Follow-up after breast cancer treatment

BackgroundBreast cancer (BC) is the most common malignancy in women. Due to improved detectability and modern methods of treatment, the number of breast cancer survivors is estimated at 6 million women globally and is still increasing. The follow-up (FU) visits carried out at the Greater Poland Cancer Centre were assessed for compliance with Polish Society of Clinical Oncology (PTOK) and European Society for Medical Oncology (ESMO) guidelines.Materials and MethodsThe database covered 484 women who were treated for breast cancer in the Greater Poland Cancer Centre in 2013. Of these, 233 attended FU visits for 5 years after completion of radical treatment and had no cancer relapse. The number of FU visits and the number and type of additional tests performed were analyzed.ResultsThe median number of FU visits over 5 years was 14, which is in line with the guidelines. 51.6% women had a mandatory annual mammography. A significant number of women had additional tests that are not recommended in the guidelines.ConclusionsThere is a need to educate both physicians and patients on the principles of FU check-ups.     

alpha-Interferon in hematological malignancies.

Recent studies have generated data demonstrating significant clinical activity of alpha-interferon therapy in each of six hematological malignancies, chronic myeloid leukaemia, essential thrombocythemia, polycythemia rubra vera, non-Hodgkin's lymphomas, multiple myelomatosis and hairy cell leukaemia.     

Centrosome aberrations in hematological malignancies

As the primary microtubule organizing center of most eukaryotic cells, centrosomes play a fundamental role in proper formation of the mitotic spindle and subsequent chromosome separation. Normally, the single centrosome of a G1 cell duplicates precisely once prior to mitosis in a process that is intimately linked to the cell division cycle via cyclin-dependent kinase (cdk) 2 activity that couples centrosome duplication to the onset of DNA replication at the G1/S transition. Accurate control of centrosome duplication is critical for symmetric mitotic spindle formation and thereby contributes to the maintenance of genome integrity. Numerical and structural centrosome abnormalities are hallmarks of almost all solid tumors and have been implicated in the generation of multipolar mitoses and chromosomal instability. In addition to solid neoplasias, centrosome aberrations have recently been described in several different hematological malignancies like acute myeloid leukemias, myelodysplastic syndromes, Hodgkin's as well as non-Hodgkin's lymphomas, chronic lymphocytic leukemias and multiple myelomas. In analogy to many solid tumors a correlation between centrosome abnormalities on the one hand and karyotype aberrations as well as clinical aggressiveness on the other hand seems to exist in myeloid malignancies, chronic lymphocytic leukemias and at least some types of non-Hodgkin's lymphomas. Molecular mechanisms responsible for the development of centrosome aberrations are just beginning to be unraveled. In general, two models with distinct functional consequences can be envisioned. First, centrosome aberrations can arise as a consequence of abortive mitotic events and impaired cytokinesis. Second, evidence has been provided that centrosome amplification can also precede genomic instability and arise in normal, diploid cells. Accordingly, this review will focus on recent advances in the understanding of both, causes and consequences of centrosome aberrations in hematological malignancies.     

Antibody-directed therapies for hematological malignancies

Malignant hematopoietic cells express lineage-restricted antigens that serve as suitable targets for antibody-directed therapy. Although several highly specific, potent and relatively nontoxic, engineered antibodies, immunoglobulin fragments and antibody conjugates have been developed, only three have gained approval for clinical use. Of these, a chimeric mouse-human anti-CD20 antibody has yielded the most impressive clinical results. Encouraging data with the other approved antibodies, and with agents in clinical trials, suggest that rational antibody design will generate effective products for several different hematological malignancies. Despite these advances, significant challenges remain in the identification of optimal cellular targets, antibody forms and treatment schedules for therapeutic applications.     

Long-term results after combined modality treatment for non-metastatic osteosarcoma

Since the introduction of multimodality treatment, the prognosis of patients with high-grade non-metastatic osteosarcoma has significantly improved. A retrospective review was performed to assess the long-term results of this approach in a single centre setting, and to investigate the impact of potential clinical prognostic factors. Between 1985 and 1993, 35 patients with stage II-A and II-B osteosarcoma underwent preoperative chemotherapy (high-dose methotrexate), wide surgery, and adjuvant chemotherapy (cisplatin-doxorubicin/bleomycin-cyclophosphamide-dactinomycin) (modified T-10A protocol). There were 19 males and 16 females. Median patient age was 17 y (range 12–42). Primary tumour sites were the extremities (83%) and axial bones (17%). In spite of an unfavourable grade 3–4 histologic response rate to high-dose methotrexate of 12%, 31 (88%) patients were able to undergo limb-sparing surgery and 28 (80%) were rendered disease free after the planned therapy. Median follow-up was 8 y. The actuarial overall survival and disease-free survival rates were 64% and 49% at 5 y, and 59% and 49% at 10y, respectively. Tumour size and primary site were significant prognostic factors for survival in univariate analyses. In conclusion, long-term survival after combined modality treatment can be achieved in more than 60% of patients with localised osteosarcoma, including non-appendicular lesions. Limb-sparing surgery is a realistic goal for most cases. The prognostic value of tumour necrosis and the efficacy of neoadjuvant chemotherapy should be interpreted according to individual high-dose methotrexate scheduling.     

Introduction of a multicenter online database for non-metastatic breast cancer in China

正Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors; and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016).     

MLL-SEPTIN gene fusions in hematological malignancies

The mixed lineage leukemia (MLL) locus is involved in more than 60 different rearrangements with a remarkably diverse group of fusion partners in approximately 10% of human leukemias. MLL rearrangements include chromosomal translocations, gene internal duplications, chromosome 11q deletions or inversions and MLL gene insertions into other chromosomes, or vice versa. MLL fusion partners can be classified into four distinct categories: nuclear proteins, cytoplasmatic proteins, histone acetyltransferases and septins. Five different septin genes (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been identified as MLL fusion partners, giving rise to chimeric fusion proteins in which the N terminus of MLL is fused, in frame, to almost the entire open reading frame of the septin partner gene. The rearranged alleles result from heterogeneous breaks in distinct introns of both MLL and its septin fusion partner, originating distinct gene fusion variants. MLL-SEPTIN rearrangements have been repeatedly identified in de novo and therapy related myeloid neoplasia in both children and adults, and some clinicopathogenetic associations are being uncovered. The fundamental roles of septins in cytokinesis, membrane remodeling and compartmentalization can provide some clues on how abnormalities in the septin cytoskeleton and MLL deregulation could be involved in the pathogenesis of hematological malignancies.     

Exploiting histone deacetylases for cancer therapy:from hematological malignancies to solid tumors

正Perturbations of the epigenomic landscape,as defined by genome-wide localization of histone post-translational modifications,DNA methylations and chromatin regulatory proteins,have been increasingly appreciated as a common feature of cancer.While epigenetic changes were previously argued as merely a consequence of the cancerous state,recent evidence collectively points to a perception that altered epigenetic states may play a causal role in cancer development(Brien et al.,2016).In fact,cancer genome     

Nucleolar immunofluorescence in human hematological malignancies.

Rabbit antibodies to the nuclear Tris extract of HeLa cells which have been shown by the indirect immunofluorescence technique to localize in nucleoli of a variety of human malignant tumors but not in a number of nontumor tissues also produced bright fluorescence in nucleoli of tumor cells in several hematological malignancies. The tumors studied included Hodgkins malignant lymphoma, non-Hodgkins malignant lymphoma, acute myeloid and acute myelomonocytic leukemia, chronic lymphatic and chronic myeloid leukemia. In contrast, none of the corresponding normal cell lines in the bone marrow exhibited bright nucleolar fluorescence. In addition, neither the cells of patients with acute infectious mononucleosis nor lymphoid hyperplasia exhibited bright nucleolar fluorescence. These studies suggest that antibodies to HeLa cell nucleolar antigens may be useful in immunodiagnosis of human malignancies.     

The role of IL-21 in hematological malignancies

IL-21, the newest member of the common γ-chain family of cytokines, has pleiotropic biological effects through regulating a variety of immune cells. Recently, the role of IL-21 in the treatment of cancers has been widely investigated. Conducted phase I trials in metastatic malignant melanoma and renal cell carcinoma have shown that rIL-21 has a favorable antitumor activity. Expression of IL-21 and IL-21R has also been found in many types of hematological malignancies, such as chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and lymphoma. Through binding with IL-21R, IL-21 induces activation of different JAK/STAT signal transduction pathways and regulates proliferation or apoptosis of tumor cells. In this review, we will discuss the expression of IL-21/IL-21R and its effect in different types of hematological malignancies.     

Polymorphism of alpha-1-antitrypsin in hematological malignancies

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ(2) = 4.42, d.f.11, p = 0.96 and χ(2) = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant.     

Cutting edge: TRAIL deficiency accelerates hematological malignancies

TNF apoptosis-inducing ligand is attracting considerable interest as a potential extrinsic tumor suppressor mechanism, although previous reports have conveyed somewhat contrasting views regarding the likely importance of this pathway. In this study, we provide the first evaluation of spontaneous tumor formation over the life span of TRAIL-deficient mice. Interestingly, >25% of these mice do develop lymphoid malignancies after 500 days of life. TRAIL suppressed the initiation and development of both tumors of lymphoid and stromal origin in the context of the loss of at least one p53 allele. Specific examination of the role of TRAIL in Her2/neu oncogene-driven mammary epithelial cancer revealed no critical role for TRAIL despite the inherent TRAIL sensitivity of such mammary carcinomas. Overall, the data indicate an important function of TRAIL in controlling carcinogenesis, but suggest that further examination of this pathway in epithelial malignancies is warranted.     

Secondary malignancies in late periods after chemoradiotherapy for lymphogranulomatosis in children

The incidence of secondary malignancies (SM) was studied in a population of 219 patients in late periods (3-29 years) after childhood and adolescence chemoradiotherapy for Hodgkin's lymphoma (HL). SMs were found in 15 (6.8%) patients. These were solid neoplasms located in the irradiated areas in 12 of them, including 4 patients with thyroid cancer and 2 with gastric cancer. All 3 cases of acute leukemia had occurred after chemoradiotherapy performed by extended programs that consisted of a large number of chemotherapy cycles. The detection rate of SM did not significantly depend on the dose of radiation, age at start of treatment, and a child's gender. The findings suggest that there is a need for the maximum concentration of an irradiation beam in the area of thyroid lesion and exposure, for limited cytotoxic therapy programs, and lifetime medical observation of the patients treated for HL in childhood.     

Attending the breast screening programme after breast cancer treatment: A population-based study

IntroductionIn the Netherlands, breast cancer patients are treated and followed at least 5 years after diagnosis. Furthermore, all women aged 50–74 are invited biennially for mammography by the nationwide screening programme. The relation between the outpatient follow-up (follow-up visits in the outpatient clinic for 5 years after treatment) and the screening programme is not well established and attending the screening programme as well as outpatient follow-up is considered undesirable. This study evaluates potential factors influencing women to attend the screening programme during their outpatient follow-up (overlap) and the (re-)attendance to the screening programme after 5 years of outpatient follow-up.MethodsData of breast cancer patients aged 50–74 years, treated for primary breast cancer between 1996 and 2007 were selected from the Netherlands Cancer Registry and linked to the National Breast Cancer Screening Programme in the Northern region. Cox regression analyses were used to study women (re-)attending the screening programme over time, possible overlap with the outpatient follow-up and factors influencing this.ResultsIn total 11 227 breast cancer patients were included, of whom 19% attended the screening programme after breast cancer treatment, 4.4% within 5 years and 15.4% after more than 5 years. Factors that independently influenced attendance within 5 years as well as more than 5 years after treatment were: interval tumours (HR 0.77; 95%CI 0.61–0.97 and HR 0.69; 95%CI 0.53–0.88, ref: screen-detected tumours), receiving adjuvant radiotherapy (HR 0.65; 95%CI 0.47–0.90 and HR 0.66; 95%CI 0.47–0.93; ref: none) and diagnosis of in situ tumours (HR 1.67; 95%CI 1.25–2.23 and HR 1.39; 95%CI 1.05–1.85; ref: stage I tumours). Non-screen related tumours (HR 0.41; 95%CI 0.29–0.58) and recent diagnosis (HR 0.89 per year; 95%CI 0.86–0.92) were only associated with attendance within 5 years after treatment.ConclusionThe interrelation between outpatient follow-up and screening should be improved to avoid overlap and low attendance to the screening programme after outpatient follow-up. Breast cancer patients should be informed that attending the screening programme during the outpatient follow-up is not necessary.