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The article presents a case study of an 18-year-old woman who presented with vaginal bleeding and protruding mass form the vagina. She was diagnosed with alveolar rhabdomyosarcoma (ARMS) originating from the cervix. The patient undergone Wertheim's operation and four cycles of vincristine, actinomycine-D, ifosfamide (VAI) chemotherapy, but the disease relapsed within three months. The patient died of disease progression.

Abstract Objective Strongyloides stercoralis is a soil-transmitted intestinal nematode that has been estimated to infect at least 60 million people, especially in tropical and subtropical regions. Strongyloides infection has been described in immunosupressed patients with lymphoma, rheumatoid arthritis, diabetes mellitus etc. Our case who has rheumatoid arthritis (RA) and bronchial asthma was treated with low dose steroids and methotrexate. Methods A 68 year old woman has bronchial asthma for 55 years and also diagnosed RA 7 years ago. She received immunusupressive agents including methotrexate and steroids. On admission at hospital, she was on deflazacort 5 mg/day and methotrexate 15 mg/week. On her physical examination, she was afebrile, had rhonchi and mild epigastric tenderness. She had joint deformities at metacarpophalengeal joints and phalanges but no active arthritis finding. Results Oesophagogastroduodenoscopy was performed and it showed hemorrhagic focus at bulbus. Gastric biopsy obtained and showed evidence of S.Stercoralis infection. Stool and sputum parasitological examinations were also all positive for S.stercoralis larvae. Chest radiography result had no pathologic finding. Albendazole 400 mg/day was started for 23 days. After the ivermectin was retrieved, patient was treated with oral ivermectin 200 μg once a day for 3 days. On her outpatient control at 15th day, stool and sputum samples were all negative for parasites. Conclusion S.stercoralis may cause mortal diseases in patients. Immunosupression frequently causes disseminated infections. Many infected patients are completely asymptomatic. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. In immunosupressed patients, to detect S.stercoralis might help to have the patient survived and constitute the exact therapy.

Abstract Background Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA) induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR), myeloid cell leukemia-1 (MCL-1), tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), TNFRSF1A-associated death domain protein (TRADD). Results We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions These are the preliminary molecular results of a novel combination treatment of ATRA and zoledronic acid, with fewer side effects as compared to conventional cytotoxic agents. With additional experimental analysis, it may serve as a good option for the treatment of refractory and elderly ovarian cancer patients, for whom there exists very limited choice of treatment.

While the connection between risk factors and suicidality (suicide attempts and ideation) and physical self-harm is well established, the preventive roles of social bonding and dietary patterns remain underexplored. This study, based on the 2021 National Ungdata Surveys in Norway among middle and high school students ( N  = 15,430), can provide novel and context-specific insights into comparable environments. The results indicated a 5% suicide attempt rate, 18.3% prevalence of physical self-harm, and 26.7% suicidal ideation in the sample. The prevalence was higher among girls, students with low socioeconomic status, middle schoolers, and non-religious individuals. Logistic regression models for suicide attempts showed that substance use and victimization (sexual harassment and bullying) were significant predictors of suicide attempts. Elevated depressive symptoms and the use of pain relievers increased the risk. For suicidal ideation, victimization and depressive symptoms were significant predictors. Concerning physical self-harming behavior, substance use and risky behaviors increased odds, whereas binge drinking had varying effects. Victimization variables and health measures were also significant predictors. Dietary patterns, social bonding measures, and self-motivation were found to be protective factors, as they decreased the likelihood of suicidal and self-harming behaviors, highlighting the critical role of strong social connections, healthy dietary habits, and well-being.

Introduction: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis., Materials and Methods: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses., Results: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses., Conclusion: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics., Competing Interests: OUD and BA are the employees of Pfizer Biopharmaceuticals Group, Istanbul, Türkiye. BOU reports research support for clinical trials through institution from Novartis, GSK, Astra Zeneca; honoraria from BMS, Amgen, Novartis, Pfizer, Astra Zeneca, Roche, MSD; support for attending meetings from Roche, Pfizer, Novartis and is on the advisory boards of Takeda, Roche, Astra Zeneca, MSD, Novartis, Amgen, Gilead. ME has support funding for medical writing from Pfizer, provides lectures for Pfizer, Novartis, Roche, Astellas, Janssen, MSD, Gen, Nobel, Deva, Eczacibasi, BMS, Takeda, Astra Zeneca, has support for attending meetings from Roche, has participation on advisory board of Novartis, Pfizer, Roche, Astellas, MSD, Deva, Astra Zeneca. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting., Methods: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR., Results: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p  < 0.001) and lower relapse (4.5 vs. 12.2%, p  < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p  < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p  < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p  < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p  < 0.001) and NCT-HP (41.5 vs. 32.1%, p  < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p  < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p  < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p  < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p  < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p  = 0.008) significantly predicted the pCR., Conclusions: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% ( n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We report that neurofibromin, a tumor suppressor and Ras-GAP (GTPase-activating protein), is also an estrogen receptor-α (ER) transcriptional co-repressor through leucine/isoleucine-rich motifs that are functionally independent of GAP activity. GAP activity, in turn, does not affect ER binding. Consequently, neurofibromin depletion causes estradiol hypersensitivity and tamoxifen agonism, explaining the poor prognosis associated with neurofibromin loss in endocrine therapy-treated ER + breast cancer. Neurofibromin-deficient ER + breast cancer cells initially retain sensitivity to selective ER degraders (SERDs). However, Ras activation does play a role in acquired SERD resistance, which can be reversed upon MEK inhibitor addition, and SERD/MEK inhibitor combinations induce tumor regression. Thus, neurofibromin is a dual repressor for both Ras and ER signaling, and co-targeting may treat neurofibromin-deficient ER + breast tumors., Competing Interests: Declaration of Interests K.C.B. and R.B.L. are stockholders and employees of Guardant Health, Inc., C.E.F. discloses an equity position in Coactigon, Inc., and M.J.E. received consulting fees from Abbvie, Sermonix, Pfizer, AstraZeneca, Celgene, NanoString, Puma, and Novartis, and is an equity stockholder, consultant, and Board Director member of BioClassifier, and inventor on a patent for the Breast PAM50 assay., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: The application of next-generation sequencing (NGS) genomic testing for somatic mutations in breast oncology has been slower than anticipated due to issues with clinical applicability and natural heterogeneity of breast cancer. This review summarizes the state of the field and considers approaches for more effective implementation., Observations: While there is an emerging role for germline genetic testing potentially predicting sensitivity to platinum salts and PARP inhibitors, the data regarding somatic mutation for prediction of drug sensitivity remains controversial. Currently, there are no guidelines or regulatory approvals for genomic somatic tumor mutation testing to direct therapy. However, some small populations show promise, such as those with ERBB2/HER2 mutation who may represent the first population to have a positive drug somatic mutation match. Similarly, those with ESR1 mutation may be the first to emerge for a negative association with the efficacy of aromatase-inhibitor treatment. One of the barriers to progress is the necessary focus on metastatic disease, which is often challenging, expensive, and risky to biopsy. In addition, because of the clonal heterogeneity of advanced disease, a single sample may not contain all the genomic information necessary for treatment. Thus, circulating tumor DNA analysis is perhaps one of the most practical and promising approaches., Conclusions and Relevance: Circulating tumor DNA analysis, once sensitive and broad enough, will accelerate progress in the quest to make NGS technologies relevant to breast cancer treatment. A broad and coordinated coalition to systematically connect somatic mutations to clinical and pharmacologic data will be critical for progress. We recommend instituting an open source encyclopedia, which would serve as a reference for NGS sequencing report interpretation and would be available to all clinicians to help direct therapy.

Purpose: Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy., Methods: All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m(2), doxorubicine 50 mg/m(2), cyclophosphamide 500 mg/m(2)) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included., Results: Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1(st) and 6(th) adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group., Conclusions: Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients., (© The Author(s) 2014.)

The present study aimed to analyze the efficacy of maintenance therapy with single agent capecitabine for human epidermal growth factor receptor (HER2) negative metastatic breast cancer (MBC) patients following disease control with 6 cycles of docetaxel plus capecitabine chemotherapy as the first-line treatment. As an initial treatment, 6 cycles of docetaxel plus capecitabine followed by maintenance therapy with capecitabine were administered. A total of 55 patients received combination therapy and 48 patients proceeded to maintenance therapy: Of these, 32 patients (66.7%) were postmenopausal and 37 (77.1%) had estrogen and progesterone receptor positive disease. The median progression-free survival rate with maintenance therapy was 5.5 months (95% CI, 0-11.4 months) and the median overall survival (OS) was 26.6 months (95% CI, 21.8-30.1 months). The use of maintenance therapy improved previous responses in 4 patients (8.3%; 2 partial and 2 complete responses) and 32 patients (66.7%) had stable disease. The median number of maintenance therapy cycles applied was 6.5 (range 1-28, total 441). The observation of side effects, including grade 3/4 neutropenia, febrile neutropenia and fatigue was more common during combination therapy. The results of the present study indicate that maintenance with single agent capecitabine therapy is an effective and tolerable treatment option for HER2 negative MBC patients in which disease control with 6 cycles of docetaxel plus capecitabine chemotherapy is achieved in the first-line setting.

Recent healthcare reform in Turkey aims at achieving universal coverage with the introduction of General Health Insurance (GHI). As part of GHI, the state assumes the provision of health insurance coverage to those unable to afford the public health insurance premiums conditional on a means-testing procedure where the official threshold is set as one-third of the gross minimum wage. This article aims at exploring in Turkey the prevalence of non-take up of means-tested health insurance for the poor and the consequent financial burdens for those poor segments outside the coverage. Based upon Statistics of Income and Living Conditions micro data, the non-take-up rate is estimated to be around 44%, where the prevalence of non-take-up is lower yet still high, i.e. around 30%, for households with very low incomes as well as those with elderly or ill members. The results from a separate health expenditure survey on urban poor, which is specifically designed and implemented by the authors, reveal that poor households without health insurance coverage are faced with significant out-of-pocket expenditures. About 5% of those households without coverage were found to have inpatient expenditures that exceeded 20% of their annual disposable household income. Also, among the households without coverage but with at least one inpatient visit over the last two years, the median expenditure was reported as high as 8% of the annual household income as opposed to 0% median value for those with GHI. The results highlight that a large proportion of poor population still lacks public health insurance despite the overarching aim of universal coverage., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Triple-negative breast cancer (TNBC) has none of the targeted treatment choices due to its distinct biological property, making this subtype a unique disease. In this study, we evaluated the impact of obesity on clinical outcomes of TNBC., Methods: The data of breast cancer patients admitted to our department were collected. TNBC was defined as lack of estrogen receptor (ER), progesterone receptor (PR) and HER-2. The body mass index (BMI) of 112 TNBC patients was calculated with weight at the time of diagnosis and height. The patients were classified into groups with a BMI of < 25 (normal/underweight), 25-29.9 (overweight) or ≥ 30 (obese). After a mean follow-up of 23.2 ± 15.5 months, there were 12 recurrences (10.71%) and 6 deaths (5.35%). Disease-free survival (DFS) and overall survival (OS) were assessed., Results: The survival analyses of all the patients did not demonstrate any differences in OS or DFS in obese as compared to non-obese patients. However, we showed that obesity was associated with a poorer OS for postmenopausal TNBC patients (p < 0.05)., Conclusion: Obesity is related to a poorer OS in postmenopausal TNBC patients. Due to the heterogeneous disease profile of TNBC, larger randomized studies will be needed to clarify the exact role of obesity in TNBC., (© 2015 S. Karger GmbH, Freiburg.)

The aim of the present study was to evaluate the application of tuberculosis preventive treatment (TB-PT). Demographic data, indications and results for cases that received TB-PT at the Ankara Tuberculosis Control Dispensary No. 7 between 2008 and 2011 were retrospectively evaluated. The 'Prevention with Drugs' registry at the dispensary was used. A total of 463 cases received TB-PT, with the indications including close contact with an active TB case (44%), positive tuberculin skin test (TST) in a child <15 years-old (25%) and immunosuppressive therapy (31%). The immunosuppressed group (n=144) were administered steroids (10%) or tumor necrosis factor (TNF)-α inhibitors (90%). Indications of TST conversion and sequela lesions were not observed among the cases. The male/female ratio was 106/98 for cases with TB close contact, 61/54 for TST-positive cases and 85/59 for immunosuppressed cases. The mean ages of these groups were 9±5.7, 9.5±3.8 and 38±14.9 years, respectively. TB-PT was completed in 364 cases (78.6%), and the rate of discontinuation due to adverse effects was 1% for TB close contact and 2% for TST-positive cases, but 5% for immunosuppressed cases. While the percentage of TB close contact cases receiving TB-PT decreased during the four-year study period, the percentage of cases with immunosuppression (in particular patients using TNF-α inhibitors) increased. Among the studied cases, only two subjects developed active TB. The first case involved a 1.5-year-old female that had close contact exposure to TB from a parent, while the other case involved a 14-year-old TST-positive male (induration size,16 mm). In conclusion, patients receiving TB-PT should be monitored and/or followed-up carefully to control any side-effects from the treatment and development of active TB.

Breast cancer is a heterogeneous group of diseases that are clinically subdivided as hormone receptor-positive, human epidermal growth factor receptor 2-positive (HER2(+)), and triple-negative breast cancer, to guide therapeutic interventions. Agents that target estrogen receptor (ER) and HER2 are among the most successful cancer therapeutics. However, de novo or acquired resistance is common, despite the development of newer agents against these pathways. As our understanding of tumor biology improves, novel targets are being identified. Notably, inhibitors against several pathways [including, among others, the phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR), cell-cycle regulation, heat shock protein, and epigenetic pathways] have demonstrated promising activity in clinical trials, and the mTOR-inhibitor everolimus has been approved for advanced or metastatic aromatase inhibitor-resistant ER(+) breast cancer. At present, there are no established targeted agents for triple-negative breast cancer (negative ER, progesterone receptor, and HER2). Although poly(ADP-ribose) polymerase inhibitors have shown promising activity in BRCA-related cancers, its value in the treatment of triple-negative breast cancers remains to be demonstrated. In this Review, we present a basic understanding of the major targeted agents in current practice and under development for the treatment of breast cancer in the context of the three clinical subgroups., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Cancer is a life-threatening disease despite the advanced therapeutic strategies now available. A common problem is that physicians and patients tend to concentrate on intensive medical treatment options and underestimate the treatment-related adverse effects. In this review, we summarize one of these adverse effects in cancer patients; sexual dysfunction (SD). In addition, current therapeutic choices with optimal doses and patient selection strategies are defined. All patients should be informed about problems associated with therapy-related SD and must be guided toward the most appropriate therapeutic options before starting treatment.

Objectives: The liver is the most common metastatic site in colorectal cancer (CRC). In this study, we evaluated if there is any difference between first-line irinotecan-based and oxaliplatin-based chemotherapies in the duration of time to disease progression (TTP) in CRC patients with only liver metastasis., Methods: We retrospectively reviewed the medical records of patients with metastatic CRC referred to the Medical Oncology Department at the Faculty of Medicine of Ege University, between January 2002 and December 2010. Seventy-seven patients had only liver metastasis and completed their first-line chemotherapy. Forty-two patients had oxaliplatin-based treatments while 12 also had bevacizumab therapy, and 35 patients had irinotecan-based treatments while 16 also had bevacizumab therapy., Results: Median TTP was 6.70 ± 0.29 months for patients treated with oxaliplatin+5-fluorouracil (5-FU) and 8.33 ± 1.15 months for patients treated with oxaliplatin+5-FU+bevacizumab. TTP was significantly improved for patients who received irinotecan+5-FU+bevacizumab (median TTP, 13.73 ± 2.10 mo) when compared with irinotecan+5-FU (median TTP, 5.13 ± 0.70 mo)., Conclusions: Although previous studies showed no survival difference between these 2 chemotherapeutic agents in metastatic CRC, there might be differences in the benefit of delaying the disease progression in subgroup populations. Irinotecan+5-FU with bevacizumab combination chemotherapy may be superior in the first-line treatment of CRC with hepatic only metastasis.

Purpose: Exposure to all active agents may be more important than specific sequence of drug administration in the treatment of patients with metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the overall survival (OS) of mCRC patients who were treated with all 5 major therapeutic agents used in this malignancy., Methods: We retrospectively reviewed the medical records of 395 mCRC patients referred to our clinic. The study included patients who received 5-fluorouracil (5-FU)-, irinotecan- or oxaliplatin-based chemotherapy and at least 3 cycles of bevacizumab and 4 weeks of cetuximab sequentially in various combinations., Results: Forty mCRC patients received the 5 major therapeutic agents effectively and sequentially, and their mean OS was 26.43±2.04 months. The 3- and 4- year OS survival rates were 26.7% and 16.7%, respectively. When survival analysis was limited to the metastatic patients with at least 6 cycles of bevacizumab therapy in addition to standard duration of other chemotherapeutic agents (N=33), the mean OS was 26.7±2.38 months. With a further survival analysis limited to metastatic patients who were treated with at least both 6 cycles of bevacizumab and 8 weeks of cetuximab in addition to other therapies (N=17), the mean OS was 44.8±11.03 months., Conclusion: This study demonstrated that in mCRC patients there may be a significant survival advantage if an adequate tumor response was achieved with all major therapeutic agents. Therefore, we believe that we should treat our patients with the 5 major therapeutic drugs as effectively as possible.