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1.
Wolters R Schwentner L Regierer A Wischnewsky M Kreienberg R Wöckel A 《Breast cancer research and treatment》2012,131(3):925-931
Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter
survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the
correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients
were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877
(18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas
a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15–1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03–1.65)). In hormone-receptor-negative (HR−) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80–1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal
obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24–2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS
(P = 0.202; HR = 1.44 (95% CI: 0.82–2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed
a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63–2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29–1.45)). In accordance with recently published results we demonstrated a negative effect
of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen.
Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed. 相似文献
2.
Ignatov A Ignatov T Weissenborn C Eggemann H Bischoff J Semczuk A Roessner A Costa SD Kalinski T 《Breast cancer research and treatment》2011,128(2):457-466
Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development
of tamoxifen resistance in vitro. This study was undertaken to evaluate the correlation between GPR30 and tamoxifen resistance
in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary
operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort
of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent
tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated
with overexpression of HER-2 (P = 0.021), EGFR (P = 0.024) and lymph node status (P = 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS)
only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter
RFS (HR = 1.768; 95% CI, 1.156–2.703; P = 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an
independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408–13.997; P = 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In
33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen
treatment (P = 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen. 相似文献
3.
Mahmoud SM Lee AH Paish EC Macmillan RD Ellis IO Green AR 《Breast cancer research and treatment》2012,132(2):545-553
Although the favourable role of T lymphocyte populations in different tumour types is established, that of B cells is still
a matter of debate and needs further clarification. The presence of tumour-infiltrating B cells may represent an antibody
response against breast tumour antigens. We used immunohistochemistry to investigate the density and localisation of B lymphocytes
infiltrating 1470 breast tumours and to identify any prognostic significance and relationship to various clinicopathological
factors. Higher numbers of CD20+ cells were found in the stroma away from the carcinoma (mean 12 cells) compared with either intratumoural or adjacent stromal
compartments (mean 1 cell). The majority of tumours showed a diffuse pattern of B cells rather than aggregates. There was
a positive correlation between higher numbers of total CD20+ B cells and higher tumour grade (r
s = 0.20, P < 0.001), ER and PgR negativity (P < 0.001), and basal phenotype (P < 0.001) subclass. In univariate survival analysis, higher total number of infiltrating CD20+ cells, irrespective of location, was associated with significantly better BCSS (P = 0.037) and longer DFI (P = 0.001). In multivariate analysis, total CD20+ B cell count (HR = 0.75, 95% CI = 0.58–0.96 for BCSS and HR = 0.72, 95% CI = 0.58–0.89, for DFI), tumour size, nodal stage,
grade, vascular invasion, HER-2 status, and total CD8+ T cell count were independently associated with outcome. This suggests that humoral immunity, in addition to the cell mediated
immunity, may be important in breast cancer. This should be considered in breast cancer immunotherapy and vaccine strategies. 相似文献
4.
Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies 总被引:1,自引:0,他引:1
Ezzeldin M. Ibrahim Abdelaziz Al-Homaidh 《Medical oncology (Northwood, London, England)》2011,28(3):753-765
Published data have shown that physical activity (PA) has a positive role on the primary prevention of breast cancer risk.
However, the role of PA on breast cancer outcome has been controversial with inconsistent data. The lack of a meta-analysis
that addresses that issue prompted the current report. A comprehensive literature search identified eight studies, of which
two studies were excluded. The remaining six studies (12,108 patients with breast cancer) were included in this meta-analysis.
Pre-diagnosis PA reduced all causes mortality by 18% but had no effect on breast cancer deaths. Post-diagnosis PA reduced
breast cancer deaths by 34% (HR = 0.66, 95% CI, 0.57–0.77, P < 0.00001), all causes mortality by 41% (HR = 0.59, 95% CI, 0.53–0.65, P < 0.00001), and disease recurrence by 24% (HR = 0.76, 95% CI, 0.66–0.87, P = 0.00001). Breast cancer mortality was reduced by pre-diagnosis PA in women with body mass index (BMI) < 25 kg/m2, while
post-diagnosis PA reduced that risk among those with BMI ≥ 25 kg/m2. On the other hand, post-diagnosis PA reduced all causes
mortality regardless of the BMI. The analysis showed that post-diagnosis PA reduced breast cancer deaths (HR = 0.50, 95% CI,
0.34–0.74, P = 0.0005), and all causes mortality (HR = 0.36, 95% CI, 0.12–1.03, P = 0.06) among patients with estrogen receptor (ER)-positive tumor, while women with ER-negative disease showed no gain. The
current meta-analysis provides evidence for an inverse relationship between PA and mortality in patients with breast cancer
and supports the notion that appropriate PA should be embraced by breast cancer survivors. 相似文献
5.
Monique J. Bijl Ron H. N. van Schaik Laureen A. Lammers Albert Hofman Arnold G. Vulto Teun van Gelder Bruno H. Ch. Stricker Loes E. Visser 《Breast cancer research and treatment》2009,118(1):125-130
Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. In
this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Breast
cancer mortality was significantly increased in patients with the *
4/*4 genotype (HR = 4.1, CI 95% 1.1–15.9, P = 0.041) compared to wild type patients. The breast cancer mortality increased with a hazard ratio of 2.0 (CI 95% 1.1–3.4,
P = 0.015) with each additional variant allele. No increased risk of all-cause mortality or all-cancer mortality was found
in tamoxifen users carrying a CYP2D6*4 allele. The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with
the model in which endoxifen formation is dependent on CYP2D6 activity. 相似文献
6.
Zhao S Liu Y Zhang Q Li H Zhang M Ma W Zhao W Wang J Yang M 《Breast cancer research and treatment》2011,130(3):809-816
The prognostic significance of circulating tumor cells (CTCs) in patients with breast cancer is controversial. We performed
a meta-analysis of published literature to assess whether the detection of CTCs in patients diagnosed with primary breast
cancer can be used as a prognostic factor. We searched Medline, Science Citation Index, and Embase databases as well as reference
lists of relevant articles (including review articles) for studies that assessed the prognostic relevance of tumor cell detection
in the peripheral blood (PB). A total of 24 eligible studies with 4,013 cases and 1,333 controls were included. Meta-analyses
were performed using a random-effects model, using the hazard ratio (HR) and 95% confidence intervals (95% CIs) as effect
measures. The positive detection of CTCs in patients was significantly associated with poor overall survival (OS) (HR = 3.00
[95% CI 2.29–3.94], n = 17, P < 0.0001) and recurrence-free survival (RFS) (HR = 2.67 [95% CI 2.09–3.42], n = 22, P < 0.0001). CTC-positive breast cancers were significantly associated with high histological grade (HR = 1.21 [95% CI 1.09–1.35],
n = 34, P < 0.0001), tumor size (>2 cm) (HR = 1.12 [95% CI 1.02–1.22], n = 31, P = 0.01). and nodal status (≥1) (HR = 1.10 [95% CI 1.00–1.21], n = 32, P = 0.037), but cytokeratin-19 (CK-19) mRNA-positive CTCs were not associated with these clinicopathological parameters of
breast cancer. Furthermore, the presence of CTCs was not associated with estrogen receptor (ER) negativity, progesterone receptor
(PR) negativity, or human epidermal growth factor receptor type 2 (HER2) positivity. Detection of CTCs in the PB indicates
poor prognosis in patients with primary breast cancer. Larger clinical studies are required to further evaluate the role of
these markers in clinical practice. 相似文献
7.
Nimmrich I Sieuwerts AM Meijer-van Gelder ME Schwope I Bolt-de Vries J Harbeck N Koenig T Hartmann O Kluth A Dietrich D Magdolen V Portengen H Look MP Klijn JG Lesche R Schmitt M Maier S Foekens JA Martens JW 《Breast cancer research and treatment》2008,111(3):429-437
Background In this study, we evaluated if PITX2 DNA methylation is a marker for disease recurrence in lymph node-negative (LNN), steroid hormone receptor-positive (HR+)
breast cancer patients. In addition, we studied the association between PITX2 DNA methylation and PITX2 gene expression. Patients and methods
PITX2 DNA-methylation was measured in tumor tissue from 412 LNN/HR+ breast cancer patients who had not received any adjuvant systemic
treatment. In addition, PITX2 DNA-methylation and mRNA expression was evaluated in 32 breast cancer cell lines. Results In univariate Cox regression analysis, DNA-methylation of PITX2 as a continuous variable was associated with early distant metastasis (HR = 1.71; P < 0.01) and poor overall survival (HR = 1.71; P < 0.01). In multivariate analysis together with the established prognostic factors age, tumor size and tumor grade, and steroid
hormone receptor levels, both associations retained their significance (for MFS, HR = 1.74; P < 0.01; for OS, HR = 1.46; P = 0.02). In the breast cancer cell lines, PITX2 DNA methylation was inversely association with PITX2A and PITX2B mRNA expression (P < 0.01). Conclusions Hypermethylation of PITX2 is, in cell lines, negatively associated with PITX2 mRNA expression and, in clinical specimens, positively associated with
breast cancer disease progression. 相似文献
8.
Keam B Im SA Kim HJ Oh DY Kim JH Lee SH Chie EK Han W Kim DW Cho N Moon WK Kim TY Park IA Noh DY Heo DS Ha SW Bang YJ 《Breast cancer research and treatment》2009,116(1):153-160
Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify
the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant
chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy
were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative
surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional
cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant
chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The
mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio ≤0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS)
of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246,
P < 0.001; HR = 7.764, P < 0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy.
Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting. 相似文献
9.
Meijer D Jansen MP Look MP Ruigrok-Ritstier K van Staveren IL Sieuwerts AM van Agthoven T Foekens JA Dorssers LC Berns EM 《Breast cancer research and treatment》2009,113(2):253-260
Purpose Two genes, TSC22 domain family, member 1 (TSC22D1) and prosaposin (PSAP) were identified in an in vitro functional screen
for genes having a causative role in tamoxifen resistance. These genes were also present in our previously established 81-gene
signature for resistance to first-line tamoxifen therapy. The aim of this study was to investigate the predictive value of
these genes for tamoxifen therapy failure in patients with recurrent breast cancer. Experimental Design The mRNA levels of TSC22D1 and PSAP were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in 223 estrogen
receptor-positive primary breast tumors of patients with recurrent disease treated with first-line tamoxifen therapy. The
main objective of this study was the length of progression-free survival (PFS). Results High mRNA levels of TSC22D1 and PSAP were significantly associated with shorter PFS and both were independent of the traditional
predictive factors (HR = 1.30, 95% CI = 1.04–1.64 P = 0.023; and HR = 1.40, 95% CI = 1.03–1.88, P = 0.029, respectively). In multivariate analysis, patients with high mRNA levels of both genes associated significantly with
no clinical benefit (OR = 0.19, 95% CI = 0.06–0.62, P = 0.006) and had the shortest PFS (HR = 2.05, 95% CI = 1.29–3.25, P = 0.002). Conclusion These results confirm our previous in vitro and tumor-related findings and are indicative for the failure of tamoxifen treatment
in breast-cancer patients. Both TSC22D1 and PSAP are associated with clinical outcome and may have a functional role in therapy
resistance.
Danielle Meijer and Maurice P.H.M. Jansen contributed equally to this work. 相似文献
10.
Purpose Clinical trials have reported conflicting results as to whether pre-operative aromatase inhibitors (AIs) improve outcome over
pre-operative tamoxifen in postmenopausal women with hormone receptor-positive breast cancer.
Methods We performed a meta-analysis comparing primary and secondary end points of pre-operative AI and pre-operative tamoxifen. The
event-based risk ratio (RR) with 95% confidence intervals (95% Cis) were derived, and a test of heterogeneity was applied.
Results Four studies (1,160 patients) met the inclusion criteria for the analysis. Meta-analysis showed that pre-operative AI was
more effective than pre-operative tamoxifen. Pooled results of clinical efficacy were as follows: clinical objective response
rate (RR, 1.29; 95% CI, 1.14–1.47; P < 0.001), ultrasound objective response rate (RR, 1.29; 95% CI, 1.10–1.51; P = 0.002), and breast conserving surgery (BCS) rate (RR, 1.36; 95% CI, 1.16–1.59; P < 0.001). Hot flashes, nausea, and fatigue were not different between the pre-operative AI and pre-operative tamoxifen groups.
Although headache was more frequent in the pre-operative AI group (P = 0.011), it was a manageable toxicity and was not clinically relevant.
Conclusion Pre-operative AI has better BCS rate than tamoxifen and in terms of toxicities, is not inferior to tamoxifen; therefore, we
could suggest pre-operative AI instead of tamoxifen for those postmenopausal patients with hormone receptor positive breast
cancer, not eligible for chemotherapy. 相似文献
11.
Dongbo Li Hongfei Ji Xingjian Niu Lei Yin Yiran Wang Yucui Gu Jinlu Wang Xiaoping Zhou Han Zhang Qingyuan Zhang 《Cancer science》2020,111(1):47-58
Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression‐free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine‐resistant breast cancer. 相似文献
12.
Du Y Zhou Q Yin W Zhou L Di G Shen Z Shao Z Lu J 《Breast cancer research and treatment》2011,129(3):839-848
Topoisomerase IIα is not only a proliferation marker of tumor cells, but is also a target for anthracycline-based chemotherapy.
Both in vitro and in vivo studies have shown that there is a relationship between topo IIα and chemosensitivity to anthracyclines,
but the predictive role of topo IIα in breast cancer patients is still controversial. A meta-analysis based on published studies
was performed to obtain an accurate assessment of the association between topo IIα and sensitivity to anthracycline-based
chemotherapy. A total of 13 eligible studies, including 2,633 cases and 2,118 controls were identified. Topo IIα was associated
with sensitivity to anthracyclines in locally advanced breast cancer patients who received neoadjuvant chemotherapy [five
studies, including three using fluorescence in situ hybridization (FISH) and two using immunohistochemistry (IHC): relative
risk (RR) = 1.93, 95% confidence interval (95% CI): 1.27–2.94, P = 0.002; two using FISH and three using IHC: RR = 1.98, 95% CI: 1.37–2.86, P < 0.001]. This association existed among three studies using FISH (RR = 2.03, 95% CI: 1.14–3.61, P = 0.017), but did not exist among three studies using IHC (P > 0.05). In early-stage breast cancer patients who received anthracycline-based adjuvant chemotherapy compared with non-taxane-based
polychemotherapy, amplification [hazard ratio (HR) = 0.64, 95% CI: 0.49–0.83, P = 0.001; HR = 0.59, 95% CI: 0.35–1.01, P = 0.056] or deletion (HR = 0.82, 95% CI: 0.67–1.00, P = 0.051; HR = 0.58, 95% CI: 0.35–0.97, P = 0.036) of topo IIα was significantly associated with better recurrence-free survival and overall survival. In summary,
the present meta-analysis suggests that topo IIα is a predictive factor for breast cancer patients who receive anthracycline-based
chemotherapy. Larger and well-designed prospective studies are required to further evaluate the predictive role of topo IIα
in clinical practice. 相似文献
13.
Ilenia Migliaccio Meng-Fen Wu Carolina Gutierrez Luca Malorni Syed K. Mohsin D. Craig Allred Susan G. Hilsenbeck C. Kent Osborne Heidi Weiss Adrian V. Lee 《Breast cancer research and treatment》2010,123(3):651-660
Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I
receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here
we investigated whether nuclear and cytoplasmic IRS-1 levels are associated with clinico-pathological characteristics and
clinical outcome in breast cancer patients. Tissue microarrays from 1,097 patients with stage I–II breast cancer were stained
by immunohistochemistry for IRS-1. Nuclear and cytoplasmic IRS-1 were scored separately according to the Allred score. Nuclear
IRS-1 showed a positive association with estrogen receptor (ER) (r = 0.09, P = 0.003) and progesterone receptor (PR) (r = 0.08, P = 0.008) status and a negative correlation with lymph node involvement (r = −0.10, P = 0.001). Cytoplasmic IRS-1 did not correlate with ER or PR but showed a positive correlation with tumor size (r = 0.10, P = 0.001) and S-phase fraction (r = 0.16, P < 0.001). In univariate analysis, tamoxifen-treated patients with tumors showing positive nuclear IRS-1 had a better recurrence-free
survival (RFS) (P = 0.009) and overall survival (OS) (P = 0.0007), while no association was shown between cytoplasmic IRS-1 and RFS or OS in the same group of patients. In multivariate
analysis of patients receiving tamoxifen, negative nuclear IRS-1 showed a significantly reduced RFS (P = 0.046) and OS (P = 0.018). Combining both PR and nuclear IRS-1, tamoxifen-treated patients with PR+/IRS-1+ tumors had a better RFS (P = 0.0003) and OS (P < 0.0001) when compared with patients with PR−/IRS-1− tumors. In conclusion, nuclear IRS-1 may be a useful marker to predict
tamoxifen response in patients with early breast cancer, particularly when assessed in combination with PR. 相似文献
14.
Neela Guha Marilyn L. Kwan Charles P. QuesenberryJr Erin K. Weltzien Adrienne L. Castillo Bette J. Caan 《Breast cancer research and treatment》2009,118(2):395-405
Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and
non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase
their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake
and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of
1,954 female breast cancer survivors, diagnosed during 1997–2000, was prospectively followed for 6.31 years and 282 breast
cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency
questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard
ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models.
Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin
intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast
cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 μg/day; HR, 0.48; 95% CI, 0.21–0.79,
P = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence
in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation
is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer
survivors. 相似文献
15.
Jansen MP Ruigrok-Ritstier K Dorssers LC van Staveren IL Look MP Meijer-van Gelder ME Sieuwerts AM Helleman J Sleijfer S Klijn JG Foekens JA Berns EM 《Breast cancer research and treatment》2009,116(2):263-271
Purpose In our microarray analysis we observed that Seven-in-Absentia Homolog 2 (SIAH2) levels were low in estrogen receptor (ER)
positive breast tumors of patients resistant to first-line tamoxifen therapy. The aim of this study was to evaluate SIAH2
for its (a) predictive/prognostic value, and (b) functional role in endocrine therapy resistance. Patients and methods SIAH2 expression was measured with quantitative Real-Time-PCR (qRT-PCR) in 1205 primary breast tumor specimens and related
to disease outcome. The functional role of SIAH2 was determined in human breast cancer cell lines ZR-75-1, ZR/HERc, and MCF7.
Cell lines were treated with estrogen (E2), anti-estrogen ICI164.384 or epidermal growth factor (EGF). Moreover, MCF7 was
treated with ICI164.384 after silencing SIAH2 expression. Results SIAH2 was not prognostic in 603 lymph node negative patients who had not received adjuvant systemic therapy. In multivariate
analysis of ER-positive tumors of 235 patients with recurrent disease, SIAH2 as continuous variable, significantly predicted
first-line tamoxifen treatment failure (OR = 1.48; P = 0.05) and progression-free survival (PFS) (HR = 0.79; P = 0.007). Furthermore, in primary breast cancer patients treated with adjuvant tamoxifen, SIAH2 predicted metastasis-free
survival (MFS) (HR = 0.73; P = 0.005). In vitro experiments showed that SIAH2 silencing in MCF7 cells resulted in resistance to ICI164.384-treatment when
compared with mock silenced cells (P = 0.008). Interestingly, in ZR cells transfected with EGFR (ZR/HERc), SIAH2 expression was induced by E2 but downregulated
by EGF. Conclusion In primary breast tumor specimens as well as in vitro low SIAH2 levels associated with resistance to endocrine therapy. Moreover,
SIAH2 expression showed an opposite regulation by E2 and EGF. 相似文献
16.
17.
《Clinical lung cancer》2023,24(3):287-294
BackgroundImmune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications.Patients and MethodsIn this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI.ResultsWe identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001).ConclusionThis study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated. 相似文献
18.
Lingxu Jiang Yingwan Luo Shuanghong Zhu Lu Wang Liya Ma Hua Zhang Chuying Shen Wenli Yang Yanling Ren Xinping Zhou Chen Mei Li Ye Weilai Xu Haiyang Yang Chenxi Lu Jie Jin Hongyan Tong 《Cancer science》2020,111(2):580-591
Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment. 相似文献
19.
Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors 总被引:1,自引:0,他引:1
Pierce BL Neuhouser ML Wener MH Bernstein L Baumgartner RN Ballard-Barbash R Gilliland FD Baumgartner KB Sorensen B McTiernan A Ulrich CM 《Breast cancer research and treatment》2009,114(1):155-167
Introduction Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast
cancer survivors have not been thoroughly evaluated. Methods Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort
study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive
protein [CRP] and serum amyloid A [SAA], measured ∼31 months after diagnosis) and several demographic, lifestyle, and clinical
characteristics in 741 disease-free breast cancer survivors. Analysis of variance and regression methods were used for statistical
analyses of log-transformed values of CRP and SAA. Results After adjusting for age, BMI, ethnicity, and study site, higher concentrations of CRP were associated with increasing concentration
of SAA (P-trend < 0.0001), increasing age (P-trend < 0.0001), increasing BMI (P-trend < 0.0001), increasing waist circumference (P-trend < 0.0001), positive history of heart failure (P = 0.0007), decreasing physical activity (P-trend = 0.005), Hispanic ethnicity (P = 0.05 vs. non-Hispanic white), and current smoking (P = 0.03 vs. never smoking). Vitamin E supplementation (P = 0.0005), tamoxifen use (P = 0.008), and radiation treatment (compared to no chemotherapy or radiation; P = 0.04) were associated with reduced CRP. Associations of CRP with clinical characteristics were not significant in the adjusted
models. In a multivariate analysis, CRP showed significant associations with waist circumference, BMI, age, history of heart
failure, tamoxifen use, and vitamin E supplementation (R
2 = 0.35). Similar, yet fewer, associations were observed for SAA (R
2 = 0.19). Conclusions This study highlights important correlates of inflammatory status in breast cancer patients. Our results are consistent with
those from similar studies of healthy women. 相似文献
20.
Rody A Karn T Ruckhäberle E Müller V Gehrmann M Solbach C Ahr A Gätje R Holtrich U Kaufmann M 《Breast cancer research and treatment》2009,113(3):457-466
Introduction Overexpression of Topoisomerase II alpha (TOP2A) has been implicated with gene amplification of the 17q21 amplicon and consecutively
with ErbB2 overexpression and amplification. However, gene amplification does not necessarily correlate with RNA and protein
expression. There is growing evidence that TOP2A protein expression is a strong prognostic and TOP2A gene amplification might
be a predictive marker (particularly for the use of anthracyclines). Methods Large scale analysis was performed using Affymetrix microarray data from n = 1,681 breast cancer patients to evaluate TOP2A expression. Results TOP2A expression showed a strong correlation with tumor size (χ2-test, P < 0.001), grading (P < 0.001), ErbB2 (P < 0.001) and Ki67 expression (P < 0.001) as well as nodal status (P = 0.042). Survival analysis revealed a significant prognostic value in ER positive (n = 994; log rank P < 0.001), but not in ER negative breast cancer patients (n = 369, P = 0.35). The prognostic impact of TOP2A expression was independent of Ki67 expression in ER positive tumors (P = 0.002 and P = 0.007 for high and low Ki67, respectively). Moreover a worse prognosis of high TOP2A expressing tumors was found in the
subgroup of ErbB2 negative tumors (P < 0.001) and a trend among ErbB2 positive tumors (P = 0.11). The prognostic value of TOP2A was independent of whether the patients were untreated or had received adjuvant therapy.
In multivariate Cox regression analysis including standard parameters TOP2A emerged to be the top prognostic marker (HR 2.40,
95% CI 1.68–3.43, P < 0.001). Conclusion TOP2A expression is an independent prognostic factor in ER positive breast cancer and could be helpful for risk assessment
in ER positive breast cancer patients.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
A. Rody and T. Karn contributed equally to this work. 相似文献