microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers is Mainly Dependent on HER2 Status-A Pilot Study.

Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student's T-test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(-) and 18 ER(-)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(-)/PgR(+) and ER(+)/PgR(-) breast cancers. However, a trend for differing expression (p-value ≤ 0.05; FDR > 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(-) group demonstrated elevated levels of four miRNAs-miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p-while the ER(-)/PgR(+) tumors were enriched in another four miRNAs-miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs-miR-29c-3p-the association with the ER(+)/PgR(-) phenotype was confirmed in the TCGA cohort (p-value = 0.024; T-test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR ≤ 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(-) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(-)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(-)/PgR(+) and ER(+)/PgR(-) tumors.

The requirements of a specialist breast centre.

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

Estrogen receptor-negative progesterone receptor-positive breast cancer - "Nobody's land" or just an artifact?

The estrogen receptor α (ER) and the progesterone receptor (PgR) are one of the most important prognostic and predictive immunohistochemical markers in breast cancer. Breast cancers may express various profiles of hormone receptors: ER(+)/PgR(+), ER(-)/PgR(-), ER(+)/PgR(-) and ER(-)/PgR(+). The existence of the latter profile is a matter of controversy since PgR expressions is induced by ER-dependent pathways in breast cancer cells. One of the most extensively propagated hypotheses trying to explain the origin of ER(-)/PgR(+) breast cancers claims that they are technical artifacts dependent on the immunohistochemical procedure. On the other hand, in recent years there is a growing body of evidence, suggesting that such cancers create a unique group with distinct molecular and clinical features. In the following review, we present background theories on the ER(-)/PgR(+) breast cancer origin and their epidemiological and clinicopathological characteristics, including the predictive and prognostic significance of these rare tumors.

International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy.

Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and disease-related factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy.

BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland.

Sixty-four Polish families with a history of breast and/or ovarian cancer were screened for mutations in the BRCA1/2 genes using a combination of denaturing high performance liquid chromatography (DHPLC) and sequencing. Two thirds (43/64; 67%) of the families were found to carry deleterious mutations, of which the most frequent were BRCA1 5382insC (n=22/43; 51%) and Cys61Gly (n=9/43; 20%). Two other recurrent mutations were BRCA1 185delAG (n=3) and 3819del5 (n=4), together accounting for 16% of the 43 mutation-positive cases. We also found three novel mutations (BRCA1 2991del5, BRCA2 6238ins2del21 and 8876delC) which combined with findings from our earlier study of 60 Northern Polish families. Moreover, screening of 43 BRCA1/2 negative families for the presence of large rearrangements by multiplex ligation-dependent probe amplification (MLPA) resulted in the finding of two additional BRCA1 mutations: a deletion of exons 1A, 1B and 2, and a deletion of exons 17-19, both present in single families. We conclude that the Polish population has a diverse mutation spectrum influenced by strong founder effects. However, families with strong breast/ovarian cancer history who are negative for these common mutations should be offered a complete BRCA gene screening, including MLPA analysis.

Cardiovascular effects of breast cancer radiotherapy.

Cardiac toxicity has been implicated as the primary reason for excess non-breast cancer mortality in early breast cancer radiotherapy studies. Refinements in radiotherapy techniques have allowed for a considerable reduction of this risk in the majority of breast cancer patients. Recent large population-based studies confirmed an increase of cardiovascular death risk in patients irradiated for cancer of the left breast and in individuals exposed to relatively low (hitherto believed to be of no cardiovascular disease risk) doses of radiation, such as atomic bomb survivors or patients treated for various benign conditions. The issue of potential radiation-related cardiac damage may also be assuming a new significance due to the widespread use of other cardiotoxic agents, such as anthracyclines, paclitaxel and trastuzumab. The aim of this review is to summarize and critically analyze the available evidence on the impact of ionizing radiation on the cardiovascular system, with special attention to recent data demonstrating previously unrecognized adverse effects. This review discusses the pathology of radiation-related cardiovascular disease, its clinical presentation, risk factors and methods of assessment, as well as technical developments minimizing cardiac exposure. Epidemiological data are presented on the incidence of radiation-induced heart disease and cardiovascular mortality in various populations of patients irradiated for breast cancer and in individuals exposed to low radiation doses. Additionally, non-cardiac radiation-related vascular morbidity and mortality in breast cancer patients are addressed.

[Late recurrence of malignant tumours 20 years after diagnosis and treatment]. / Pózne wznowy nowotworów zlosliwych po 20 latach od rozpoznania i leczenia.

Late recurrence of malignant tumours is very rare phenomenon. Seven cases of late recurrent malignancy (melanoma--2 cases, clear cell renal cancer, stomach sarcoma, breast cancer, basal cell carcinoma, ovarian cancer) after 20-32 (average 22.3) years from diagnosis and treatment were described. The histopathological examination results of primary and recurrent tumours were identical. Six patients died at the age from 40 to 89 (mean 66.8) years. The survival of patients after recurrence was from 4 to 11 (mean 7.3) months.

Changes in lateral dimensions of irradiated volume and their impact on the accuracy of dose delivery during radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: To assess changes in lateral dimensions of irradiated volume during head and neck cancer radiotherapy and to determine their impact on the accuracy of dose delivery. PATIENTS AND METHODS: Lateral dimensions of irradiated volumes were measured in five predefined points prior to treatment and then bi-weekly. For each measurement, midline dose was calculated and verified using in vivo dosimetry. Early radiation reactions, patient weight changes and the need to modify radiotherapy accessories were also recorded. The study included 33 head and neck cancer patients irradiated using parallel opposed megavoltage fields. RESULTS: Body mass changes during radiotherapy ranged from -18 to +4 kg (median -5). Lateral dimension changes >5 mm (range -37 to +16) occurred in 32 patients (97%). For axis measurements, the degree of lateral dimension changes were correlated with treatment field size (P = 0.022) and degree of mucositis (P = 0.017). Axis doses calculated for changed dimensions varied from those prescribed by -2.5 to +6% (median +2%). Differences larger than 5% were present in 4.8% of calculations. In 17 patients (52%), radiotherapy accessories had to be modified during treatment. The need to modify radiotherapy accessories correlated with larger treatment portals (P = 0.004), more weight loss during treatment (P = 0.01) and higher initial N stage (P = 0.04). CONCLUSIONS: Changes of irradiated volume lateral dimensions during head and neck cancer radiotherapy may lead to considerable dose delivery inaccuracies. Watchful monitoring, corrections to calculated dose when changes observed are significant and radiotherapy accessories modification during the course of treatment are strongly recommended.

Intraocular malignant teratoid medulloepithelioma in an adult: clinicopathological case report and review of the literature.

PURPOSE: To report a case of intraocular medulloepithelioma, an embryonal tumour with extremely rare presentation in adults. METHOD: The case of a 44-year-old man with intraocular malignant teratoid medulloepithelioma, primarily diagnosed as intraocular teratoma, is described and the literature on this subject is reviewed. RESULTS: The patient presented with progressive proptosis caused by a tumour in the left eyeball. He had a 28-year history of loss of vision in the left eye. Histopathological examination of the enucleated eye demonstrated an intraocular teratoma. No adjuvant treatment was given. Six months later the patient presented with massive progression in the left orbit and intracranial invasion. Cisplatin-based chemotherapy was administered, but discontinued after two cycles due to poor tolerance and lack of response. At subsequent pathology review, a final diagnosis of malignant teratoid medulloepithelioma was made. Salvage radiotherapy (60 Gy in 30 fractions) resulted in partial response of the intracranial lesion. However, the patient died 6 months later due to intracranial tumour progression. CONCLUSION: Medulloepithelioma should be considered in the differential diagnosis of intraocular tumours in adults, especially in the case of coexisting, long-standing ocular symptoms. In some cases this disease is very aggressive.

Radiotherapy for breast cancer in patients undergoing breast reconstruction or augmentation.

Due to increasing indications for postmastectomy radiotherapy and a growing demand for breast reconstruction or augmentation, increasing numbers of patients are currently being exposed to both these treatments. In view of the wide range of available techniques for breast reconstruction, either prosthetic or autologous, and their various sequencing in relation to radiotherapy, physicians can be faced with numerous clinical situations requiring comprehensive knowledge of the topic. This review discusses physical, radiobiological and clinical aspects of combining breast reconstruction and radiotherapy. The available data indicate the feasibility of such combinations, although at the expense of increased risk of complications and less satisfactory cosmesis. Of the two methods of breast reconstruction: using autologous tissue or prosthesis, the former seems to provide better cosmesis and a lower risk of complications in conjunction with radiotherapy. To minimize the risk of unfavourable outcome, the techniques and timing of both breast reconstruction and radiotherapy should be given meticulous attention.

Report on the 4th European Breast Cancer Conference, Hamburg, Germany, 16-20 March 2004.

The 4th European Breast Cancer Conference, organized under the auspices of the European Organization for Research and Treatment of Cancer Breast Cancer Group, of the European Breast Cancer Coalition (Europa Donna) and of the European Society of Mastology (EUSOMA), was held in Hamburg, Germany on 16-20 March 2004. The leading theme of the conference was partnership among scientists, clinicians, carers, advocates and patients. The present article provides a brief description of the most important conference presentations on molecular biology, epidemiology, prevention, pathology, diagnosis and treatment at all stages of breast cancer.

The effects of tamoxifen on the female genital tract.

Tamoxifen is an effective and relatively non-toxic compound used in palliative and adjuvant treatment of breast cancer. More recently its preventive role in breast cancer has also been demonstrated. However, tamoxifen use is related to some increase in the risk of endometrial cancer and to a significant rise in the incidence of benign endometrial pathologies. The activity of tamoxifen against breast cancer is mainly achieved by blocking the oestrogen receptor, whereas the effect of this compound on the female genital tract is mostly related to its agonistic properties. Despite numerous studies no effective methods of tamoxifen-user surveillance have been developed and currently no active screening for endometrial cancer, apart from yearly gynaecological examination, is recommended in these patients. In other parts of the genital tract, tamoxifen increases the risk of some benign conditions and may cause difficulties in the interpretation of cervical smears. Further studies are warranted to develop more effective surveillance and methods decreasing the detrimental effects of tamoxifen on the female genital tract.

[Efficacy and feasibility evaluation in long term pamidronate treatment of bone metastases]. / Ocena skutecznosci i tolerancji dlugotrwalego leczenia pamidronianem przerzutów do kosci.

UNLABELLED: The aim of our study was to evaluate the efficacy and feasibility of long-term pamidronate treatment. MATERIAL AND METHODS: Thirty-six patients (pts) undergoing long-term (> 9 months) pamidronate treatment for bone metastases of breast cancer (30 pts), prostate cancer (3), multiple myeloma (2) and renal carcinoma (1) were retrospectively analyzed. The indication for pamidronate treatment were appearance of bone metastases (21 pts), progression of bone lesions (13) or intolerance of clodronate (2). Pamidronate was administered as an intravenous infusion, most commonly at a dose of 90 mg monthly. Skeletal complications including pathologic fractures, the need for palliative radiotherapy or bone surgery, spinal cord compression and hypercalcemia as well as occurrence of new bone or visceral lesions were assessed. The use of analgesics and subjective bone pain relief were used to evaluate the analgetic effect of pamidronate therapy. Adverse events of pamidronate treatment were noted. RESULTS: Patients received a median of 15 pamidronate infusions (range 9-35). Complete pain control was observed in 7 pts (19%), partial in 21 (58%) and stabilization in 8 (22%). Mean time to maximal effect was 5 months (range 0-17). There were 5 cases (14%) of fever and 6 cases (17%) of flu-like syndrome after pamidronate administration. New bone lesions appeared in 16 pts (44%) after a median of 12 months (range 1-28). Other skeletal complications included pathologic fractures (9 pts, 25%) and hypercalcemia (2 pts, 5.6%); 13 pts (36%) required radiotherapy. Symptomatic progression occurred in 27 pts (75%), with a median progression-free time of 14 months (range 5-35) from the beginning of pamidronate treatment. CONCLUSIONS: Long-term treatment with pamidronate in patients with bone metastases is well tolerated and effective in decreasing bone pain, thus maintaining considerably high quality of life.