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.

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.

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.

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.

A rare case of Merkel cell carcinoma with ovarian metastasis.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that normally occurs in sun-exposed areas of the skin. Risk factors are immundeficency and Merkel cell polyomavirus.Treatment options are surgery, radiotherapy, chemotherapy and immunotherapy in clinical trials. CASE REPORT: We describe a case of an 80-year-old woman with ovarian metastasis of MCC six years after excision of a cutaneous MCC on the cheek. DISCUSSION: To our knowledge only three cases with ovarian metastasis of MCC have been described so far. Our case is the second with distant metastasis to the ovary spreading from a primary tumor in the skin of the head, in the other two cases the primary tumor was in the inguinal skin. CONCULSION: MCC is a highly aggressive cutaneous and mucosal malignancy with frequent recurrence, lymph node and distant metastases. There is no clear consensus how to treat metastatic disease.

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.

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.

Overweight, obesity, and breast cancer screening: results from the 2012 Swiss Health Survey.

Obesity is associated with poor breast cancer (BC) prognosis. Larger tumor size and more advanced disease stage at diagnosis could partly explain this outcome and nonadherence of obese women to BC screening may play a role. We examined the relationship between BMI (kg/m) and the use of mammography in Switzerland as well as separately in the German-speaking part with mainly opportunistic screening and in the French-speaking part with organized programs. We analyzed the data of 50-69-year-old women (n=3121) of the Swiss Health Survey 2012. Study participants were classified as underweight (BMI<18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25-29), or obese (BMI≥30). Outcome measures were dichotomized into 2 years or less since most recent mammography versus more than 2 years or never. We carried out multivariable logistic regression analyses, adjusting for sociodemographics, lifestyle, and self-perceived health. In Switzerland, 47% of women aged 50-69 years had had BC screening within the last 2 years, 35% of women in the German-speaking and 78% of women in the French-speaking part. In the total group, mammography use was higher in overweight than in normal-weight women (adjusted odds ratio 1.21, 95% confidence interval 0.98-1.49). Stratified by region, this effect was only maintained in women of the German-speaking part (adjusted odds ratio 1.41, 95% confidence interval 1.08-1.85; P-interaction<0.001). There were no differences in mammography attendance between normal-weight and obese and underweight women. In the 2012 Swiss Health Survey, overweight, obesity, and underweight were no barriers to mammography. In the German-speaking part, overweight women even attended mammography screening more often than normal-weight women.

Lifestyle and health-related predictors of cervical cancer screening attendance in a Swiss population-based study.

BACKGROUND: Since the implementation of cervical cancer (CC) screening, incidence and mortality rates have decreased worldwide. Little is known about lifestyle and health-related predictors of cervical cancer screening attendance in Switzerland. Our aim was to examine the relationship between lifestyle and health-related factors and the attendance to CC screening in Switzerland. METHODS: We analyzed data of 20-69 years old women (n=7319) of the Swiss Health Survey (SHS) 2012. Lifestyle factors included body mass index, smoking status, alcohol consumption, physical activity and attention to diet. Health-related factors of interest were diabetes, hypertension, high cholesterol levels, chronic diseases, self-perceived health, and psychological distress. We performed multivariable logistic regression analyses with the dichotomized CC screening status as outcome measure and adjusted for demographic factors. RESULTS: Obesity, low physical activity, and not paying attention to diet were statistically significantly associated with lower CC screening participation. High cholesterol levels and history of chronic diseases were statistically significantly positively associated with screening participation. CONCLUSION: Being obese, physically inactive and non-attention to diet are risk factors for CC screening attendance. These findings are of importance for improving the CC screening practices of low-user groups.

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.

Self-detection and clinical breast examination: comparison of the two "classical" physical examination methods for the diagnosis of breast cancer.

UNLABELLED: This is the first comprehensive analysis comparing specific aspects of tumor detection between the two "traditional" breast cancer detection methods self-detection (SD) and clinical breast examination (CBE). a) Which method is better in detecting smaller tumors? Both methods showed similar mean tumor diameters (SD: 22.1 mm vs. CBE: 21.9 mm; p = 0.991). b) Different frequency distributions of tumor locations would indicate that certain locations in the breast are more difficult to palpate: comparison of both methods showed comparable results (p = 0.835). c) General differences in tumor sizes with regard to certain locations would be of importance because the patients and/or the physicians could be educated to pay particular attention to certain locations during physical examination, where larger tumors tend to be found: tumors located in the central region were with 25.0 mm significantly larger than those in the peripheral regions of the breast (superior: 21.6 mm, p = 0.001; inferior: 21.6 mm, p = 0.015; lateral: 21.9 mm, p = 0.002; medial (20.9 mm, p = 0.001). Tumor sizes within the four peripheral regions did not differ significantly. d) Patients whose tumors were found by CBE were older than those whose tumors were found by SD (67 years vs. 60 years, p < 0.001). CONCLUSION: annual CBE should be an integral part of general medical care in older women.

The impact of overweight and obesity on breast cancer: data from Switzerland, so far a country little affected by the current global obesity epidemic.

This review presents results from the project "The Impact of Overweight/Obesity on Breast Cancer: data from Switzerland". Swiss data is interesting because the general female population is distinctive in two areas when compared to that of most other industrialized countries: Switzerland has comparatively low rates of overweight (22-23%) and obesity (7-8%) and has rather stable rates of overweight and obesity. The entire project comprised three major issues: (I) etiology of breast cancer (BC). There is a consistently shown association between obesity and postmenopausal BC risk in countries with high obesity prevalence rates in the literature. In our Swiss study group, however, we did not find higher rates of overweight and obesity in postmenopausal BC cases than in the general population. A possible explanation for this observation may be a curvilinear dose-response relationship between BMI and postmenopausal BC risk, so that an increased risk may only be observed in populations with a high prevalence of obese/very obese women; (II) tumor characteristics. BMI was significantly associated with tumor size; this applied not only to the cases where the tumor was found by self-detection, but also to lesions detected by radiological breast examinations. In addition, a higher BMI was positively correlated with advanced TNM stage, unfavorable grading and a higher St. Gallen risk score. No associations were observed between BMI and histological subtype, estrogen receptor status, HER2 status and triple negative BC; (III) patient compliance and persistence towards adjuvant BC therapy. Many studies found that the prognosis of overweight/obese BC patients was significantly lower than that of normal weight patients. However, failure of compliance and persistence towards therapy on the part of the patient is not a contributing factor for this observed unfavorable prognosis. In most therapy modes, patients with increasing BMI demonstrated greater motivation and perseverance towards the recommended treatment.

Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer.

This study evaluated the impact of family history (FH) on tumor detection, the patient's age and tumor size at diagnosis in breast cancer (BC). Furthermore, we investigated whether the impact of FH on these features was dependent on degree of relationship, number of relatives with a BC history, or the age of the affected relative at the time that her BC was diagnosed. Out of the entire cohort (n = 1,037), 244 patients (23.5%) had a positive FH; 159 (15.3%) had first-degree relatives affected with BC and 85 patients (8.2%) had second-degree affected relatives. Compared to women who had no BC-affected relatives, the tumors of women who had positive FH were more often found by radiological breast examination (RBE: 31.7%/27.2%, p = 0.008), and they were smaller (general tumor size: 21.8 mm/26.4 mm, p = 0.003; size of tumors found by breast self-examination (BSE): 26.1 mm/30.6 mm, p = 0.041). However, this positive effect of increased use of BC screening and smaller tumor sizes was only observed in patients whose first-degree relatives were affected (comparison with second-degree affected relatives: RBE: 43.8%/24.7%; odds ratio 2.38, p = 0.007; general tumor size: 19.3 mm/26.3 mm; mean difference (MD) -6.9, p = 0.025; tumor size found by BSE: 22.5 mm/31.0 mm; MD -8.5, p = 0.044). When more second-degree relatives or older relatives were diagnosed with BC, the tumors of these patients were similarly often detected by RBE (relationship: 24.7%/27.2%, p = 0.641; age: 33.7 %/27.2 %, p = 0.177) and had similar tumor sizes (general size: 26.3 mm/26.4 mm, p = 0.960; BSE: 31.0 mm/30.6 mm, p = 0.902) as those of women without a FH. Women with a positive FH generally use mammography screening more often and perceive changes in the breast earlier than women without such history. The increased awareness of BC risk decreases if the relationship is more distant.

[Development of overweight and obesity in breast cancer patients and its significance for diagnosis and clinical management: results of the Basel Breast Cancer Database 1990-2009]. / Entwicklung von Übergewicht und Adipositas beim Mammakarzinom und ihre Bedeutung für Diagnose und klinisches Management: Resultate der Basler Mammakarzinom-Datenbank 1990-2009.

Greater body fatness was found to be a risk factor for postmenopausal breast cancer (BC); furthermore this factor appears to be associated with poor prognosis. These findings were tested by analyzing 1459 patients whose cases were recorded in the Basler Mammakarzinom-Datenbank (1990-2009) and the Swiss Health Surveys (1992-2007). Considering only postmenopausal women, no association between a rising body mass index (BMI) and BC development was observed. BMI was found to be a significant factor for tumor size (this applied to self-detected tumors and for lesions detected by radiological examinations) and had a positive correlation to advanced disease stage, unfavorable grading and a higher St. Galler risk score. In most therapy modes, patients with increasing BMI demonstrated a higher compliance and persistence to adjuvant therapies.

Impact of body mass index on prognostically relevant breast cancer tumor characteristics.

BACKGROUND: This study analyzes the association of body mass index (BMI) and prognostically relevant breast cancer (BC) characteristics in a country that has been rather spared of the global obesity epidemic. PATIENTS AND METHODS: Based on 20-year data (1999-2009, n = 1,414) of the prospective relational BC database of the University Hospital Basel, Switzerland, the associations between BMI, tumor size and stage, histological subtype, grading, hormonal receptor status, HER2 status and 'triple-negative' status were evaluated. Multivariate analysis considered BMI and patient's age. RESULTS: The association between increasing BMI and the above-mentioned variables were as follows (results described in each case: Beta-coefficient or odds ratio, 95% confidence interval, p value): tumor size, (1) entire cohort: 0.03 (0.01-0.05), p < 0.001, (2) tumor found by self-palpation: 0.05 (0.03-0.07), p < 0.001, (3) tumor found by radiological examination: 0.03 (0-0.07), p = 0.044; advanced TNM stage: 1.16 (1.02-1.31), p = 0.022; histological subtype: 1.04 (0.89-1.22), p = 0.602; unfavorable grading: 1.11 (1.00-1.25), p = 0.057; positive estrogen receptor status: 0.95 (0.83-1.09), p = 0.459; positive HER2 status: 0.92 (0.74-1.15), p = 0.467; presence of a 'triple-negative' carcinoma: 1.19 (0.93-1.52), p = 0.165. Consideration of only postmenopausal BC patients (n = 1,063) did attenuate the results, but did not change the direction of the associations with BMI. CONCLUSION: BMI was positively associated with TNM stage, grading and tumor size for tumors that were found by self-detection, as well as for those lesions detected by radiological breast examinations.

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.

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.

Impact of body mass index on compliance and persistence to adjuvant breast cancer therapy.

Several authors found that the prognosis of overweight and obese breast cancer (BC) patients was lower than that of normal weight patients. We present the first study which evaluates the impact of body mass index (BMI) on compliance (i.e. to start a recommended therapy) and persistence to adjuvant BC therapy. An unselected cohort of 766 patients (≤75 years) diagnosed from 1997 to 2009 was analyzed in relevance to the four adjuvant therapy modalities: (A) radiation, (B) chemotherapy, (C) therapy with trastuzumab, and (D) endocrine therapy. With respect to compliance, multivariate analyses calculated Odds ratios (ORs) >1 for increased BMI in all four therapy modalities, i.e. increased BMI had a positive influence on compliance. The results were significant for radiotherapy (OR,2.37;95%CI,1.45-3.88;p < 0.001) and endocrine therapy (OR,1.92;95%CI,1.21-3.04;p = 0.002) and showed a trend in chemotherapy (OR,1.42;95%CI,0.97-2.08;p = 0.063). Analyzing persistence, increasing BMI had ORs <1 for chemotherapy and therapy with trastuzumab, both not reaching statistical significance. For endocrine therapy, increasing BMI was a significant predictor for persistence (OR,1.35;95%CI,1.08-1.80;p = 0.042). Failure of compliance and persistence to adjuvant therapy does not pose a contributing factor for the observed unfavorable prognosis in overweight/obese BC patients. In most therapy modes, patients with increasing BMI demonstrated a higher motivation and perseverance to the recommended treatment.

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.

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.