Stage I Breast Cancer in the Modern Era: A Retrospective Cohort Study of 328 Patients Diagnosed from 2002 to 2006 with a 14-Year Median Follow-Up.

INTRODUCTION: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. METHODS: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. RESULTS: Most patients were treated by lumpectomy, sentinel node biopsy, and adjuvant endocrine therapy, and most (82%) were of subtype luminal A. Adjuvant chemotherapy was administered to 25.6% of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (<1 cm vs. 1-2 cm) impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. CONCLUSION: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal A patients.

Successful treatment of mediastinal seminoma in a hemodialysis patient.

BACKGROUND: Extragonadal germ cell tumors (GCTs) are relatively uncommon neoplasms, affecting primarily men during the third and fourth decades of life. CASE REPORT: We describe an unusual case of mediastinal seminoma in a 21-year-old male on chronic peritoneal dialysis for renal failure of uncertain etiology. The patient was treated with chemotherapy consisting of etoposide and cisplatin (EP) combined with hemodialysis. Cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2)) were given on days 1, 3, and 5 for induction. Hemodialysis was started 1 h after completion of etoposide infusion. Following this course of treatment, another 4 cycles of cisplatin (20 mg/m(2)), and etoposide (50 mg/m(2)) were given on successive days from day 1 to 5. Hemodialysis was carried out daily, prior to the start of chemotherapy. Subcutaneous PEG-filgrastim was given on day 6 in all cycles. The patient's status after the first post-induction treatment was complicated by a pseudomonas infection. Tumor response to chemotherapy was prompt with remission lasting to date, 17 months after diagnosis. CONCLUSION: This case report is the second description of chemotherapy given to a hemodialysis patient with extragonadal GCT. We suggest that treatment with EP combined with hemodialysis according to the presented protocol is feasible, and may result in a favorable outcome.

Cell-free DNA concentration in patients with clinical or mammographic suspicion of breast cancer.

Mammography has a crucial role in the detection of breast cancer (BC), yet it is not limitation-free. We hypothesized that the combination of mammography and cell-free DNA (cfDNA) levels may better discriminate patients with cancer. This prospective study included 259 participants suspected with BC before biopsy. Blood samples were taken before biopsy and from some patients during and at the end of treatment. cfDNA blood levels were measured using our simple fluorescent assay. The primary outcome was the pathologic diagnosis of BC, and the secondary aims were to correlate cfDNA to severity, response to treatments, and outcome. Median cfDNA blood levels were similar in patients with positive and negative biopsy: 577 vs. 564 ng/ml (p = 0.98). A significant decrease in cfDNA blood level was noted after the following treatments: surgery, surgery and radiation, neo-adjuvant chemotherapy and surgery, and at the end of all treatments. To conclude, the cfDNA level could not be used in suspected patients to discriminate BC. Reduction of tumor burden by surgery and chemotherapy is associated with reduction of cfDNA levels. In a minority of patients, an increase in post-treatment cfDNA blood level may indicate the presence of a residual tumor and higher risk. Further outcome assessment for a longer period is suggested.

Lymphangiogenesis in Classical Hodgkin Lymphoma - Preliminary Study with Clinicopathological Correlations.

A role for lymphangiogenesis in metastatic breast and prostate cancers has been suggested recently. The relevance of lymphangiogenesis in cancer as a rule, and more specifically in classical Hodgkin lymphoma, is poorly understood in comparison with that of angiogenesis. In a preliminary (pilot) study we have investigated the role of lymphatic vessels growth in 19 cases of classical Hodgkin lymphoma stained with the D2-40 (podoplanin) antibody. In each case, three lymphatic vessels hot spots were scrutinized twice. Of the 57 hot spots thus identified, we chose 15 at random for photography, microvessel counting and image analysis. We determined the mean perimeter, surface area, major axis length and complexity factor for each hot spot and correlated them with clinical and biological features of classical Hodgkin lymphoma. No correlations were found with clinical features. No associations were noted with the standard immuno-markers of classical Hodgkin lymphoma. However, significant inverse correlations were shown with pRb, BAX and IκB-α expression. The mean lymphatic major axis length was inversely correlated with the complexity factor. Last, we carried out an additional clinicopathological correlation of the expression of pRb, BAX and IκB-α in a cohort of classical Hodgkin lymphoma patients previously published.

Relevance of the Measles Virus Expression in Cancer - an Update.

Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.

Early exposure to a clinical oncology course during the preclinical second year of medical school.

PROBLEM: Although only some medical students pursue a career in oncology, all should have a basic understanding of the issues surrounding cancer and its treatment. The authors designed and implemented a one-week introductory clinical oncology course for second-year medical students at Ben Gurion University of the Negev. The course presents a holistic approach to caring for patients with cancer that goes beyond the biological aspects of the disease. APPROACH: In 2013, the authors interviewed four former students and surveyed all current students before and after they completed the course to evaluate its reception and effectiveness. OUTCOMES: Of the 86 students in the course, 77 (90%) completed both the pre- and postcourse surveys. After taking the course, more students reported being concerned about ethical issues, being emotionally stirred by the course, being comfortable speaking with a cancer patient about death and dying, and being comfortable with the fact that the course dealt with issues of death and loss and with "how to live with cancer." In addition, more students reported a fear of causing a cancer patient suffering because of a treatment yet viewed cancer optimistically. Finally, more students considered specializing in oncology. NEXT STEPS: That students reported increased empathy toward cancer patients despite increased trepidation about causing them suffering is promising. Such courses may be one way to counteract the decrease in empathy among students as they progress through medical school. As such, medical schools might consider including this type of curriculum in their preclinical oncology studies.

Cell-free DNA blood levels in colorectal cancer patients do not correlate with mismatch repair-proficiency.

UNLABELLED: While sporadic cases of colorectal cancer (CRC) most commonly arise via the well-characterized chromosomal instability pathway (CIN), most other cases develop via a serrated neoplasia pathway (CIMP), in which methylation of CpG islands results in silencing of DNA nucleotide mismatch repair (MMR)-related genes, and a high level of microsatellite instability (MSI). MSI-high tumors typically show proximal location, mucinous histology, poor differentiation, and lymphocytic infiltration. Cell-free circulating DNA (CFD) may become elevated in CRC patients compared to healthy individuals. Because of these biological differences, we hypothesized that compared to MMR-proficient tumors MMR-deficient CRCs may produce higher CFD blood levels. PATIENTS AND METHODS: Forty-one patients with newly-diagnosed CRC from all stages were studied for MMR-proficiency status, and CFD and carcinoembryonic antigen (CEA) blood levels. MMR proficiency was evaluated in formalin-fixed, paraffin-embedded tissues by immunohistochemistry (IHC) for MLH1/MSH2. CFD plasma levels were measured with SYBR gold nucleic acid gel staining on fluorometry. MMR-proficiency status was studied by clinicopathological parameters, CFD and CEA blood levels. RESULTS: Tumors were MMR-proficient, and -deficient in 16 patients (39%), and 25 patients (61%), respectively. The mean age of MMR-deficient patients was approximately 10 years higher than that of MMR-proficient patients (61.2±8.4 years versus 71.9±9.7 years, p=0.07). MMR-deficient tumors were more often proximally-located, (p=0.018). The mean CFD plasma levels in MMR-proficient, and MMR-deficient patients were 795±431 ng/ml, and 906±494 ng/ml, respectively (p=0.68). The mean CEA serum levels in MMR-proficient and MMR-deficient patients were 10.4±17.6 µg/l, and 15±48 µg/l, respectively (p=0.46). CONCLUSION: Compared to MMR-proficient CRCs, MMR-deficient tumors occurred in older patients, and were more commonly proximally-located. Despite the presence of distinct biological and histopathological characteristics, both tumor types produced similar CFD blood levels.

Hypertriglyceridemia in patients with metastatic breast cancer and treatment with capecitabine.

Several reports have described hypertriglyceridemia (HTG) in cancer patients, including breast cancer patients treated with capecitabine (CAP). However, the exact range of HTG in patients with metastatic breast cancer (MBC) treated with CAP has clearly not been defined. A retrospective analysis on 54 patients with MBC treated with CAP longer than 2 months was conducted. HTG was defined as triglyceride blood level above 150 mg/dl. Baseline data included age, body mass index (BMI), tumour characteristics, treatment duration, concomitant treatment with lapatinib, diagnosis of dyslipidemia, and diabetes mellitus, as well as antihyperlipidemic therapy. Clinically significant HTG (triglycerides >300 mg/dl) was found in 4/54 (7%) of patients. Post-treatment HTG was associated only with concomitant treatment with lapatinib (P<0·01). Three of the patients had dyslipidemia before treatment with CAP, and one patient also had diabetes-mellitus. No HTG-related complications occurred. Clinically significant HTG in MBC patients treated with CAP may be associated with pre-existing risk factors, such as dyslipidemia or diabetes-mellitus.

EML4-ALK-positive non-small cell lung cancer in a patient treated with azathioprine for ulcerative colitis.

EML4-ALK-positive lung cancer is a novel cancer entity associated with light or never smoking, younger age, and adenocarcinoma with acinar or signet-ring cell type histology. Another mutation of ALK with NPM, resulting in NPM-ALK fusion mutation, was described in patients with anaplastic large cell lymphoma (ALCL). It was subsequently reported in organ transplant recipients and patiens undergoing immunosuppressive therapy. We describe a case of lung cancer in a 36-year-old nonsmoking woman with ulcerative colitis treated with azathioprine, who was diagnosed with EML4-ALK-positive, metastatic lung cancer two months postpartum. Crizotinib 300 mg/day has been effective in maintaining response after chemotherapy failed. The resemblance of this case to ALK-positive ALCL in organ transplant recipients suggests that similar mechanisms may be responsible for the development of both ALK-positive lung cancer and ALCL in patients receiving immunosuppressive therapy.

The prognostic importance of cathepsin D and E-cadherin in early breast cancer: A single-institution experience.

Molecular tools have increasingly been used for decision-making in patients with early breast cancer (EBC). Nevertheless, simple tools such as immunohistochemistry may still be required in particular cases to complement traditional and molecular prognosticators. In this study, the prognostic significance of three well-known immunohistochemical biomarkers, cathepsin D, E-cadherin and Ki67, was studied in 270 patients with EBC, followed by a median time of 126 months in a single institution. Histological examination was performed to confirm the histopathological diagnosis and select specimens. The specimens were evaluated using immunohistochemistry and survival curves were plotted. Results revealed the following patient characteristics: node-negative/1-3 lymph nodes in 228 (86%) patients, hormone receptor-positive in 217 (80%); triple-negative in 31 (11%), and Her2-overexpression in 23 (9%) patients. Breast cancer-related events occurred in 37 patients (14%). A total of 217 patients (80%) survived. Receiver operating characteristic analysis for breast cancer-specific survival showed an area under curve for the clinicopathological model of 0.75 (95% CI, 0.64-0.86), 0.79 (95% CI, 0.68-0.90) for the three-biomarker model, and 0.82 (95% CI, 0.72-0.92) for the E-cadherin and cathepsin D only model. We propose that a simple prognostic model based on combined scores of E-cadherin and cathepsin D may aid treatment decisions in patients with EBC.