Invasive lobular carcinoma of the breast: long-term prognostic value of Ki67 and histological grade, alone and in combination with estrogen receptor

Abstract

BackgroundThe aim of the present study was to investigate the long-term impact of prognostic factors in invasive lobular carcinoma (ILC) of the breast, with a primary focus on Ki67 and histological grade, alone and in combination with estrogen receptor (ER).Material and methodsOne hundred and ninety two well-characterised patients with ILC were included in the study. Ki67, histological grade and ER were evaluated and combined into a prognostic index (KiGE). All grade 1 tumours and ER-positive (ER+) grade 2 tumours with Ki67 ≤ 30% were classified as low-KiGE and all the others as high-KiGE.ResultsOverall, 31% of the patients have died from breast cancer. The median follow-up of the patients still alive was 21 years. Age, tumour size, axillary lymph node status (nodal status), histological grade, Ki67 and KiGE were significant prognostic factors for breast cancer mortality (BCM) in univariable analysis. In a multivariable model, adjusted for adjuvant treatment, age and progesterone receptor (PgR), the strongest prognostic factors for BCM were: Nodal status (hazard ratio (HR) = 2.9, 95% confidence interval (95% CI): 1.4-6.1), KiGE (HR = 2.0, 95% CI: 1.1-3.6), and tumour size (HR = 1.9, 95% CI: 0.98-3.8). By combining these three factors, 37% of the ILC’s could be further divided into a low-risk group, consisting of node negative small (≤ 20 mm) low-KiGE tumours, with a BCM of 5% (95% CI: 1-13%) at 10 years and 12% (95% CI: 5-22%) at 20 years follow-up. None of these patients recieved chemotherapy and only 2 recieved endocrine treatment with tamoxifen.ConclusionsThe combination of Ki67, histological grade and ER into KiGE, together with tumour size and nodal status make it possible to identify a large group of ILC patients with such a good long-term prognosis that chemotherapy can be safely avoided and exclusion of endocrine therapy considered.

Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining

“…Interestingly, in this study, this did not impact the calculated PIs in these carcinomas significantly, as they were still comparable to that of the human observers. Ki67 PI among the lobular carcinomas in this study varied between 0-45 %, most being below 10 % (median 7 %), similar to other study cohorts [17]. The good agreement despite dilution with stromal tissue may in these cases probably be explained by the somewhat similar Ki67 PI in the neoplastic and stromal tissues.…”

Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage ‘pure’ and ‘mixed’ lobular breast cancer

“…Indeed, a study conducted in a large series of ‘pure’ ILC cases adopting a pre-determined Ki67 cut-off of 20 % demonstrated no independently significant prognostic role of Ki67 on prognosis [ 28 ]. Similarly, in another retrospective study the Ki67 value was a significant prognostic factor in univariate analysis, but did not reach significance after adjustment for others known prognostic factors [ 29 ].…”

Factors Affecting Survival After Mastectomy in Invasive Lobülar Carcinoma of the Breast

“…Ancak İLK'nın tanı anında yüksek yaş, büyük tümör boyutu, multisentrisite, multifokalite, bilateralite, hormon reseptör pozitifliği, HER2 negatifliği gibi faktörlerle daha sık ilişkili olduğu bildirilmektedir (9)(10). Meme kanserinde yaş, tümör çapı, lenf nodu metastazı, ER, PR, histolojik grad ve HER2 durumu prognoz ve adjuvan tedavi kararının değerlendirilmesinde önemli faktörler olarak kabul edilmektedir (13). Bizim çalışmamızda hastaların yaklaşık olarak %80'i 40 yaş üzerinde olup, yaş hastalıksız sağkalım için bir risk faktörü olarak saptanmadı.…”