Abstract Backgound: Obesity and related metabolic imbalances, including increased activity of free fatty acids, may promote tumor growth and metastasis. Fatty acids are mainly stored as triacylglycerols. Yet, the role of serum-triglycerides on breast cancer prognosis is still undefined. Methods: A population based survival study among 575 breast cancer patients identified within the Tromsø study during 1979-2008, was conducted. Pre-diagnostic serum triglycerides, high density lipoprotein-cholesterol, total cholesterol, height and weight were measured. Histopathological and clinical data were obtained from medical records, and hormone receptor, HER2 status, and Ki-67 were re-analyzed on tissue microarray blocks. Multivariate Cox proportional Hazard regression models were used to study the associations between patient characteristics including s-triglycerides, and breast cancer survival. Results: Among 575 women with invasive breast cancer (stage 1-3), a total of 87 women were diagnosed with triple negative breast cancer (TNBC). Patients diagnosed with TNBC, compared to non-TNBC, were likely to be younger at diagnosis (55.3 vs 57.9 years, p=0.061), they had larger tumors (29.7 mm vs 22.5 mm, p=0.001), and higher Ki-67 (31.1% vs 15.9%, p<0.001). After a mean follow-up of 8.4 years, TNBC patients with above median levels of s-triglycerides (> 0.98mmol/L) compared to TNBC patients with below median levels of s-triglycerides (≤ 0.98mmol/L) had 3.0 times higher risk for breast cancer recurrence or breast cancer specific death (HR 3.02, 95% CI 1.21-7.55), and 3.4 times higher overall mortality risk (HR 3.41, 95% CI 1.38-8.45). Among the TNBC patients, women with above median s-triglycerides had 15% lower 5-year disease-free survival (76% vs 91%) and 18% lower 5-year overall survival (74% vs 92%) compared to women with below median s-triglycerides. Conclusions: Our results strongly support s-triglycerides as an important biomarker for breast cancer outcomes among triple negative breast cancer patients. Table 1: Multivariable adjusted Hazard Ratios (HRs) for incidence breast cancer recurrence or breast cancer specific death, and incidence overall mortality by pre-diagnostic serum-triglycerides among non-triple negative breast cancer (TNBC) and TNBC patients Non-TNBC, n=488 TNBC, n=87 Recurrence or breast cancer specific death (n=90)Overall mortality (n=104) Recurrence or breast cancer specific death (n=24)Overall mortality (n=33) nHR (95% CI)HR (95% CI)nHR (95% CI)HR (95% CI)s-Triglycerides Median ≤ 0.98 mmol/l2571.001.00431.001.00> 0.98 mmol/l2310.87 (0.56-1.35)1.06 (0.70-1.62)443.02 (1.21-7.55)3.41 (1.38-8.45) Tertiles ≤ 0.82 mmol/l1731.001.00261.001.000.83 – 1.22 mmol/l1660.74 (0.44-1.23)0.81 (0.49-1.36)311.37 (0.38-4.98)0.98 (0.31-3.08)≥ 1.23 mmol/l1490.88 (0.50-1.54)1.17 (0.66-1.96)306.63 (1.64-19.3)3.87 (1.52-12.0)p-trend 0.4950.357 0.0050.007 Multivariate Cox proportional Hazard regression model. Adjusted for BMI and age at attendance (continuous), age at diagnosis (continuous), breast cancer stage at diagnosis (categorical), and current smoking (categorical). Abbreviation: CI, confidence interval; n, number of cases; TNBC, triple negative breast cancer Citation Format: Lofterød T, Mortensen ES, Nalwoga H, Wilsgaard T, Frydenberg H, Risberg T, Eggen AE, McTiernan A, Aziz S, Wist EA, Reitan JB, Akslen LA, Thune I. Serum-triglycerides among triple negative breast cancer patients as a biomarker of poor outcome [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-02.

Background: Obesity is both an independent risk factor, and a prognostic factor of postmenopausal breast cancer. In contrast, the association between premenopausal obesity/leanness, and subsequent weight gain and breast cancer outcomes, is still unclear. Furthermore, the association between adult weight gain, weight and age at diagnosis, and tumor characteristics is less studied. Methods: During 1979-2007, a total of 18 990 women, aged 18-87 years, answered questionnaires and underwent clinical examination at a total of five repeated health surveys (attendance rate 68-82%). Height and weight were measured at each survey, and before surgery, among those women diagnosed with breast cancer during follow-up. Careful review of the respective medical records, including histopathological workup, was performed. Multivariate Cox Proportional Hazard models were used to study the importance of Body Mass Index (BMI kg/m 2 ) and weight change on breast cancer risk, and to evaluate variation in breast tumor characteristics. Results: During a median follow-up of 23.3 years, 579 women with invasive breast cancer were identified, and the cases were histologically verified. These breast cancer cases had a mean age at diagnosis of 56.3 years, and mean BMI at diagnosis of 25.3 kg/m 2 . Most (67 %) of the breast cancer patients had estrogen receptor (ER) positive tumors, 48 % had progesterone receptor (PgR) positive tumors, and 41 % had lymph node positive disease. We divided all participating women in three groups of weight change ( 15 kg). When we compared women with less than 5 kg weight gain, to women with weight gain 5-15 kg, and to women with weight gain above u003e15kg, we observed a RR of 1.43 (95% CI 1.07-1.90) and a RR of 1.86 (95% CI 1.30-2.68), respectively, for postmenopausal breast cancer. We divided women by quartiles of BMI (kg/m 2 ) at entry, and observed that women in the lowest quartile of BMI (≤ 21.45 kg/m 2 ), who had a subsequent weight gain u003e15 kg, had a RR of 2.40 (95% CI 1.07-5.38) for postmenopausal breast cancer compared to women with the same BMI at entry, but who remained stabile in weight. We observed a 6 year difference in age at diagnosis for women diagnosed with breast cancer, who at study entry were in the same BMI group ( 2 ), but subsequently either experienced a large weight gain (u003e15 kg), or remained stabile in weight (59.5 years vs. 64.4 years, p=0.007). Furthermore, we observed a 15 year difference in age at diagnosis for women diagnosed with breast cancer, who at study entry were in the same BMI group (≥ 25kg m 2 ), but subsequently either experienced a large weight gain (u003e 15 kg), or remained stabile in weight (60.3 years vs. 74.9 years, p=0.007). Conclusion: Avoiding large weight gain during pre- and postmenopausal years may both protect against, and delay onset of postmenopausal breast cancer. Our findings support the importance of weight gain as a modifiable lifestyle factor for early onset of breast cancer. Citation Format: Lofterod T, Frydenberg H, Flote VG, Risberg T, Eggen AE, McTiernan A, Mortensen E, Wist EA, Akslen LA, Reitan JB, Wilsgaard T, Thune I. Weight gain during pre- and postmenopausal years results in earlier onset of breast cancer. The Tromso cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-06.

Abstract Background: Obesity is both an independent risk factor, and a prognostic factor of postmenopausal breast cancer. In contrast, the association between premenopausal obesity/leanness, and subsequent weight gain and breast cancer outcomes, is still unclear. Furthermore, the association between adult weight gain, weight and age at diagnosis, and tumor characteristics is less studied. Methods: During 1979-2007, a total of 18 990 women, aged 18-87 years, answered questionnaires and underwent clinical examination at a total of five repeated health surveys (attendance rate 68-82%). Height and weight were measured at each survey, and before surgery, among those women diagnosed with breast cancer during follow-up. Careful review of the respective medical records, including histopathological workup, was performed. Multivariate Cox Proportional Hazard models were used to study the importance of Body Mass Index (BMI kg/m2) and weight change on breast cancer risk, and to evaluate variation in breast tumor characteristics. Results: During a median follow-up of 23.3 years, 579 women with invasive breast cancer were identified, and the cases were histologically verified. These breast cancer cases had a mean age at diagnosis of 56.3 years, and mean BMI at diagnosis of 25.3 kg/m2. Most (67 %) of the breast cancer patients had estrogen receptor (ER) positive tumors, 48 % had progesterone receptor (PgR) positive tumors, and 41 % had lymph node positive disease. We divided all participating women in three groups of weight change (< 5kg, 5-15 kg, >15 kg). When we compared women with less than 5 kg weight gain, to women with weight gain 5-15 kg, and to women with weight gain above >15kg, we observed a RR of 1.43 (95% CI 1.07-1.90) and a RR of 1.86 (95% CI 1.30-2.68), respectively, for postmenopausal breast cancer. We divided women by quartiles of BMI (kg/m2) at entry, and observed that women in the lowest quartile of BMI (≤ 21.45 kg/m2), who had a subsequent weight gain >15 kg, had a RR of 2.40 (95% CI 1.07-5.38) for postmenopausal breast cancer compared to women with the same BMI at entry, but who remained stabile in weight. We observed a 6 year difference in age at diagnosis for women diagnosed with breast cancer, who at study entry were in the same BMI group (< 25kg/m2), but subsequently either experienced a large weight gain (>15 kg), or remained stabile in weight (59.5 years vs. 64.4 years, p=0.007). Furthermore, we observed a 15 year difference in age at diagnosis for women diagnosed with breast cancer, who at study entry were in the same BMI group (≥ 25kg m2), but subsequently either experienced a large weight gain (> 15 kg), or remained stabile in weight (60.3 years vs. 74.9 years, p=0.007). Conclusion: Avoiding large weight gain during pre- and postmenopausal years may both protect against, and delay onset of postmenopausal breast cancer. Our findings support the importance of weight gain as a modifiable lifestyle factor for early onset of breast cancer. Citation Format: Lofterød T, Frydenberg H, Flote VG, Risberg T, Eggen AE, McTiernan A, Mortensen E, Wist EA, Akslen LA, Reitan JB, Wilsgaard T, Thune I. Weight gain during pre- and postmenopausal years results in earlier onset of breast cancer. The Tromsø cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-06.

Inflammation may initiate and promote breast cancer development, and be associated with elevated circulating levels of inflammation markers. A total of eight 130 initially healthy women, participated in the population-based Tromsø study (1994–2008). Pre-diagnostic high-sensitivity C-reactive protein (hs-CRP) was assessed. During 14.6 years of follow-up, a total of 192 women developed invasive breast cancer. These cases were followed for additional 7.2 years. Detailed medical records were obtained. We observed an overall positive dose–response relationship between pre-diagnostic hs-CRP and breast cancer risk (hazard ratio (HR) = 1.06, 95 % CI 1.01–1.11). Postmenopausal women with above median levels of hs-CRP (>1.2 mg/l) had a 1.42 (95 % CI 1.01–2.00) higher breast cancer risk compared to postmenopausal women with hs-CRP below median. Postmenopausal women, who were hormone replacement therapy non-users, and were in the middle tertile (0.8–1.9 mg/l), or highest tertile of hs-CRP (>1.9 mg/l), had a 2.31 (95 % CI 1.31–4.03) and 2.08 (95 % CI 1.16–3.76) higher breast cancer risk, respectively, compared with women in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18 % increase in disease-free interval (95 % CI 0.70–0.97), and a 22 % reduction in overall mortality (95 % CI 0.62–0.98). Our study supports a positive association between pre-diagnostic hs-CRP and breast cancer risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

Abstract Introduction: Detection of disseminated tumor cells (DTC) after completion of systemic adjuvant treatment is a strong predictor of early systemic relapse and death. This analysis can discover early failure of a chosen adjuvant systemic treatment. In this study, we wanted to evaluate the value of DTC detection in bone marrow (BM) as a surrogate marker for response to docetaxel rescue treatment, to predict the effect of this treatment. Further, we wanted to compare disease free survival between patients treated with docetaxel resulting in eradication of DTC after treatment and patients treated with docetaxel where DTC persists after treatment. The follow up of the study is still ongoing. Here, we present the preliminary descriptive data from the study. Materials and Methods: A total of 1128 pts with node positive or high risk node negative disease (T1c/T2GII-IIIN0) was enrolled in the period from October 2003 to May 2008. All patients had completed primary surgery and received 6 cycles of adjuvant antracycline containing chemotherapy. The first BM aspiration was performed 8–12 weeks after termination of adjuvant chemotherapy (BM1). A second BM aspiration was performed 6 months later (BM2). The processing of BM and DTC analysis (by ICC) were performed as previsously described (Wiedswang G et al, J Clin Oncol 2003). If BM2 was positive (+) for DTC, the patient was treated with docetaxel (3qw, 6 courses) Docetaxel-treated patients were reexamined at the inclusion hospital with new BM analysis at approximately 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion. Results: Of 997 patients with conclusive DTC results for both BM1 and BM2, 83 patients (8.3%) were BM1 positive and 78 (7.8%) BM2 positive. Among the BM1+ patients, 15 (18.1%) were BM2+. The concordance between BM1 and BM2 were 87%. Of the patients positive at one or both time points, the concordance was 10% (15/146). The BM1 was not significantly associated with primary tumor characteristics (although borderline significance for Grade and ER status), whereas for BM2, DTC+ patients had increased frequency of node positive disease and pN2-3 stage (p=0.001, chi-square), and were positively associated with lobular carcinoma (p=0.01, chi-square). At BM1 24.7% of the DTC+ patients had >1 DTC, and 9.9% had ≥3 DTC. For BM2, 48.2% had >1 DTC, and 25.7% had ≥3 DTC. For patients with positive BM2 receiving docetaxel, the BM3 turned DTC negative in 55 of 66 evaluable cases (83.3%), and 48 of 59 were negative in BM4 (81.4%). Of 67 patients with a conclusive BM result at either BM3 or BM4, 12 were BM positive. Of 16 patients with ≥3 DTC before docetaxel treatment, only 4 patients were positive after treatment (25%). Conclusions: DTC status after adjuvant antracycline containing chemotherapy changes during the first 9 months of FU, with increased DTC positivity among patients with pN+ disease and lobular carcinomas. After docetaxel rescue treatment, the majority of patients experience disappearance of the DTCs. The clinical significance of these results awaits mature FU data, but the present results may indicate possibility for eradication of residual disease by alternative chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-07.

Abstract Background: Mutations in TP53 and its upstream p53-activator Chk2, are known to be associated with resistance to anthracycline and mitomycin treatment in locally advanced breast cancer. However, this association is not fully predictive, as some tumours are therapy resistant despite harbouring wild-type TP53 and CHK2. ATM is an upstream activator of both p53 and Chk2. Here, we explored ATM mutational status and expression levels with respect to anthracycline/mitomycine resistance in locally advanced breast cancers having primary chemotherapy with doxorubicin or 5FU-mitomycin and previously analyzed for TP53 and CHK2 status. Methods: In order to investigate ATM's potential predictive role, we performed MLPA-analysis, qPCR on ATM mRNA, ATM promoter methylation analyses and complete sequencing of the entire ATM coding region in patient biopsies from two prospective studies on resistance to doxorubicin and 5-FU/mitomycin in locally advance breast cancer (n=36 and n=38, respectively). Results: We performed complete sequencing of the ATM coding exons in 74 patients including 17 patients revealing primary resistance to chemotherapy. ATM mutations were detected in tumours from 5 patients. No mutation was detected among tumors resistant to chemotherapy. In addition, we observed 9 polymorphic variants present in more than one tumour, affecting or not affecting the amino acid sequence of the ATM protein (n = 34 patients in total). No correlation was observed between polymorphism status and response to therapy. No methylation of the ATM promoter, large deletions or duplication/amplifications of the ATM gene was observed. ATM expression levels varied substantially, with a ratio of 49 between the highest versus lowest level recorded. Among patients with no mutations in TP53 or CHK2, low ATM expression levels were significantly correlated to lack of response to doxorubicin or 5-FU/mitomycin (p=0.023; Mann-Whitney test). In contrast, ATM-levels were not suppressed in non-responding tumors harbouring TP53 or CHK2 mutations (p=0.642; Mann-Whitney test). Defining ATM mRNA levels in the lower 50%, 33% or 25% of the patient cohort to be reduced, tumors with either reduced levels of ATM or mutations affecting TP53 or CHK2 revealed a high risk for therapy resistance (p=0.004, p=0.001 and p=0.006, using the different ATM-level cut-offs; Fischer exact test). Interestingly, in a similar prospective study with a smaller number of patients displaying progressive disease upon treatment with epirubicin (n = 10), we find 2 out 5 TP53 and CHK2-wild-type non-responding tumors to express very low levels of ATM (within the lowest 5% of the cohort). Conclusions: Our data suggests that low expression of ATM may substitute for TP53 and CHK2 mutations causing resistance to anthracycline-and mitomycin therapy in breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-01-02.

Aromatase inhibitors improve relapse-free survival in early breast cancer, but there is concern about possible detrimental effects on bone mineral density (BMD) and plasma lipids. This paper presents the results of a 2-year study evaluating the effects of exemestane versus placebo on BMD, bone markers, plasma lipids and coagulation factors, including a 1-year follow-up after termination of treatment in 147 patients. During treatment, the mean annual rate of loss of BMD in the lumbar spine was 2.17% in the exemestane group versus 1.84% in the placebo group (n.s.) and 2.72% versus 1.48%, respectively, in the femoral neck (P=0.024). A loss of BMD above that expected in both arms of this study could be due to low vitamin D status (88% of all patients had vitamin D levels <30 ng/ml). The changes observed with exemestane were partially reversed during a 1-year follow-up, with no significant difference between the two arms. Similarly, the moderate decrease in high-density lipoprotein (HDL)-cholesterol was reversed. The bone marker values decreased, although a difference at 6 months of follow-up was still recorded, in particular for the markers of bone synthesis.

554 Background: To evaluate potential detrimental effects of the aromatase inactivator exemestane on bone, 147 postmenopausal women with early breast cancer were randomised to receive either exemestane for 2 years or placebo (J. Clin. Oncol. 23 [22], 5126–5137, 2005). Exemestane increased the annual bone loss from the femoral neck (2.72%) compared to placebo (1.48%; P = 0.024) with a non-significant increase in the lumbar spine (exemestane 2.17% versus placebo 1.84%). The annual bone loss was higher than expected in the placebo arm. Methods: Various biomarkers involved in bone metabolism (25-hydroxyvitamin D, parathormone, calcium, estrogens, androgens) were analysed to elucidate their influence on bone status at baseline and BMD loss during treatment with exemestane compared to placebo. Results: Using a cut-off value of 30 ng/ml for 25-hydroxyvitamin D (J. Clin. Endocrinol. Metab. 90 [6], 3800–3801, 2005), the majority of study participants suffered from vitamin D deficiency (56 of 62 patients in the placebo group and 52 of 59 in the exemestane group). The mean levels (95% confidence interval) of vitamin D were 22.6 ng/ml (21.2 - 24.1) in the placebo group and 21.6 ng/ml (20.0 - 23.3) in the treatment group, revealing no differences between these groups. Low serum calcium levels at baseline were found to be significantly correlated to low BMD in the femoral neck in the exemestane group. However, individual levels of vitamin D, parathormone and estradiol at baseline were not correlated significantly to BMD. Conclusions: Considering an annual bone loss of 0.5% to be representative for postmenopausal women (Osteoporos. Int. 15, 881–886, 2004), our data indicate that vitamin D deficiency could be the most important factor elevating bone loss among patients treated with exemestane as well as in the placebo group. These findings, together with the observation of a moderate additional effect of exemestane on bone loss, underlines the need for proper vitamin D substitution of postmenopausal women in general and in breast cancer patients during treatment with aromatase inhibitors in particular. [Table: see text]

531 Background: Aromatase inhibitors may increase bone loss. We reported (Proc Am Soc Clin Oncol 2004; 23:6, Abs 518) that a 2-year treatment with E (Aromasin), a steroidal aromatase inactivator, had a non-significant effect on annual rate of bone mineral density (BMD) loss in the lumbar spine (LS) and a small significant effect on the femoral neck (FN) as compared to placebo (P) in EBC patients (pts). E treatment induced a significant increase in all bone turnover markers. Methods: Randomized, double-blind study evaluating the effect of E (25 mg/day p.o.) or P on bone metabolism in 147 pts. BMD in the LS and the FN was measured by dual-absorptiometry before, during (at 6, 12 and 24 months) treatment and at 1-year FU after discontinuation. Bone resorption and formation markers were also assessed. Here we report results for the 57 pts on E and 64 pts on P evaluated for BMD up to 1-year FU. Results: At 1-year FU LS BMD loss in the E group improved as compared to end of treatment (mean % change from baseline at month 24 and 1-year FU: −3.59% and - 2.16%, t-test: p= 0.0003), albeit remaining greater than P (mean % change at 1-year FU: −1.61%). The effects seen in the FN BMD at the end of E therapy extended up to 1-year FU (mean % change at month 24 and 1-year FU: −4.42% and −4.28%, t-test: p= NS) and remained greater than P (mean % change at 1-year FU: −2.73%). Within 6 month of E withdrawal, bone resorption markers returned to or below baseline values and were not significantly different from P, while bone formation markers remained moderately increased. Conclusions: After E withdrawal, the LS BMD tended to normalize while the FN BMD loss stabilized; the effect on bone resorption but not on formation markers faded within 3–6 months after withdrawal. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacia Italia S.p.A./ Pfizer Group AstraZeneca, Novartis, Pfizer

BACKGROUND:The aim of this study was to evaluate the cost-effectiveness of trastuzumab in patients with metastatic breast cancer (MBC) in a model-based cost-effectiveness analysis (CEA). Trastuzumab has shown considerable activity in patients with MBC that overexpress HER2. However, significant resources have been allocated to finance this new therapy. Due to ever increasing pressures on health care budgets, economic evaluations are requested in order to compare health effects with costs.METHODS:All available data on trastuzumab in MBC presented at the San Antonio breast cancer conference in late 2003 and all data on Medline in December 2003 were analysed for life years (LY) gained and quality of life (QoL) with regard to the use of this new monoclonal antibody. Randomised studies comparing standard chemotherapy, with or without trastuzumab, were focused. The costs were calculated according to Norwegian prices as of January 2003.RESULTS:The LY gained ranged between 0.3 and 0.7 years. The median cost per patient treated was 44 196 yielding costs per life year saved in the range 63 137-162 417 depending on survival gain and discount rate employed. A sensitivity analysis documented the price of trastuzumab and the survival benefit the two major factors influencing the cost-effectiveness ratio.CONCLUSION:The economic evaluation indicates that trastuzumab is not cost effective in metastatic breast cancer. Reduced drug costs and/or improved survival may alter the conclusion.

Objectives: To investigate medical students' self-assessments of their communication skills through medical school related to background factors, curriculum design and perceived medical school stress.Methods: Medical students at all year levels attending Norwegian universities in the spring of 2003 were mailed the Oslo Inventory of Self-reported Communication Skills (OSISCS) developed by the authors. Of the total number of students (N = 3055), 60% responded. One school had a traditional curriculum, the other three ran integrated models.Results: Students assessed their instrumental communication skills to increase linearly year by year, while the relational skills showed a curve-linear trajectory reaching the optimum level half-way into the curriculum. Students attending the traditional school reported lower levels of instrumental skills compared to the students from the integrated schools. In relational skills, a similar difference was maintained halfway into the curriculum, but disappeared towards the end. Perceived medical school stress correlated to the self-reported end point levels of the two types of communication skills.Discussion: The trajectories of self-reported instrumental and relational skills indicate significant variations in facilitating mechanisms between curricula, cognitive processing and perceived medical school stress.Conclusions: Self-reported instrumental and relational communication skills develop differently in medical students over the years according to the type of curriculum.Practice implications: Curricula should be evaluated for improvement implementations. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

An open-label, non-randomized, compassionate-use study was carried out to investigate the effects of oral capecitabine at a dose of 1 250 mg/m(2) twice daily on days 1 to 14 every 21 days in anthracycline- and taxane-pretreated advanced/metastatic breast cancer patients. Forty-eight patients were enrolled from April 2000 to December 2001. Twenty-four patients (50%) had metastases to the liver, 18 to bone, 13 to lung, 10 to regional lymph nodes, 8 to pleura, 7 to the thoracic wall, 5 to skin, 3 to the mediastinum, 1 to breast and 1 had metastasis to the abdomen. Thirty-three patients (69%) had metastases to more than one site. Median age of the patients was 55 years ( range 35 - 74). Three patients had an ECOG performance status (PS) of 0, 32 PS 1 and 13 PS 2, respectively. Fourteen patients (29%; 95% CI 16 to 42%) obtained a partial response (PR) while 16 (33%) had stable disease (SD) as the best response, of whom 6 had stabilization for more than 24 weeks. This gives a clinical benefit (PR + SD > 24 weeks) of 42% ( 95% CI 28 to 56). Dose reduction was necessary in 29% of the patients. Median dose reduction was 25%. Grades 2 and 3 hand-foot syndrome (PPE) was observed in 17 patients (36%). Eleven patients experienced grades 2 and 3 gastrointestinal toxicity, and haematological toxicity grade 3 was observed in 3 patients (6%). Median time to progression was 107 days (CI 95% 85 to 129), and median overall survival was 281 days ( CI 95% 164 to 398). Third-line, oral capecitabine in anthracycline- and taxane-pretreated metastatic breast cancer appears to be effective and has an acceptable toxicity profile.

650 Background: Estrogens (Es) favorably modify the lipid profile. Aromatase inhibitors reduce Es; LDL and triglycerides (tri) increase have been observed (Elisaf, EJC 2001). We report the effect of exemestane (E, Aromasin), a steroidal aromatase inactivator, on lipid profile and coagulation in postmenopausal early breast cancer (EBC) patients (pts). Methods: We conducted a randomized, double blind study on the effect of E on bone metabolism, endocrinological and metabolic parameters in postmenopausal pT1N0 or T2N0 (with no other risk factors) or ductal carcinoma in situ (DCIS) pts. ER and/or PgR+ve or unknown pts with bone mineral density (BMD) within 2 SD of the mean for 65-years (yrs) women were randomized to E 25 mg day or placebo (P) p.o. for 2 yrs, with a 1-yr follow-up. Primary objective was non-inferiority on BMD. Planned sample size was 128 BMD-evaluable pts. Cholesterol (Chol), HDL-cholesterol (HDL-c), tri, Apo-AI, Lipoprotein A (Lipo-AI), Apo B, PT, APTT, fibrinogen (Fib) and homocysteine (hoc) were evaluated at baseline (BS), 6, 12, and 24 months (mos). Results: 147 pts have been enrolled, 73 E and 74 P. Median age: 61 yrs (E) and 60 yrs (P). Median time from menopause: 9.7 yrs E and 8.0 yrs P. ER and/or PgR: +ve 130 pts, unknown 17 (15 with DCIS). E was well tolerated, 70% of pts had drug-related events on E and 73% on P. Nine pts withdrew on E and 3 on P for adverse events (1 E for DVT and 2 P for increased Fib or apoplexia). No PT changes from BS were observed on both arms. At 24 mos median Fib was reduced by 1.2% on E and 4.8% on P, and median APTT by 3% on both. Lipid profile evolution is described in the Table. Out of 64 E pts, 4 developed Gr. 2 Chol, and 1 Gr. 1 Tri elevation. Out of 62 P pts, 7 developed Gr. 2 and 1 Gr. 1 Chol, 3 Gr. 1 Tri elevations. Conclusions: After 2 yrs of E, lipid profile and homocysteine levels are similar in E and P pts, except for a modest reduction in HDL-c on E. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Italia S.p.A. Pfizer Co. Pfizer Co.

In this first reported study of weekly paclitaxel administered as first-line chemotherapy for metastatic breast cancer, paclitaxel 100 mg/m2 was administered in a 1-h infusion on a weekly basis to 35 patients who may previoulsly have received adjuvent chemotherapy(but not taxane-containing regimens), but not for advanced or metastatic disease. A median of 14 infusions per patient was given at a mean delivered dose intensity of 94 mg/m2 per week. In 33 assessable patients, a complete response (CR) was observed in 1 patient and partial responses (PRs) in 12 patients, producing an overall response rate of 40%. Stable disease (SD) was observed in 17 patients, of whom 9 were stabilized for more than 24 weeks. Thus, clinical benefit (CR + PR + SD≥ 24 weeks) was observed in 67% of the patients. Time to progression was 189 days, the duration of response 180 days and overall survival 544 days. Five patients developed grade 3 neutropenia and five patients grade 3 comparable response rates and less toxicity than when the drug is given every three weeks. .

Goals of work It is well documented that an increasing proportion of cancer patients today use complementary and alternative medicine, mostly alongside conventional therapies. This study investigates the use of complementary and alternative medicine among oncology health workers and the reported effects. Patients and methods In June 2002, we conducted a national multicentre survey including 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. The response rate was 61.5%. Main results We found that females were more often users of both complementary and alternative methods than males (39% versus 15% and 47% versus 17%) and that few oncologists had tried such treatments compared to nurses, therapeutic radiographers and clerks (20/12% versus 50/40%, 41/33% ,and 31/50%). Interestingly, the majority of those who had tried unconventional methods reported some or very good effects. Acupuncture, homeopathy, aromatherapy and massage were the most popular therapies. Sub-group analyses including only oncologists showed that female physicians were more often users of both complementary and alternative methods compared to males (33% versus 12%, 25% versus 3%). Moreover, participants below the age of 35 years and Christians more often reported use. Conclusions This survey demonstrates that significant proportion of oncology health workers in Norway have used non-proven therapies and that most have had a positive experience. Differences in use is highly dependent on gender, profession, age and religion.

This study examines the association between alternative medicines (AM) and cancer survival. A national multicentre study was carried out in Norway in December 1992 to assess the prevalence of AM use among cancer patients. One of the aims of this study was to assess the association between AM and long-time survival. In January 2001, survival data were obtained with a follow-up of 8 years for 515 cancer patients. A total of 112 (22%) assessable patients used AM. During the follow-up period, 350 patients died. Death rates were higher in AM users (79%) than in those who did not use AM (65%). In a Cox regression model adjusted for demographic, disease and treatment factors, the hazard ratio of death for any use of AM compared with no use was 1.30, (95% Confidence Interval (CI) 0.99, 1.70; P=0.056), suggesting that AM use may predict a shorter survival. Sensitivity analyses strengthened the negative association between AM use and survival. AM use had the most detrimental effect in patients with an ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 (hazard ratio for use=2.32, 95% CI, 1.44, 3.74, P=0.001), when compared with an ECOG PS of 1 or higher. The use of AM seems to predict a shorter survival from cancer. The effect appears predominantly in patients with a good PS.

Hamre and colleagues state that our study does not justify “speculations about causal links between AM use and cancer survival”. We agree. As we explain in our paper [ 1 Risberg T. Vickers A. Bremnes R.M. Wist E.A. Kaasa S. Cassileth B.R. Does use of alternative medicine predict survival from cancer?. Eur. J. Cancer. 2003; 39: 372-377 Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar ]: “the association observed … cannot establish a causative relationship”. Indeed, we explicitly discount a causal link by stating ”we do not believe that AM treatment directly influences survival” and instead we hypothesise that ”shorter survival among AM users might be explained by patients’ correct perception of the gravity of their disease”.

Purpose of the study: To study the association between mental distress and the use of alternative medicine (AM) among cancer patients. Patients and methods: A longitudinal questionnaire-based study was carried out at the Department of Oncology, University Hospital of Tromsø, Norway, during the period 1990–1991. The level of mental distress in 158 patients aged less than 75 years was assessed 4 months after first admission to the cancer ward. The patients answered five questions about mental distress selected from the General Health Questionnaire (GHQ). The questions were scored continuously according to the Likert scoring procedure. The level of mental distress was also ranked from 1 (little or no mental distress) to 3 (high mental distress). Results: A total of 53 of the 158 patients reported use of AM at inclusion of the study or during the 4 months of follow-up. Among patients with low mental distress, 21% were users of AM, 36% of patients with medium distress and 48% in patients with high level of mental distress (p-value for linear trend = 0.02). Adjusted for all known relevant variables, patients with medium level of mental distress had 1.9 times higher prevalence of use of AM than patients with low level of mental distress, patients with high mental distress had a 2.9 times higher prevalence (p = 0.15 and 0.07, respectively). Analyzed as a continuous variable (Likert score between 5 and 20), mental distress was associated with use of AM (p = 0.007). Conclusion: These findings suggest that seeking alternative treatment is more common among mentally distressed cancer patients.