High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer

Nishimukai, Arisa; Yagi, Tomoko; Yanai, Ayako; Miyagawa, Yoshimasa; Enomoto, Yukie; Murase, K; Imamura, Michiko; Takatsuka, Yuichi; Sakita, Isao; Hatada, Takuya; Miyoshi, Yasuo

doi:10.1016/j.clbc.2014.12.007

Cited by 42 publications

(32 citation statements)

References 23 publications

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“…When we analyzed the prognostic value according to the level of PR expression, the low PR expression group showed an intermediate prognosis better than the negative PR and worse than the high PR expression group. Nishimukai et al reported that low PR expression is associated with prognosis of ER-positive and HER2-negative breast cancer [25], which agrees with our study.…”

Section: Discussionsupporting

confidence: 93%

“…Although the role of Ki-67 as a prognostic factor is controversial in breast cancer, many studies have shown a relationship between Ki-67 and HR [25,36]. When we divided luminal B HER2-negative breast cancer patients into two subgroups according to a Ki-67 level with cutoff 50 %, the subgroup with higher Ki-67 (>50 %) was related with the negative ER or PR group.…”

Section: Discussionmentioning

confidence: 91%

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Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

et al. 2017

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Background: The luminal subtype of breast cancer is sensitive to anti-estrogen therapy and shows a better prognosis than that of human epidermal growth factor receptor2 (HER2)-enriched or triple-negative breast cancer. However, the luminal type of breast cancer is heterogeneous and can have aggressive clinical features. We investigated the clinical implications of single hormone receptor negativity in a luminal B HER2-negative group. Methods: We collected luminal B HER2-negative breast cancer data that were estrogen receptor (ER) and/or progesterone receptor (PR) positive, Ki 67 high (>14 %), and HER2 negative and divided them into the ERand PR-positive group and the ER-or PR-negative group. We analyzed the clinical and pathological data and survival according to ER or PR loss. Results: There were no statistical differences in TNM stage, breast and axillary operative methods, or number of tumors between the ER-and PR-positive group and ER-or PR-negative group. However, the ER-or PR-negative group was associated with older age (≥45 years), higher histological grade, lower Bcl-2 expression, and far higher Ki 67 (>50 %). Disease-free survival (DFS) and overall survival (OS) were shorter in the ER-or PR-negative group than that in the ER-and PR-positive group (p = 0.0038, p = 0.0071). Conclusions: ER-or PR-negative subgroup showed worse prognosis than ER-and PR-positive subgroup in the luminal B HER2-negative group. We could consider the negativity of ER or PR as prognostic marker in luminal B HER2-negative subtype of breast cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

et al. 2017

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“…Paradoxically however, PR positive patients had better DFS. This result initially appears contradictory, but is in line with other published data [16,[21][22][23]. Low PR expression has been associated with low DFS in ER positive/Her2 negative patients [21], and poor outcome in the Luminal B subgroup [22].…”

Section: Discussionsupporting

confidence: 87%

“…Retrospective studies suggest that PR positivity can be categorized into 3 groups (< 10, 10 to 60 and ≥60 fmol/mg), which can predict the response to adjuvant tamoxifen, and might also be the second most critical factor, equal or even of greater value that ER expression, in predicting DFS [25,26]. The combination of PR expression with Ki-67 seems to improve the accuracy of IHC-based classification of luminal A and luminal B breast cancer, especially for postmenopausal women [21].…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer – a Single Centre Study. (PPLB – 01)

Agrawal

Banswal

Saha

et al. 2016

Indian J Surg Oncol

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Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart from increasing breast conservation rates, also provides an opportunity to assess tumour response to chemotherapy, with Pathological Complete Response (pCR) described as an independent prognostic factor and a surrogate marker for better outcome and survival. Our primary aim was to identify clinical and pathological factors associated with pCR following NACT in patients with LABC treated at our institution. Our secondary aim was to analyze the impact of pCR and associated factors on disease free survival (DFS) and overall survival (OS). A retrospective analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013. Clinical and histological variables were analyzed for association with pCR (no invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier curves and Cox regression model was used for survival analysis. All values were twosided, and statistical significance was defined as p < 0.05. 240 patients were included. The median tumor size was 6 cm, with T4 disease in 49.8 %. 45 % of tumors were of low grade (G1 + G2) and 53.8 % of high grade (G3). Estrogen Receptor (ER) was positive in 70.8 %, progesterone receptor (PR) in 53.3 % and Her2 in 38.8 %. The preferred NACT regimen was sequential anthracycline and taxane and 88.8 % of patients received this regimen. Of 93 potential Her2 Positive patients, only 23 received trastuzumab. Overall 23.2 % patients had pCR. At median follow up of 21 months (range, 3-42), 16.3 % of patients had recurrent disease, and 6.7 % had died. High tumor grade (p = 0.04), PR negative status (p < 0.01) and trastuzumab treatment (p = 0.01) were significant predictors of pCR in univariate analysis. On multivariate analysis PR negativity (OR 3.2, 95 % CI = 1.6 to 6.04, p = 0.001) and Trastuzumab use (OR 0.24, 95 % CI = 0.1 to 0.6, p = 0.004) were significant. Patients with pCR had positive associations with survival (p < .02,OS& .02,DFS) and interestingly PR positivity had positive association with DFS (p = 0.02) in Kaplan-Meier curves. On Cox regression, PR positivity (HR = 0.3, p < 0.01) and pCR (HR = 0.2, p < 0.01) correlated with DFS, though not with early OS. for the PR positive patients were paradoxical. Though less likely to have pCR (15 %, vs 32 % if PR negative), they had better DFS (p = 0.02), and achieving pCR had no survival benefit in this group. In contrast, PR negative patients, irrespective of ER status, had a high pCR rate, and achieving pCR had survival advantage (p < 0.05,DFS& p < 0.02,OS). PR negative patients without pCR had the worst DFS (p < 0.01) among all. High grade and Trastuzumab treatment as predictors of pCR, and pCR as a surrogate marker for survival are well recognized, and are supported by our findings. In present cohort, PR negativity showed prognostic importance independent of ER status. However these results were derived from sub-group, posthoc analysis of data from a pre-existing cohort, without 'apriori' hypothesis for survival analy...

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“…However as already shown in other studies, we also found that ER (+) PR (+) tu-mors tend to have better survival rates than ER (+) and PR(-) tumors. [21,22] Jirström et al suggest that Cyclin D1 is associated with ER and PR receptors and may interact with antiestrogen therapy. They immunohistochemically assessed CCND1 gene amplification in 500 breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cyclin D1 and its relationship to hormone receptors and survival in breast cancer

Alanyalı¹

2017

TJ Oncol

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OBJECTIVEThe aim of the present study was to evaluate rate of cyclin D1 expression and examine its relationship to clinicopathological factors and impact on prognosis in breast cancer patients. METHODSTotal of 85 estrogen receptor (ER)-positive breast cancer patients were included. Expression of cyclin D1, ER, progesterone receptor (PR), and Ki-67 were determined using immunohistochemistry evaluation. RESULTSPatients' median age was 49 years (range: 27-83 years) and cyclin D1 was positive in 90.5% of the patients. Cyclin D1 expression was positively correlated with rate of ER positivity and Ki-67 expression (r=0.4; p<0.0001 and r=0.3; p=0.001, respectively). Five-year disease-free and overall survival (OS) rates were not different between patients with or without cyclin D1 expression (81% vs 79% and 93% vs 87%; p=0.8 and 0.4, respectively). High modified Bloom-Richardson grade (p=0.04), high nuclear grade (p=0.021), and PR negativity (p=0.011) were found to be poor prognostic factors for OS rate in univariate analysis. CONCLUSIONIn this study, cyclin D1 was not found to be prognostic factor; however, it is correlated with ER positivity and Ki-67 expression in breast cancer patients.

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High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer

Cited by 42 publications

References 23 publications

Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer – a Single Centre Study. (PPLB – 01)

Expression of Cyclin D1 and its relationship to hormone receptors and survival in breast cancer

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