Cost-effectiveness of endocrine therapy versus radiotherapy versus combined endocrine and radiotherapy for older women with early-stage breast cancer

PurposeTo evaluate the cost-effectiveness of endocrine therapy (ET), radiation therapy (XRT), and combination ET + XRT as post-surgical treatment for older women with early-stage breast cancer from the societal perspective.MethodsWe constructed a Markov state-transition model consisting of three mutually exclusive health-states: Disease-Free, Recurrence, or Death. Osteoporotic fracture, radiation-induced breast fibrosis, and radiation pneumonitis were modeled as treatment-related adverse events (AEs). Cancer registry-linked-Medicare data were used to assess probability of recurrence and total costs, after propensity adjustment to account for treatment selection, among women aged >65 years diagnosed with estrogen receptor positive or progesterone receptor positive (ER+/PR+) breast cancer receiving ET, XRT, or ET + XRT in 2007–2011. Following randomized controlled trials, overall survival was assumed equivalent, but locoregional recurrence varied. Indirect costs and health-state utilities were literature-driven and varied in sensitivity analyses. Costs and outcomes were discounted at 3% annually.ResultsIn a cohort of 10,000 women over ten years, we estimated 1620 total recurrences in the ET-only group, 1296 in the XRT-only group, and 1076 with ET + XRT. Compared to ET-only, the base-case incremental cost-effectiveness ratio (ICER) was $10,826 per quality-adjusted life-year (QALY)-gained for XRT-only and $26,834/QALY-gained for ET + XRT. Similarities in cost and effectiveness between treatments led to highly sensitive results. We also present clinically-relevant patient preference scenarios for recurrence risk-averse patients and near-term AE risk-averse patients.ConclusionsThe cost-effectiveness of regimens including ET and/or XRT in older women with early-stage breast cancer is sensitive to small differences in costs, as well as risk of, and utilities associated with, locoregional recurrence, suggesting that patient preferences concerning treatment benefits and risks should be considered by physicians.     

Systemic therapy for older women with breast cancer

Breast cancer is a common problem in older women. As the number of medical illnesses increases with age and the life expectancy decreases, the benefits of systemic therapy for women with breast cancer become questionable. All women over age 65 years are at high enough risk of breast cancer to consider the risk/benefit ratio of preventive therapy with tamoxifen (Nolvadex) or participation in the Study of Tamoxifen and Raloxifene (STAR) trial. Adjuvant chemotherapy and hormonal therapies for early breast cancer significantly improve disease-free and overall survival; recommendations for their use are based on risk of tumor recurrence. Use of tamoxifen in the adjuvant setting in women with receptor-positive tumors is a relatively simple decision in light of its favorable toxicity profile. The delivery of adjuvant chemotherapy is a more complicated decision, and the patient's wishes, estimated life expectancy, presence of comorbid conditions, and estimated benefit from treatment should be considered. The primary goal of the treatment of metastatic breast cancer is palliation. We discuss trials specific to older women and make appropriate treatment recommendations. Unfortunately, there is a paucity of data from clinical trials in women over age 70 years. However, because the clinical trial is the primary scientific mechanism for testing the efficacy of a treatment, every effort should be made to enter older women into treatment protocols.     

Adjuvant endocrine therapy for premenopausal women with early breast cancer

Adjuvant endocrine therapy is a pivotal component of treatment for premenopausal women with early-stage hormone receptor-positive breast cancer. Currently, the standard endocrine therapy for premenopausal women is tamoxifen; a role for ovarian suppression or ablation has also been identified. Uncertainty remains about the optimal use of endocrine therapy in this setting. The role of ovarian suppression with tamoxifen or aromatase inhibitor, the optimal duration of adjuvant endocrine therapy and the utility of biomarkers and pharmacogenetic studies to select therapy are questions worthy of further investigation.     

Optimizing endocrine therapy for premenopausal and postmenopausal women with breast cancer

The majority of invasive breast cancer patients present with hormone receptor-positive disease, and modulation of estrogen receptor (ER) activation is an essential component of systemic adjuvant therapy for these women. While tamoxifen has traditionally been the primary adjuvant endocrine therapy for all ER-positive women, recent trials evaluating the use of aromatase inhibitors (AIs) have challenged this standard in postmenopausal women, and ongoing trials are examining the optimal use of endocrine therapy in younger women. Issues regarding the optimal approach to endocrine therapy in both pre- and postmenopausal women are examined in this review.     

Controversies in adjuvant endocrine therapy for pre- and post-menopausal women with breast cancer

Nearly 80% of breast cancer are hormone receptor positive. The efficacy of hormonal adjuvant therapy of breast cancer was expressed in the most recent EBCTG overview analysis of randomised trials using adjuvant tamoxifen. Five years of adjuvant tamoxifen led to proportional risk reduction, in terms of recurrence and mortality for hormone receptor positive patients, of 47% and 26%, respectively. This benefit was constant, regardless of menopausal status, age or whether or not chemotherapy was administered. More recent trials evaluating the use of aromatase inhibitors have challenged the standard of hormonal therapy in post-menopausal patients. However, many questions have been raised from these trials: (a) the optimal management of patients with hormone receptor positive breast cancer in terms of selection of hormonal agents and its sequence and duration; (b) the role of ovarian suppression in pre-menopausal patients; and (c) the actual role of biomolecular markers in clinical decision.     

乳腺癌内分泌治疗的现状与展望

内分泌治疗是乳腺癌治疗的重要手段之一,其重要性受到了越来越广泛的重视。因此,了解乳腺癌内分泌治疗的发展历程,正确把握乳腺癌的治疗策略,将有助于提高乳腺癌的内分泌治疗效果。1乳腺癌内分泌治疗的历史乳腺癌内分泌治疗的历史可以追溯到1896年,当时,Beatson首先报道3例绝经前晚期乳腺癌,在切除双侧卵巢后2例肿瘤明显缩小。此后100年以来,随着对乳腺癌了解的逐步深入,乳腺癌内分泌治疗经历了肾上腺切除、卵巢切除、雄激素、雌激素、孕激素、抗雌激素、芳香化酶抑制剂治疗等发展过程(表1)。目前,虽然卵巢切除术(手术去势)仍作为绝经前乳…     

Letrozole as adjuvant endocrine therapy in postmenopausal women with breast cancer

The third-generation aromatase inhibitor letrozole offers a promising approach to treating hormone-sensitive breast cancer for postmenopausal women, through potent and specific inhibition of estrogen synthesis. In neoadjuvant and first-line treatment, letrozole demonstrated superior efficacy compared with tamoxifen in randomized Phase III trials. Initial results of Breast InterGroup 1-98, a large ongoing randomized trial investigating primary adjuvant endocrine treatment with either letrozole or tamoxifen, have recently been presented. Patients treated with letrozole demonstrated a 19% improvement in disease-free survival and a significant reduced risk of distant recurrences, holding out the prospect of a survival advantage over tamoxifen treatment with further maturation of the trial. For patients who have already completed 5 years of tamoxifen, extended endocrine therapy with letrozole is a new therapeutic option based on the results of the MA-17 trial. The optimal use of aromatase inhibitors remains an open question, at least until results from randomized trials (BIG 1-98, TEAM) investigating the sequential use of an aromatase inhibitor and tamoxifen in comparison with continuous monotherapy become available.     

Completion of adjuvant radiation therapy among women with breast cancer

BACKGROUND: Optimal treatment for breast cancer often involves lengthy multimodality care including 5 to 6 weeks of radiotherapy, but few studies have evaluated adherence to radiotherapy outside the context of a therapeutic clinical trial. METHODS: Using a SEER-Medicare database, the authors identified women age 66 years or older with Stage I to III breast cancer diagnosed between 1992 and 2002. They evaluated rates of completion of radiotherapy, defined as a minimum of 25 sessions. Multivariate logistic regression analyses were performed to determine factors associated with completion of radiotherapy, and Cox multivariate models were used to determine the impact of radiotherapy completion on local recurrence. RESULTS: Some 24,510 patients were included in the study. Eighty-seven percent of patients completed 25 or more radiotherapy sessions. In multivariate logistic regression models, mastectomy (HR 1.26, 95% CI 1.10-1.43), hospitalization during treatment (2.87, 2.49-3.31), earlier year of diagnosis, and black race (1.36, 1.14-1.63) were associated with increased risk of non-completion of radiotherapy. Among 21,269 patients treated with breast conservation, incomplete radiotherapy was associated with higher risk of local recurrence. A total of 98.7% of patients who did not complete radiation therapy were free of recurrence at 5 years vs. 97.5% of patients who completed radiation therapy (HR 1.46, CI 1.09-1.95). CONCLUSION: This study demonstrates relatively high rates of completion of radiation therapy among a population of older woman with breast cancer. However, those who did not complete a full course of radiotherapy had small but statistically significant higher risk of breast cancer recurrence. Future efforts should focus on intervening with women at high risk of not receiving adjuvant radiotherapy and increasing rates of radiotherapy completion.     

Tumour characteristics among women with very low-risk breast cancer

It has been proposed that a proportion of non-palpable breast cancers that are diagnosed through mammography represents a very low-risk subgroup of cancers that may not affect survival (overdiagnosis). The salient pathologic features of cancers in this theoretical subgroup are not known, and therefore, it is not possible to predict which patients have a cancer of this type. We reviewed the clinical characteristics and survival experiences of 715 patients with an invasive breast cancer of 5.0 cm or less. The tumour from each patient was represented in triplicate on a tissue microarray. Cases were divided into low-risk and moderate-/high-risk categories based on lymph node status and palpability. Low-risk cancers were those that were non-palpable, node-negative and were only detected by mammographic screening. All other cancers were high/moderate risk. The two groups of cancer patients were compared for a number of tumour characteristics, based on immunohistochemistry. There were 79 low-risk cancers and 636 moderate-/high-risk cancers. The low-risk cancers were characterized by ER-positivity, PR-positivity, HER2-negativity, ck5/6-negativity, EGFR-negativity and p53-negativity. About 54 of the 79 low-risk cancers (68 %) were of the luminal A subtype versus 335 of 636 moderate-/high-risk cancers (53 %; p = 0.008). Among 42 women with a non-palpable, mammogram-detected PR+ HER2- cancer of 5.0 cm or less, the 15-year distant recurrence-free survival rate was 100 %. Small breast cancers that are PR+ and HER2- and that are detectable by mammogram alone have a very low risk of recurrence. A proportion of these may represent examples of overdiagnosis.     

Association of cardiovascular disease with health-related quality of life among older women with early-stage breast cancer undergoing adjuvant endocrine therapy

IntroductionDue to the improved overall survival and life expectancy of older women with breast cancer, cardiovascular disease (CVD) arose as the primary cause of non-cancer-related deaths in this population. Therefore, assessing the health-related quality of life (HRQoL) of breast cancer patients with comorbid CVD is becoming increasingly vital. Our study aimed to evaluate the association between comorbid CVD and HRQoL among older women with early-stage breast cancer who are receiving adjuvant endocrine therapy (AET) in the United States.Materials and MethodsWe conducted a retrospective cohort study using the 2006–2017 Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data. We identified female patients over the age of 65 who were diagnosed with stage I-III hormone receptor-positive breast cancer and treated with AET. HRQoL was assessed by the physical and mental component summary (PCS & MCS) in the health survey. CVD was defined as a history of acute myocardial infarction (AMI), congestive heart failure (CHF), angina, stroke, or other heart-related conditions. We performed multivariate linear regression models while controlling for covariates.ResultsAmong 3,904 older women, a history of CHF [β = −1.97, p = 0.025], stroke [β = −3.00, p < 0.010], or other heart-related condition [β = −1.10, p = 0.046] was significantly associated with lower PCS. However, no significant differences in PCS scores were found between women with a history of AMI or angina and those without these conditions. Having a history of CHF [β = −1.72, p = 0.033] or stroke [β = −1.48, p = 0.038] was significantly associated with lower MCS, whereas a history of angina, AMI, or other heart conditions was not associated with significant differences in MCS. Our study did not observe any significant differences in PCS and MCS between the two types AETs.DiscussionThe study found that older women with early-stage breast cancer who were being treated with AETs had a lower HRQoL if they had a history of CHF or stroke. These comorbidities were identified as strong predictors for decreased HRQoL. The findings highlight the significance of managing cardiovascular diseases in such patients for better HRQoL while they receive AET treatment.