PURPOSE To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. PATIENTS AND METHODS The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. CONCLUSION Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.
Background. Approximately 14% of Early Breast Cancers, EBCs, and 25% of Metastatic BCs, MBCs, are HER2 positive. There is an effective treatment (trastuzumab) for both EBC (9% increased absolute disease free survival at fi ve years) and MBC (fi ve to nine months ' prolonged overall survival). Patients with BC are treated within each of the six different Health Care Regions (HCRs) in Sweden. This aim of this project was to study the introduction and usage of trastuzumab in BC in the six HCRs in Sweden. Materials and methods. We used offi cial sales data and cancer statistics in the model, and HER2 positive proportions of 25% (prevalent population in year 2000; fi rst year of trastuzumab sales) and 14% and treatment times of 38 weeks and 52 weeks for MBC and EBC, respectively, based on clinical trial data. We used years 2000-2004 for the MBC analyses. In year 2005 data on trastuzumab in EBC were presented, and approval came in year 2006. We studied years 2006-2008 for the use in both EBC and MBC. Results. The percentage trastuzumab treated MBC patients for the entire period in the different HCRs (quarter 4 2000 to end 2004) was: North 57%,
The high prices of new anticancer drugs and the marginal added benefit perceived by some stakeholders have fuelled a debate on the value of anticancer drugs in the European Union, even though an agreed definition of what constitutes a drug's value does not exist. In this Perspective, we discuss the value of drugs from different viewpoints and objectives of decision makers: for regulators, assessment of the benefit-risk balance of a drug is a cornerstone for approval; payers rely on cost-effectiveness analyses carried out by health technology assessment agencies for reimbursement decisions; for patients, treatment choices are based on personal preferences and attitudes to risk; and clinicians can use several scales (such as the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS)) that have been developed as an attempt to measure value objectively. Although a unique definition that fully captures the concept of value is unlikely to emerge, herein we discuss the importance of understanding different perspectives, and how regulators can help to inform different decision makers.
Objective We aimed to determine the longitudinal prevalence and the predictors of sickness absence (SA) and disability pension (DP) in breast cancer (BC) women who eventually developed relapse. Methods A total of 1293 BC women, who were ages 20–63 years, diagnosed between 1996 and 2011 and by 2016 had all developed relapse, were identified in Swedish registers and were followed from two years before to five years after their primary diagnosis, while they were relapse‐free. Annual prevalence of SA and DP was calculated. Logistic regression was used to estimate adjusted odds ratios (AOR) for long‐term SA (>30 days) at one (y1) and three (y3) years post‐diagnosis. Results Prevalence of long‐term SA was 68.1% in y1 and 16.3% in y5. Prevalence of DP progressively increased from 16.3% in y1 to 29.0% in y5. Predictors of long‐term SA included age <50 years (y1:AOR = 1.79 [1.39–2.29]), TNM stage III (y1:AOR = 1.54 [1.03‐2.31]; y3:AOR = 2.21 [1.32–3.72]), metastasis (y1:AOR = 1.64 [1.26–2.12]; y3:AOR = 1.51 [1.05–2.18]), comorbidity (y1:AOR = 2.41 [1.55–3.76]; y3 AOR = 4.62 [2.49–8.57]) and any combination of radiotherapy, chemotherapy and hormonal therapy (y1:AOR = 2.05–5.71). Conclusion Among BC women who later developed relapse, those who had higher stages of BC, had comorbidity and received neoadjuvant and/or adjuvant therapy were at significantly higher risk of needing long‐term SA after their diagnosis.
Purpose Considering that breast cancer is a heterogeneous disease, we aimed to improve prediction of patients at high-risk for metastatic disease utilizing a nested case-control design uniquely enabling enrichment for relevant phenotypes. Methods In Sweden cancer registration has a legal basis and the Swedish Cancer Registry has a breast cancer coverage of more than 96% in validation studies. We identified women diagnosed with primary breast cancer from January 1, 1997, to December 31, 2005, in the Stockholm health care region. Patients developing distant metastatic disease (cases) were selected and controls (free from distant disease) were randomly matched by adjuvant therapy, age and calendar period at diagnosis. The nested case-control study included 768 study subjects (621 patients including two patients with bilateral breast tumors) with detailed manually collected clinical information and complete follow-up (according to the national guidelines by the Swedish Breast Cancer Group (SweBCG)). Primary tumor grade, Human Epidermal Growth Factor Receptor 2 (HER2) and Ki-67 expression was reassessed and scored by a breast cancer pathologist. All patients were profiled with the Affymetrix array (Human Cancer G110) containing in total 52,378 probes, both including control probes of different types, as well as probes corresponding to human transcripts. The study subjects were randomly and equally divided into the discovery set or validation set. Metastatic onset predictive capacity was compared including either clinical variables only (1) or combining clinical and genetic information (2), estimating ROC curves and AUC. Results Convincingly, genes and pathways found to be differentially expressed in our nested case-control study included a wide-spectra of well known as well as candidate regulators of the metastatic cascade. In our study, 313 annotated genes (under the strict Bonferroni cut-off) were differentially expressed in patients developing distant metastatic disease in contrast to patients free from disseminated disease. Our metastasis gene signature model accommodates 50 genes predicting risk for metastatic disease after adjustment of standard clinical markers. Regulation of immune response activity was a common feature among the genes as included. It is clear from the area under the ROC curve, AUC, that the predictive capacity of the metastasis gene signature model (2), also validated in the validation set of study subjects, was superior to the model with clinical variables only (1), as evidenced by AUC (0.86; 95% CI, 0.83 to 0.89 for the metastasis gene signature and 0.73; CI, 0.71 to 0.76 for clinical variables only). The gene signature model predicted both high-risk of early and later onset of metastatic disease. Conclusion In our nested case-control study, we identified genes and pathways differentially expressed in patients developing distant metastatic disease compared to patients without disseminated disease. Our validated metastasis gene signature model enabled better risk prediction compared to standard clinical markers, capturing both high-risk of early and later metastatic disease onset, of potential vital importance in the clinical setting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-17.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.