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Tamoxifen is an established treatment for breast cancer, but its long-term effects on survival and on secondary cancers are not fully evaluated. We studied 30 years outcome of 4124 postmenopausal patients who were randomized to receive (totally) two or five years of adjuvant tamoxifen. After 5 years of follow-up, when tamoxifen treatment was finished in both groups, until 15 years of follow-up, overall mortality (HR 0.80, 95% CI 0.72–0.90, p < 0.001), breast cancer mortality for all patients (HR 0.80, 95% CI 0.68–0.94, p = 0.006) and breast cancer mortality for patients with estrogen receptor positive disease (HR 0.67, 95% CI 0.55–0.83, p < 0.001) were significantly reduced in the five-year group as compared to the two-year group. After 15 years, the difference remained but did not further increase. In the five-year group, the incidence of contralateral breast cancer was gradually reduced during the entire period of observation. The incidence of lung cancer was also reduced in the five-year group. In contrast there was an increased endometrial cancer incidence in the five-year group and for those receiving 40 mg of tamoxifen this incidence was further increased. Three more years of tamoxifen therapy reduced the risk of breast cancer mortality. The difference was established during the first 15 years after randomization. Moreover, the incidence of contralateral breast cancer gradually decreased for 30 years. The incidence of lung cancer was reduced in the five-year group. In contrast the incidence of endometrial cancer was increased. • After 30 years of follow-up, 5 years as compared to 2 years of tamoxifen. • Had reduced breast cancer mortality. • Had reduced all-cause mortality. • Had reduced the incidence of contralateral disease. • Had increased the incidence of endometrial cancer. [ABSTRACT FROM AUTHOR]

Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors. Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy. In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006–2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32–4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01–2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40–3.25 for arrhythmia; HR 2.03; 95% CI: 1.15–3.58 for ischemic heart disease). Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy. • A potential negative impact of aromatase inhibitors as adjuvant treatment on risk for cardiovascular events has been proposed. • We investigated the risk for cardiovascular events in breast cancer patients treated with aromatase inhibitors in a retrospective cohort study. • Use of aromatase inhibitors for four years or more was associated with increased risk for ischemic heart disease and arrhythmia. • Our findings support the need to include this information to the risk-benefit assessment concerning endocrine therapy. [ABSTRACT FROM AUTHOR]

Bakground The aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant. Methods A consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI. Results In total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and AIs and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively. Conclusions N o difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and Methods Eligibility criteria were: consecutive patients with age ≥65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. Results Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65–90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). Conclusion BCS and ET without RT seem to be a safe treatment option in women ≥ 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors. [ABSTRACT FROM AUTHOR]

Objective To investigate the use and impact of granulocyte colony-stimulating factors (G-CSF) on chemotherapy delivery and neutropenia management in breast cancer in a clinical practice setting. Methods IMPACT Solid was an international, prospective observational study in patients with a physician-assessed febrile neutropenia (FN) risk of ≥20%. This analysis focused on stages I–III breast cancer patients who received a standard chemotherapy regimen for which the FN risk was published. Chemotherapy delivery and neutropenia-related outcomes were reported according to the FN risk of the regimen and intent of G-CSF use. Results 690 patients received a standard chemotherapy regimen; 483 received the textbook dose/schedule with a majority of these regimens (84%) having a FN risk ≥10%. Patients receiving a regimen with a FN risk ≥10% were younger with better performance status than those receiving a regimen with a FN risk <10%. Patients who received higher-risk regimens were more likely to receive G-CSF primary prophylaxis (48% vs 22%), complete their planned chemotherapy (97% vs 88%) and achieve relative dose intensity ≥85% (93% vs 86%) than those receiving lower-risk regimens. Most first FN events (56%) occurred in cycles not supported with G-CSF primary prophylaxis. Conclusion Physicians generally recommend standard adjuvant chemotherapy regimens and were more likely to follow G-CSF guidelines for younger, good performance status patients in the curative setting, and often modify standard regimens in more compromised patients. However, G-CSF support is not optimal, indicated by G-CSF primary prophylaxis use in <50% of high-risk patients and observation of FN without G-CSF support. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of urogenital symptoms and vaginal atrophy in postmenopausal breast cancer patients on adjuvant endocrine therapy. Study Design: A population-based, cross-sectional study on postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched control subjects. Vaginal atrophy was assessed by gynecologic examination and atrophy-related symptoms by validated questionnaires. Results: In all, 57.6% of aromatase inhibitor-treated and 32.4% of tamoxifen-treated breast cancer patients rated at least 1 vaginal atrophy symptom as moderate/severe, which was significantly more common than in control subjects (P < .01). Aromatase inhibitor-treated patients more often had moderate or severe vaginal atrophy (P < .05), a more atrophic cytohormonal evaluation, and significantly higher vaginal pH (P < .05) than all control subjects, irrespective of hormonal use. Conclusion: Our findings indicate that the frequency of vaginal atrophy symptoms, particularly in aromatase inhibitor-treated women, might have been underestimated in previous clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To determine how much proton and intensity modulated photon radiotherapy (IMRT) can improve treatment results of node-positive left-sided breast cancer compared to conventional radiation qualities (X-rays and electrons) after breast-conserving surgery in terms of lower complication risks for cardiac mortality and radiation pneumonitis.Methods and material: For each of 11 patient studies, one proton plan, one IMRT, and two conventional (tangential and patched) plans were calculated using a three-dimensional treatment-planning system, Helax-TMS™. The evaluation of the different treatment plans was made by applying the normal tissue complication probability model (NTCP) proposed by Ka¨llman (also denoted the relative seriality model) on the dose distributions in terms of dose-volume histograms. The organs at risk are the spinal cord, the left lung, the heart, and the non-critical normal tissues (including the right breast).Results: The comparison demonstrated that the proton treatment plans provide significantly lower NTCP values for the heart and lung when compared to conventional radiation qualities including IMRT for all 11 patients. At a prescribed dose of 50 Gy in the PTV, the calculated mean NTCP value for the patients decreased, on the average, from 14.7 to 0.6% for the lung (radiation pneumonitis) for the proton plans compared with the best plan using conventional radiation qualities. The corresponding figures for the heart (cardiac mortality) were from 2.1 to 0.5%. The figures for cardiac mortality for IMRT, tangential technique and the patched technique were 2.2, 6.7, and 2.1%, respectively.Conclusions: Protons appear to have major advantages in terms of lower complication risks when compared with treatments using conventional radiation qualities for treating node-positive left-sided breast cancer after breast-conserving surgery. [Copyright &y& Elsevier]

Aim Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis. Methods Distant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins. Results Young women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR− tumours (hazard ratio [HR] 0.47 [0.24–0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22–4.50]). Young women with luminal B PR− tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17–17.6]). Conclusions The higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours. [ABSTRACT FROM AUTHOR]

Abstract: Study aim: Amenorrhoea is a common side-effect to chemotherapy of premenopausal women. We examine the association between chemotherapy-induced leucopaenia and the development of amenorrhoea in premenopausal women with breast cancer. Materials and methods: In a multi-centre, randomised, controlled study, 1016 premenopausal women received seven series of FEC (F: fluorouracil, E: epirubicin and C: cyclophosphamide) for early stage breast cancer. In the first series, all patients received standard dose (F: 600mg/m2, E: 60mg/m2 and C: 600mg/m2). Patients with leukocyte nadir 1.0–1.9×109/l continued with standard dose for the remaining six series (STANDARDREGISTERED, n =279). Patients with leukocyte nadir ⩾2×109/l were randomised to standard (STANDARDRANDOMISED, n =373) or increased (TAILORED, n =364) dose of E and C. After each series, leukocyte nadir was evaluated. Absent bleeding after the 5th–7th series of FEC was interpreted as amenorrhoea. Results: The risk of amenorrhoea increased with age. In age-stratified analysis of the STANDARD groups (equal dose, different initial leukocyte nadir) low leukocyte nadir was associated with amenorrhoea for patients in the age-group 25–39years (P =0.010). In age-stratified analysis in the randomised groups (different doses, same initial leukocyte nadir) a dose related increased risk of amenorrhoea was found for age-groups 25–39 (RR: 1.15, 95% confidence interval (CI): 1.06–1.24) and 40–44years (RR:1.21, 95% CI: 1.001–1.47). Conclusion: Age is the most important risk factor of amenorrhoea after FEC chemotherapy. However, for younger patients, lower leukocyte nadir in response to STANDARD FEC treatment or increased doses of C and E were associated with increased risk of amenorrhoea. [Copyright &y& Elsevier]