent breast tissue sections stained with Ki67 and H&E. The registration is followed by segmentation of positive and negative nuclei within tumor regions from Ki67 images. The true Ki67 Index is then approximated with a linear model of the area of positive to the total area of tumor nuclei.ResultsWhen tested on 75 images of Ki67 stained breast cancer biopsies, the proposed method resulted in an average root mean square error of 3.34. In comparison, an expert pathologist resulted in an average root mean square error of 9.98 and an existing automated approach produced an average root mean square error of 5.64.ConclusionsWe show that it is possible to approximate the true Ki67 Index accurately without detecting individual nuclei and also statically demonstrate the weaknesses of commonly adopted approaches that use both tumor and non-tumor regions together while compensating for the latter with higher order approximations.

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Prognostic impact of proliferation for resected early stage ‘pure’ invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation

Cited by 18 publications

References 21 publications

Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model

Targeted next-generation sequencing identifies genomic abnormalities potentially driving the prognosis of early-stage invasive lobular breast carcinoma patients stratified according to a validated clinico-pathological model

Differential impact of prognostic parameters in hormone receptor–positive lobular breast cancer

Relationship between the Ki67 index and its area based approximation in breast cancer

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