Noncompliance with palliative systemic therapy in patients with distant metastatic breast cancer: a blind spot for oncologists?

PURPOSE: The goal of our study was to provide a general overview of noncompliance with palliative systemic therapy in distant metastatic breast cancer (MBC). METHODS: We analyzed an unselected cohort of 339 patients who were diagnosed with MBC over a 22-year period (1990-2011, age restriction: ≥ 85 years old). RESULTS: Forty patients (11.8%) rejected the offered or recommended systemic therapy (age distribution of this noncompliance subgroup: ≤60 years at MBC diagnosis: 7.9%; 60-70 years: 13.2%; > 70 years: 15.6%). The rate of noncompliance was equally distributed over time (1990-1999: 12.2% vs. 2000-2011: 11.5%, p = 0.87). Compared to patients who had received palliative antineoplastic systemic therapy, those who remained untreated were significantly older (70 vs. 61 years, p = 0.015), had shorter metastatic disease survival (2 vs. 27 months, p < 0.001), had more often an aggressive tumor subtype (hormone-receptor negative carcinomas: 48.7% vs. 22.2%, p < 0.001), and had more often secondary MBC (95.0% vs. 73.6%, p = 0.001). CONCLUSIONS: Although the high rate of noncompliance in the subgroup of elderly patients was not unexpected, it is noticeable that even in the subgroup of patients who were younger than 60 years, approximately 8% also rejected any systemic therapy before a MBC-related death occurred This group of younger women rarely had any relevant comorbidities, were potential candidates for chemotherapy and knowingly declined the therapy options. Such patients are never or seldom seen by oncologists in their daily practice and therefore play a minor role in their personal perception of disease. Nevertheless, these under-reported cases make up a significant proportion of MBC.

Radiological Staging for Distant Metastases in Breast Cancer Patients with Confirmed Local and/or Locoregional Recurrence: How Useful are Current Guideline Recommendations?

BACKGROUND: Breast cancer patients with local and/or locoregional recurrence (LR) are at higher risk of developing distant metastases (DM) at a later time. Once LR has been confirmed, some international interdisciplinary guidelines recommend performing radiological examinations for DM to determine the course of further therapy (curative or palliative approach). This study analyzed the metastatic patterns of patients with LR with particular regard to the frequency of concurrent diagnosis of LR and DM; in other words: are radiological staging procedures actually justified for DM at the time of diagnosis of LR? METHODS: This study included all patients (n = 1368) who were diagnosed and treated for nonmetastatic breast cancer (Stage I-III) at the University Women's Hospital Basel, Switzerland between 1990 and 2009. RESULTS: In 137 patients, LR was diagnosed without a history of DM: in-breast/thoracic wall only, n = 90 (65.7%); involvement of axillary/supra-/infraclavicular lymph nodes, n = 47 (34.3%). DM was found at the time of diagnosis of LR in 44 patients (32.1%). Concurrent diagnosis of LR and DM occurred significantly more often in patients with lymph node recurrence compared with those with in-breast/chest wall recurrence (48.9% vs. 23.3%; p = 0.004). CONCLUSIONS: Approximately one-third of patients with a LR had synchronous DM at the time of their local/locoregional event. For this reason, routine systemic staging imaging at the time of LR should be an absolute requirement for planning further therapy. Confirmation of DM may spare the patients radical surgical interventions with questionable impact on survival in the face of an incurable disease.

Long-Term Survival and Cure in Distant Metastatic Breast Cancer.

BACKGROUND: Previous data showed that distant metastatic breast cancer (MBC) might be curable in up to 3% of the cases in selected patients, mostly young, with good performance status and with low-volume metastatic disease, mainly by an aggressive multidisciplinary approach including aggressive combination chemotherapy regimens. These long-lasting responses question the belief that MBC is wholly incurable. This study evaluates the rate of long-term survivors and potentially cured patients in an unselected cohort of MBC patients. METHODS: We analyzed the data from 342 patients in whom distant MBC was diagnosed from 1990 to 2011. For this study, we defined a metastatic disease survival (MDS) of 9 years as inclusion criterion for long-term survivorship. RESULTS: Eighteen patients (5.3%) were long-term survivors (MDS: 126 months; range, 108-300 months). The rate of long-term survivors was equally distributed over time (1990-1999: 4.3% vs. 2000-2011: 5.9%, p = 0.63). Compared to patients who had a lower MDS, long-term survivors had significantly more often primary MBC (p = 0.005) and hormone receptor-positive carcinomas (p = 0.015). Age at MBC diagnosis, presence of visceral metastases, and limited number of metastatic sites at the time of MBC diagnosis appeared to have no significant impact on long-term survival. Long-term survival was not associated with the use of chemotherapy (50.0% vs. 65.7% in the control group, p = 0.21). Eight patients (2.3%) developed a complete remission and presented with no evidence of disease at the time of last follow-up (MDS: 234.5 months). CONCLUSION: Since long-term survivors in MBC comprise a relatively heterogeneous group, the factors that lead to the quite rare and felicitous case of long-term survival or even cure can hardly be evaluated systematically. Some patients may be considered cured of their disease. This fraction may be small, but the chance of survival, and even of cure, truly exists. Perhaps we must accept that the factors contributing to long-term survival remain an enigma. It appears, however, that aggressive chemotherapy is not the only key factor to long-term remission.

Use of Palliative Endocrine Therapy in Patients with Hormone Receptor-Positive Distant Metastatic Breast Cancer: How Often, How Effective, How Long?

BACKGROUND: This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. METHODS: An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. RESULTS: In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. CONCLUSIONS: Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET.

Breast cancer screening attendance in two Swiss regions dominated by opportunistic or organized screening.

BACKGROUND: In Switzerland, the French-speaking region has an organized breast cancer (BC) screening program; in the German-speaking region, only opportunistic screening until recently had been offered. We evaluated factors associated with attendance to breast cancer screening in these two regions. METHODS: We analyzed the data of 50-69 year-old women (n = 2769) from the Swiss Health Survey 2012. Factors of interest included education level, place of residence, nationality, marital status, smoking history, alcohol consumption, physical activity, diet, self-perceived health, history of chronic diseases and mental distress, visits to medical doctors and cervical and colorectal cancer screening. Outcome measures were dichotomized into ≤2 years since most recent mammography versus >2 years or never. RESULTS: In the German- and French-speaking regions, mammography attendance within the last two years was 34.9 % and 77.8 %, respectively. In the French region, moderate alcohol consumption (adjusted OR 2.01, 95 % CI 1.28-3.15) increased screening attendance. Compared to those with no visit to a physician during the recent year, women in both regions with such visits attended statistically significantly more often BC screening (1-5 times vs. no visit: German (adjusted OR 3.96, 95 % CI 2.58-6.09); French: OR 7.25, 95 % CI 4.04-13.01). Non-attendance to cervical screening had a negative effect in both the German (adjusted OR 0.44, 95 % CI 0.25-0.79) and the French region (adjusted OR 0.57, 95 % CI 0.35-0.91). The same was true for colorectal cancer screening (German (adjusted OR 0.66, 95 % CI 0.52-0.84); French: OR 0.52, 95 % CI 0.33-0.83). No other factor was associated with BC screening and none of the tests of interaction comparing the two regions revealed statistically significant results. CONCLUSION: The effect of socio-demographic characteristics, lifestyle, health factors and screening behavior other than mammography on non-attendance to BC screening did not differ between the two regions with mainly opportunistic and organized screening, respectively, and did not explain the large differences in attendance between regions. Other potential explanations such as public promotion of attendance for BC screening, physicians' recommendations regarding mammography participation or women's beliefs should be further investigated.

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

Personal or first-degree family breast cancer history: which has higher impact on tumor detection and tumor size in breast cancer.

PURPOSE: A woman's risk of developing breast cancer (BC) is increased if she has a personal history (PH) or family history (FH) of the disease. We compared the impact of the two risk factors PH and FH on tumor detection and tumor size at diagnosis in a cohort of BC patients. METHODS: The study cohort comprised 1,037 invasive BC patients (≤70 years at diagnosis). From these, 92 patients (8.5%) had a positive PH and 151 patients (13.7%) had a positive first-degree FH. RESULTS: Compared to the tumors of patients without PH or FH, the lesions of patients who had a positive PH or a positive FH were more often found by radiologic breast examinations (RBE) (PH: 49.4%, FH: 43.4%, no PH/FH: 26.2%; both comparisons p < 0.001). In patients with a positive FH, the tumors were slightly less often found by RBE as in patients with a positive PH (p = 0.468). Patients with a positive PH or FH had smaller tumors compared with those without such a history (PH: 19.7 mm, FH: 19.6 mm, no PH/FH: 26.7 mm; p = 0.015/p < 0.001). The tumor sizes of patients with a positive PH were almost identical to those of patients with a positive FH (p = 0.999). CONCLUSIONS: In women with a positive FH or PH of BC, the increased awareness of BC risk led to the detection of smaller tumors compared to women who have not had this experience. However, comparison of the two risk factors showed that they had a similar impact on the RBE detection rate of BC lesions and that the tumor sizes were nearly identical.

Compliance and persistence of endocrine adjuvant breast cancer therapy.

This study evaluates compliance and persistence in adjuvant endocrine breast cancer (BC) therapy by clearly analyzing reasons of therapy cessation by differentiating clinical meaningful situations. In order to illuminate the complex field of personal motivation to therapy, a single institution study with a more individual-based approach might better be suited to provide a detailed case documentation than the more epidemiologic approach of large database studies. An unselected cohort of 698 patients (≤ 80 years) diagnosed with hormonal receptor-positive BC from 1997 to 2008 at the University Hospital Basel, Switzerland, was analyzed. The term "non-persistence" was exclusively used for patients where the discontinuation of endocrine therapy (ET) could have been modified by more intensive care and improved counseling (e.g., in women who lost faith/motivation to therapy or those who suffered from therapy-related side effects). These cases must be differentiated from cases where therapy cessation was inevitable (e.g., due to recurrent disease or severe intercurrent illness). Out of the 685 patients to whom ET was recommended, 42 patients (6.1%) refused and never began treatment (non-compliance). Women younger than 50 were more likely to be non-compliant (P < 0.001). 12.9% of the patients who started therapy were non-persistent to therapy. Patients who were treated by general practitioners tended to be non-persistent more often compared to those treated by oncologists (17.7% vs. 11.3%; P = 0.07). The aim of a non-persistence rate between 10 and 15% is realistic when patients are treated by specialized oncologists. Interventions are needed to support patients, particularly the younger ones, to comply with therapy. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in BC treatment, are provided with current knowledge as to guarantee an optimal patient management.

Eligibility, compliance and persistence of extended adjuvant endocrine therapy for breast cancer.

BACKGROUND: Extended therapy (ET) beyond the standard five years of tamoxifen-containing treatment is a widely discussed therapy option in adjuvant endocrine breast cancer (BC) therapy which might offer an opportunity for further protection against late relapses. In this study we evaluated eligibility, compliance and persistence of extended adjuvant endocrine BC therapy. PATIENTS AND METHODS: Data concerning all BC patients (≤75 years) who initiated endocrine adjuvant therapy between 1999 and 2005 (n = 286) was analyzed. RESULTS: One hundred and thirty-eight patients were valid candidates for an ET according current guidelines; this represents 48.3% of the individuals who started endocrine therapy five years ago. Of these, 89 (64.5%) received a corresponding offer/recommendation by their treating physicians. Advanced age (p = 0.002), favorable disease stage (p = 0.011), and follow-up at a general practitioner (p < 0.001) were significant factors where a recommendation for an ET was not made. Of the 89 patients who were offered an ET, 64 followed this proposal (compliance: 84.7%). Eighteen patients (28.1%) were non-persistent to the ET; therapy-related adverse effects were the main reason for discontinuation. Sixteen patients received an ET beyond current guidelines (tamoxifen or an aromatase inhibitor alone was given longer than five years); this represents 11.0% of all patients who completed five years of endocrine therapy. CONCLUSIONS: Only a minority of the patients who started an endocrine therapy were actually eligible for an ET. Patients who were offered/recommended an ET had a high rate of compliance and persistence. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in the treatment of BC patients, are provided with current therapy guidelines as to guarantee an optimal patient management.

Impact of overweight and obesity on postmenopausal breast cancer: analysis of 20-year data from Switzerland.

PURPOSE: Greater body fatness has been identified as a risk factor for postmenopausal breast cancer. For countries with low overweight/obesity rates, data on prevalence and time course of overweight/obesity in women with breast cancer in comparison to women in the general population is limited. The Swiss female population is distinctive for two reasons: (a) low rates of overweight/obesity compared with other western countries, and (b) no obesity epidemic, i.e. stable rates of overweight/obesity for more than 10 years. METHODS: Overweight and obesity were analyzed in 51 to 80-year-old breast cancer patients initially diagnosed between 1990 and 2009. Patient data was derived from the Basel Breast Cancer Database (BBCD). This data was compared with the data of women of the same age from the four Swiss Health Surveys (SHS) conducted between 1992 and 2007. Differences between measured (BBCD) and self-reported (SHS) data were corrected using equations approved for the Swiss population. RESULTS: Of 958 postmenopausal BBCD patients, 32% were overweight and 20% were obese. Of the 14,476 women of the SHS, 38% were overweight and 17% were obese. In the BBCD, there was no change in the prevalence of overweight/obesity over the last 20 years. The four SHS show a convex curvature for obesity, i.e. a transient increase. No significant differences were observed between BBCD and corrected SHS data for overweight and obesity during this period. CONCLUSIONS: In this Swiss study group with a comparably low prevalence of overweight and obesity, no association between body fatness and postmenopausal breast cancer was observed.

Young women with breast cancer: how many are actually candidates for fertility preservation?

PURPOSE: There are no data regarding the actual need for fertility preservation (FP) in breast cancer (BC) patients. Our study provides a practical needs assessment for reproductive medicine by analyzing an unselected cohort of young BC patients. This assessment considers oncological factors as well as the patient's obstetrical and gynecological history and reproductive outcome after BC diagnosis. We aimed to identify how many patients are actually potential candidates for FP and how many patients might consequently use their cryopreserved gametes to achieve pregnancy. METHODS: Based on a prospective BC database, we analyzed all patients who were ≤40 years at initial diagnosis (time period of diagnosis: 1990-2007; n=100; 7.7% of the entire BC cohort; median age: 35.9 years). RESULTS: Using an algorithm of exclusion criteria considering disease-specific, therapy-specific and family history characteristics, 36 patients who received chemotherapy were identified as potential "classical" candidates for FP. After 5 years, 22 women were identified as potential candidates for using their cryopreserved gametes to achieve pregnancy; the majority of these patients were childless (n=16, 72.7%) and in their late reproductive years (n=12, 54.5%). CONCLUSIONS: Our study demonstrates that in a cohort of young BC patients only a minority of women are candidates for FP. Young BC patients who wish to have children in the future usually carry risk factors both from oncological and reproductive medicine perspective. Due to this high-risk profile, the rarity of BC in young age and the limited number of patients who might actually have opted for FP, these women must be offered timely and multidisciplinary counseling in highly specialized centers.

Drug switch because of treatment-related adverse side effects in endocrine adjuvant breast cancer therapy: how often and how often does it work?

Therapy-related adverse side effects are a main reason for non-persistence to adjuvant endocrine breast cancer therapy. This study reports frequency of drug-related adverse side effects that were so severe that a modification of the therapy was necessary. We evaluated how many patients discontinued adjuvant endocrine therapy because of these side effects (non-persistence). Last, we analyzed how often a drug switch was undertaken for this reason and how often this measure led to the patient successfully continuing their endocrine therapy. Data concerning all postmenopausal breast cancer patients (≤ 80 years), who initiated endocrine adjuvant therapy between 1998 and 2008 in a Swiss breast center (n = 400), were analyzed. Out of these 400 women, 37 (9.3%) were defined as being non-persistent to the therapy; out of these, 24 (64.9%) because of therapy-related side effects. About 78 patients (19.5%) suffered from severe therapy-related side effects that made a modification of therapy necessary. Out of these 78 cases, 14 patients (17.9%) stopped the therapy without attempting a drug switch (non-persistence). In 64 patients (82.1%; 16% of all women who started endocrine therapy), a drug switch was undertaken. Out of these 64 cases, in 52 cases (81.3%) endocrine therapy was completed after therapy modification. Patients who reported one major adverse effect were more likely to continue the endocrine therapy after a drug switch (P = 0.048) compared with those who suffered from at least two different side effects. In 10 of the 64 cases (15.6%), modification of the therapy was not successful and the patients stopped the treatment prematurely (non-persistence) because of ongoing side effects. In cases when therapy-related side effects occur, a drug switch is a promising step to further improve persistence and, by doing so, the outcome of breast cancer patients.

Success and failure of primary medical, nonoperative management in breast cancer.

BACKGROUND: Nonoperative but systemic therapy as first-line management is offered to some patients with breast cancer (BC) who have assumed limited life expectancy, such as older women or those who have distant metastases at initial presentation. We evaluated rates of and predicting factors for success and failure of this therapy approach. METHODS: Seventy-five patients who were initially treated only systemically, and cases in which local control while avoiding surgery was the intended long-term therapy goal were analyzed. Additionally, two stage-dependent subgroups were distinguished (A: stage I-III, n = 31; B: stage IV, n = 44). Failure of therapy was defined as when secondary surgery had to be performed due to locoregional progression or in case of no surgery when severe locoregional clinical signs/symptoms were observed during the further course. RESULTS: Patients in group A were older than those in group B (81 vs. 67.5 years; P < 0.001) and showed an increased survival (5-year rates: 40.2% vs. 24.3%). In 24 patients of the entire cohort (32%), secondary surgery had to be performed; surgery was performed more often in group A (58.1% vs. 13.6%). In the cases in which no surgery was performed (n = 51), 11 women (21.6%) suffered from severe locoregional symptoms in the palliative situation (A: n = 1; B: n = 10). Although the presence of stage IV was a significant factor for therapy success (odds ratio (OR), 2.59; 95% confidence interval (CI), 0.95-7.05; P = 0.039), skin involvement was associated with failure of therapy (OR, 3.57; 95% CI, 1.16-11.11; P = 0.031). CONCLUSIONS: Nonoperative treatment may be offered to selected patients with BC who have assumed limited life expectancy. These women must be openly informed that this approach is not successful in nearly half of the cases.

Eligibility, compliance and persistence of sequential therapy with aromatase inhibitors following 2-3 years of tamoxifen in endocrine adjuvant breast cancer therapy.

OBJECTIVE: This study evaluated the eligibility, compliance and persistence of sequential therapy, i.e. a switch to an aromatase inhibitor (AI) following 2-3 years of tamoxifen, in adjuvant endocrine breast cancer (BC) treatment. METHODS: Data concerning 388 BC patients (age ≤70 years) who started endocrine adjuvant therapy between 1998 and 2008 were analyzed. RESULTS: From the 263 patients who started therapy with tamoxifen, 167 (63.5%) were eligible for a sequential therapy. Fifty-nine patients (35.3%) were offered a switch by their physicians; women who had their follow-up at oncological units received the offer more often when compared to those treated by general practitioners (p < 0.001). Out of these 59 patients, 50 followed the proposal (compliance 84.7%). Of those who agreed to a sequential therapy, 2 (4%) were non-persistent to endocrine therapy; in 9 cases (18.0%), a re-switch to tamoxifen was done due to AI-related adverse side effects. CONCLUSIONS: Only a minority of the patients who started an endocrine adjuvant BC therapy was eligible for sequential therapy. Patients who underwent a switch had a high rate of persistence. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in the treatment of BC patients, are provided with current therapy guidelines.

Suicide in breast cancer patients: an individual-centered approach provides insight beyond epidemiology.

BACKGROUND: Epidemiologic studies have identified increased suicide rates among breast cancer (BC) patients. The population-based approach, however, has considerable methodic shortcomings. None of the studies have been carried out in a prospective manner and none reported suicide rates from a country in which physician-assisted suicide (PAS) is legal. PATIENTS AND METHODS: All cases recorded by a prospective Swiss BC database during a 17-year period (1990-2006; n = 1165) were analyzed. Using an individual-centered approach, the cases of women who committed suicide are reported according to the psychological autopsy method. RESULTS: In six patients (0.5%; 5.1/1.000 patients), suicidal death was identified. In four patients, suicide was committed during late stages of metastatic BC. In two cases, comorbid conditions were associated with suicide. Three women chose PAS. CONCLUSION: The individual-centered approach is a well-suited innovative concept to increase the knowledge regarding the relationship between cancer and suicide. We found a two to seven times higher suicide rate than those reported in epidemiologic studies. The population-based approach can barely elucidate the immense variety of one of the most personal decisions: the act of intentionally ending one's own life. These studies suffer from systematic failure of analysis since they did not a) consider the potential confounding role of comorbid medical and/or psychiatric conditions, and b) report in which disease stage suicide was committed, since the decisive disease-related event whether and when metastatic disease occurred was not recorded. Furthermore, epidemiologic data stems from countries in which PAS is prohibited and therefore not included in official statistics. This grey area of medicine accounts for a greater scope of underreporting than had previously been assumed.

Wnt and hedgehog gene pathway expression in serous ovarian cancer.

OBJECTIVE: Ovarian cancer has very heterogeneous histological classification, and response to therapy of the same grade and type varies. We studied genes in the Wnt and hedgehog (Hh) pathways, which are essential for embryonic development and which play critical roles in proliferation in a variety of human cancers. Variations in these pathway genes causing proliferation could play a role in the variation in tumor progression and response to therapy. METHODS/MATERIALS: Using real-time polymerase chain reaction, we studied 16 primary grade 3 International Federation of Gynecology and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched homolog 1, patched homolog 2, Indian Hedgehog (HH), sonic HH, and Smoothened, a G protein-coupled receptor protein. Normal ovary epithelial cell line was used as control. RESULTS: We found wide variation of up-regulation of pathway component and target genes in the primary tumor samples and apparent cross talk between the pathways. AXIN2, a Wnt target gene, showed increased expression in all serous ovarian cancer samples. Fibroblast growth factor 9 was also overexpressed in all tumors with greater than 1000-fold increase in gene expression in 4 tumors. Expression of Hh pathway genes varied greatly. More than half of the tumor samples showed involvement of Hh signaling or pathway activation either by expression of transcription factors and Hh ligands or by overexpression of Indian HH/sonic HH and the receptor-encoding patched homolog 1/patched homolog 2. CONCLUSION: We found a wide variation in fold expression of genes involved in the Wnt and Hh pathway between patient samples.

Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy.

INTRODUCTION: In the western world, cannabis is the most widely used drug of abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical reaction in individuals with a particular predisposition, is characterized by cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms are unresponsive to antiemetic drugs, compulsive hot baths result in a considerable symptom relief. METHODS: We report the first case of cannabinoid hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our clinic in the 10th week of gestation. CONCLUSION: Before undertaking time-consuming and expensive medical examinations to rule out other medical reasons for therapy-resistant hyperemesis in pregnancy, obstetricians should determine whether compulsive bathing or showering provides symptomatic relief and ask specific questions regarding possible/suspected cannabis consumption.

[An Unusual Reason for Nocturia Combined with Cognitive Decline and Gait Disturbance]. / Nicht alltägliche Ursache der Nykturie bei demenzieller Entwicklung und Gangunsicherheit.

An Unusual Reason for Nocturia Combined with Cognitive Decline and Gait Disturbance Abstract. We present the case of a woman with frequency, nocturia, and painful bladder without urinary incontinence. Further examination showed cognitive decline and gait disturbance. A magnetic resonance imaging of the neurocranium showed normal pressure hydrocephalus. After lumbar puncture with cerebrospinal fluid evacuation the symptoms improved. The clinical triad of gait disturbance, cognitive decline and urinary symptoms like frequency with or without incontinence is typical for normal pressure hydrocephalus (Hakim-Adams triad).

Metastatic Breast Cancer as a Chronic Disease: Evidence-Based Data on a Theoretical Concept.

BACKGROUND: We challenge the concept of metastatic breast cancer (MBC) as a chronic disease. METHODS: We analyzed an unselected cohort of 367 patients who were diagnosed with MBC over a 22-year period (1990-2011). RESULTS: In order to create a "chronic disease subgroup", we separated those patients from the entire cohort in whom systemic therapy was not applied after the diagnosis of MBC (n = 53; 14.4%). Three hundred fourteen patients (85.6%) comprised the "chronic disease subgroup". The vast majority of those patients (89.8%) died of progressive disease after a median metastatic disease survival (MDS) of 25 months. Twenty patients (6.4%) died of non-MBC-related causes (MDS 38.5 months). Approximately 1 in 4 patients (26.8%) died within the first year after the MBC diagnosis. The 3- and 5-year MDS rates were 35.4 and 16.2%, respectively. Only 12 patients (3.8%) were exceptional survivors (MDS >10 years). CONCLUSION: The term "chronic disease" might be appropriate in selected MBC cases, bringing MBC into alignment with "classical" chronic diseases such as diabetes and hypertension. However, most cases display fundamental differences with regard to temporal progression and above all the case fatality rate. More than 90% of patients in the "chronic disease subgroup" died of the disease with a MDS of 2-3 years (even those who underwent systemic palliative therapies). Doctors and patients might understand the term "chronic disease" differently. The term must be used sparingly and explained carefully in order to create a common level of communication based on a shared understanding which avoids awakening false hopes and fostering misleading expectations.

Adjuvant radiation therapy in stage III node-positive uterine cancer.

OBJECTIVES: To determine the association of adjuvant radiotherapy and outcomes of women with stage III node-positive uterine cancer. METHODS: All patients with surgically-staged stage III node-positive uterine cancer from the Surveillance Epidemiology and End Results database of the US National Cancer Institute from 1988 to 2001 were identified. Data were analyzed using Kaplan-Meier and logistic regression methods. RESULTS: Of 943 women, the median age was 64 years (range: 28-93). 82.1%, 8.6%, and 6.8% were White, Black, and Asian respectively. The median number of removed nodes was 11. 54.9% had a single positive node and 45.1% had 2-5 positive nodes. Endometrioid, papillary serous, sarcomas, and clear cell carcinomas comprised of 69.7%, 16.3%, 9.9%, and 4.1% of histologies, respectively. 67.3% of the women underwent adjuvant radiotherapy with a 5-year disease-specific survival of 67.9% compared to 53.4% in those without radiotherapy (p<0.001). Adjuvant radiotherapy improved the survival from 54.4% to 74.3% (p<0.001) in those with a single positive node and from 52.4% to 59.7% (p=0.089) in those with 2-5 positive nodes. On multivariate analysis, older age, non-endometrioid histology, and lack of adjuvant radiotherapy remained as significant independent prognostic factors for worsened survival. CONCLUSIONS: Our data suggest that adjuvant radiotherapy is associated with a significant survival benefit in women with single-positive node endometrioid uterine cancers. Prospective clinical trials are warranted to confirm these findings.