Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with astrocytoma treated with chemotherapy

Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas aeruginosa infection, has distinct pathognomonic features and a high mortality rate in patients with bacteremia, but when recognized early is easily treated. In this case report we describe this disseminated infection in an adult patient treated with chemotherapy for an astrocytoma

Clinical experience with venlafaxine in the treatment of hot flushes in women with a history of breast cancer

OBJECTIVE: To obtain practical experience with venlafaxine for hot flushes in breast cancer patients and incorporate this in a treatment protocol. METHOD: Twenty-two women with a history of breast cancer (mean age 49.2 years, range 35-65) were referred for consideration of treatment with venlafaxine for hot flushes. Patients received extensive information on treatment with venlafaxine and were advised to self-monitor the frequency of their hot flushes. RESULTS: Eight women did not start venlafaxine because they had no postmenopausal complaints, were lost to follow-up, had too low a frequency of hot flushes, or refused treatment. Eventually 14 women started venlafaxine. Two of them did not tolerate venlafaxine, four reported some effect but stopped because of side effects, two women had no effect whatsoever. Six women observed a clear ( > 50%) reduction in their hot flush frequency that was maintained at a median follow-up of 13 months. CONCLUSION: The group of patients referred for treatment was more heterogeneous and more patients dropped out because of side effects than expected. Extensive patient education, patient selection and evaluation of the treatment effect (by self-monitoring of hot flush frequency) are mandatory to avoid useless (continuation of) treatment and to prepare patients for side effects. Under these conditions, a substantial minority of patients benefit from venlafaxine

Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy

Purpose: Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment. Patients and Methods: This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis. Results: The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance. Conclusion: Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting

Toxicity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2-associated breast cancer

Treatment with (neo)adjuvant chemotherapy for breast cancer, as currently given, causes cell damage by induction of double-strand DNA breaks. Because BRCA1 and BRCA2 proteins play a role in the repair of DNA damage, the efficacy of (neo)adjuvant chemotherapy may be increased in BRCA1/2-associated breast cancer patients. As a downside, acute chemotherapy-related toxicity may also be increased. We selected all female patients who were treated at the Erasmus MC Cancer Institute, with (neo)adjuvant chemotherapy for primary or locoregional recurrence of breast cancer (PBC/LR) between January 1, 2004 and December 31, 2014. The primary outcome was the relative total dose intensity (RTDI), calculated for anthracyclines and taxanes separately. Secondary outcomes were the occurrence of febrile neutropenia, delay in chemotherapy administration, and switch to another chemotherapy regimen due to toxicity. In total, 701 patients treated for PBC/LR were eligible for data analyses, among which 85 BRCA1/2 mutation carriers (n = 67 BRCA1 and n = 18 BRCA2). The mean RTDI for anthracyclines was not significantly different between both groups (98.7 % in the BRCA1/2, 96.6 % in the sporadic group, p = 0.27). Also the mean RTDI for taxanes was not significantly different between the groups (93.6 % in the BRCA1/2-associated, 90.0 % in the sporadic group, p = 0.12). Linear regression analysis revealed no significant effect of BRCA1/2 mutation carriership on the RTDIs. No significant differences were found in the percentages of patients presenting with febrile neutropenia, having a delay in chemotherapy administration or switching to an altered chemotherapy regimen. Additionally, the odds ratios showed no significant effect of BRCA1/2 mutation carriership on the secondary outcome variables. (Neo)adjuvant chemotherapy-related toxicity was not different between BRCA1/2-associated and sporadic breast cancer patients suggesting that the DNA damage repair mechanism of non-cancer cells with only one normal copy of either the BRCA1 or BRCA2 gene is sufficiently functional to handle acute chemotherapy-associated toxicity

Curatieve resectie van solitaire claviculametastase

Achtergrond Het gemetastaseerd mammacarcinoom wordt beschouwd als niet-curabele ziekte waarbij patiënten alleen in aanmerking komen voor palliatieve systemische behandeling. Bij geselecteerde patiënten met beperkte metastasen wordt echter langdurige ziektevrije overleving beschreven na chirurgische resectie als onderdeel van de multidisciplinaire behandeling. Casus Een 49-jarige vrouw had pijn en een zwelling ter plaatse van haar linker sleutelbeen. Zij was 4 jaar eerder behandeld met mammasparende therapie en adjuvante systemische therapie voor een lobulair mammacarcinoom links (stadium pT1N0M0). Aanvullend beeldvormend onderzoek en histologisch onderzoek van een biopt resulteerden in de diagnose ‘solitaire claviculametastase’. Er werd besloten in opzet curatief te behandelen met inductiechemotherapie gevolgd door een mediale clavicularesectie en aanvullende radiotherapie, en een wijziging van de endocriene therapie. Conclusie Een solitaire claviculametastase van een mammacarcinoom is zeldzaam. Bij patiënten met een solitaire ossale metastase van een mammacarcinoom met gunstige prognostische factoren kan chirurgische resectie worden overwogen als onderdeel van een multidisciplinaire behandeling met curatieve intentie

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer

Purpose: For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. Methods: In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. Results: In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47–0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38–0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13–1.06), although this additional analysis was underpowered for definite conclusions. Conclusions: This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isol

Prognostic Impact of HER2 and ER Status of Circulating Tumor Cells in Metastatic Breast Cancer Patients with a HER2-Negative Primary Tumor

BACKGROUND: Preclinical and clinical studies have reported that human epidermal growth factor receptor 2 (HER2) overexpression yields resistance to endocrine therapies. Here the prevalence and prognostic impact of HER2-positive circulating tumor cells (CTCs) were investigated retrospectively in metastatic breast cancer (MBC) patients with a HER2-negative primary tumor receiving endocrine therapy. Additionally, the prevalence and prognostic significance of HER2-positive CTCs were explored in a chemotherapy cohort, as well as the prognostic impact of the estrogen receptor (ER) CTC status in both cohorts. METHODS: Included were MBC patients with a HER2-negative primary tumor, with ≥1 detectable CTC, starting a new line of treatment. CTCs were enumerated using the CellSearch system, characterized for HER2 with the CellSearch anti-HER2 phenotyping reagent, and characterized for ER mRNA expression. Primary end point was pr

Repeated nipple fluid aspiration

Background: Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method. Methods: In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation. Results: In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects. Conclusions: Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers

Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one’s status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995–2000 versus 2001–2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76 %) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34 %, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions