21-gene RT-PCR assay in lymph node negative (LN-), estrogen receptor positive (ER+) breast cancer: An economic analysis including prognostic and predictive information

6024 Background: The prognostic accuracy of a 21-gene RT-PCR assay has undergone validation in 668 evaluable LN-, ER+ early stage breast cancer patients receiving tamoxifen on NSABP B-14 (Paik, NEJM 2004) and its economic evaluation (Hornberger, Am J Man Care 2005). Assay predictive accuracy for response to chemotherapy or tamoxifen has also undergone recent validation in 651 patients on NSABP B-20 and 645 patients on NSABP B-14 (Paik, SABCS 2004). Methods: Based on the model recurrence score (RS), women with LN−, ER+ breast cancer with and without adjuvant chemotherapy (C) or tamoxifen (T) were classified as high (RS ≥31), intermediate (RS 18–30) or low (RS <18) risk of distant recurrence at 10 years. Incremental costs ($), life-years (LYs), quality-adjusted LYs (QALYs) and cost-effectiveness (C/E; cost per LY gained) were estimated for: RS-guided treatment (RSGT) with T for low and intermediate risk patients and C+T for high-risk patients, compared to either T alone or C+T for all patients. Results: Under base case assumptions, no significant difference in life expectancy at 10 years is estimated between the RSGT and C+T strategies whereas RSGT is associated with a gain in individual life expectancy of 2.7 LYs compared to T alone. RSGT is estimated to yield a net cost savings of $4,502 compared to C+T with an incremental C/E of $1,059 per LY saved compared to T alone. At a utility of 90% associated with adjuvant chemotherapy, RSGT is associated with a gain in individual QALYs of 1.82 compared to T alone at a cost utility of $1,573/QALY and a gain in 3.21 QALYs compared to C+T. RSGT is associated with lower expected cost than C+T for total chemotherapy costs above $3,998. The gain in LYs with RSGT compared to T alone increases with healthy age-specific life expectancy (years) while the cost per LY gained decreases. Conclusions: Treatment based on the RSGT compared to T alone is associated with acceptable C/E ratios and substantially lower toxicity and cost compared to C+T. [Table: see text] [Table: see text]

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CK-19 Expression by RT-PCR in the Peripheral Blood of Breast Cancer Patients Correlates with Response to Chemotherapy

Breast Cancer Research and Treatment ◽

10.1023/a:1010621901102 ◽

2001 ◽

Vol 66 (3) ◽

pp. 249-254 ◽

Cited By ~ 14

Author(s):

Ana Rita Manhani ◽

Reinaldo Manhani ◽

Heloisa P. Soares ◽

Israel Bendit ◽

Fabiana Lopes ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Peripheral Blood ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Response To Chemotherapy

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Cost-effectiveness of subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf for the treatment of high-risk HER2+ early breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18846 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18846-e18846

Author(s):

Jesse Sussell ◽

Joshua A. Roth ◽

Svenn Hansen ◽

Craig S. Meyer ◽

Anita M. Fung

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Cost Effectiveness ◽

High Risk ◽

Neoadjuvant Therapy ◽

Early Breast Cancer ◽

Standard Therapy ◽

Healthcare Sector ◽

Base Case ◽

Life Years

e18846 Background: Standard therapy for high-risk HER2+ early breast cancer (EBC) begins with neoadjuvant dual targeted therapy with pertuzumab (P) + trastuzumab (T) + chemotherapy (CTX). After surgery, patients who achieve pathological complete response (pCR) should complete one year of dual targeted therapy, while patients with residual disease should receive ado-trastuzumab emtansine (T-DM1). Recently, a subcutaneously administered formulation of P, T, and hyaluronidase-zzxf (Phesgo) was approved for use in the U.S. This study assesses the value of this new formulation in EBC patients vs. a strategy in which patients initiate standard therapy, but discontinue P following ascertainment of pCR. Methods: We developed a six-state Markov model to assess EBC costs and quality-adjusted life years (QALYs) from a healthcare sector perspective over a lifetime time horizon. Two strategies were modeled: 1) Neoadjuvant therapy with subcutaneous P, T, and hyaluronidase-zzxf + CTX with adjuvant continuation if pCR is achieved, and T-DM1 if not (“intervention”), and 2) neoadjuvant therapy with infused P, T + CTX with adjuvant infused T if pCR is achieved, and T-DM1 if not (“comparator”). Event-free and invasive-disease free survival were derived from the PEONY and KATHERINE/APHINITY trials, respectively. Utility values, drug prices, and procedure costs were derived from KATHERINE EQ-5D data, Wholesale Acquisition Costs, and claims analyses, respectively. We assessed comparator costs using both biosimilar and branded T pricing. The primary outcome was the incremental cost-effectiveness ratio (ICER). Outcomes were discounted at 3%/year and costs are presented in 2020 U.S. dollars. Uncertainty in outcomes was assessed through Monte Carlo simulation (1,000 replicates). Results: The table shows key results. The intervention resulted in a gain of 0.092 QALYs. With biosimilar T pricing in the comparator (base case), the intervention increased costs by $7,575 (ICER = $81,793). With branded T pricing in the comparator (scenario analysis), the intervention increased costs by $982 (ICER = $10,602). In probabilistic analyses, the intervention was favored in 52% and 81% of simulations at a willingness-to-pay of $100,000/QALY with biosimilar and branded T pricing, respectively. Conclusions: This study provides additional evidence to support adjuvant continuation of P+T among patients achieving pCR. Neoadjuvant P, T, and hyaluronidase-zzxf + CTX (with adjuvant continuation of dual targeted therapy) is expected to be cost-effective ( < $100,000/QALY) vs. neoadjuvant P and T + CTX (with adjuvant T continuation) for patients with high-risk HER2+ EBC irrespective of whether the comparator uses biosimilar or branded T.[Table: see text]

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Survival outcomes in patients with IDC and ILC breast cancer: A well matched single institution study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13056 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13056-e13056

Author(s):

Michael Grimm ◽

Bhuvaneswari Ramaswamy ◽

Maryam B. Lustberg ◽

Robert Wesolowski ◽

Sagar D. Sardesai ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Metastatic Breast ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Her2 Status ◽

Single Institution ◽

First Line ◽

Response To Chemotherapy ◽

Significant Difference

e13056 Background: Invasive lobular carcinoma (ILC) accounts for only 10-15% of all invasive breast cancers but has distinct clinicopathologic characteristics and genomic profiles. In particular, metastatic lobular cancers (mILC) have unique sites of metastasis and it is unclear if the response to initial endocrine therapy differs from metastatic ductal cancers (mIDC). Therefore we have undertaken a single-institution, retrospective analysis to compare overall outcomes and response to initial endocrine therapy (ET) in patients (pts) with metastatic ILC and IDC. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts treated for metastatic IDC and ILC at The Ohio State University Comprehensive Cancer Center from January 1, 2004 to December 31, 2014. Pts diagnosed with mIDC were matched on age, year of diagnosis, estrogen receptor/progesterone receptor and HER2 status and site of metastasis 2:1 to patients diagnosed with mILC. Overall survival (OS) was defined as the time from metastasis to death or last known follow-up. Progression-free survival (PFS) was defined as time from metastasis to progression on first-line ET. Time to chemotherapy (TTC) was defined as time from starting ET for metastasis to initiation of chemotherapy. Kaplan Meier (KM) methods were used to calculate median OS, PFS and TTC. Results: A total of one hundred sixty one pts with metastatic breast cancer were included in this analysis. The demographic features between the two groups were well balanced and included in the table below. The median OS was 2.6 yrs (95% CI: 1.55, 3.22) for mILC and 2.2 yrs (95% CI: 1.95, 2.62) for mIDC. A subset of 111 patients who started on endocrine therapy were used in the PFS and TTC analyses. The median PFS following first-line ET was 2.2 yrs (95% CI: 0.1.0, 2.7) for mILC and 1.4 yrs (95% CI: 0.91, 1.90) for mIDC. Median TTC was 2.1 yrs (95% CI: 1.71, 4.92) for mILC and 2.4 yrs (95% CI: 1.90, 4.77) for mIDC. There was no statistically significant difference in outcomes between the two groups. Conclusions: Outcomes in patients with ILC and IDC have been varied, with several studies reporting that patients with ILC have worse outcomes and response to chemotherapy. Our retrospective study examining outcomes in mILC in comparison with mIDC showed no difference in OS. Given the concern of resistance to conventional therapies in patients with lobular cancers, it is reassuring to see that the median PFS on first line ET and TTC was similar to metastatic ductal cancers.[Table: see text]

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A Smartphone-Based App to Improve Adjuvant Treatment Adherence to Multidisciplinary Decisions in Patients With Early-Stage Breast Cancer: Observational Study

Journal of Medical Internet Research ◽

10.2196/27576 ◽

2021 ◽

Vol 23 (9) ◽

pp. e27576

Author(s):

Jing Yu ◽

Jiayi Wu ◽

Ou Huang ◽

Xiaosong Chen ◽

Kunwei Shen

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Endocrine Therapy ◽

Adjuvant Treatment ◽

Early Stage ◽

Compliance Rate ◽

Multidisciplinary Treatment ◽

Significant Difference ◽

Noncompliance Rate

Background Multidisciplinary treatment (MDT) and adjuvant therapy are associated with improved survival rates in breast cancer. However, nonadherence to MDT decisions is common in patients. We developed a smartphone-based app that can facilitate the full-course management of patients after surgery. Objective This study aims to investigate the influence factors of treatment nonadherence and to determine whether this smartphone-based app can improve the compliance rate with MDTs. Methods Patients who had received a diagnosis of invasive breast cancer and had undergone MDT between March 2013 and May 2019 were included. Patients were classified into 3 groups: Pre-App cohort (November 2017, before the launch of the app); App nonused, cohort (after November 2017 but not using the app); and App used cohort (after November 2017 and using the app). Univariate and multivariate analyses were performed to identify the factors related to MDT adherence. Compliance with specific adjuvant treatments, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapy, was also evaluated. Results A total of 4475 patients were included, with Pre-App, App nonused, and App used cohorts comprising 2966 (66.28%), 861 (19.24%), and 648 (14.48%) patients, respectively. Overall, 15.53% (695/4475) patients did not receive MDT recommendations; the noncompliance rate ranged from 27.4% (75/273) in 2013 to 8.8% (44/500) in 2019. Multivariate analysis demonstrated that app use was independently associated with adherence to adjuvant treatment. Compared with the patients in the Pre-App cohort, patients in the App used cohort were less likely to deviate from MDT recommendations (odds ratio [OR] 0.61, 95% CI 0.43-0.87; P=.007); no significant difference was found in the App nonused cohort (P=.77). Moreover, app use decreased the noncompliance rate for adjuvant chemotherapy (OR 0.41, 95% CI 0.27-0.65; P<.001) and radiotherapy (OR 0.49, 95% CI 0.25-0.96; P=.04), but not for anti-HER2 therapy (P=.76) or endocrine therapy (P=.39). Conclusions This smartphone-based app can increase MDT adherence in patients undergoing adjuvant therapy; this was more obvious for adjuvant chemotherapy and radiotherapy.

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Cost-effectiveness analysis of genomic profiling in early breast cancer in Colombia

10.21203/rs.3.rs-264520/v1 ◽

2021 ◽

Author(s):

Leonardo Rojas ◽

María Rojas-Reyes ◽

Diego Rosselli ◽

Andres F. Cardona

Keyword(s):

Breast Cancer ◽

Sensitivity Analysis ◽

Cost Effectiveness ◽

Adjuvant Chemotherapy ◽

Early Breast Cancer ◽

National Health System ◽

Cost Effective ◽

Decision Analytic Model ◽

United States Dollar ◽

Life Years

Abstract BackgroundThe best strategy to establish indication for adjuvant chemotherapy in early breast cancer (EBC) in Colombia is unknown. This study aimed to identify the cost-effectiveness of various strategies to establish the necessity of adjuvant chemotherapy.MethodsThis study used an adapted decision-analytic model to compare cost and outcomes of care that includes Oncotype DX™ (ODX) or Mammaprint™ (MMP) test with routine care without ODX or MMP tests (application of adjuvant chemotherapy for all patients) over a 5-year time horizon, and the from the perspective of the Colombian National Health System (NHS) perspective (payer). Data were obtained from published literature and clinical trial database. The study population was composed of women with EBC, hormone-receptor positive (HR+), Her2-negative, lymph-node negative (LN0), with high-risk clinical criteria for recurrence. The outcome measures were incremental cost-effectiveness ratio (ICER; 2019 United States Dollar [USD] per quality-adjusted life years [QALY] gained) and net monetary benefit (NMB).ResultsODX increases QALYs by 0.05 and MMP by 0.03 with savings of $2,445 and $570 compared with the standard strategy, respectively. The ICER for ODX was −$41,857 and that for MMP was −$18,253 per QALY; NMB was $2,821 and $771, respectively. Both tests were cost effective under defined threshold. When the two tests were compared, ODX was more cost effective than MMP. Sensitivity analysis revealed that, with a threshold of 1 GDP per capita, ODX will be cost effective in 95.5% of the cases compared with 70.2% of MMP. Probabilistic sensitivity analysis revealed that ODX was a consistently superior strategy.ConclusionsGenomic profiling using ODX or MMP tests to define the need of adjuvant chemotherapy treatment in patients with HR + and Her2 − EBC is a cost-effective strategy that allows Colombian NHS saving money.

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Περιεγχειρητική κινητική αγγειορυθμιστικών παραγόντων σε ασθενείς με καρκίνο του μαστού

10.12681/eadd/36972 ◽

2014 ◽

Author(s):

Γεώργιος Γεωργίου

Keyword(s):

Breast Cancer ◽

Breast Adenocarcinoma ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Study Group ◽

Rt Pcr ◽

Altered Expression ◽

Female Patients ◽

Significant Difference ◽

Circulating Levels

Βackground: angiogenesis is seen during the multiple stages of carcinogenesis, aswell as during the process of surgical wound healing, a fact which has led tosubstantial debate over the last decades about the potential impact of surgery upon thefinal outcome of ceratin patients treated for breast cancer.Aim: the present research aims at investigating the potential effect of surgery on theprocess of angiogenesis, by studying a number of factors that are related to the latter,in patients suffering from breast cancer before and after the time of the procedure,whilst comparing these results with those of patients that were operated on their breastfor non-malignant disease.Material-Methods: blood from 10 female patients with breast adenocarcinoma(Study Group) was collected via venipuncture before surgery (labeled as PRO), aswell as on post-operative day 3 (labeled as D3) and day 7 (labeled as D7). Moreover,blood samples were also taken from 6 female patients with fibroadenoma (ControlGroup) before surgery (PRO) and on day 3 afetr surgery (D3). These samples weremeasured for detection of circulating levels of three established angiogenesisbiomarkers using ELISA (Enzyme-Linked ImmunoSorbent Assay): VascularEndothelial Growth Factor-A (VEFG-A), Interleukin-8 (IL-8) and basic FibroblastGrowth factor (bFGF or FGF-2). In addition, circulating transcripts of 84 agiogenesirelatedgenes were determined using RT-PCR (Real Time Polymerase ChainReaction). The two groups of patients were firstly compared to each other regardingtheir results. Also, patients belonging to the Study Group were analized at differenttime points regarding surgery. Finally, the results were investigated againstclinicopathological data and patient outcome.Results: using ELISA we were able to detect increased levels of circulating VEGF-Aand IL-8 in the Study Group patients compared to the Control Group patientspreoperatively (p=0,0381 and p=0,0218 respectively), while for bFGF there was nostatistically significant difference documented. Surgery resulted in a significantincrease in VEGF-A levels on D3 (p=0,0389) and D7 (p=0,0172) as compared toPRO levels. Perioperative kinetics of IL-8 showed a mild trend towards increase,which, however, was not statistically significant. Postoperative levels of bFGF wereslightly increased on D3, but on D7 they were even lower than preoperative values(p=0,0205). Using RT-PCR certain differences between the Study Group and theControl Group were recorded regarding the circulating transcripts of a great numberof angiogenesis-related genes preoperatively: upregulation of VEGF-C, EGF, IL-8,FGF-1, SPHK1, NRP1, LAMA5, COL4A3, TEK, EFNA3, EFNB2. AKT1, ITGB3,THBS1, CCL11, TIMP3 and downregulation of CXCL10. Moreover, mastectomyinduced an altered expression in several key-genes in breast cancer patients:upregulation of THBS1, COL4A3, BAI1, ITGB3 and downregulation of EREG,SERPIFN1, CXCL9, CXCL10, IL1B, CCL2, CXCL1, HIF1A, NOTCH4. Conclusions: patients suffering from breast cancer have a different angiogenic profilein comparison to patients with fibroadenoma, as documented through their differencesin circulating levels of angiogenic factors. These levels are greatly changed after thesurgical procedure. VEGF showed a transient increase, while bFGF initially increasedbut only to finally decrease to levels that were even lower than the preoperative ones.Moreover, mastectomy promoted a shift in the expression pattern of a broad panel ofangiogenesis-related gene transcripts.

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Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2013.54.9931 ◽

2014 ◽

Vol 32 (31) ◽

pp. 3513-3519 ◽

Cited By ~ 17

Author(s):

Julia Bonastre ◽

Sophie Marguet ◽

Beranger Lueza ◽

Stefan Michiels ◽

Suzette Delaloge ◽

...

Keyword(s):

Breast Cancer ◽

Decision Making ◽

Cost Effectiveness ◽

Adjuvant Chemotherapy ◽

Cost Effective ◽

Gene Signature ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Life Years ◽

Er Positive

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) –positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, −€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Conclusion Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC.

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PD-L1 expression and TOP3A mutation as prognostic factors for adjuvant chemotherapy in triple negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.541 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 541-541

Author(s):

Xue Wang ◽

Peng Yuan ◽

Feng Du ◽

Lina Cui ◽

Fangchao Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Disease Free Survival ◽

Genetic Alterations ◽

Functional Enrichment ◽

Pathway Enrichment Analysis ◽

Genetic Characteristics ◽

Significant Difference

541 Background: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is markedly heterogeneous and lacks specific targets. The aim of this study is to explore potential predictors and therapeutic targets based on clinical and genetic characteristics. Methods: 138 patients with triple-negative breast cancer after surgical treatment were 1:1 randomly assigned to the paclitaxel combined with carboplatin (TCb) group or the epirubicin combined with cyclophosphamide sequential paclitaxel (EC-T) adjuvant chemotherapy group. PD-L1 was retrospectively analyzed by surgically resected specimens, and 733 cancer-related genes were detected by NGS. Pathway enrichment analysis was performed using DAVID for functional enrichment genetic alterations. Cox regression models and Kaplan-Meier were used to evaluate disease-free survival (DFS). Results: In this study, there was no significant difference in DFS between the TCb and EC-T groups. 31 (22.5%) of 138 TNBC patients were positive for PD-L1 expression, including 15 (10.9%) patients positive for PD-L1 in tumor cells (TCs) and 29 (21.0%) patients positive for PD-L1 in tumor-infiltrating immune cells (TICs). Patients with positive PD-L1 expression, either in TCs or TICs, achieved better DFS [HR=0.13 (95% CI: 0.02-0.93), p=0.016], the difference was also shown in the EC-T group [HR=0 (95% CI: 0- inf), p=0.037], but not in the TCb group [HR=0 (95% CI: 0.04-2.1), p=0.189]. In addition, we identified 7 patients with mutations in DNA topoisomerase IIIα(TOP3A), a homologous recombination (HR)-related gene, and patients with mutations in this gene had worse DFS than those without mutations [HR=4]. However, there was no statistically significant association between BRCA mutation and response to either therapeutic regimens. Conclusions: In this TNBC patient population, immunohistochemistry (IHC) and NGS analyses identified potential prognostic markers. PD-L1 positive and TOP3A mutation were significantly associated with early triple-negative breast cancer prognosis.

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Cellular Compatibility of a New Tantalum-Niobium Scaffold Material

10.21203/rs.3.rs-39637/v1 ◽

2020 ◽

Author(s):

Jianan Ouyang ◽

Zhenhan Deng ◽

Kang Chen ◽

Jianyi Xiong ◽

Ying Li ◽

...

Keyword(s):

Cell Proliferation ◽

Type I Collagen ◽

Material Surface ◽

Control Group ◽

Type I ◽

Scaffold Material ◽

Rt Pcr ◽

Pcr Assay ◽

Porous Tantalum ◽

Significant Difference

Abstract [Objective] To determine the cellular compatibility of porous tantalum-niobium (Ta-Nb) material. [Method] Rabbit osteoblasts were co-cultured with porous Ta-Nb material. The cell proliferation was detected by CCK-8 method, and the cell adhesion was observed under scanning electron microscope (SEM). The expressions of type-I collagen and osteocalcin were detected by RT-PCR assay. [Results] CCK-8 detection indicated that the cell proliferation on the porous Ta-Nb material showed no difference from that of the control group (P>0.05). SEM revealed that a large amount of cells adhered onto the surface and in the pores of the material. The number of cells on the material surface increased obviously over time. RT-PCR assay showed that with the prolonging of the time of co-culture, the expression of type-I collagen was enhanced (P<0.05), while the osteocalcin expression exhibited no significant difference (P>0.05[Conclusion] Porous Ta-Nb scaffold material can be used to promote the adhesion, growth and differentiation of osteoblasts with satisfactory cellular compatibility.

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