Out-of-Pocket Cost Modeling of Adjuvant Antiestrogen and Radiation Therapy After Lumpectomy for Early-Stage Breast Cancer Across Medicaid and Medicare Plans.

PURPOSE: The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency. METHODS AND MATERIALS: Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon. RESULTS: Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option. CONCLUSIONS: This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced.

Budget impact analysis of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan.

'Cost saving' was suggested in our recent economic evaluation of chemoprevention of breast cancer targeting women at high risk in Japan. However, this budget impact analysis reveals that the introduction of chemoprevention appears to be not budget saving for approximately 20 years, whereas the level of budget impact seems affordable.

Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis.

BACKGROUND: Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer. This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). METHODS: We created a Markov model to determine whether tamoxifen or aromatase inhibitor monotherapy maximized 5-year disease-free survival for patients with the wild-type CYP2D6 genotype (wt/wt). Annual risks of recurrence with aromatase inhibitors and tamoxifen in breast cancer patients who were not selected by CYP2D6 genotype were derived from the Breast International Group 1-98 trial. Genotype frequencies and the hazard ratio for cancer recurrence on tamoxifen among patients with the *4/*4 genotype relative to the wt/wt or wt/*4 genotypes (HR(*4/*4) = 1.86) were based on data from an analysis of the North Central Cancer Treatment Group trial of adjuvant tamoxifen. We explored the impact of CYP2D6(*4) heterozygosity on disease-free survival for wt/wt patients by studying a range of effect (ie, recurrence on tamoxifen) estimates, from no effect of the single mutation (Eff(wt/*4) = 0, recurrence rate in wt/*4 patients same as that in wt/wt patients) to complete effect (Eff(wt/*4) = 1 recurrence rate in wt/*4 patients same as that in *4/*4 patients). RESULTS: With HR(*4/*4) = 1.86 and Eff(wt/*4) = 0.5, the 5-year disease-free survival of tamoxifen-treated patients with no mutations (wt/wt) was 83.9%, that is, essentially the same as that (84.0%) for genotypically unselected patients who were treated with aromatase inhibitors. With greater HR(*4/*4) estimates, disease-free survival with tamoxifen exceed that with aromatase inhibitors in wt/wt patients, even at lower assumed Eff(wt/*4) ratios. CONCLUSIONS: Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those who have with concerns about either the relative toxicity or the increased cost of aromatase inhibitors.

Economic impact of Tibolone compared with Continuous-Combined Hormone Replacement Therapy in the management of climacteric symptoms in postmenopausal women.

BACKGROUND: Deciding whether to treat postmenopausal women suffering from climacteric symptoms with Continuous Combined Hormone Replacement Therapy (CCHRT) has become increasingly difficult after the release of the Women's Health Initiative results. As a result, development of alternatives to CCHRT is required. Tibolone, which is a synthetic steroid that has estrogenic, progestogenic and androgenic properties, is reported to be a promising alternative. It has been used in Europe, in the same indication as CCHRT, for approximately 20 years but is not yet available in Canada. OBJECTIVE: We carried out a cost-utility analysis comparing a 3-year-treatment course with Tibolone 2.5mg and conjugated equine estrogens (CEE)/medroxyprogesterone acetate (MPA) (0.625 mg/2.5 mg) in the management of postmenopausal women with climacteric symptoms. METHODS: A Markov model, considering persistence, vaginal bleeding and climacteric symptoms, was elaborated to compare the different options in terms of cost and Quality Adjusted Life Years (QALYs), according to a public third-party payer perspective. RESULTS: Compared with CEE/MPA, Tibolone led to an increase in cost (dollars 485 for Tibolone versus dollars 232 for CEE/MPA) and a slight increase in QALYs (2.08 for Tibolone versus 2.05 for CEE/MPA). Consequently, the incremental cost per QALY gained ratio was dollars 9198. CONCLUSION: According to the results, Tibolone seems to be a cost-effective alternative to CEE/MPA. However, those results should be interpreted with caution insofar as the difference in terms of QALY is clinically difficult to value and taking into account the limited data on Tibolone's long-term innocuity.

[A cost-effectiveness study of first-line hormone therapy in post-menopausal patients with metastatic breast cancer on neoadjuvant treatment]. / Estudio coste-efectividad de la terapia hormonal en primera línea en pacientes postmenopáusicas en cáncer de mama metastásico y en tratamiento neoadyuvante.

OBJECTIVE: Breast cancer is a hormone-dependent tumor, which expands therapy options. The aim of this study was to perform a pharmacoeconomic assessment of these drugs in post-menopausal patients with metastatic breast cancer or on neoadjuvant therapy. METHOD: To assess the efficacy of both drug classes a meta-analysis was carried out from papers obtained in a Medline literature search (1997 - June 2004) using the following keywords: breast cancer, postmenopausal, aromatase inhibitors, antiestrogens, tamoxifen, neoadjuvant. Effectiveness parameters included: objective response, percentage with conservative surgery in neoadjuvancy; in metastatic breast cancer, time to progression. Costs were considered from drug acquisition data. To determine result strength a sensitivity analysis was undertaken, with modified costs and effectiveness. RESULTS: Results show a higher effectiveness for aromatase inhibitors as compared to antiestrogens. In neoadjuvant therapy: 56.38% versus 36% for objective response rate, and 47.64% versus 35% for conservative surgery. In metastatic cancer: 9.96 versus 6.61 months for time to progression (p

Osteoporosis management in a Medicaid population after the Women's Health Initiative study.

OBJECTIVE: Publication of the Women's Health Initiative (WHI) study has changed our understanding on the effects of hormone replacement therapy. This study was designed to evaluate patterns of antiosteoporosis medication (AOM) use in a Medicaid population before and after the release of the WHI study results. METHODS: A descriptive time series analysis was conducted among women 50 years of age and older who were enrolled in the Pennsylvania Medicaid program from December 1, 2001, through December 31, 2002. All AOMs were identified, including estrogens, bisphosphonates, selective estrogen receptor modulators (SERMs), and calcitonin. The monthly prevalence of each AOM and drug class was estimated. Comparisons between pre-WHI (December 1, 2001-July 30, 2002) and post-WHI (August 1, 2002-December 31, 2002) study periods were made for overall AOM use by AOM drug class as well as by recipient characteristics. RESULTS: The overall prevalence of AOM did not change between pre-WHI and post-WHI study publication. However, there were significant changes in the prevalence of certain AOM drug classes. Estrogen use decreased significantly after the WHI study release for all age and racial groups. The prevalence for bisphosphonates and SERM increased significantly in the post-WHI period. CONCLUSIONS: The WHI study influenced patterns of use of all types of AOM, decreasing estrogen and increasing nonestrogen use among postmenopausal women in a Medicaid program. These results suggest that the WHI study affected patterns of use of bone protective pharmacotherapy, with a shift in bone protection therapy use from estrogen to nonestrogen AOMs.

Lasofoxifene (Pfizer).

Pfizer is developing lasofoxifene, an oral naphthalene derivative selective estrogen receptor modulator identified under a collaboration with Ligand, for the treatment of osteoporosis and vaginal atrophy. In August 2004, Pfizer submitted a New Drug Application to the Food and Drug Administration (FDA) seeking approval of lasofoxifene for the treatment of osteoporosis; however, in September 2005, the FDA issued a non-approvable letter.

Assessment and management of women's sexual dysfunctions: problematic desire and arousal.

INTRODUCTION: Women frequently report low sexual desire or interest. An associated lack of subjective arousal during sexual activity is clinically highly apparent but has not been the focus of traditional sexual inquiry, definitions of dysfunction, or management. The frequent poor correlation of women's subjective sexual arousal and observable increases in genital congestion in response to sexual stimulation has not been reflected in assessment, diagnosis, or management. AIM: To provide recommendations/guidelines for the assessment and management of women's sexual dysfunctions focusing on low desire, low interest, and lack of arousal. METHODS: An international consultation, in collaboration with major sexual medicine associations, assembled over 200 multidisciplinary experts from 60 countries into 17 committees. One subcommittee of five members focused on women's sexual desire and arousal, developing over a 2-year period various recommendations. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based scientific literature, widespread internal committee discussion, public presentation, and debate. RESULTS: Women's sexual response in health can be reconceptualized as a circular model of overlapping phases of variable order influenced by psychological, societal, and biological factors. Subsequent revisions to definitions of arousal and desire disorder are given. Recommendations regarding assessment and management focus on factors reducing arousability and satisfaction. These include women's mental health and feelings for their partner, generally and at the time of sexual activity. Recommendations reflect the poor correlation of subjective arousal and increases in genital vasocongestion. CONCLUSION: Further outcome research of management based on new conceptualization of sexual response and revised definitions of dysfunction is needed. The basis of the variable correlation between genital vasocongestion and subjective arousal needs clarification as do the biological underpinnings of sexual response and their changes with age and life cycle.

Medical management of osteoporosis.

Osteoporosis is a cause of considerable morbidity and mortality in men and women. Medical intervention can reduce the progression of osteoporosis and decrease the fracture risk associated with low bone mineral density. In this article, we review the evidence for medical therapies for osteoporosis, including estrogen, calcitonin, bisphosphonates, selective estrogen receptor modulators, and the newest approved agent, recombinant human parathyroid hormone. We also discuss several controversial areas in osteoporosis treatment, including the management of men with osteoporosis, approach to monitoring the effects of osteoporosis therapy, and need for cost-effective strategies for osteoporosis treatment.

Treatment of breast cancer in countries with limited resources.

Early and accurate diagnosis of breast cancer is important for optimizing treatment. Local treatment of early stage breast cancer involves either mastectomy or breast-conserving surgery followed by whole-breast irradiation. The pathologic and biologic properties of a woman's breast cancer may be used to estimate her probability for recurrence of and death from breast cancer, as well as the magnitude of benefit she is likely to receive from adjuvant endocrine therapy or cytotoxic chemotherapy. Ovarian ablation or suppression with or without tamoxifen is an effective endocrine therapy in the adjuvant treatment of breast cancer in premenopausal women with estrogen receptor (ER)-positive or ER-unknown breast cancer. In postmenopausal women with ER- and/or progesterone receptor (PR)-positive or PR-unknown breast cancer, the use of tamoxifen or anastrozole is effective adjuvant endocrine therapy. The benefit of tamoxifen is additive to that of chemotherapy. Cytotoxic chemotherapy also improves recurrence rates and survival, with the magnitude of benefit decreasing with increasing age. Substantial support systems are required to optimally and safely use breast-conserving approaches to local therapy or cytotoxic chemotherapy as systemic therapy. Locally advanced breast cancer (LABC) accounts for at least half of all breast cancers in countries with limited resources and has a poor prognosis. Initial treatment of LABC with anthracycline-based chemotherapy is standard and effective. Addition of a sequential, neoadjuvant taxane thereafter increases the rate of pathologic complete responses. Neoadjuvant endocrine therapy may benefit postmenopausal women with hormone receptor-positive LABC. After an initial response to neoadjuvant chemotherapy, the use of local-regional surgery is appropriate. Most women will require a radical or modified radical mastectomy. In those women in whom mastectomy is not possible after neoadjuvant chemotherapy, the use of whole-breast and regional lymph node irradiation alone is appropriate. In those women who cannot receive neoadjuvant chemotherapy because of resource constraints, mastectomy with node dissection, when feasible, may still be considered in an attempt to achieve local-regional control. After local-regional therapy, most women should receive additional systemic chemotherapy. Women with LABC that has a positive or unknown hormone receptor status benefit from endocrine therapy with tamoxifen. The treatment of LABC requires multiple disciplines and is resource intensive. Efforts to reduce the number of breast cancers diagnosed at an advanced stage thus have the potential to improve rates of survival while decreasing the use of limited resources.

Allopathic and complementary alternatives to hormone replacement therapy.

Management of the menopause is a rapidly growing concern due to the ageing human population. The overall female lifespan has increased over the last century and up to a third of a woman's life is now spent in menopause. To that end, significant attention has been placed on maximising the quantity and quality of life in the menopausal years. The optimal management strategies are ones that are highly flexible and sensitive to an individual's expectations and concerns. Thus, while traditional oestrogen replacement therapy has been in place for > 20 years, there is now a greater interest in alternatives to this modality for those women who cannot or will not use it. This article reviews some of the alternative therapies that are being incorporated both in the allopathic and complementary medicine arenas.

[Metastatic breast cancer: what are the objectives?]. / Il carcinoma metastatico della mammella: quali obiettivi?

UNLABELLED: The medical approach to the treatment of metastatic breast cancer has changed in the last decade since the introduction of new drugs that demonstrate high activity and better tolerability profiles. The hormonal treatment, usually considered the first choice therapy for ER-positive metastatic breast cancer patients, has seen several improvements with the discovery of new selective aromatase-inhibitor agents and pure antiestrogens. New aromatase-inhibitors have shown higher activity and fewer side effects compared to megestrol acetate in second line treatment. The first line treatment has unchanged so far, but in the next future is possible that different agents, with lower toxicity, will replace tamoxifen since studies comparing this agent with pure antiestrogens or selective aromatase-inhibitors are ongoing. These new drugs would provide a better palliation of metastatic breast cancer in terms of higher clinical benefit, tolerability and quality of life. Chemotherapy is often used in ER-negative patients or in aggressive hormone refractory disease. Randomized trials have demonstrated that anthracyclin-containing regimens were more effective than combinations without anthracyclines. New cytotoxic drugs with high activity, such as taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine and capecitabine, have been introduced. Compared with older therapies, improved objective response rates and/or improved duration of response have been reported with these newer agents alone or in combination with other drugs. However, no clear improvement of overall survival has been shown so far. Taxanos alone or in combination are today considered the second line treatment of choice and studies are assessing the value of a taxane-anthracycline containing regimen in first line treatment. Some new agents (vinorelbine) showed, alone or in combination, an interesting cost-effectiveness ratio with similar or higher "quality adjusted progression free survival" if compared to taxanes. Promising are also the results of agents that own low toxicity with comparable efficacy such as liposomal anthracycline. Attempts to improve overall survival with increased dose intensity or with high dose chemotherapy are disappointing. CONCLUSIONS: Since the goal of treatment of metastatic breast cancer is disease control rather than disease skill i.e. palliation of patients with complications of progressive cancer, the new agents have brought significant improvements (higher response rates, median time to progression, cost benefit and better tolerability). Future progresses for this disease, hopefully even in overall survival, will depend on the introduction of new therapies such as immunotherapy, inhibition of intracellular signaling, interference with tumor angiogenesis, gene-therapy and the development of vaccines.