Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers

Sato, Kazumi; Miyashita, Minoru; Ishida, Toru; Suzuki, Akihiko; Tada, Hiroshi; Watanabe, Go; Sato‐Tadano, Akiko; Watanabe, Mika; Ohuchi, Noriaki

doi:10.1007/s12282-014-0575-6

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…The associations between lipoproteins and breast cancer development and prognosis may vary by type of lipoproteins, as we observed a positive association between the larger HDLs and PgR expression in breast tumors, but no associations between the smaller and more dense HDL4 and PgR expression. Recently, PgR expression < 20 % has been associated with poor prognosis [ 36 , 47 , 48 ], and patients initially diagnosed with PgR+ breast cancer had a worse outcome if recurrence of disease was PgR− [ 49 ]. Moreover, the TransAttack study showed that the lowest PgR percentage quartile had an unfavourable prognosis as compared to the highest quartile [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

et al. 2016

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BackgroundHigh-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear.MethodsAmong 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics.ResultsThe breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression.ConclusionOur findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0225-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

et al. 2016

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“…Recently in studies that included women with luminal tumors, it was observed a positive association between the Ki‐67 index and the PR expression in relations to overall disease‐free survival and other clinical outcomes; characterizing a better prognosis group between luminal tumors . These data reinforce that constant molecular subclassification may contribute to an even better therapeutical approach, as well as a better understanding of clinical outcomes associated with each breast cancer tumoral phenotype.…”

Section: Discussionmentioning

confidence: 80%

Effect of Ki-67 on Immunohistochemical Classification of Luminal A to Luminal B Subtypes of Breast Carcinoma

et al. 2015

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It has recently been proposed to include an immunohistochemical marker of cell proliferation, Ki-67, as an element with which to classify the molecular subtypes of breast cancer. The objective of this study was to evaluate the effect of the introduction of the Ki-67 marker on the molecular classification of breast cancer by immunohistochemistry. This study was performed on 234 cases of invasive ductal carcinoma of the breast submitted to two immunohistochemical classification panels, one including Ki-67 and the other not. The data obtained with the two classifications were correlated with well-established prognostic factors such as histologic grade, the number of lymph nodes affected and tumor size. The molecular classification without Ki-67 identified: 136 cases of luminal A (58.1%), 19 cases of luminal B (8.1%), 27 cases of human epidermal growth-factor receptor 2 overexpressing (11.5%), 27 cases of basal-like (11.5%), and 25 cases of nonbasal-like triple-negative tumors (10.7%). When Ki-67 was included, this situation changed significantly, with the following cases being identified: 72 cases of luminal A (30.8%) and 83 cases of luminal B tumors (35.5%), resulting in a Kappa score of 0.216. Evaluation of correlations between the luminal A and luminal B tumor subtypes and the selected prognostic factors showed a statistically significant difference only when Ki-67 was included and only with respect to histologic grade (p < 0.001). The new classification with Ki-67 significantly altered the prevalence of the luminal A and luminal B subtypes and improved correlation with the histologic grade.

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“…Especially, the low PR expression has had a high correlation with poor prognosis in postmenopausal patients 11) . PRlow or negative luminal B-like breast cancer showed significantly higher histological grade than that of PR-high luminal B-like breast cancer 12) . In our study, nuclear grade and Ki-67 labeling index were not significant different between PR+ group and PR− group, but showed tendency to higher nuclear grade and Ki-67 labeling index in PR− group.…”

Section: Discussionmentioning

confidence: 81%

Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers

Uchida

Matsui

Notsu

et al. 2016

Nichidai Igaku Zasshi

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Background: It remains unknown whether knowledge of the status of progesterone receptor (PR) expression is useful for distinguishing between luminal A and B breast cancer subtypes and for providing an accurate prognosis for patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer. We aimed to assess the role of PR status in determining the biology and prognosis of early ER+ and HER2− breast cancer.Methods: This was a retrospective study of 105 patients with ER+ and HER2− breast cancer who underwent surgery between 2005 and 2013. Relapse-free survival (RFS), distant-metastasis-free survival (DFS) and overall survival (OS) were evaluated. The prognostic value of PR was evaluated using a Cox regression model.Results: Apart from the menstruation status, there were no significant differences between the PR+ and PR− patients. PR− patients exhibited a tendency towards a higher nuclear grade and Ki-67 labeling index. In particular, postmenopausal patients with PR expression status < 10% exhibited a significantly higher nuclear grade and tendency towards a higher Ki-67 labeling index. After a median follow-up of about 5 years, the 5-year RFS, DFS and OS rates of the PR+ and PR− patients were not significantly different. PR was not a significant prognostic factor by multivariate analysis.Conclusion: PR status does not have prognostic value for patients with early ER+ and HER2− breast cancer who received adequate therapies. However, it may be reasonable to use PR status for distinguishing between luminal A and B breast cancer subtypes.

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Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers

Abstract: Our results show the possibility that PgR status has some influence on the prognosis for Luminal HER2-negative breast cancers. Therefore, attention should be paid to the PgR status as well as Ki-67.

Cited by 16 publications

References 22 publications

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Effect of Ki-67 on Immunohistochemical Classification of Luminal A to Luminal B Subtypes of Breast Carcinoma

Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers

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