Metastatic breast cancer: are we treating the same patients as in the past?

BACKGROUND: Early detection and improved (neo)-adjuvant treatment has extended survival of breast cancer over the last decades. It remains controversial whether a survival benefit is achieved once metastases have occurred. This study investigates survival trends in metastatic breast cancer (MBC) looking at the distribution of prognostic factors and the time period of the diagnosis of the primary and metastatic disease. PATIENTS AND METHODS: In this retrospective study, 1635 patients, diagnosed with MBC and treated at three German cancer centers, were included. For the survival analysis, patients were grouped into three time periods [1980-1994 (a), 1995-1999 (b) and 2000-2009 (c)], which were chosen according to the availability of new antineoplastic drugs for the treatment of MBC. Additionally, patients were divided into three risk groups using the simultaneously published prognostic score. RESULTS: The analysis of overall survival according to the date of primary diagnosis demonstrated a significant decline compared with the reference (a): (a versus b) hazard ratio (HR) = 1.37; P < 0.001; (a versus c) HR = 2.45; P < 0.001. Considering the time of first occurrence of metastasis, survival remains unchanged over the three periods (a versus b): HR = 0.94 P = 0.436; (a versus c): HR = 0.95; P = 0.435. However, a significant shift towards more unfavorable risk factors was seen. CONCLUSIONS: Although survival in MBC remains unchanged over time, patients developing metastatic disease have a more aggressive disease that is presumably compensated by more effective treatment. This alteration of tumor biology in MBC may be explained by a negative selection of patients with adverse risk profiles due to the advantages of the adjuvant therapy.

Codon 12 ras mutations in patients with myelodysplastic syndrome: incidence and prognostic value.

To determine the prevalence of activated rasoncogenes (N-ras, Harvey-ras Kirsten-ras), DNA derived from peripheral blood of 51 patients with myelodysplastic syndrome (MDS) was investigated. The method was based on the polymerase chain reaction (PCR) technique to amplify DNA, followed by restriction fragment length polymorphism (RFLP) analysis. Among the French-American-British (FAB) subtypes, N-ras mutations were found in two patients with refractory anemia with excess of blasts (RAEB), in one patient with refractory anemia with excess of blasts in transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter survival duration than other MDS patients of the same FAB subtypes, although these findings proved to be not statistically significant (P > 0.1). Interestingly, all but one patient with N-ras mutation developed acute myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12 of the N-ras gene might serve as a negative prognostic factor at diagnosis of MDS.

Treatment of high risk myelodysplastic syndromes with idarubicin and cytosine arabinoside supported by granulocyte-macrophage colony-stimulating factor. (GM-CSF).

In this prospective study, patients with "high risk' primary MDS, namely RAEB or RAEBt, were treated with combination chemotherapy (CT) supported by GM-CSF. The induction CT consisted of idarubicin 6 mg/m2 days 1-3 and cytosine-arabinoside 200 mg/m2 in 12 h infusion, days 1-5. The GM-CSF 3 micrograms/kg s.c. was given on day 6 until the neutrophil count was 1 x 10(9)/l. Postremission CT consisted of two similar courses. Patients not in remission after two courses of CT were considered as treatment failures. Twenty-two patients with a median age of 64 years, range 50-79 years (11 RAEB and 11 RAEBt) were evaluable. Twelve out of 22 patients (54.5%) achieved complete remission (CR) and four, partial remission. Six patients were resistant to treatment; there were two toxic deaths; seven patients achieved CR after the first course and five after two courses. The median time of neutrophil recovery to 1 x 10(9)/l was day 15 (range 3-22) after the first course of treatment and day 14 (range 4-21) after the second. Thirteen out of 22 patients developed febrile episodes after the first course of treatment and nine after the second. The median duration of CR was 12 months. The median survival for CR patients was 24 months, for non-CR patients, 12 months; while survival for the whole population was 18 months. In conclusion, the results of this study indicate that the administration of moderately intensive CT supported by GM-CSF in "poor risk' MDS gives promising results; the response rate is high for this disease, while the incidence of toxic death is low. GM-CSF appears to accelerate neutrophil recovery and probably reduces the incidence of infection.

Second malignancies following treatment for Hodgkin's disease: a Greek experience.

The risk and the type of second malignancies (SM) developing in 217 treated Hodgkin's disease (HD) patients were studied. The median age of the patients was 35 years (range 14-83) and the M/F ratio 1.8. Treatment consisted of radiotherapy alone (24 patients, 11%), chemotherapy alone (96 patients, 44.3%), or a combination of both modalities (43 patients, 19.8%), while 54 patients (24.9%) received salvage treatment. The median follow-up time was 67 months (range 12-224). Ten patients developed a SM with a 5-year and 10-year actuarial risk of 3.3% and 5.4%, respectively. There were 3 cases of ANLL and MDS (actuarial risk of 2.4% at 6 years), 1 case of non-Hodgkin's lymphoma and 6 cases of solid tumors (actuarial risk of 2.4% at 6 years). The risk of developing SM was higher in males and older patients (> 40 years). SM represent a serious late side effect of successful treatment for HD. The possibility of developing a SM must be taken into consideration in the initial treatment of the disease.

Primary granulocytic sarcoma of the testis.

An unusual case of a 44-year-old patient with primary left testicular granulocytic sarcoma is presented. Iliac and paraaortic lymph node involvement was also demonstrated at staging laparotomy. The patient was treated with left orchiectomy and early intensive chemotherapy, but relapsed with a right testicular mass 14 months later. No evidence of leukemic progression was found at that time, and he was treated with right orchiectomy, combined with irradiation to the scrotum, inguinal, iliac and paraaortic lymph nodes. Unfortunately, he developed myelogenous leukemia 7 months later. A complete remission of 6 months duration was achieved with combination chemotherapy. The patient then relapsed, and an effort to induce a second remission was unsuccessful. He eventually died almost 3 years after initial diagnosis. We conclude that primary granulocytic sarcoma represents a systemic disease. Despite early intensive treatment its prognosis remains poor.

A simple method for the detection of Chlamydia trachomatis infections in general practice.

Chlamydial infection is an important cause of genital tract disease in women and is often silent. Collection, storage and transportation of specimens required for culture pose problems which have made studies difficult and diagnosis impractical outside hospitals or sexually transmitted disease clinics.The direct monoclonal antibody test (MicroTrak, Syva) for detecting chlamydiae is comparable with the traditional culture method in sensitivity and specificity. The test requires only the preparation of a smear on a slide, making it convenient for use in general practice. The feasibility of using this procedure in an inner city practice was demonstrated in tests on 188 women who required pelvic examination. Of 169 women from whom valid specimens were obtained 18 (10.7%) were found to have a chlamydial infection. Only three of the infected women were asymptomatic and the organisms were associated particularly with dysuria. The value of the test in comparison with other procedures currently available for detecting chlamydiae is emphasized.

Primary amoebic meningoencephalitis in Nigeria (report of two cases in children).

Two cases of PAME in children occurring during dusty harmattan period in Northern Nigeria are reported. In the absence of history of swimming or any other water related sport, and as suggested in our two previous reports, a dustbone infection as an important route of infection in PAME in this area is stressed. A need to fully investigate any atypical case of meningitis and meningoencephalitis in this area is emphasised.

The therapeutic effect of taking a patient's history by computer.

Sixty young women who presented at a general-practice health centre had their medical and social history taken by a computer before having an interview with the doctor. The average length of the automated interview was 90 minutes for the 54 patients who completed the programme, during which an average of 211 questions were answered. The patients found this method acceptable and we think that one of the main reasons for this was that the computer programme was so designed that the patients felt that the doctor was involved throughout.The computer/patient interview also appeared to have therapeutic benefits, and the computer's summary of the history was a sensitive indicator of those topics about which the patient was most concerned. This combination enabled the doctor to communicate more quickly and in greater depth in the time available. In effect, the time which the doctor could spend with the patient was magnified.We suggest that the benefits of this system for taking a history from a patient, of which one is the fact that any language or combination of languages can be used, could be extended to all classes of society.