Project description:Women over age 65 with breast cancer are often not treated in accordance with current guidelines as far as adjuvant therapy is concerned, because of the lack of adequate scientific evidence.This article is based on a selective review of pertinent literature retrieved by a PubMed search, as well as on the German S3 guidelines for the diagnosis, treatment, and follow-up care of breast cancer, the treatment recommendations of the German Working Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO) and the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie), US National Comprehensive Cancer Network, and the Cochrane database.Women over age 65 are underrepresented in randomized trials of treatments for breast cancer. Geriatric assessment is essential for therapeutic decision-making. Endocrine treatment is feasible for nearly all patients with hormone-sensitive tumors. In selected patients over age 65, chemotherapy significantly improves overall survival. The best evidence regarding toxicity is available for anthracycline monotherapy and for combined therapy with doxorubicin/cyclophosphamide or taxane/doxorubicin. Women without cardiac disease can be given trastuzumab, which may lead to reversible cardiotoxicity. Adjuvant radiotherapy significantly improves local tumor control and survival. Adjuvant radiotherapy that is carried out with modern treatment planning, as recommended by the current guidelines, is no more toxic to older patients than to younger ones; thus, it should always be given, unless there is a special reason not to.Women with breast cancer over age 65 whose life expectancy is greater than 5 years, and who are not otherwise too ill, should be given chemotherapy, trastuzumab, and radiotherapy as standard adjuvant treatment. Adjuvant therapy can be reduced or omitted in frail patients. Patients over age 65 should be given the opportunity to enroll in clinical trials.
Project description:BackgroundTamoxifen decreases mammographic density. Whether compliance affects this relationship is unclear as is the relationship between other types of adjuvant treatment and changes in mammographic density.MethodsThis prospective cohort study included 2490 women diagnosed with breast cancer during 2001-2015 in Sweden. Mammographic density was assessed within 3 months of diagnosis and 6-36 months post diagnosis. Logistic regression was performed to study the association between each respective adjuvant treatment and mammographic density reduction (annual dense area decrease >15%).ResultsIntention-to-treat analyses using treatment information from the regional cancer registries showed that tamoxifen-treated patients more frequently experienced mammographic density reductions compared with nontreated patients (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.25 to 1.99), as did chemotherapy-treated patients (OR = 1.28, 95% CI = 1.06 to 1.54). For chemotherapy, the association was mainly seen in premenopausal women. Neither aromatase inhibitors nor radiotherapy was associated with density change. Tamoxifen use based on prescription and dispensation data from the Swedish Prescribed Drug Register showed that users were more likely to have density reductions compared with nonusers (adjusted OR = 2.24, 95% CI = 1.40 to 3.59). Moreover, among tamoxifen users, tamoxifen continuers were more likely than discontinuers to experience density reductions (adjusted OR = 1.50, 95% CI = 1.04 to 2.17).ConclusionsOur results indicate that adherence influences the association between tamoxifen and mammographic density reduction. We further found that chemotherapy was associated with density reductions and propose that this is largely secondary to chemotherapy-induced ovarian failure.
Project description:BACKGROUND:Fatigue is one of the most common and disabling side effects of cancer and its treatment. Although research typically has focused on fatigue that occurs during and after treatment, patients may experience fatigue even before treatment onset. The current study was designed to identify biobehavioral risk factors associated with fatigue before adjuvant therapy in women with early-stage breast cancer. METHODS:Patients with stage 0 to stage IIIA breast cancer (270 women) were recruited before the onset of adjuvant or neoadjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy. Host factors that may influence fatigue were identified from an empirically based, biobehavioral model and assessed using self-report questionnaires, medical record review, and blood collection (for genetic data). Fatigue was assessed by questionnaire. Linear regression analyses were used to evaluate the association between host factors and dimensions of fatigue, with general fatigue as the primary dimension of interest. RESULTS:Fatigue was elevated at the pretreatment assessment compared with published controls. Bivariate analyses identified demographic, cancer-related, and biobehavioral correlates of fatigue. In the multivariable model, predictors of general fatigue included younger age, lower educational level, lower cancer stage, and history of childhood maltreatment (all P values <.05), with the full model accounting for approximately 18.4% of the variance in fatigue. Secondary analyses identified common and specific predictors of emotional, mental, and physical dimensions of fatigue. CONCLUSIONS:Among women who have not yet initiated treatment of breast cancer, demographic and psychosocial factors are associated with elevated fatigue and could be used to identify at-risk patients for early intervention.
Project description:PurposeThis study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies ("tamoxifen plus ovarian function suppression group [T+OFS group]" versus "tamoxifen group [T group]") and the chronological changes in sleep disturbances in each group.MethodsPremenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT.ResultsAmong the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA; however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2-5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes.ConclusionUnlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period.Trial registrationClinicalTrials.gov Identifier: NCT04116827.
Project description:BACKGROUND:Recreational physical activity has been consistently associated with reduced breast cancer risk. Less is known about how family history of breast cancer affects the association and whether it varies by menopausal status. METHODS:The Sister Study is a cohort of 50,884 women who had a sister with breast cancer but no prior breast cancer themselves at enrollment. Women reported all recreational sport/exercise activities they participated in over the past 12 months. Hours/week and MET-hours/week of physical activity were considered in association with breast cancer risk. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated with Cox regression. Extent of family history, examined as a modifier, was characterized by a Bayesian score incorporating characteristics of the family structure. RESULTS:During follow-up (average 8.4 years), 3,023 cases were diagnosed. Higher hours/week (HR?7vs<1 = 0.77; 95% CI, 0.66-0.90) and MET-hours/week (HRquartile4vs1 = 0.75; 95% CI, 0.67-0.85) of physical activity were associated with reduced postmenopausal breast cancer risk. Hours/week and MET-hours/week were associated with suggestively increased premenopausal breast cancer risk (MET-hours/week HRquartile4vs1 = 1.25; 95% CI, 0.98-1.60). Associations did not vary with extent of family history. However, the increased risk in premenopausal women may be limited to those with stronger family history. CONCLUSIONS:In women with a family history of breast cancer, physical activity was associated with reduced postmenopausal, but not premenopausal, breast cancer risk and was not modified by extent of family history. IMPACT:This was the first study to examine the association between physical activity and breast cancer risk in a large population with a family history of breast cancer.
Project description:BACKGROUND:Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL). METHODS:Women diagnosed with early breast cancer (N?=?143, mean age?=?52?±?10?years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18?weeks (end of chemotherapy), and 26?weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time. RESULTS:Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26?weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26?weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26?weeks. No significant effect of the intervention was found on major macronutrients intake. CONCLUSIONS:A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1?year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients. TRIAL REGISTRATION:The APAD study was prospectively registered on ClinicalTrials.gov (NCT01495650; date of registration: December 20, 2011).
Project description:Patients with the triple negative subtype of breast cancer have an overall poor outcome, with earlier relapses, distinct patterns of metastases, and lack of specific targets for treatment selection. Classification of these tumors has begun to be modified by inclusion of immunohistochemistry for various markers, and gene profiling. Further characterization of this subtype of breast cancer may aid in the identification of new targeted therapies. Anthracyclines and taxanes remain the standard of care in the adjuvant setting. However, novel anti-angiogenesis, anti-tubulin, and DNA repair agents are already under evaluation in (neo) adjuvant trials. Molecular characterization is being included in trials to identify optimal adjuvant strategies. The aim of this manuscript is to review data concerning the molecular characterization of triple negative breast cancers as well as the clinical outcomes of treating patients with existing adjuvant treatments, and to highlight newer adjuvant research strategies in development.
Project description:Adjuvant bisphosphonate therapy is increasingly used in postmenopausal breast cancer patients. This is based on level-one evidence that bisphosphonates, particularly zoledronic acid, can effectively prevent cancer treatment-induced bone loss in breast cancer patients receiving estradiol-lowering endocrine therapies such as aromatase inhibitors. Furthermore, emerging data from large clinical trials suggest that additional anticancer benefits can be derived due to a positive impact on the bone marrow microenvironment.