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Background
The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor–positive (hr+), human epidermal growth factor receptor 2–positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.Methods
A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib–letrozole, letrozole, anastrozole, or trastuzumab–anastrozole as first-line treatment. Clinical inputs for lapatinib–letrozole and letrozole were taken from the EGF30008 trial (). Clinical inputs for anastrozole and trastuzumab–anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer’s price list, the Quebec list of medications, and NCT00073528imsBrogan. Other costs were taken from the Ontario Health Insurance Plan’s Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.Results
Quality-adjusted life years gained with lapatinib–letrozole were 0.236 compared with trastuzumab–anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib–letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab–anastrozole. Results from the societal perspective were similar.Conclusions
In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib–letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab–anastrozole. 相似文献3.
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Francisco J. Esteva Stacy L. Moulder Ana M. Gonzalez-Angulo Joe Ensor James L. Murray Marjorie C. Green Kimberly B. Koenig Mong-Hong Lee Gabriel N. Hortobagyi Sai-Ching Yeung 《Cancer chemotherapy and pharmacology》2013,71(1):63-72
Purpose
Obese women with breast cancer have worse prognosis than women with normal body mass index. Endocrine therapy resistance is in part mediated by insulin resistance in obese women with breast cancer. We investigated the tolerability and pharmacokinetics of exemestane in combination with metformin and rosiglitazone in nondiabetic overweight and obese postmenopausal women with hormone receptor–positive metastatic breast cancer.Methods
Patients had previously received chemotherapy and endocrine therapy for breast cancer. Exemestane was given as 25 mg orally per day. Metformin (M) and rosiglitazone (R) were given twice daily. Dose level 1 consisted of M 1,500 mg/day and R 6 mg/day. Dose level 2 consisted of M 2,000 mg/day and R 8 mg/day. Plasma concentrations of exemestane were measured on days 1, 8, and 15.Results
Twenty patients were enrolled. Fourteen patients received exemestane, metformin, and rosiglitazone. Six patients received exemestane with metformin only (2,000 mg/day). Both regimens were well tolerated at the highest doses tested, and there were no notable changes in plasma exemestane levels. Six patients (30 %) had stable disease for 6 months or longer.Conclusions
Oral daily administration of exemestane (25 mg) and metformin (2,000 mg) with and without rosiglitazone (8 mg) daily was well tolerated. Exemestane pharmacokinetics were not altered by metformin and rosiglitazone. 相似文献8.
Annalen Bleckmann Andreas Leha Stephan Artmann Kerstin Menck Gabriela Salinas-Riester Claudia Binder Tobias Pukrop Tim Beissbarth Florian Klemm 《Molecular oncology》2015,9(1):155-166
Introduction
Various studies have identified aberrantly expressed miRNAs in breast cancer and demonstrated an association between distinct miRNAs and malignant progression as well as metastasis. Even though tumor‐associated macrophages (TAM) are known mediators of these processes, little is known regarding their miRNA expression upon education by malignant cells in vivo.Methods
We profiled miRNA and mRNA expression of in vitro tumor‐educated macrophages (TEM) by indirectly co‐culturing with estrogen‐receptor‐positive (ER+) MCF‐7 breast cancer cells. The prognostic power of the resulting miRNA list was investigated in primary breast cancer datasets and compared to other signatures. Furthermore, miRNA expression levels were correlated to mRNA expression of macrophage markers and the impact on prognosis was assessed.Results
Through the evaluation of the group effects between differentially‐expressed miRNAs and their target mRNAs in TEM, the power of detecting regulated miRNAs was greatly increased. The resulting list of 96 miRNAs predicts disease‐free survival (DFS) in external datasets of ER+ breast cancer patients and performs well in comparison with other miRNA signatures. Clustering with the predefined miRNA list revealed a significant difference in survival between the two resulting patient groups. Furthermore, an optimized miRNA list, based on correlations with macrophages markers, proved even more capable at identifying patient clusters significantly differing in DFS.Conclusions
In vitro profiling of TEM and subsequent bioinformatic verification identified miRNAs with a high prognostic power for DFS when transferred into the clinical setting of primary breast cancer. The resulting miRNAs not only verify previously established findings but also lead to new prognostic markers. Furthermore, our data suggest that TAM contribute to the total miRNA expression profile of ER + breast cancers. 相似文献9.
Wheeler SB Carpenter WR Peppercorn J Schenck AP Weinberger M Biddle AK 《Breast cancer research and treatment》2012,131(1):207-216
Adherence to consensus guidelines for cancer care may vary widely across health care settings and contribute to differences
in cancer outcomes. For some women with breast cancer, omission of adjuvant chemotherapy or delays in its initiation may contribute
to differences in cancer recurrence and mortality. We studied adjuvant chemotherapy use among women with stage II or stage
III, hormone receptor–negative breast cancer to understand health system and socio-demographic correlates of underuse and
delayed adjuvant chemotherapy. We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to examine the
patterns of care for 6,678 women aged 65 and older diagnosed with stage II or stage III hormone receptor–negative breast cancer
in 1994–2002, with claims data through 2007. Age-stratified logistic regression was employed to examine the potential role
of socio-demographic and structural/organizational health services characteristics in explaining differences in adjuvant chemotherapy
initiation. Overall utilization of guideline-recommended adjuvant chemotherapy peaked at 43% in this population. Increasing
age, higher co-morbidity burden, and low-income status were associated with lower odds of chemotherapy initiation within 4 months,
whereas having positive lymph nodes, more advanced disease, and being married were associated with higher odds (P < 0.05). Health system–related structural/organizational characteristics and race/ethnicity offered little explanatory insight.
Timely initiation of guideline-recommended adjuvant chemotherapy was low, with significant variation by age, income, and co-morbidity
status. Based on these findings, future studies should seek to explore the more nuanced reasons why older women do not receive
chemotherapy and why delays in care occur. 相似文献
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C L Downey S A Simpkins J White D L Holliday J L Jones L B Jordan J Kulka S Pollock S S Rajan H H Thygesen A M Hanby V Speirs 《British journal of cancer》2014,110(7):1744-1747
Background:
A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour–stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas.Methods:
TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed.Results:
Tumours with ⩾49% stroma were associated with better survival in female (OS P=0.008, HR=0.2–0.7; RFS P=0.006, HR=0.1–0.6) and male breast cancer (OS P=0.005, HR=0.05–0.6; RFS P=0.01, HR=0.87–5.6), confirmed in multivariate analysis.Conclusions:
High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR. 相似文献11.
S. Djalalov J. Beca E. Amir M. Krahn M.E. Trudeau J.S. Hoch 《Current oncology (Toronto, Ont.)》2015,22(2):84-96
Background
Aromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)–positive early breast cancer.Methods
The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with er-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs.Results
The sequential tam–ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai–tam strategy, ai–tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis.Conclusions
In postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost. 相似文献12.
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To estimate the clinical significance of estrogen receptor (ER) β in breast cancer we reviewed some reports and compared them
with our preliminary results. The structure of ER β is similar to that of ER α. The DNA binding domain of ER β is 96% conserved
compared with ER α, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen
responsive elements on target genes and that they may also bind similar ligand. The target tissues of ER β such as testis,
prostate, lung, brain, thymus, and ovary, are different from those of ER α, ovary, uterus, endometrium, and breast. Although
the function of ER β in breast cancer progression is not well understood, 30-50% of breast cancers may express ER β mRNA signals.
Additionally, ER β may be a useful prognostic factor in patients with breast cancer, because tumors that co-expressed ER α
and ER β might be node positive and tend to be of higher grade. Further characterization of the function of ER β and its isoforms
in breast cancer is warranted. 相似文献
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Jose P. Leone MD Bernard F. Cole PhD Meredith M. Regan ScD Beat Thürlimann MD Alan S. Coates MD Manuela Rabaglio MD Anita Giobbie-Hurder MS Richard D. Gelber PhD Bent Ejlertsen MD Vernon J. Harvey MD Patrick Neven MD PhD Istvan Láng MD PhD Herve Bonnefoi MD Andrew Wardley MD Aron Goldhirsch MD Angelo Di Leo MD Marco Colleoni MD Ines Vaz-Luis MD MSc PhD Nancy U. Lin MD 《Cancer》2021,127(5):700-708
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Amita Sneh Yadwinder S. Deol Akaansha Ganju Konstantin Shilo Thomas J. Rosol Mohd W. Nasser Ramesh K. Ganju 《Breast cancer research and treatment》2013,138(3):727-739
Psoriasin (S100A7) is a calcium-binding protein that has shown to be highly expressed in high-grade ductal carcinoma in situ (DCIS) and a subset of invasive breast cancers. However, its role in invasion and metastasis is not very well known. In this study, we have shown that S100A7 differentially regulates epidermal growth factor (EGF)-induced cell migration and invasion in ERα? MDA-MB-231 cells and ERα+ MCF-7 and T47D breast cancer cells. Further signaling studies revealed that S100A7 enhances EGF-induced EGFR phosphorylation and actin remodeling that seems to favor lamellipodia formation in ERα? cells. In addition, S100A7 overexpression enhanced NF-κB-mediated matrix metalloproteinase-9 (MMP-9) secretion in MDA-MB-231 cells indicating its role in enhanced invasiveness. However, S100A7 overexpression inhibited migration and invasion of MCF-7 cells by inactivating Rac-1 pathway and MMP-9 secretion. Moreover, S100A7 overexpressing MDA-MB-231 cells showed enhanced metastasis compared to vector control in in vivo nude mice as detected by bioluminescence imaging. Our tissue microarray data also revealed predominant expression of S100A7 in ERα? metastatic carcinoma, especially in lymph node regions. Overall these studies suggest that S100A7 may enhance metastasis in ERα? breast cancer cells by a novel mechanism through regulation of actin cytoskeleton and MMP-9 secretion. 相似文献