Health state utilities for metastatic breast cancer.
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ABSTRACT:
SUBMITTER: Lloyd A
PROVIDER: S-EPMC2360509 | biostudies-other | 2006 Sep
REPOSITORIES: biostudies-other
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Project description:A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary tumor growth was impaired in mice injected with parental cell line, but not in mice injected with Gln-ind cells.
| S-EPMC3343010 | biostudies-literature
Project description:BackgroundBurdens related to time spent receiving cancer care may be substantial for patients with incurable, life-limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment-related decision-making.MethodsEstimates of time spent receiving cancer-related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time-in-motion quality improvement evaluation (process mapping); (b) cross-sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy).ResultsAverage total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents.ConclusionTime spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method.
| S-EPMC7666754 | biostudies-literature
Project description:BackgroundMetastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question.ObjectivesTo assess the effects of breast surgery in women with metastatic breast cancer.Search methodsWe conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies.Selection criteriaThe inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy.Data collection and analysisTwo review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies.Main resultsWe included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence).Authors' conclusionsBased on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.
| S-EPMC6494198 | biostudies-literature
Project description:Introduction: When cancer patients have advanced disease and a primary cure is no longer possible, the focus is on maintaining the patient's quality of life. Recent therapeutic advances in breast cancer treatment mean that even patients with metastatic disease can remain stable for long periods of time. The aim of this study was to look at the health-related quality of life (HRQL) of these patients and compare it with data for the general population and to show the differences in outcomes for different survey instruments used to measure quality of life. Material and Methods: A total of 96 breast cancer patients with metastatic disesae or receiving adjuvant therapy were questioned about their quality of life. Patients were investigated using the established survey instruments EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and EQ VAS. All patients filled out questionnaires. Statistical analysis was done using MS Excel and SPSS. Results: Although the questionnaires were completed at the same time, the different questionnaires showed significant differences with regard to the level of stress experienced by the patient. When the EQ VAS questionnaire was used, the patient's current state of health was assessed as significantly better than with the EORTC QLQ-C30. Overall, all aspects of patients' quality of life were found to be in need of optimization and HRQL of patients was significantly poorer in all areas compared to the reference population. Conclusion: To improve the quality of life of patients with metastatic disease, it is necessary to continuously monitor the success of therapy. The choice of survey tools is highly relevant as assessments differ considerably depending on the choice of questionnaire.
| S-EPMC5065420 | biostudies-literature
Project description:IntroductionAlthough there is a lack of data on health-state utility values (HSUVs) for calculating quality-adjusted life-years in Japan, cost-utility analysis has been introduced by the Japanese government to inform decision making in the medical field since 2016.ObjectivesThis study aimed to determine whether the Lloyd model which was a predictive model of HSUVs for metastatic breast cancer (MBC) patients in the UK can accurately predict actual HSUVs for Japanese patients with MBC.DesignThe prospective observational study followed by the validation study of the clinical predictive model.Setting and participantsForty-four Japanese patients with MBC were studied at 336 survey points.MethodsThis study consisted of two phases. In the first phase, we constructed a database of clinical data prospectively and HSUVs for Japanese patients with MBC to evaluate the predictive accuracy of HSUVs calculated using the Lloyd model. In the second phase, Bland-Altman analysis was used to determine how accurately predicted HSUVs (based on the Lloyd model) correlated with actual HSUVs obtained using the EuroQol 5-Dimension 5-Level questionnaire, a preference-based measure of HSUVs in patients with MBC.ResultsIn the Bland-Altman analysis, the mean difference between HSUVs estimated by the Lloyd model and actual HSUVs, or systematic error, was -0.106. The precision was 0.165. The 95% limits of agreement ranged from -0.436 to 0.225. The t value was 4.6972, which was greater than the t value with 2 degrees of freedom at the 5% significance level (p=0.425).ConclusionsThere were acceptable degrees of fixed and proportional errors associated with the prediction of HSUVs based on the Lloyd model for Japanese patients with MBC. We recommend that sensitivity analysis be performed when conducting cost-effectiveness analyses with HSUVs calculated using the Lloyd model.
| S-EPMC8638153 | biostudies-literature
Project description:Little is known about the effect of breast cancers on health-related quality of life among women diagnosed between age 18 and 44 years. The goal of this study is to estimate the effect of breast cancer on health state utility by age at diagnosis (18-44 years versus ?45 years) and by race/ethnicity.The analytic sample, drawn from the 2009 and 2010 Behavioral Risk Factor Surveillance System and analyzed in 2013, included women diagnosed with breast cancer between age 18 and 44 years (n=1,389) and age ?45 years (n=6,037). Health state utility values were estimated using Healthy Days variables and a published algorithm. Regression analysis was conducted separately by age at diagnosis and race/ethnicity.The breast cancer health state utility decrement within 1 year from date of diagnosis was larger for women diagnosed at age 18-44 years than for women diagnosed at age ?45 years (-0.116 vs -0.070, p<0.05). Within the younger age-at-diagnosis group, Hispanic women 2-4 years after diagnosis had the largest health state utility decrement (-0.221, p<0.01), followed by non-Hispanic white women within 1 year of diagnosis (-0.126, p<0.01).This study is the first to report estimates of health state utility values for breast cancer by age at diagnosis and race/ethnicity from a nationwide sample. The results highlight the need for separate quality of life adjustments for women by age at diagnosis and race/ethnicity when conducting cost-effectiveness analysis of breast cancer prevention, detection, and treatment.
| S-EPMC5841540 | biostudies-literature
Project description:Angiogenesis has become an important target in the treatment of several solid tumors, including breast cancer. As monotherapy, antiangiogenic agents have demonstrated limited activity in metastatic breast cancer (MBC); therefore, they have generally been developed for use in combination with chemotherapies. Thus far, the experience with antiangiogenic agents for MBC has been mixed. The results from one study assessing addition of the monoclonal antibody bevacizumab to paclitaxel led to approval of bevacizumab for MBC. However, the modest improvement of progression-free survival rates in subsequent MBC studies has led to reappraisal of bevacizumab. Phase III studies have not produced evidence supporting use of the multikinase inhibitor sunitinib alone or in combination with MBC chemotherapy. Experience with sorafenib in a phase IIb program indicates potential when used in select combinations, particularly with capecitabine; however, phase III confirmatory data are needed. Although antiangiogenic therapies combined with chemotherapy have increased progression-free survival rates for patients with MBC, increases in overall survival times have not been observed. Some studies have tried to combine antiangiogenic agents such as bevacizumab and sunitinib or sorafenib, but that approach has been limited because of toxicity concerns. Sequential use of antiangiogenic agents with differing mechanisms of action may be an effective approach. Despite setbacks, angiogenesis will likely remain an important target of treatment for selected patients with MBC.
| S-EPMC3425519 | biostudies-other
Project description:This article reviews the clinically most relevant presentations at the American Society of Clinical Oncology (ASCO) annual meeting 2018 on the topic of metastatic breast cancer. In the randomized placebo-controlled phase 3 trial MONALEESA-3, testing ribociclib vs. placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative (HER2-) advanced breast cancer (ABC), an increase of median progression-free survival (PFS) from 12.8 months to 20.5 months by the addition of the CDK4/6 inhibitor was reported (HR 0.59; P > 0.01). Taselisib, an alpha specific PI3K inhibitor, was tested in combination with fulvestrant in pretreated HR+/HER2- ABC patients with PIK3CA mutations in the placebo-controlled phase 3 trial SANDPIPER. PFS was significantly longer (7.4 months vs 5.4 months; HR 0.70, P < 0.01) but severe adverse events were more frequent (32% and 9%) in the taselisib group. In triple-negative breast cancer, the AKT inhibitor capivasertib (AZD5363) was combined with paclitaxel as first-line treatment in the placebo-controlled phase 2 trial PAKT. In patients with altered PIK3CA, AKT1 or PTEN, median PFS increased from 3.7 months to 9.3 months (HR 0.30; two-sided P = 0.01). No treatment effect was shown in the non-altered group. The most common adverse events attributed to capivasertib were diarrhea, fatigue and stomatitis. Results of two phase I trials of trastuzumab antibody-drug conjugates (ADCs) indicated HER2 as a non-oncogenic surface target in breast cancer patients expressing HER2.
| S-EPMC6280779 | biostudies-literature
Project description:BackgroundSocioeconomic differences in receipt of adjuvant treatment contribute to persistent disparities in breast cancer (BCA) outcomes, including survival. Adjuvant endocrine therapy (AET) substantially reduces recurrence risk and is recommended by clinical guidelines for nearly all women with hormone receptor-positive non-metastatic BCA. However, AET use among uninsured or underinsured populations has been understudied. The health reform implemented by the US state of Massachusetts in 2006 expanded health insurance coverage and increased the scope of benefits for many with coverage. This study examines changes in the initiation of AET among BCA patients in Massachusetts after the health reform.MethodsWe used Massachusetts Cancer Registry data from 2004 to 2013 for a sample of estrogen receptor (ER)-positive BCA surgical patients aged 20-64 years. We estimated multivariable regression models to assess differential changes in the likelihood initiating AET after Massachusetts health reform by area-level income, comparing women from lower- and higher-income ZIP codes in Massachusetts.ResultsThere was a 5-percentage point (p-value< 0.001) relative increase in the likelihood of initiating AET among BCA patients aged 20-64 years in low-income areas, compared to higher-income areas, after the reform. The increase was more pronounced among younger patients aged 20-49 years (7.1-percentage point increase).ConclusionsThe expansion of health insurance in Massachusetts was associated with a significant relative increase in the likelihood of AET initiation among women in low-income areas compared with those in high-income areas. Our results suggest that expansions of health insurance coverage and improved access to care can increase the number of eligible patients initiating AET and may ameliorate socioeconomic disparities in BCA outcomes.
| S-EPMC8088064 | biostudies-literature
Project description:We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients.Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy.Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy.Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.
| S-EPMC4453676 | biostudies-other