Cost‐effectiveness of the Norwegian breast cancer screening program

The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation‐wide coverage since 2005. All women aged 50–69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost‐effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost‐effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost‐effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ～30% in 2020 for women aged 55–80 years. The NBCSP is a highly cost‐effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16–30%, at the cost of 112,162 NOK per QALY gained.     

Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases.

BACKGROUND: Bisphosphonates are recommended to prevent skeletal related events (SREs) in patients with breast cancer and bone metastases (BCBM). However, their clinical and economic profiles vary from one agent to the other. MATERIALS AND METHODS: Using modeling techniques, we simulated from the perspective of the UK's National Health Service (NHS) the cost and quality adjusted survival (QALY) associated with five commonly-used bisphosphonates or no therapy in this patient population. The simulation followed patients into several health states (i.e. alive or dead, experiencing an SRE or no SRE, and receiving first or second line therapy). Drugs costs, infusion costs, SREs costs, and utility values were estimated from published sources. Utilities were applied to time with and without SREs to capture the impact on quality of life. RESULTS: Compared to no therapy, all bisphosphonates are either cost saving or highly cost-effective (with a cost per QALY < or = 6126 pounds sterlings). Within this evaluation, zoledronic acid was more effective and less expensive than all other options. CONCLUSIONS: Based on our model, the use of bisphosphonates in breast cancer patients with bone metastases should lead to improved patient outcomes and cost savings to the NHS and possibly other similar entities.     

Genomic analysis of the 8p11-12 amplicon in familial breast cancer

Amplification of 8p11-12 has been recurrently reported in sporadic breast cancer. These studies define a complex molecular structure with a set of minimal amplified regions, and different putative oncogenes that show a strong correlation between amplification and over-expression such as ZNF703/FLJ14299, SPFH2/C8orf2, BRF2 and RAB11FIP. However, none of these studies were carried out on familial breast malignancies. We have studied the incidence, molecular features and clinical value of this amplification in familial breast tumors associated with BRCA1, BRCA2 and non-BRCA1/2 gene mutations. We detected 9 out of 80 familial tumors with this amplicon by chromosomal comparative genomic hybridization. Next, we used a high-resolution comparative genomic hybridization array covering the 8p11-12 region to characterize this chromosomal region. This approach allowed us to define 2 cores of common amplification that largely overlap with those reported in sporadic tumors. Our findings confirm the molecular complexity of this chromosomal region and indicate that this genomic event is a common alteration in breast cancer, present not only in sporadic but also in familial tumors. Finally, we found correlation between the 8p11-12 amplification and proliferation (Ki-67) and cyclin E expression, which further proves in familial tumors the poor prognosis association previously reported in sporadic breast cancer.     

Evaluation of RAD50 in familial breast cancer predisposition

The genes predisposing to familial breast cancer are largely unknown, but 5 of the 6 known genes are involved in DNA damage repair. RAD50 is part of a highly conserved complex important in recognising, signalling and repairing DNA double-strand breaks. Recently, a truncating mutation in the RAD50 gene, 687delT, was identified in 2 Finnish breast cancer families. To evaluate the contribution of RAD50 to familial breast cancer, we screened the whole coding region for mutations in 435 UK and 46 Finnish familial breast cancer cases. We identified one truncating mutation, Q350X, in one UK family. We screened a further 544 Finnish familial breast cancer cases and 560 controls for the 687delT mutation, which was present in 3 cases (0.5%) and 1 control (0.2%). Neither Q350X nor 687delT segregated with cancer in the families in which they were identified. Functional analyses suggested that RAD50 687delT is a null allele as there was no detectable expression of the mutant protein. However, the wild-type allele was retained and expressed in breast tumors from mutation carriers. The abundance of the full-length RAD50 protein was reduced in carrier lymphoblastoid cells, suggesting a possible haploinsufficiency mechanism. These data indicate that RAD50 mutations are rare in familial breast cancer and either carry no, or a very small, increased risk of cancer. Altogether, these results suggest RAD50 can only be making a very minor contribution to familial breast cancer predisposition in UK and Finland.     

Effects of screening for breast cancer on its age-incidence relationships and familial risk

Mammographic screening programs for breast cancer have been implemented in many countries and opportunistic mammographies are taken as a diagnostic method. The consequences of the wide application of this technology to age-incidence relationships in breast cancer have not been clarified nor is its effect on familial risk estimation. It was assumed that if screening and diagnostic methods bias familial risk, the highest risk should be noted for sisters diagnosed close in time. Age-specific incidence data were collected from the EUCAN database and from cancer registries of Finland, Norway and Sweden. The Swedish Family-Cancer Database was used to analyse risks for breast cancer among sisters, depending on the time since the first sister was diagnosed with breast cancer. Age-incidence patterns deviated between Germany, with low mammographic coverage, and Sweden, the Netherlands, the UK and France, with variable levels of coverage. The annual age-incidence patterns in Finland, Norway and Sweden changed in concert with the targeted mammographic service. The risk of breast cancer for women with an affected sister, diagnosed between ages 50 to 64 years, was significantly higher within the same or the subsequent year of the sister's diagnosis compared to 5+ years, accounting for 7.3% of all patients. The ordered increase in age-specific incidence of breast cancer in the women targeted by screening studied suggests that mammographic screening is one important factor responsible for the shift of the age of onset for breast cancer towards middle age. However, the effects on the estimation of familial risk are so far small.     

Novel genetic variants in microRNA genes and familial breast cancer

MicroRNA (miRNA) plays an important role in tumorigenesis, but whether miRNA is a cancer predisposition factor or not is still unknown. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis, we screened genetic variants in 17 selected miRNA genes, which are predicted to regulate key breast cancer genes, in 42 patients with familial breast cancer. Seven novel genetic variants were observed in 7 primary or precursor miRNA genes. Among them, 1 rare variant in the precursor of miR‐30c‐1 and 1 rare variant in the primary precursor of miR‐17 were only observed in noncarriers of BRCA1/2 mutations. In functional assays, these 2 variants resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR‐30c‐1 and miR‐17. In the target in vitro assay, we observed that miR‐17 could bind to the 3′UTR of BRCA1 mRNAs, which is predicted to be a target for miR‐17. Our findings suggest that functional genetic variants in miRNA genes can potentially alter the regulation of key breast cancer genes. Whether they confer genetic susceptibility to breast cancer remains to be determined. © 2008 Wiley‐Liss, Inc.     

Familial risk of cancer: data for clinical counseling and cancer genetics

Familial risks for cancer are important for clinical counseling and understanding cancer etiology. Medically verified data on familial risks have not been available for all types of cancer. The nationwide Swedish Family-Cancer Database includes all Swedes born in 1932 and later (0-to 68-year-old offspring) with their parents, totaling over 10.2 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry up to year 2000. Standardized incidence ratios (SIR) and 95% confidence limits (CI) were calculated for age-specific familial risk in offspring by an exact proband status. The familial risks for offspring cancer were increased at 24/25 sites from concordant cancer in only the parent, at 20/21 sites from a sibling proband and at 12/12 sites from a parent and sibling proband. The highest SIRs by parent were for Hodgkin's disease (4.88) and testicular (4.26), non-medullary thyroid (3.26), ovarian (3.15) and esophageal (3.14) cancer and for multiple myeloma (3.33). When a sibling was affected, even prostate, renal, squamous cell skin, endocrine, gastric and lung cancer and leukemia showed SIRs in excess of 3.00. The highest cumulative risks were found for familial breast (5.5%) and prostate (4.2%) cancers. We identified reliable familial risks for 24 common neoplasms, most of which lack guidelines for clinical counseling or action level. If, for example, a familial SIR of 2.2 would be use as an action level, counseling would be needed for most cancers at some diagnostic age groups. The present data provide the basis for clinical counseling.     

Cost effectiveness of gene expression profiling for early stage breast cancer: A decision-analytic model

BACKGROUND:

Gene expression profiling (GEP) is being used increasingly for risk stratification to identify women with lymph node‐negative, estrogen receptor‐positive, early stage breast cancer who are most likely to benefit from adjuvant chemotherapy. The authors of this report evaluated the cost effectiveness of recurrence score‐guided treatment using 2 commercially available GEP tests, Oncotype DX (Genomic Health, Redwood City, Calif) and MammaPrint (Agendia Inc., Irvine, Calif), from a third‐party payer's perspective.

METHODS:

A 10‐year Markov model was developed to compare the costs and quality‐adjusted life‐years (QALYs) of treatment decisions guided by either Oncotype DX or MammaPrint in a hypothetical cohort of women with early stage, lymph node‐negative, estrogen receptor‐positive breast cancer who may experience recurrence. Outcomes included no recurrence, recurrence, and death. The costs considered included gene test costs, the costs of adjuvant chemotherapy and other chemotherapy (including premedication, oncology visits, and monitoring for adverse events), the cost of treating recurrence, costs associated with the treatment of adverse events, and end‐of‐life care costs.

RESULTS:

The model demonstrated that the patients who received the Oncotype DX test to guide treatment spent $27,882 (in US dollars) and gained 7.364 QALYs, whereas patients who received the MammaPrint test to guide treatment spent $21,598 and gained 7.461 QALYs. Sensitivity analyses demonstrated that the results were robust to changes in all parameters.

CONCLUSIONS:

The model suggested that MammaPrint is a more cost‐effective GEP test compared with Oncotype DX at a threshold willingness‐to‐pay of $50,000 per QALY. Because Oncotype DX is the most frequently used GEP in clinical practice in the United States, the authors concluded that the current findings have implications for health policy, particularly health insurance reimbursement decisions. Cancer 2012. © 2012 American Cancer Society.     

Immunoprofile from tissue microarrays to stratify familial breast cancer patients

Familial breast cancer (BC) is a heterogeneous disease with variable prognosis. The identification of an immunoprofile is important to predict tumor behavior for the routine clinical management of familial BC patients. Using immunohistochemistry on tissue microarrays, we studied 95 familial BCs in order to analyze the expression of some biomarkers involved in different pathways. We used unsupervised hierarchical clustering analyses (HCA), performed using the immunohistochemical score data, to define an immunoprofile able to characterize these tumors. The analyses on 95 and then on a subset of 45 tumors with all biomarkers contemporarily evaluable, revealed the same biomarker and patient clusters. Focusing on the 45 tumors we identified a group of patients characterized by the low expression of estrogen receptor (P = 0.009), progesterone receptor (P < 0.001), BRCA1 (P = 0.005), nuclear Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) (P = 0.026) and hypoxia inducible factor-1 alpha (P < 0.001), and also by the higher expression of MIB1 (P = 0.043), cytoplasmic NHERF1 (P = 0.004), cytoplasmic BRCT-repeat inhibitor of hTERT expression (P = 0.001), vascular endothelial growth factor (VEGF) (P = 0.024) and VEGF receptor-1 (P = 0.029). This immunoprofile identified a more aggressive tumor phenotype associated also with a larger tumor size (P = 0.012) and G3 grade (P = 0.006), confirmed by univariate and multivariate analyses. In conclusion, the clinical application of HCA of immunohistochemical data could allow the assessment of prognostic biomarkers to be used simultaneously. The 10 protein expression panel might be used to identify the more aggressive tumor phenotype in familial BC and to direct patients towards a different clinical therapy.     

局部晚期乳腺癌改良根治术后两种辅助放化疗模式的疗效与成本效果分析

目的：结合疗效从经济学角度对局部晚期乳腺癌改良根治术后 FEC －T 后程同步放疗和序贯放疗模式进行分析,为术后辅助治疗模式选择提供参考。方法：采用成本－效果分析对155例改良根治术后接受FEC －T 后程同步放疗或序贯放疗的局部晚期乳腺癌病例进行疗效评价及成本效果分析。结果：中位随访39个月。与序贯模式比较,后程同步放疗模式未增加不良反应;缩短平均治疗时间6．2周,改善3年无复发生存率（92．3％ vs 81．8％,P ＝0．046）,有改善3年的无疾病进展生存率和总生存率趋势;3年无疾病进展生存率的成本－效果比,后程同步模式为999．96元／％,序贯模式为1349．31元／％,增量成本－效果比为－889．38元／％。结论：改良根治术后 FEC －T 后程同步放疗模式及序贯放疗模式都具有良好耐受性及疗效。后程同步放疗模式有更好的疾病控制及成本－效果比,可作为局部晚期乳腺癌的改良根治后辅助治疗模式的良好选择。     

Familial breast cancer registry program in patients referred to the cancer institute of Iran

Introduction: Annually a considerable number of people die because of breast cancer, a common diseaseamong women also in Iran. Identifying risk factors and susceptible people can lead to prevention or at leastearly diagnosis. Among susceptibility risks, 5-10% of patients have a family history predisposing factor whichcan influence the risk of incidence among the family. Having a registry program can be a more practical wayto screen high risk families for preventive planning. Method: Based on inclusion criteria, a questionnaire wasprepared and after a pilot study on a small number of patients, actual data were collected on 400 patients andprocessed in SPSS 16.0. Results: Totally, 28.2%of the patients were younger than 40 years old and 36.8% hadthe included criteria for familial breast cancer (FBC). 102 patient’s samples could be compared for receptorpresentation. Similar to other studies, the number of triple negative breast cancers increased as the age decreased.Conclusion: The high percentage of patients with FBC among 400 cases in this study demonstrates that in orderto design an infrastructural diagnostic protocol and screening of patients with FBC, a precise survey related tofrequency and founder mutations of FBC is needed nationwide.     

A study on the cost effectiveness of sestamibi scintimammography for screening women with dense breasts for breast cancer

The potential impact of Sestamibi scintimammography (SSMM) on the cost effective management of women with dense breasts is not known. This study addresses this issue quantitatively by examining the impact of SSMM based screening strategies on the 3,000,000 women over 40 with very dense breasts (DY patterns) without palpable masses and who have had one or more prior mammograms, who undergo routine screening each year. Quantitative decision tree sensitivity analysis was used to compare the conventional mammography (MM) strategy (strategy A), which does not subject patients with negative mammograms to any further examination until their next screening, with two decision strategies for screening with SSMM SSMM after a negative mammogram (strategy B) or SSMM as the only screening test for women already identified as having dense breasts by a previous mammogram (strategy C). Cost effectiveness was measured by calculating the incremental cost effectiveness ratio (ICER) of strategies B and C, which is the cost of achieving an additional year of life in the screening population by choosing a SSMM based decision strategy rather than the conventional strategy. Strategies B and C reduced the number of false negative diagnoses by 62% and 8%, respectively. The ICER was $632,000 and $3.18M per life year for strategy B and C, respectively. To be cost effective, the pretest probability of cancer in the study population must be greater than 3% for strategy B or the cost of SSMM must be less than $50 for strategy C. These results show the ICER of an SSMM based breast cancer screening strategy in the management of patients with dense breasts is not currently within the range ($50,000 per year life saved) of other commonly performed medical interventions that are considered cost effective.     

Effectiveness and cost-effectiveness of sentinel lymph node biopsy compared with axillary node dissection in patients with early-stage breast cancer: a decision model analysis

Background:

Sentinel lymph node biopsy (SLNB) is less invasive than axillary lymph node dissection (ALND) for staging early breast cancer, and has a lower risk of arm lymphoedema and similar rates of locoregional recurrence up to 8 years. This study estimates the longer-term effectiveness and cost-effectiveness of SLNB.

Methods:

A Markov decision model was developed to estimate the incremental quality-adjusted life years (QALYs) and costs of an SLNB-based staging and management strategy compared with ALND over 20 years'' follow-up. The probability and quality-of-life weighting (utility) of outcomes were estimated from published data and population statistics. Costs were estimated from the perspective of the Australian health care system. The model was used to identify key factors affecting treatment decisions.

Results:

The SLNB was more effective and less costly than the ALND over 20 years, with 8 QALYs gained and $883 000 saved per 1000 patients. The SLNB was less effective when: SLNB false negative (FN) rate >13% 5-year incidence of axillary recurrence after an SLNB FN>19% risk of an SLNB-positive result >48% lymphoedema prevalence after ALND <14% or lymphoedema utility decrement <0.012.

Conclusion:

The long-term advantage of SLNB over ALND was modest and sensitive to variations in key assumptions, indicating a need for reliable information on lymphoedema incidence and disutility following SLNB. In addition to awaiting longer-term trial data, risk models to better identify patients at high risk of axillary metastasis will be valuable to inform decision-making.     

Assessing the cost effectiveness of adjuvant therapies in early breast cancer using a decision analysis model

Summary Background: We have developed a decision analysis model that uses the results of available randomized controlled trials to model the natural history of early breast cancer and assess the potential clinical and financial effects of using adjuvant therapies. Patients and Methods: The original model was used to assess the impact of chemotherapy in hypothetical groups of 45-year-old and 60-year-old node-negative, estrogen receptor-negative women. Using the 1992 Early Breast Cancer Trialists' Collaborative Group report, we have expanded and revised the model to assess: 1) the role of tamoxifen alone, chemotherapy alone, or combined therapy in pre-menopausal women, and 2) chemotherapy in elderly women with node-negative, estrogen receptor-negative cancer. Results: For pre-menopausal women, we found that chemotherapy increases quality adjusted life expectancy and survival by a substantial amount at a cost less than most accepted medical interventions. Combined therapy is beneficial and cost-effective in estrogen receptor-positive cancer. For the elderly, chemotherapy prolongs survival but to a lesser extent compared to younger women. The cost of this benefit is high but within the range of commonly reimbursed procedures for women under age 75 without other co-existing conditions. Conclusions: For most patients some form of adjuvant therapy is beneficial and cost-effective. The model builds upon the data derived from collaborative efforts assessing the effectiveness of adjuvant therapies. The model highlights the need for an equal commitment to assessing the economic and quality of life impacts of breast cancer treatments.This minisymposium was presented December 8, 1992, at the annual San Antonio Breast Cancer Symposium, and was sponsored by educational grants from Amgen and from Bristol-Myers Oncology Division.     

Controlling the cost of breast cancer

Breast cancer management is an important part of the health-care system. In the current harsh economic climate, these costs have to be controlled, and achieving this without compromising quality of care is a daunting challenge. This article discusses the need to find effective and well-targeted chemotherapeutic regimens, which, when combined with appropriate implementation of novel strategies, will provide the optimum treatment for patients while maintaining economic viability.     

Management of familial breast cancer risk

Women who are members of breast cancer families are at increased risk for breast cancer. The cloning of BRCA1 and BRCA2 has made it possible to identify mutation carriers within some of these families. Management of breast cancer risk in these families, which presents enormous challenges to patients and clinicians, is addressed. Management should begin with a full evaluation of the patient, including construction of a three-generation pedigree, ascertainment of non-genetic factors that may impact on risk, information on previous and current breast health, practice of and attitudes toward screening, and the psychosocial impact of family history on the individual. Patient priorities in risk management should be explicitly reviewed; these may include survival, cancer prevention, breast preservation, optimization of quality of life or minimization of disruption of day-to-day activities. Approaches to risk management involve screening (usually considered the mainstay), anti-estrogens, prophylactic surgery and/or lifestyle modifications. Specific gene therapy may become available in the future. Management decisions should be individualized to reflect risk levels and patient priorities and goals, within bounds that are medically and scientifically reasonable. An explicit examination of different time-frames (1, 5, 10 years) is recommended given the rapid evolution of knowledge in this area.     

Patient navigation for breast and colorectal cancer in 3 community hospital settings: An economic evaluation

BACKGROUND:

The Ralph Lauren Cancer Center implemented patient navigation programs in sites across the United States building on the model pioneered by Harold P. Freeman, MD. Patient navigation targets medically underserved with the objective of reducing the time interval between an abnormal cancer finding, diagnostic resolution, and treatment initiation. In this study, the authors assessed the incremental cost effectiveness of adding patient navigation to standard cancer care in 3 community hospitals in the United States.

METHODS:

A decision‐analytic model was used to assess the cost effectiveness of a colorectal and breast cancer patient navigation program over the period of 1 year compared with standard care. Data sources included published estimates in the literature and primary costs, aggregate patient demographics, and outcome data from 3 patient navigation programs.

RESULTS:

After 1 year, compared with standard care alone, it was estimated that offering patient navigation with standard care would allow an additional 78 of 959 individuals with an abnormal breast cancer screening and an additional 21 of 411 individuals with abnormal colonoscopies to reach timely diagnostic resolution. Without including medical treatment costs saved, the cost‐effectiveness ratio ranged from $511 to $2080 per breast cancer diagnostic resolution achieved and from $1192 to $9708 per colorectal cancer diagnostic resolution achieved.

CONCLUSIONS:

The current results indicated that implementing breast or colorectal cancer patient navigation in community hospital settings in which low‐income populations are served may be a cost‐effective addition to standard cancer care in the United States. Cancer 2012. © 2012 American Cancer Society.     

Cost-effectiveness of chemoprevention of breast cancer using tamoxifen in a postmenopausal US population

BACKGROUND:

Previous cost‐effectiveness analyses of tamoxifen therapy account for breast cancer risk reduction during active treatment but not for its persistent protective effect after active treatment.

METHODS:

A detailed, continuous time, mathematical model of breast cancer and healthcare processes was used to simulate a postmenopausal population aged <55 years in a virtual trial comparing tamoxifen treatment with no treatment for lifetime follow‐up. Unlike previous work, the current model of tamoxifen therapy is based on a meta‐analysis of 4 randomized, placebo‐controlled chemoprevention trials with breast cancer risk reduction continuing for 10 years after treatment termination. Cancer incidence and survival data were derived from Surveillance, Epidemiology and End Results statistics. Noncancer disease incidences, quality‐adjusted life year (QALY) utility weights, and costs were derived from the literature.

RESULTS:

Tamoxifen treatment (vs no treatment) saved 29 QALYs in a population of 1000 postmenopausal women aged <55 years with an additional cost of $333,000 over the population's lifetime (average cost‐effectiveness ratio, $11,530 per QALY). Tamoxifen therapy, compared with no treatment, was cost saving when higher risk populations were targeted (5‐year risk ≥1.66%). The cost‐effectiveness results were sensitive to parameters that characterized menopausal symptoms and adverse side effects of tamoxifen.

CONCLUSIONS:

The current results indicated that tamoxifen chemoprophylaxis for postmenopausal women aged <55 years is a cost‐effective health policy that reduces breast cancer incidence and improves life expectancy. Focusing on a postmenopausal population aged <55 years minimized the threat of adverse events associated with tamoxifen. Cancer 2011. © 2011 American Cancer Society.