Purpose
This review proposes an overall vision of the protective and therapeutic role of melatonin in breast cancer: from the specific cases of blind women and their reduction of breast cancer ...incidence to all clinical uses of the sleep hormone in breast cancer.
Methods
We reviewed studies focused on (1) the correlation between blindness and breast cancer, (2) the correlation between melatonin and breast cancer occurrence in the general population, (3) melatonin therapeutic use in breast cancer, and (4) we discussed the properties of melatonin that could explain an anticancer effect.
Results
(1) Seven studies of breast cancer risk in blind women related significant incidence decreases, up to 57%, among totally blind women. The limited number of studies and the absence of adjustment for confounding factors in most studies limit conclusions. None of these studies established melatonin profiles to determine whether blind women with a decreased breast cancer incidence produced higher levels of melatonin. (2) In the general population, 5 meta-analyses and 12 prospective-cohort studies focused on melatonin levels at recruitment and breast cancer occurrence. All reported the absence of correlation in premenopausal women, whereas in postmenopausal women, most studies showed significantly decreased risk for women with highest melatonin levels. (3) The therapeutic interest of melatonin associated with chemotherapy, radiotherapy, and hormonotherapy is poorly documented in breast cancer to conclude on a positive effect. (4) Melatonin effects on mammary carcinogenesis were only reported in in vitro and animal studies that demonstrated antiestrogenic, antioxidant, oncostatic, and immunomodulatory properties.
Conclusion
The preventive role of high endogenous melatonin on breast cancer as well as its beneficial therapeutic use remains to be proven.
Background. Invasive aspergillosis is associated with high death rates. Factors associated with increased mortality have not yet been identified in a large population of patients with various ...underlying conditions. Methods. We retrospectively reviewed 385 cases of suspected or documented aspergillosis that occurred during a 9-year period. We identified 289 episodes that fulfilled the criteria for possible, probable, or proven invasive aspergillosis according to the international definition criteria and that was treated with an anti-Aspergillus active antifungal drug. Clinical and microbiological variables were analyzed for their effects on overall and attributable mortality. Significant variables in univariate analysis were introduced into a multivariate Cox model. Results. Twelve-week overall and disease-specific survival rates were 52.2% (95% confidence interval, 46.5%–57.9%) and 59.8% (95% confidence interval, 54.0%–65.4%), respectively. Receipt of allogeneic hematopoietic stem cell or solid-organ transplant, progression of underlying malignancy, prior respiratory disease, receipt of corticosteroid therapy, renal impairment, low monocyte counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion, and proven or probable (as opposed to possible) aspergillosis are predictors of increased overall mortality. Similar factors are also predictors of increased attributable mortality, with the following exceptions: pleural effusion and low monocyte counts have no impact, whereas neutropenia is associated with a higher attributable mortality. Conclusions. Identification of predictors of death helps in the identification of patients who could benefit from more-aggressive therapeutic strategies. Initiation of therapy at the stage of possible infection improves outcome, and this finding calls for the development of efficient preemptive strategies to fill the gap between empirical and directed therapy.
This study aimed to illustrate the epidemiological situation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by focusing on the changes published after 2019 and particularly ...the new approaches of cosmetic and reconstructive breast surgery.
Article search was performed from January 2019 to date using the PubMed database. Fourteen articles were included in the qualitative evaluation of international data. Moreover, the latest reports regarding the total number of BIA-ALCL cases and number of deaths were identified.
Estimates of the risk and incidence have increased significantly recently, affecting 1 in every 2,969 women with breast implants and 1 in 355 patients with textured implants after breast reconstruction. The average exposure time to diagnosis was 8 (range: 0-34) years. Approximately 80% of BIA-ALCL cases were diagnosed at IA-IIA stages, for which the treatment was breast implant removal, full capsulectomy, and excision of all suspected lymph nodes. Globally, at least 949 cases were reported to date.
At present, BIA-ALCL is an emerging pathology of interest. Data collection initiated since 2016 through different case registration databases is essential to ensure surveillance and to continue to increase the number of studies on this recently discovered pathology.
•Patients treated with ruxolitinib are at higher risk of mycobacterial infection.•Tuberculosis under ruxolitinib can occur without any prior tuberculosis.•Mycobacterial infections under ruxolitinib ...can occur early or late.
Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur.
•We report the use of ponatinib in chronic myelogenous leukemia (CML) patients who failed at least two lines of tyrosine kinase inhibitors (TKI) in a real-life setting.•This observational study ...reports similar rates of survival and molecular responses.•A slight increase in the cardiovascular ponatinib-related toxicity was observed.
Ponatinib represents a remarkable progress in the treatment of heavily pretreated chronic myelogenous leukemia (CML) and de novo Philadelphia chromosome-positive ALL patients despite significant toxicity in clinical trials. To date, “real-life” data remain few and the use of ponatinib in this setting and its consequences remain mostly unknown. We report, within a national observational study, the use of ponatinib in unselected CML patients who had previously failed ≥2 lines of tyrosine kinase inhibitor (TKI) therapy (or one line if an Abelson (ABL)T315I mutation was identified), in real-life conditions (2013–2014) in a compassionate program. Our analysis has been focused on 48 chronic phase CML patients recorded. With a median follow-up of 26.5 months since ponatinib initiation, the overall survival (OS) rates (80.5% at 3 years) and cumulative incidence of major molecular response (81.8% at 18 months) were similar to those of the phase II study, with no influence of BCR-ABL mutations nor the reason of ponatinib prescription. A specific subanalysis of the preexisting cardiovascular risk factors and events occurring on ponatinib is described. These events occurred after a median time on ponatinib of 5.8 months (excluding hypertension) and were observed in 29/48 patients (47%), even in those already on anti-aggregants/coagulants. The majority were not severe and resolved, but two cases were fatal. Other hematological or nonhematological nonvascular adverse events were similar to those previously described in trials. This observational study reports similar rates of survival, molecular responses, and a slight increase in the cardiovascular toxicity of ponatinib in real-life conditions, prompting improved control of cardiovascular risk factors and selection of patients.
In order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has ...not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a “pick a winner” approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our “pick a winner” randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.
Accelerated phase (AP) CML at onset and have poorer prognosis than CP-CML. We hypothesize that off-license use of second generation TKI (TKI2) as front-line therapy might counterbalance this poor ...prognosis, with limited toxicity. In "real-life" conditions, newly diagnosed patients meeting the ELN cytological criteria for AP-CML or harboring ACA and treated with first-line TKI2 were included in this retrospective multicenter observational study. We enrolled 69 patients 69.5 % male, median age 49.5 years, median follow-up 43.5 months, segregated into hematologic AP HEM-AP (n = 32) and cytogenetically defined AP ACA-AP (n = 37). Hematologic parameters were worse in HEM-AP spleen size (p = 0.014), PB basophils (p < .001), PB blasts (p < .001), PB blasts+promyelocytes (p < .001), low hemoglobin levels (p < .001). Dasatinib was initiated in 56 % patients in HEM-AP and in 27 % in ACA-AP, nilotinib in 44 % and 73 % respectively. Response and survival do not differ, regardless of the TKI2: 81 % vs 84.3 % patients achieved CHR, 88 % vs 84 % CCyR, 73 % vs 75 % MMR respectively. The estimated 5-year PFS 91.5 % (95%CI: 84.51–99.06 %) and 5-year OS 96.84 % (95%CI: 92.61–100 %). Only BM blasts (p < 0.001) and BM blasts+promyelocytes (p < 0.001) at diagnosis negatively influenced OS. TKI2 as front-line therapy in newly diagnosed AP-CML induce excellent responses and survival, and counterbalance the negative impact of advanced disease phase.
•Newly diagnosed accelerated phase (AP)-CML at onset are a rare situation.•The use of TKI2 first-line induces an estimated 5-year PFS of 91.5 % and 5-year OS of 96.84 %, in “real-life” conditions.•Response and survival do not differ, regardless of the TKI2.•Only BM blasts (p < 0.001) and BM blasts+promyelocytes (p < 0.001) at diagnosis negatively influence overall survival.
Primary myelofibrosis (PMF) and polycythaemia vera (PV) are rare BCR‐ABL1‐negative myeloproliferative neoplasms, associated with an increased risk of thrombosis, haemorrhagic complications and ...progression to fibrosis or leukaemia or fibrosis for PV. Both diseases are characterised by biological and clinical heterogeneity, leading to great variability in their management in routine clinical practice. In this review, we present an updated overview of the diagnosis, prognosis and treatment of PMF and PV, and we discuss how our multidisciplinary expert group based across France translates this evidence‐based knowledge into routine clinical practice.
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