Antihormonal Treatment Research Articles

Methylation patterns in serum DNA for early identification of disseminated breast cancer

BackgroundMonitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA.MethodsWe used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints.ResultsA total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC.ConclusionsDetection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent.

Breast cancer and pregnancy.

Background In the past decades the incidence of pregnancy-associated breast cancer (PABC) increased. Possible explanations are the trend to postpone childbearing and the general increase in the incidence of breast cancer. Materials and methods A sytematic review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of breast cancer during pregnancy. We also cover the issue of pregnancy following a diagnosis of breast cancer including fertility preservation and prognosis. Results Ultrasound is the imaging method of choice in pregnancy, but mammography can also be performed as the fetal irradiation dose is low. To avoid a delay in diagnosis every sonographic mass in pregnant women which does not clearly correspond to a cyst needs further investigation by biopsy. Treatment should follow as close as possible the guidelines for non-pregnant patients. Administration of chemotherapy is possible after the first trimester. There is a large body of evidence for the use of anthracyclines. In contrast radiotherapy, trastuzumab and antihormonal treatment by tamoxifen are contraindicated during pregnancy. Pregnancy does not seem to influence prognosis. Most adverse obstetric outcomes are related to preterm delivery, which should therefore, whenever possible, be avoided. Young patients with breast cancer and incomplete family planning should be referred for counseling about fertility preservation options before the initiation of adjuvant treatment. A pregnancy following breast cancer does not have a negative impact on prognosis. Conclusion Multidisciplinary management of women with breast cancer in pregnancy is mandatory and data should be collected to allow further improvement in management.

Partner social constraints and early-stage breast cancer: Longitudinal associations with psychosexual adjustment.

Women with breast cancer (BC) who perceive social constraints on their disclosure of cancer-related concerns are more likely to experience distress and have difficulty adjusting after diagnosis. Much of the existing research on psychosocial adjustment is cross-sectional in nature and an important area of concern that has received little attention is psychosexual adjustment to cancer surgery and treatment. This study examined whether perceived partner social constraints were associated with psychosexual adjustment over time in 108 BC survivors. Early-stage BC patients completed measures of partner social constraints, psychosexual adjustment, and relationship dissatisfaction approximately 1 month, 8 months, and 4 years after initial surgery. Latent growth curve modeling revealed partner social constraints to be a significant time-varying, within-person predictor of psychosexual adjustment at each time point after controlling for relationship dissatisfaction. BC surgery type, reconstructive surgery, cancer stage, chemotherapy, or antihormonal adjuvant treatment did not moderate this effect. Findings point to a long-term link between social constraints and psychosexual outcomes in BC patients and clinical implications for women coping with BC. (PsycINFO Database Record

Abstract 1079: Preclinical activity of the FGFRinhibitor BAY 1163877 alone or in combination with antihormonal therapy in breast cancer

Abstract BAY 1163877 is an orally available, highly potent and selective pan fibroblast growth factor receptor (FGFR) inhibitor. In an ongoing Phase 1 clinical trial (NCT01976741) BAY 1163877 showed clinical responses at exceptional tolerability in patients suffering from different tumor types including urothelial bladder carcinoma or lung tumors, which were selected based on elevated FGFR1-3 mRNA expression. In the preclinical phase, the compound demonstrated significant single agent anti-tumor activity in various tumor models with different FGFR alterations leading to FGFR overexpression (e.g. FGFR gene amplifications or mutations). Genetic alterations of FGFRs can also be found in breast cancer with 7.5 - 17% of all tumors harboring a FGFR1 gene amplification. Elevated FGFR1 mRNA levels can be found in up to 22% of breast cancer cell lines as well as clinical samples. Other FGFR alterations include FGFR2 or FGFR4 gene amplifications as well as elevated FGFR mRNA levels, which were reported in all breast cancer subtypes. We therefore investigated BAY1163877 monotherapy in various breast cancer models. Due to the favorable clinical safety profile of BAY1163877, we also examined a combination treatment with early line antihormonal therapies in hormone receptor positive breast cancer. In vitro profiling of BAY 1163877 in a number of breast cancer cell lines showed a clear association of efficacy with expression levels of different FGFR isoforms. The efficacy was further investigated in several patient- or cell line-derived breast cancer in vivo models. For instance, BAY 1163877 alone dosed 38mg/kg twice daily induced tumor growth inhibition of greater than 90% in a subcutaneous mouse syngeneic 4T1 breast cancer model expressing elevated levels of FGFR2. Resistance to endocrine therapy appears associated with FGFR1 gene amplification and may explain the poor prognosis of FGFR1 overexpressing tumors treated with adjuvant tamoxifen. We therefore investigated the combination of the panFGFR-inhibitor BAY 1163877 with the clinically used antihormonal compound fulvestrant in selected luminal breast cancer PDX models. Some of these models showed resistance to antihormonal treatment in monotherapy but improved in vivo efficacy in combined treatment using BAY 1163877 and fulvestrant. These data may warrant further clinical investigation of BAY1163877alone or in combination with antihormonal therapy in patients with FGFR overexpressing breast cancer. Citation Format: Oliver Politz, Peter Ellinghaus, Sebastian Bender, Sylvia Gruenewald, Franziska Siegel, Marie-Pierre Collin, Sabine Zitzmann-Kolbe, Dominik Mumberg, Karl Ziegelbauer. Preclinical activity of the FGFRinhibitor BAY 1163877 alone or in combination with antihormonal therapy in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1079. doi:10.1158/1538-7445.AM2017-1079

Aromatase inhibitor maintenance therapy in high grade advanced ovarian cancer to delay first recurrence.

5515 Background: Ovarian cancer (OC) is mostly diagnosed as G3 serous advanced stage disease with survival of only 20% in 5 years. Maintenance therapy after 1st line chemotherapy is increasingly used, particularly with Bevacizumab or PARP inhibitors. However, the effect of antihormonal treatment in breast cancer but also in relapsed gynecological cancers has been shown. Also in low grade OC, data are highly supportive of antihormonal treatment. In a previous study of ours, also high grade serous cancers express high amounts of estrogen receptor (ER). The aim of this study was to analyze whether a maintenance antihormonal therapy in advanced OC adds a benefit in relation to the time of recurrence. Methods: All newly diagnosed G3 FIGO III/IV OC cases at our Hospital were assessed prospectively for ER expression. Patients with positive ER status (> 10%) were treated as maintenance therapy with Letrozol 2.5mg 1x/d or not. Progression free survival was recorded and analyzed according to Kaplan-Meier. Patients with macroscopic residual disease post surgery receiving Bevacizumab maintenance treatment were also included. Results: We identified 51 patients with G3 serous OC FIGO III/IV expressing ER. Hereby, 24 patients received and 27 patients did not receive Letrozol after adjuvant chemotherapy. Time to progression ranged from 4 to 121 months. The use of Letrozol was associated with a significant prolonged progression free interval. After 12 months, only 65% of women in the control group vs 84% in the Letrozol group were progression-free. After 24 months, the effect was even stronger (46% in the control group vs 74% with Letrozol (p= 0.02)). Within the subgroup of patients with residual disease treated with Bevacizumab a similar effect was seen with 41% of patients progression free after 12 months vs 89% when taking Letrozol in addition to Bevacizumab. Conclusions: The use of Letrozol as a maintenance therapy after the 1st line treatment in G3 advanced stage serous OC patients was associated with a longer recurrence free interval in our cohort. These findings warrant a randomized controlled trial comparing all existing maintenance regimen as this might have a major influence on cost development in OC treatment.

Novel Strategies in Hormone Receptor-Positive Advanced Breast Cancer: Overcoming Endocrine Resistance

Resistance to standard endocrine therapies in hormone receptor-positive advanced breast cancer represents a significant clinical challenge. Different intracellular signaling pathways mediate independent activation of the estrogen receptor (ER), promoting tumor cell proliferation despite anti-hormonal treatment. Recently, the inhibition of cell cycle regulators, CDK4 and CDK6, has demonstrated to significantly enhance the effectiveness of endocrine therapy by overcoming or delaying resistance to estrogen blockade. Strategies such as inhibition of the PI3K/mTOR pathway or epigenetic modulation of ER-related gene expression are closely following the trail of CDK inhibitors. Here, we seek to review the most recent efforts to improve outcomes in these patients, in an attempt to extend endocrine treatment and defer the need for cytotoxic regimens. We also discuss future directions to be considered in the treatment of ER-positive disease, as mechanisms of resistance to these new agents arise.

Antihormonal treatment associated musculoskeletal pain in women with breast cancer in the adjuvant setting.

PurposeAntihormonal treatment is an effective therapy in the adjuvant setting. However, musculoskeletal pain is a common adverse effect encountered in patients receiving this treatment. We aimed to evaluate the risk factors for the development of antihormonal treatment-associated musculoskeletal pain (AHAMP) and its impact on the health-related quality of life (HRQOL).Patients and methodsA cross-sectional survey of 78 consecutive breast cancer patients receiving adjuvant antihormonal treatment for early-stage breast cancer in an academic medical oncology clinic was conducted. AHAMP was assessed by Health Assessment Questionnaire (HAQ) and 10 cm visual analog scale (VAS). HRQOL was assessed by self-administered short form 36 and Functional Assessment of Cancer Therapy-Breast subscale surveys.ResultsAHAMP was found to be present in 37 (47.7%) patients. In multivariate regression analysis, having a normal body mass index (<30 kg/m2), cigarette smoking, and low serum vitamin D level (20 ng/mL) were found to be independent risk factors. In HRQOL assessment, physical and mental scores were found to be significantly lower in patients with joint arthralgia.ConclusionAHAMP has an adverse effect on the quality of life of breast cancer patients receiving adjuvant antihormonal treatment, and assessment of predictive factors is important for identification of patient groups at risk of developing this condition.

Abstract 3926: Nanomechanical profiling of breast cancer: A novel tool for cancer diagnostics and prognostics

Abstract A crucial point in making treatment decisions for cancer patients is the assessment of tumor aggressiveness. Currently, for breast cancer, established prognostic markers exist that are routinely assessed by standard pathological examination. However, these parameters are often not sufficient to stratify patients, especially those with early stages of breast cancer and adjuvant therapy is frequently administered to patients who might have been cured by surgery and anti-hormonal treatment alone. The goal to avoid over- and under-treatment has led to an intensive search for prognostic and predictive markers in early breast cancer. Physical interactions between cancer cells and the extracellular matrix (ECM) that occur at the molecular (nanometer) scale are crucial for the metastatic process. Consequently, nanomechanical alterations of cells and ECM due to cancer progression can serves as potentially suitable markers of cancer aggressiveness that may help to optimize treatment strategies. This motivated us to develop an atomic force microscope (AFM)-based method for measuring nanomechanical (stiffness) profiles of unadulterated tissues in native physiological buffer conditions with an unprecedented stiffness sensitivity resolved at nanometer-scale spatial resolution. An AFM utilizes a ∼10 nm-sharp stylus or tip that makes ∼10’000 miniscule indentations across tissue. In our initial study using transgenic mouse model of human breast cancer we could show that the “softest” nanomechanical phenotype (∼0.4 - 0.8 kPa) present at the primary tumor site closely corresponded to the stiffness of the metastatic lesions obtained from the lungs of the same mouse (Plodinec et. al; Nature Nanotech. 2012). In this study, we have analyzed human 187 breast cancer samples from breast biopsies and tumor resections including primary breast cancers of various stage and grade, lymph node metastases, and non-neoplastic breast parenchyma. Post-AFM samples were fixed, paraffin embedded in an oriented manner and used for routine histology. Data showed for all human breast cancer samples, distinct stiffness phenotypes in comparison to the surrounding non-neoplastic and morphologically normal breast tissue and revealed specific nanomechanical profiles of phenotypes that lead to metastases. Interestingly, patients presenting nanomechanical changes in the adjacent tissue, which was histologically characterized as tumor free, typically exhibited local and/or distant metastases. Overall, our findings demonstrate the first application of nanomechanical profiling in a clinical setting that allows for fast, on-site assessment of specimen and does not suffer from inter-observer variability such as other markers (Obermann et al, Pathologe, 2012). The relative size and distribution of nanomechanical profiles can provide an indicator of cancer aggressiveness, and therefore orientate therapy choice, and support patient follow-up. Citation Format: Marija Plodinec, Christian Raez, Philipp Oertle, Adrian Hodel, Maja Fünfschilling, Roderick YH Lim, Ellen C. Obermann. Nanomechanical profiling of breast cancer: A novel tool for cancer diagnostics and prognostics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3926.

Abstract 2825: Identification of CDK4/6-response biomarkers using estrogen receptor-positive breast cancer patient-derived xenografts (PDX)

Abstract Endocrine resistance is a clinical challenge for the treatment of estrogen receptor positive (ER+) breast cancer (BC). CDK4/6 blockade in combination with endocrine therapy has shown clinical activity in metastatic ER+ BC refractory to anti-hormonal treatment. However, there is a need for biomarkers that can predict the response to this treatment and improve patient stratification. We aimed to address this issue using xenograft models established from samples of ER+ BC patients. Six ER+ PDXs were treated with continuous doses of a CDK4/6 inhibitor (LEE011, 75mg/kg, 6IW) and a PI3K-alpha inhibitor (BYL719, 35mg/kg, 6IW) as single agents and in combination, and intrinsic sensitivity to these agents was evaluated. The models were then genomically characterized using a capture-based sequencing panel and by digital PCR. One PDX model was intrinsically sensitive to single-agent CDK4/6 inhibition and experienced tumor regression, but all individual tumors eventually escaped therapy after 50 days of treatment. This particular model harbored an ESR1-mutation and concomitant losses of CDKN2A/B. At relapse, we identified the acquisition of an RB1 frameshift mutation. Interestingly, upfront combined treatment with a PI3K-alpha inhibitor delayed the onset of tumor progression. Two out of the remaining five CDK4/6-resistant PDXs harbored either a frameshift mutation in RB1 (plus loss of heterozygosity) or had low pRb protein expression. Two other resistant models harbored CCND1 and MYC amplifications. The remaining one harbored a TSC1 loss. In all the CDK4/6-resistant PDX, however, the combination of CDK4/6 and PI3K-alpha inhibition resulted in tumor regression. From our results, we conclude that loss of G1-cell cycle checkpoint control, such as mutation/loss of RB1 and CCND1-amplification, is associated with lack of response to CDK4/6 blockade in ER+ BC PDX. The addition of a PI3K-alpha inhibitor results in improvement of disease control in all experimental models tested. Citation Format: Violeta Serra, Marta Palafox, Maria-Teresa Herrera, Martin A Rivas, Marta Guzmán, Olga Rodriguez, Judit Grueso, Meritxell Bellet, Mafalda Oliveira, Cristina Saura, Emmanuelle di Tomaso, Giordi Camponigro, Nicholas C. Turner, Javier Cortés, José Baselga. Identification of CDK4/6-response biomarkers using estrogen receptor-positive breast cancer patient-derived xenografts (PDX). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2825.

Changes in Sexual Orientation after Treatment for Prostate Cancer

Objective: According to the statistics, one in six men develops prostate cancer. There are several therapeutic options for prostate cancer. Anti-hormone therapy is one of treatment leading to an 80–90% remission. A significant percentage of men who received anti-hormonal treatment complain of decreased libido and erectile dysfunction. Similarly, these men may also suffer from hot flashes, weight gain, growth of [male] breast tissue (gynecomastia), lack of energy and initiative, depression and mental disorders. In this paper, I would like to present a therapeutic case of a man who received sexual counseling at the Israel Cancer Association, and who, upon receiving antihormonal treatment, changed his sexual orientation after having contracted prostate cancer. Design and Method: A series of meetings were conducted, encompassing an interview and sexual counseling. The Klein Sexual Orientation Grid (KSOG) was used in order to evaluate the patient’s sexual orientation. Results: According to the GRID several parameters such as sexual attraction and sexual behavior were significantly different in the comparison between the past and the present. Parameters such as social preference and hetero/gay style did not change. The remaining results will be presented. Conclusions: Following an analysis of this case, it may be concluded that a person’s sexual orientation can change during his lifetime. The hypothesis is that a life-changing event such as cancer, including all the side effects of difficult antihormonal treatments, has the potential to evoke a change in the person’s overall experience and in his sexual experience in particular.

Lower Breast Cancer Mortality in Patients Aged 70+ Achievable

The last sentence of the article requires further comment: “US breast cancer patients >70 years of age have a higher 5-year survival rate than German patients” (1). The authors mention that systemic treatment is less frequently provided with advancing age. However, this only applies to aggressive chemotherapy, not to antihormonal therapy. Regarding the range of side effects associated with antihormonal treatment, it has to be distinguished between aromatase inhibitors and tamoxifen. The latter directly targets the cancer cell. Its use over a period of 10 years is superior to that over 5 years and results in a better prognosis (2): 21% recurrence rate vs. 25%, and 12% mortality rate vs. 15%, respectively.

Pronounced Interindividual But Not Intraindividual Variation in Tamoxifen and Metabolite Levels in Plasma During Adjuvant Treatment of Women With Early Breast Cancer.

Tamoxifen is still an important antihormonal treatment option for patients with breast cancer and estrogen receptor-positive tumors. More than 20% of patients relapse despite treatment. The drug is usually dosed 20 mg/d irrespective of interindividual variation in drug clearance. To study interindividual and intraindividual variation in plasma levels we measured tamoxifen and metabolite levels in plasma on 2 occasions, with at least 4 weeks in between, of 39 women (19 premenopausal and 20 postmenopausal women) on adjuvant treatment (20 mg/d) of early breast cancer. We used an ultra-performance liquid chromatography with a mass spectrometry detection method for identification and quantification of tamoxifen, N-desmethyltamoxifen, 4-OH-tamoxifen, and endoxifen. Follicle-stimulating hormone, luteinizing hormone, and estradiol levels were also measured. The plasma concentrations of tamoxifen and its metabolites showed a pronounced interindividual variation, whereas intraindividual concentrations were rather stable. Despite the same dosage, interindividual tamoxifen concentrations varied from 51 to 307 ng/mL (124 ± 57, mean ± SD) and endoxifen values showed a range from 3.2 to 19 ng/mL (10.4 ± 5.2, mean ± SD), that is, 6-fold variation for both. Large interindividual variation of tamoxifen and endoxifen with stable intraindividual levels, and too low levels of endoxifen in a considerable proportion of patients strongly support that therapeutic drug monitoring and individualized dosing could lead to optimal exposure and hopefully better outcome. A randomized outcome study between conventional dosing and therapeutic drug monitoring-guided dosing is needed to show whether this approach works.

Factors affecting local recurrence and distant metastases of invasive breast cancer after breast-conserving surgery in Chiang Mai University Hospital.

BackgroundThe purpose of this study was to collect data regarding breast cancer profiles and factors that affect local recurrence and distant metastasis after breast-conserving surgery (BCS) in Chiang Mai University Hospital.Materials and methodsThis study was a retrospective review in a single institution of newly diagnosed invasive breast cancer patients who were treated with BCS between April 9, 2001 and December 25, 2011.ResultsA total of 185 patients treated with BCS were included in this study, with an average age of 46.83 years. The average recurrence age was 41.1 years and the average nonrecurrence age was 47.48 years, with a recurrence rate of 10.27%. Premenopause was significant in recurrence (P=0.047), as well as non-estrogen-expression patients (P=0.001) and patients who did not receive antihormonal treatment (P=0.011).ConclusionThe recurrence rate in our institute was 10.27%. Factors affecting recurrence after BCS included young age, premenopausal status, nonexpression of the estrogen receptor, and patients who had not received antihormonal treatment. The recurrence rate was higher in the first 90 postoperative months.

Abstract ES4-3: Regimens in HER2+ disease

Abstract The discovery of the HER2 alteration and subsequent development of HER2-targeted therapy has substantially improved the natural history of HER2-positive metastatic breast cancer. In the past 17-years, four biologically targeted agents have been approved for the treatment of this disease subtype. These therapeutic advances have, in large part, been responsible for the significant improvement in median overall survival that can be expected now for a patient diagnosed with advanced HER2+ disease. While this progress has been remarkable, long-term durable remission is still rare, as the vast majority of patients will experience tumor progression with all available therapies. Thus the development of agents that prevent or circumvent mechanisms of resistance is still needed. During this educational session, data relating to the use of trastuzumab, lapatinib, pertuzumab and trastuzumab emtansine will be explored in detail. Regimens involving chemotherapy, anti-hormonal treatment, and combinations of HER2-targeted agents will be evaluated. Specifically, questions surrounding optimal choice for first- and second-line therapy will be addressed by discussing the results of the CLEOPATRA, EMILIA and MARIANNE trials. The challenge of treating central nervous system metastases will be examined with a focus on promising agents under clinical investigation. In addition, differences in treatment response and disease outcome will be explored based on hormone receptor co-expression or activation of the PI3K pathway. As key evidence is discussed, the audience will be led through the decision-making process using case-based examples. Finally, innovative treatments undergoing clinical evaluation will be considered with a critical appraisal of preclinical and early clinical data. It is expected that by the end of this session, audience members will possess an in-depth understanding of data relating to optimal treatment of HER2+ advanced disease and will be aware of promising avenues of research for continued areas of unmet need. Citation Format: Hurvitz SA. Regimens in HER2+ disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES4-3.

Prostate cancer. Part 1: Review of cell kinetics over the years 1966-2015 and future perspectives of the new grading of the International Society of Urological Pathology (ISUP)

Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.

The application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part II. Diagnosis after treatment initiation, future perspectives.

Similarly to the applications described in the first part of this publication, positron emission tomography with computed tomography (PET/CT) is also gaining importance in monitoring a tumour's response to therapy and diagnosing breast cancer recurrences. This is additionally caused by the fact that many new techniques (dual-time point imaging, positron emission tomography with magnetic resonance PET/MR, PET/CT mammography) and radiotracers (16α-18F-fluoro-17β-estradiol, 18F-fluorothymidine) are under investigation. The highest sensitivity and specificity when monitoring response to treatment is achieved when the PET/CT scan is made after one or two chemotherapy courses. Response to anti-hormonal treatment can also be monitored, also when new radiotracers, such as FES, are used. When monitoring breast cancer recurrences during follow-up, PET/CT has higher sensitivity than conventional imaging modalities, making it possible to monitor the whole body simultaneously. New techniques and radiotracers enhance the sensitivity and specificity of PET and this is why, despite relatively high costs, it might become more widespread in monitoring response to treatment and breast cancer recurrences.

Addressing the psychosocial wellbeing of teenage children of cancer patients and survivors.

Thomas is 13 years old. His parents report a sharp decline in his school grades caused, according to his teachers' opinions, by listlessness and lack of concentration. The parents of Julia, 16 years old, describe her as restless, evasive, isolated, and withdrawn from others and from her usual activities. Linda, 18 years old, is described by her parents as indecisive, uncertain, and almost lethargic. Normally resolute and a high academic achiever, she appears locked in herself, unable to make choices. We first learned about them through the accounts of their concerned parents. Claire, 19 years old, lost weight and exercised hard enough to induce amenorrhea after her young mother underwent treatment for breast cancer, including antihormonal treatment. These four teenagers have in common a parent diagnosed with cancer, undergoing or having just completed treatment.

Chemotherapy of prostate cancer

The prognosis of patients with advanced prostate cancer has improved over the last few years. In addition to the new antihormonal treatment, chemotherapy with agents such as docetaxel and cabazitaxel has contributed to the improved prognosis. After the introduction of abiraterone and enzalutamide, conventional chemotherapy seemed to become less important but the discussion about the use of chemotherapy for hormone-sensitive prostate cancer has gained attention again. Combining docetaxel with conventional androgen deprivation therapy (ADT) improves survival compared to ADT alone. In addition, docetaxel and cabazitaxel now represent the standard for first and second line therapy in patients with castration-resistant prostate cancer.

Total antioxidative capacity and zinc concentration in dogs suffering from perianal tumours

Abstract The aim of the study was to determine total antioxidative capacity (TAC) and zinc concentration in serum of dogs suffering from perianal tumours just before the start of the antihormonal treatment (AHT) and one and six months later. The study was performed on 45 dogs divided into two groups: control group suffering from non-malignant tumours (N = 24) and a group with malignant neoplastic changes (N = 21). Serum TAC and zinc concentrations were measured using photometric and atomic absorption spectrophotometric methods. Six months after the start of the AHT, TAC was significantly lower by 10.6% in dogs with malignant tumours when compared to controls (P = 0.03). In the non-malignant group, serum zinc concentration was higher before the treatment than in the malignant group, while the opposite results were observed six months later (P &lt; 0.001). In the non-malignant group, gradually decreasing values of serum zinc concentration at each stage of the investigation were observed, while the opposite results were obtained in the malignant group (P &lt; 0.05). The obtained results indicate that malignant neoplastic process is associated with significantly reduced TAC. Determination of serum zinc concentration in dogs with non-malignant and malignant perianal tumours may have practical diagnostic and prognostic values and may serve towards increasing the effectiveness of AHT monitoring.

Cosmetic Outcomes and Quality of Life in Thai Women Post Breast Conserving Therapy for Breast Cancer.

To evaluate the correlation between cosmetic outcome (CO), body image, and quality of life in post breast-conserving therapy (BCT) women. This cross-sectional study concerned one-year post-completed BCT Thai women. The data included subjective and objective CO with a questionnaire covering demographic and clinical data, anti-hormonal treatment status, Eastern Cooperative Oncology Group (ECOG) performance status, Self-Reported Cosmetic Outcomes (SRCO), Self-Reported Breast Symmetry (SRBS), Body Image Scale (BIS), and the Functional Assessment of Cancer Therapy with Breast Cancer subscale (FACT-B). Participants had breast photographs taken for the evaluation of objective cosmetic outcome (OCO) after breast cancer conservation treatment. The relationship between CO and FACT-B was tested using Spearman's rank correlation Results: A total 127 participants volunteered for the study. The participant characteristics were age 52(±9), Buddhist 87%, married 65%, body mass index 25.0(±4.6), breast cup size A-C 91%, college educated 60%, employed 66%, ECOG 0-1 95%, tumor size less than or equal to 2 cm 55%, no lymph node metastasis 98%, and taking tamoxifen 57%. Two percent of the participants regretted their decision to undergo BCT. The SRCO was excellent in 2%, good in 68%, fair in 30%, and poor in 0%. For SRBS, rates were 17%, 58%, 24% and 1% for excellent, good, fair and poor cosmetic outcomes, respectively. The BCCT scores were excellent 24%, good 39%, fair 32%, and poor 6%. The median total QOL score of the participants was 130 (93-144). There was no significant correlation between CO and FACT-B scores. The significance of CO for FACT-B in Thai women with breast cancer could not be assessed in detail because of a very low level of correlation. The results may be due to the effects of cultural background.