Patient beliefs and tamoxifen discontinuance in older women with estrogen receptor--positive breast cancer.

PURPOSE: To investigate the patterns and predictors of tamoxifen discontinuance throughout a 2-year period in a cohort of women 65 years or older with newly diagnosed, estrogen receptor (ER)-positive breast cancer, focusing on the role of patients' beliefs about the risks and benefits of tamoxifen therapy. SUBJECTS AND METHODS: We enrolled a convenience sample of women cared for in four geographic regions of the United States with stage 1 (>/= 1 cm), stage II, or stage IIIA disease; no prior history of breast cancer; and no simultaneously diagnosed second primary breast cancer. Data sources included medical records and telephone interviews with patients at 3, 6, 15, and 27 months following definitive surgery. RESULTS: Of the 597 women with ER-positive tumors, 516 women (86%) were prescribed tamoxifen, and of these, 88 (17%) stopped taking tamoxifen during the 2-year follow-up period. Of the women who stopped taking tamoxifen, the majority (68%) took it for less than 1 year. Women with neutral or negative beliefs about the value of tamoxifen (3.0; 95% CI, 1.6 to 5.6) and those with positive nodes (odds ratio = 2.5; 95% CI, 1.0 to 6.3) were more likely to discontinue tamoxifen therapy. CONCLUSION: How women with early-stage breast cancer perceive the risks and benefits of tamoxifen therapy seems critical for sustaining adherence to adjuvant tamoxifen therapy. Interventions designed to educate women about the benefits and risks of tamoxifen therapy may help to reduce discontinuance.     

Predicting adherence to tamoxifen for breast cancer adjuvant therapy and prevention

Treatment with the selective estrogen receptor modulator (SERM) tamoxifen for 5 years has produced dramatic breast cancer-related benefits in (a) the adjuvant setting, with 30% to 50% reductions in recurrence, contralateral disease, and mortality and (b) the prevention setting of healthy high-risk women, where tamoxifen reduces the risk of invasive and noninvasive breast cancer by 50%. Despite these striking data, adherence to tamoxifen is low, and low adherence is associated with poor survival. Although toxicity is a major predictor of poor adherence after starting therapy, pretreatment (baseline) predictors of poor tamoxifen adherence have been minimally studied. The adherence-survival link underscores the critical need to identify early predictors of poor adherence, and recent work is beginning to address this need. A major baseline predictor of poor adherence to prevention is current smoking, which is interestingly absent from studies of adherence to adjuvant therapy. Other important prevention adherence factors include breast cancer risk, extremes of age, non-white ethnicity, low socioeconomic status, and alcohol use. The strongest adjuvant therapy predictors are age (especially very young), ethnicity, and socioeconomic status. Future studies involving prospective systematic evaluation of these and other potential predictors in endocrine chemoprevention (e.g., other SERMs and aromatase inhibitors) are critical, as is the development of effective/targeted interventions to improve adherence and thus treatment outcomes in at-risk women.     

Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women.

PURPOSE: To identify predictors of adjuvant tamoxifen use, side effects, and discontinuation in older women. PATIENTS AND METHODS: We followed a cohort of 303 women > or = 55 years of age diagnosed with stage I or stage II breast cancer for nearly 3 years. Data were collected from women's surgical records and from computer-assisted telephone interviews at 5, 21, and 33 months after primary tumor therapy. RESULTS: Two hundred ninety-two (96%) of 303 patients in the study provided information about tamoxifen use. Tamoxifen use was reported by 189 patients (65%); 26 (15%) discontinued use during the follow-up period. Patients who were 65 to 74 years of age (relative to those 55 to 64 years of age), had stage II disease, were estrogen receptor-positive, saw a greater number of breast cancer physicians, and had better perceptions of their abilities to discuss treatment options with physicians had greater odds of tamoxifen use. Those who had better physical function, had received standard primary tumor therapy, and had obtained helpful breast cancer information from books or magazines had lesser odds of tamoxifen use. Patients > or = 75 years of age (relative to those 55 to 64 years of age) and patients with better emotional health had significantly lesser odds of reporting side effects. Patients who were estrogen receptor-positive were less likely to stop taking tamoxifen; patients who experienced side effects were more likely to stop taking tamoxifen. CONCLUSION: Deviations from a prescribed course of adjuvant tamoxifen occur relatively frequently. The clinical consequences of this deviation need to be identified.     

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

ABSTRACT: INTRODUCTION: In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. METHODS: Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. RESULTS: Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. CONCLUSION: Toremifene may be a valid and safe alternative to tamoxifen in premenopausal women with endocrine-responsive breast cancer.     

Women's perceptions and experience of adjuvant tamoxifen therapy account for their adherence: breast cancer patients' point of view

Objective: The aim of this study on primary breast cancer patients undergoing adjuvant tamoxifen treatment was to determine how their perceptions of the treatment and their experience of side‐effects contributed to their adherence to the treatment. Methods: A consecutive series of primary breast cancer patients eligible for tamoxifen therapy were studied qualitatively by conducting semi‐structured in‐depth interviews at two French cancer centres. Results: The women aged 35–65 (N=34) were struggling with several issues involving their understanding and experience of the treatment, which have not been documented so far. These issues included confusion about the ‘hormonal’ nature and activity of tamoxifen and the etiology of the changes in their menopausal status, as well as the symbolic associations formed by patients about the paradox of taking a treatment that has aging effects but saves lives. Conclusions: This study shows the great physical burden often associated with tamoxifen treatment and brings to light women's own complex representations of the treatment and their interpretation of the side‐effects. Better communication between health‐care providers and patients should ultimately help to prevent refusal or discontinuation of tamoxifen treatment. Copyright © 2009 John Wiley & Sons, Ltd.     

Tamoxifen treatment in Danish breast cancer patients and 5-year risk of arterial atherosclerotic events: a null association

Although the effectiveness of tamoxifen in preventing the recurrence of breast cancer is well established, associations between tamoxifen and the occurrence of atherosclerotic events are not as clear. Breast cancer patients taking tamoxifen have lower serum cholesterol and other lipid levels than those not taking tamoxifen, suggesting that tamoxifen might prevent atherosclerotic events, but the existing studies are conflicting. We examined the relation between tamoxifen and incident hospitalization of angina pectoris, acute myocardial infarction, heart failure, and stroke. The study population of 16,289 women was identified from the Danish Breast Cancer Cooperative Group nationwide clinical database and includes women diagnosed with stage I or II estrogen receptor-positive breast cancer between 1990 and 2004 at ages 45 to 69. Use of a large population-based sample with complete outcome ascertainment allowed us to calculate precise measures of risks, risk ratios, and adjusted hazard ratios comparing tamoxifen-treated patients with untreated patients. We found strong evidence for null associations for each of the four outcomes of interest during the first year and first 5 years after the start of therapy. These findings are important in risk/benefit analyses as tamoxifen therapy in postmenopausal women is being replaced with aromatase inhibitors.     

Clinical and biomarker predictors of side effects from tamoxifen

Tamoxifen decreases breast cancer recurrence, mortality, and breast cancer risk in high-risk women. Despite these proven benefits, tamoxifen use is often limited due to side effects. We identified predictors of tamoxifen-induced side effects based on clinical variables and serum tamoxifen metabolite biomarkers in a cross-sectional study of patients taking tamoxifen. We enrolled 241 women and collected data on demographics, tamoxifen use and side effects, as well as potential clinical and serum predictors. We used logistic regression models and adjusted for age, body mass index, ethnicity, education, prior post-menopausal hormone therapy (HT), tamoxifen duration, and endoxifen levels to identify factors associated with side effects. Common tamoxifen attributed side effects were hot flashes (64%), vaginal dryness (35%), sleep problems (36%), weight gain (6%), and depression, irritability or mood swings (6%). In multi-variate models, tamoxifen duration, age, prior post-menopausal HT, and endoxifen levels all predicted side effects. Women who had been on tamoxifen for >12 months were less likely to report side effects (OR 0.15, 95% CI 0.04–0.58) or severe side effects (OR 0.05, 95% CI 0.005–0.58) compared to women on tamoxifen for <12 months. Compared to women younger than 50, women who were age 60–70 and older than 70 were less likely to report side effects (OR 0.22, 95% CI 0.03–1.35; OR 0.13, 95% CI 0.01–0.99; respectively). Women who previously took post-menopausal HT were more likely to report severe side effects. Women with higher endoxifen levels were more likely to report side effects (OR 1.67, 95% CI 1.01–2.77 per standard deviation increase in endoxifen). Clinicians should consider closely monitoring adherence in women taking tamoxifen, especially in younger women, and women who previously took HT. The association between endoxifen levels and side effects is consistent with the data that suggest that endoxifen is the most highly active metabolite of tamoxifen.     

Adherence to adjuvant therapy in post-menopausal breast cancer patients: a review

This review aimed to address the concept of adherence to adjuvant therapy in post-menopausal women. Thirteen studies were included in the review. Study quality was assessed using Critical Appraisal Skills Programme and CONSORT tools. Adherence to adjuvant medication was assessed using a variety of methods. Estimates of adherence rates to adjuvant therapies indicated that of the post-menopausal women prescribed adjuvant therapy, between 15% and 55% were adherent to tamoxifen from 1 to 5 years of follow-up, albeit two studies proposed adherence rates greater than 85%; these data may be flawed due to the methods of data collection. Between 31% and 73% of women were adherent to anastrozole, letrozole or exemestane from 1 year of treatment. These estimates of adherence are based on a variety of reported records including self-report. Current evidence on the assessment of adherence to adjuvant therapies in post-menopausal women indicate that the adherence rates of medication maybe suboptimal and therefore therapeutic efficacy is questionable and may increase the risk of cancer recurrence and reduce disease survival rates. Concerted research is needed to investigate adherence rates, examine patient health beliefs in the medication management of post-menopausal breast cancer patients and also develop new measures to assess adherence with medication.     

Breast Nurse Intervention to Improve Adherence to Endocrine Therapy Among Breast Cancer Patients in South Ethiopia

IntroductionMany women in rural Ethiopia do not receive adjuvant therapy following breast cancer surgery despite the majority being diagnosed with estrogen-receptor-positive breast cancer and tamoxifen being available in the country. We aimed to compare a breast nurse intervention to improve adherence to tamoxifen therapy for breast cancer patients.Methods and MaterialsThe 8 hospitals were randomized to intervention and control sites. Between February 2018 and December 2019, patients with breast cancer were recruited after their initial surgery. The primary outcome of the study was adherence to tamoxifen therapy by evaluating 12-month medication-refill data with medication possession ratio (MPR) and using a simplified medication adherence scale (SMAQ) in a subjective assessment.ResultsA total of 162 patients were recruited (87 intervention and 75 control). Trained nurses delivered education and provided literacy material, gave additional empathetic counselling, phone call reminders, and monitoring of medication refill at the intervention hospitals. Adherence according to MPR at 12 months was high in both the intervention (90%) and control sites (79.3%) (P = .302). The SMAQ revealed that adherence at intervention sites was 70% compared with 44.8% in the control sites (P = .036) at 12 months. Persistence to therapy was found to be 91.2% in the intervention and 77.8% in the control sites during the one-year period (P = .010).ConclusionBreast nurses can improve cost-effective endocrine therapy adherence at peripheral hospitals in low-resource settings. We recommend such task sharing to overcome the shortage of oncologists and distances to central cancer centers.     

Potential role of tamoxifen in prevention of breast cancer

Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed.     

Risk of menopause during the first year after breast cancer diagnosis.

PURPOSE: Premenopausal women with breast cancer often enter a premature menopause during initial treatment of their malignancy, with resulting loss of childbearing capacity, onset of menopausal symptoms, and subsequent prolonged exposure to long-term risks of menopause. Adjuvant therapy is believed to contribute to this early menopause. PATIENTS AND METHODS: One hundred eighty-three premenopausal women with locoregional breast cancer (tumor-node-metastasis staging system classification, T1-3 N0-1 M0) who had undergone surgical treatment and provided information on menopausal status at diagnosis and 1 year later were enrolled. Systemic adjuvant therapy was recorded. Univariate and multivariate predictors of menopause were examined. RESULTS: Age, weight gain, tumor stage, nodal stage, and systemic adjuvant therapy (chemotherapy, tamoxifen) were all significant univariate correlates of menopause. In multivariate analysis, age, chemotherapy, and hormone therapy (tamoxifen) made significant independent contributions to the onset of menopause. CONCLUSION: Age and systemic chemotherapy are the strongest predictors of menopause in women with locoregional breast cancer. They independently contribute to menopause. A graphic representation of our multivariate model allows an estimation of risk of menopause according to patient age and planned adjuvant treatment, and it may facilitate clinical decision-making.     

Women��s interest in taking tamoxifen and raloxifene for breast cancer prevention: response to a tailored decision aid

Although tamoxifen can prevent primary breast cancer, few women use it as a preventive measure. A second option, raloxifene, has recently been approved. The objective of the study was to determine women's interest in tamoxifen and raloxifene after reading a decision aid (DA) describing the risks and benefits of each medication. Women with 5-year risk of breast cancer ≥ 1.66 from two large health maintenance organizations were randomized to receive a DA versus usual care. After reading an on-line DA that discussed the risks and benefits of tamoxifen and raloxifene, women completed measures of risk perception, decisional conflict, behavioral intentions, and actual behavior related to tamoxifen and raloxifene. 3 months following the intervention, 8.1% of participants had looked for additional information about breast cancer prevention drugs, and 1.8% had talked to their doctor about tamoxifen and/or raloxifene. The majority, 54.7%, had decided to not take either drug, 0.5% had started raloxifene, and none had started tamoxifen. Participants were not particularly worried about taking tamoxifen or raloxifene and did not perceive significant benefits from taking these drugs. Over 50% did not perceive a change in their risk of getting breast cancer if they took tamoxifen or raloxifene. After reading a DA about tamoxifen and raloxifene, few women were interested in taking either breast cancer prevention drug.     

Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial.

In a multicenter trial of adjuvant therapy in stage II breast cancer, 719 postmenopausal patients were randomized to one of three treatment regimens: radiotherapy only or in combination with adjuvant tamoxifen for one year, or adjuvant tamoxifen without radiotherapy. At twelve years of follow-up (median 9 years), no statistically significant differences in survival or recurrence-free survival were observed. However, the rate of loco-regional recurrency was lower among patients treated with both radiotherapy and tamoxifen. The rate of bilateral breast cancer was reduced in tamoxifen-treated patients whereas the rate of new primary malignancies other than breast cancer was somewhat higher in tamoxifen-treated patients. Adjuvant therapy in breast cancer may influence not only breast cancer recurrences and mortality but also later disease patterns and cause-specific mortality.     

Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer.

BACKGROUND: Women diagnosed with breast cancer have a twofold to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrogen receptor (ER)-positive and ER-negative contralateral tumors. METHODS: Using data from a population-based tumor registry that collects information on the ER status of breast tumors, we followed 8981 women residing in western Washington State who were diagnosed with a primary unilateral invasive breast cancer during the period from 1990 through 1998 to identify cases of contralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or regional stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received neither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen. By reviewing selected patient abstracts, we estimated that 94% of the subjects were classified correctly with respect to tamoxifen use. The risk of contralateral breast cancer associated with tamoxifen use was estimated with the use of Cox regression. All statistical tests were two-sided. RESULTS: Of the 89 tamoxifen users and 100 nonusers of tamoxifen diagnosed with contralateral breast cancer, 112 had ER-positive tumors, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The risk of developing an ER-positive and an ER-negative contralateral tumor among tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4.9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxifen. This difference in risk by ER status was statistically significant (P<.0001). CONCLUSIONS: Tamoxifen use appears to decrease the risk of ER-positive contralateral breast tumors, but it appears to increase the risk of ER-negative contralateral tumors.     

Tamoxifen-treated breast carcinoma patients and the risk of acute myocardial infarction and newly-diagnosed angina

BACKGROUND: It is known that tamoxifen therapy favorably affects blood cholesterol levels and other cardiovascular disease risk factors; however, to our knowledge, few studies to date have reported a lower risk of heart disease for breast carcinoma patients who are treated with tamoxifen. METHODS: A nested, matched, case-control study design was used with data from the General Practice Research Database to examine whether patients with breast carcinoma who had been treated with tamoxifen were at reduced risk of having a first acute myocardial infarction (MI) or of developing angina compared with unexposed women. All women between age 30 years and age 85 years who had been diagnosed with breast carcinoma and treated with tamoxifen, or who had been diagnosed with carcinoma of the bladder or colorectum, or nonmelanoma skin cancer between January 1991 and December 1999 were identified. From this population, all women were identified who had newly diagnosed acute MI or angina that occurred at least 1 year after their cancer diagnosis. Four female control participants were matched to each case based on age (+/- 1 year), date of MI or angina diagnosis (corresponding date for matched controls), and date of cancer diagnosis (+/- 6 months). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using conditional logistic regression, controlling for the matching factors, and adjusting for important risk factors, including body mass index, use of hormone replacement therapy, smoking status, and treated hypertension. RESULTS: Current users of tamoxifen had a reduced rate ratio of acute MI or angina (adjusted OR, 0.4; 95% CI, 0.2-0.7) compared with nonusers. The effect persisted with increasing cumulative dose and length of use. CONCLUSIONS: The treatment of breast carcinoma with tamoxifen was found to reduce a woman's risk of acute MI or angina during the 5 years of recommended therapy.