- Email: [email protected]
Elderly and Lifestyle
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409 Invited SNPs and haplotypes associated to gene expression in breast cancer: Can they lead us to the susceptibility markers in the GWAS quest? V. Kristensen1,2,3 . 1 K.G. Jebsen Center for Breast Cancer Research, Institute for, Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2 Department of Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, Lørenskog, Norway; 3 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. Current understanding of the genetic risk is limited to high-penetrance mutations (notably BRCA1 and BRCA2), moderate-risk alleles in genes such as ATM, CHEK2, TERT and PALB2, common lower penetrance alleles, of which more than 30 have been identified so far, principally through genomewide association studies (GWAS). The effect sizes of the newly identified loci are generally modest (the highest OR was 1.26) but the high levels of statistical significance, the consistent results in the follow up studies, the generally higher effect sizes for familial cases and the fact that most of the excess of significant associations was concentrated among SNPs selected on the basis of an association in the combined breast cancer GWAS all indicate that these are robust associations. The risk for loci already identified by GWAS is currently underestimated due to currently unknown mutations and many more disease loci remain to be found. The existing data suggest that a very large number of loci, perhaps several thousand, contribute to polygenic susceptibility to breast cancer. Phenotype stratification through molecular subclasses, expression QTLs, HLA profiles, methylation profiles, treatment responses will beinevitably important for revealing novel susceptibility. Many recent studies will be discussed to emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles. No conflicts of interest 410 Proffered paper oral Trends in breast cancer mortality in thirty European countries C. Pizot1 , M. Boniol2 , P. Boyle3 , P. Autier4 . 1 International Prevention Research Institute, Statistics, Lyon, France; 2 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, Statistics, Lyon, France; 3 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, President, Lyon, France; 4 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, Research, Lyon, France Background: Since the 1980s, important changes have taken place in the detection and management of breast cancer. To help decipher factors contributing to changes in trends, we analysed breast cancer mortality in 30 European countries until 2010 and made comparisons with results obtained for the period extending until 2006. Material and Methods: Breast cancer deaths and population were extracted from the WHO database. Age-standardized rates were computed using the European standard population. Results: In 1987−89, breast cancer mortality rates were highest (41.9 per 100,000) in England and Wales and lowest (20.0 per 100,000) in Romania. In 2008−10, these rates were 25.4 and 22.0 respectively, indicating that from 1989 to 2010, mortality decreased by 40.8% in England while it increased by 11.4% in Romania. The median 22-year change in the 30 countries was 27.1%, and in 2008−10, mortality ranged from 17.8 in Spain to 28.8 in Denmark. Mortality changes were largest in women under 50 (from −71.3% to −21.4%) and smallest in women 70 and over (from −29.5 to +81.5%). Compared to previous analyses, trends in Central European countries stabilized or decreased more than 5 years ago. Declines in mortality rates were 25% steeper between 2003 and 2010 than between 1989 and 2010, and faster declines were noticeable at all ages. At the same time, mortality rates are converging, indicating that over time, breast cancer mortality will homogenize across European countries. Mortality decreases were greatest in countries with higher mortality in 1987−89, with some notable exceptions. In 1987−89, rates in Italy, France and Norway were 29.7, 28.0 and 27.4, respectively, but 22-year declines in mortality rates were 26.4%, 15.8% and 34.5%, respectively. Moreover, lowest mortality reductions in women under 50 were observed in France
Poster Discussion Session (−21.4% for a European median of −47.3%). A similar situation is observed in Finland, although less severe. Conclusions: If current conditions remain equivalent, sustained decreases in breast cancer mortality will persist in coming years. The homogenization of mortality rates is a marker of general improvement in treatment and access to care, and of shared risk factors across populations. France devotes substantial amounts of resources to cancer care and reasons why breast cancer mortality do not follow trends in surrounding countries need to be investigated. No conflicts of interest
Friday, 21 March 2014
10:30–11:30
POSTER DISCUSSION SESSION
Elderly and Lifestyle 412 Poster discussion DCIS distribution of grades in 5,126 screened and non-screened women and estimated risk of overdiagnosis in breast cancer screening: A model of progression P. van Luijt1 , E.A.M. Heijnsdijk1 , J. Fracheboud1 , M.J.M. Broeders2 , J. Wesseling3 , G.J. den Heeten2 , H.J. de Koning1 . 1 Erasmus MC University Medical Center Rotterdam, Public Health, Rotterdam, Netherlands; 2 Radboud University Medical Centre, Dept for health evidence, Nijmegen, Netherlands; 3 The Netherlands Cancer Institute, Pathology, Amsterdam, Netherlands Background: Ductal carcinoma in situ (DCIS) might represent either early detection of breast cancer destined to become invasive, lethal or be overdiagnosed. The malignant potential is dependent on grade, which can be low (I), intermediate (II), or high (III). We aimed to determine whether distribution of DCIS grade is dependent on mammography screening status and to estimate overdiagnosis rate by grade. Materials and Methods: We extracted grade from pathologic reports of 5,126 Dutch women of all ages in 2007–2009 with incident cases of DCIS, provided by PALGA: Dutch Pathology Registry. We established the incidence rate of the different DCIS grades by patients’ screening status and age. We added the distribution of the DCIS cases in our microsimulation model (MISCAN) and estimated overdiagnosis rates by DCIS grade. Results: Overall, 18.3% of DCIS were grade I, 30.9% grade II, and 50.8% grade III. This distribution did not differ by screening status. We found an inverse linear trend for grade with five-year age-groups: Higher age is associated with lower DCIS grade and vice versa. Overdiagnosis as proportion of all cancers in women of the screening age was 61% for DCIS I, 57% for DCIS II, 45% for DCIS III, and 2% for invasive cancer. For women with a grade III DCIS in the ages 50−60 this overdiagnosis rate was 21−29%, compared to 50−66% in women with grade III DCIS in the ages 60−75. Conclusions: Most DCIS are high grade. DCIS grade distribution depends on age, not on screening status. The estimated overdiagnosis rate among DCIS lesions is extremely high, except for younger women with a grade III DCIS, and calls for a non-treatment randomized controlled trial for low grade DCIS. Conflict of interest: Corporate-sponsored research: SCOR global Health 413 Poster discussion Does background enhancement at breast MRI influence diagnostic accuracy in mass versus non-mass-like lesions? N. Hansen1 , C.K. Kuhl1 , A. Barabasch1 , K. Strobel1 , S. Schrading1 . 1 RWTH Aachen University Hospital, Diagnostic and Interventional Radiology, Aachen, Germany Background: Purpose of our study was to determine the influence of background enhancement on diagnostic performance of breast MRI. Material and Methods: 335 women with 494 breasts underwent dynamic contrast-enhanced breast MRI in our institution from May 2010 to November 2012. Background enhancement in MRI was scored on a 4-point-scale from absent to strong. BIRADS diagnoses were assigned per breast. BIRADS6 lesions were excluded from analysis. Diagnoses were validated either by biopsy (BIRADS 4/5) or MRI follow-up >12 months (BIRADS 1−3). Sensitivity, specificity and PPV were calculated and compared for all classes of background enhancement and type of lesion. Fisher’s exact test was used for statistical analysis.
Poster Discussion Session
Friday, 21 March 2014
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Table (abstract 415): Number of women by age group who underwent specific treatments (percentage of eligible women in each age group who had treatment)
Surgery in women with Charlson comorbidity score 0 Radiotherapy following breast conserving surgery Chemotherapy given to women with Charlson comorbidity score 0
60−64
65−69
70−74
75−79
80−84
85+
Total
441 313 281 164 117
343 (86.6%) 231 (85.6%) 200 (86.6%) 94 (23.7%) 61 (22.6%)
231 (84.9%) 152 (86.9%) 108 (85.0%) 41 (15.1%) 32 (18.3%)
228 (75.8%) 121 (75.2%) 86 (78.2%) 23 (7.6%) 8 (5.0%)
117 (54.4%) 68 (65.4%) 29 (69.1%) 6 (2.8%) 2 (1.9%)
55 (26.2%) 29 (29.0%) 11 (11.0%) 2 (1.0%) 0 (0%)
1415/1888 (75.0%) 914/1165 (78.5%) 715/844 (84.7%) 330/1888 (17.5%) 220/1165 (18.9%)
(89.3%) (87.9%) (88.9%) (33.2%) (32.9%)
Results: Sensitivity of MRI in breasts categorized as MR-ACR1, 2, 3, and 4 was 98% (64/65), 100% (31/31), 100% (15/15), and 100% (5/5), respectively. Specificity was 83% (175/211), 72% (76/105), 57% (26/46), and 38% (6/16). PPV was 64% (64/100), 52% (31/60), 43% (15/35), and 33% (5/15). For mass-like lesions, specificity decreased from 26% (9/35) with MR-ACR1−2 to 25% (3/12) with MR-ACR3−4 and PPV from 70% (60/86) to 59% (13/22), respectively. For non-mass-like lesions, specificity decreased from 20% (10/49) to 16% (4/25) and PPV from 47% (35/74) to 25% (7/28). Conclusions: Background enhancement does not seem to interfere with the ability to identify invasive breast cancers and DCIS in MRI (p = 1). This, however, is achieved at the expense of specificity, which decreases significantly with MR-ACR3−4 (p < 0.05). PPV, in contrast, decreases more severely for non-mass-like lesions than for mass-like lesions (25% vs 59% with MR-ACR3−4). No conflicts of interest 414 Poster discussion Impact of comprehensive geriatric assessment on treatment decision and follow-up in older breast cancer patients 1
1
2
3
4
5
H. Bode , J. Bastin , C. Kenis , L. Decoster , J.P. Lobelle , K. Milisen , K. Van Puyvelde6 , J. Flamaing7 , H. Wildiers8 . 1 University Hospitals Leuven, General Medicine, Leuven, Belgium; 2 University Hospitals Leuven, General Medical Oncology and Geriatric Medicine, Leuven, Belgium; 3 University Hospitals Brussels, General Medical Oncology, Brussels, Belgium; 4 University Hospitals Leuven, Statistics, Leuven, Belgium; 5 University Hospitals Leuven, Centre for Health Services and Nursing Research and Department of Geriatric Medicine, Leuven, Belgium; 6 University Hospitals Brussels, Department of Geriatric Medicine, Brussels, Belgium; 7 University Hospitals Leuven, Department of Geriatric Medicine, Leuven, Belgium; 8 University Hospitals Leuven, Department of General Medical Oncology, Leuven, Belgium Background: We performed this study to investigate the impact of comprehensive geriatric assessment (CGA) on treatment decisions in a large cohort of older breast cancer patients. We also studied the functional evolution during treatment and the development of severe toxicity in patients receiving chemotherapy and we looked for predictive baseline markers of functional decline and toxicity. Patients and Methods: 379 older breast cancer patients were recruited in 2 Belgian university hospitals. Only patients aged 70 years or older with a newly diagnosed or progressive breast cancer for which treatment initiation or change was considered, were eligible. At baseline, a CGA and oncological parameters were obtained. The impact of CGA on treatment decision was assessed by offering a questionnaire to the treating physicians. At 2−3 months follow-up, functionality was reassessed and severe toxicity in patients receiving chemotherapy (n = 98) was recorded. Predictors for functional decline and toxicity were identified by multivariate analysis. Results: 79.2% of treating physicians were aware of CGA results at the time of treatment decision. CGA revealed new geriatric information in 70.5% of cases, leading to geriatric intervention in 5.4% of patients. Treatment was adapted according to age and standard clinical approach in 41.1% of cases and CGA results led to an additional change of treatment decision in 5.4%. At follow-up, 47.9% of patients was dependent on activities of daily living (ADL) (compared to 54.1% at baseline) and 64.7% was dependent on instrumental activities of daily living (IADL) (compared to 58.1% at baseline). Functional decline at 2−3 months was predicted by baseline ADL, IADL and ECOG-PS, but no markers were found to predict chemotherapy toxicity. Conclusions: CGA revealed previously unknown information in 70.5% of the older breast cancer patients. 20.8% of physicians were not aware of CGA results at time of treatment decision, while CGA led to geriatric interventions in 5.4% of cases and additionally changed treatment decision in 5.4%. A proper communication appears to be indispensible. Baseline functionality measures (ADL, IADL, ECOG-PS) were found to be predictive for functional decline at 2−3 months, but predictors for severe chemotherapy toxicity could not be identified. No conflicts of interest
415 Poster discussion A population based study of the management of older women with breast cancer taking into account levels of comorbidity A. Moran1 , S. Tabasum2 , C. Connor3 , B. Magee4 , V. Pope5 , R. Audisio6 , C. Holcombe7 , N. Bundred8 . 1 North West Knowledge and Intelligence Team, Public Health England, Manchester, United Kingdom; 2 The Christie NHS Trust, Cancer Intelligence, Manchester, United Kingdom; 3 The Christie NHS Trust, Clinical Oncology, Manchester, United Kingdom; 4 The Christie Hospital NHS Trust, Clinical Oncology, Manchester, United Kingdom; 5 Mid-Cheshire Hospitals, Department of Breast Surgery, Crew, United Kingdom; 6 St Helens and Knowsley NHS Trust, Department of Breast Surgery, St Helens, United Kingdom; 7 Royal Liverpool University Hospital, Department of Breast Surgery, Liverpool, United Kingdom; 8 University Hospital of South Manchester, Department of Breast Surgery, Manchester, United Kingdom Background: Several studies and audits have reported that many older women with breast cancer do not receive ‘standard treatment’, including a study of women diagnosed in 1999 in the same population (Lavelle K, et al.; BJC (2007) 96, 1197–1203). However, it is not clear how much of this is due to increasing levels of comorbidity in older age groups. Methods: All women resident in Greater Manchester, Merseyside or Cheshire diagnosed in 2009 with breast cancer at age 60 or older were identified from the North West Cancer Registry. Details on patient and tumour variables and patient management were abstracted from hospital notes. A Charlson comorbidity score was calculated. Of the 2314 women identified on the registry database, 1888 (82%) were included in the study. Results: The table shows a large decrease with age in the use of surgery, radiotherapy following breast conserving surgery and chemotherapy. Older women with a Charlson comorbidity score of 0 were still less likely to undergo surgery or receive chemotherapy. Conclusion: These results show lower uptake of standard treatment in older women, which is not explained by increasing levels of comorbidity with age. Though the decrease in uptake with age is not as marked as in the previous study by Lavelle, the results suggest that many older women are still under-treated. Conflict of interest: Corporate-sponsored research: The work outlined in this abstract is funded by Roche Products. I have previously received other research grants from Roche.
416 Poster discussion Effect of diabetes mellitus on early breast cancer patients receiving neoadjuvant therapy C. Fontanella1 , B. Lederer1 , J. Huober2 , B. Gerber3 , K.M. Mehta1 , V. Nekljudova1 , S. Gabe1 , G. von Minckwitz1 , M. Untch4 , S. Loibl1 . 1 German Breast Group, Medicine and Research, Neu-Isenburg, ¨ Germany; 2 Universitats-Frauenklinik, Breast Center, Ulm, Germany; 3 ¨ Universitats-Frauenklinik, Breast Center, Rostock, Germany; 4 Helios Klinikum Berlin-Buch, Breast Center, Berlin, Germany Background: Recent data suggested that diabetes mellitus (DM) may negatively affect outcome of neoadjuvant chemotherapy (NAT) of breast cancer (BC) patients. Material and Methods: From 2005 to 2011, 4,065 BC patients were enrolled in GeparQuattro and GeparQuinto trial. We evaluate the incidence of DM at the time of BC diagnosis and its impact on outcome of NAT. We defined pathological complete response (pCR) as ypT0 ypN0 and distant disease-free survival (DDFS) as time from diagnosis to recurrence of tumour or death from any cause, excluding ipsilateral BC recurrence, regional invasive recurrences, contralateral BC, and in situ carcinomas. We performed cross-tabulations and c2 -test to evaluate the effect of DM with respect to categorical variables and Cox proportional hazards regression analyses (including age, body mass index [BMI], number of comorbidities, hormone receptor and HER2 status, tumour [cT] and nodal [cN] stage, grading, histotype, adverse events [AE], and dose of chemotherapy) to
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investigate the effect of DM on DDFS. In addition, a Kaplan–Meier analysis was performed. Results: Overall 2.8% (n = 112) of patients had a diagnosis of DM; 33.9% (n = 38) of DM patients received concomitant metformin. DM patients had a median age of 61 years (36 to 78) and a median BMI of 30.3 kg/m2 (19.5 to 45.2), compared with median age 49 (21 to 78) and median BMI 24.9 (16.2 to 58.0) in non-DM patients. DM patients were diagnosed with a more advanced tumour (cT4d 17.6% vs 7.7%, p < 0.001) and nodal stage (cN2−3 14.8% vs 4.9%, p < 0.001). DM patients were more likely to have a reduction in taxane dose; 17.7% of DM patients received a median of <60 mg/m2 /cycle of docetaxel vs 7.9% of non-DM patients (p < 0.001). No significant correlation with reduction in epirubicin (<60% of planned dose: 3.8% DM vs 1.4% non-DM, p = 0.308) and cyclophosphamide dose (<60% of planned dose: 7.8% DM vs 7.8% non-DM, p = 0.196). No differences were observed in grade 3−4 both haematological (DM 86.6% vs non-DM 89.7%, p = 0.208) and non-haematological (DM 45.5% vs. non-DM 39.5%, p = 0.291) AE. No difference was observed in pCR rate (DM 18.8% vs. non-DM 19.1%, p = 0.921). DM patients had an increased risk of distant recurrence (HR 2.04, CI 1.14–3.64, p = 0.016; 5-year DDFS rate DM 68.6% vs non-DM 78.2%, p < 0.001). Conclusion: In our data, DM patients presented with a more advanced stage than non-DM patients. A detrimental impact of DM on DDFS in BC patients receiving NAT was observed. No conflicts of interest
417 Poster discussion Influence of body mass index on long-term outcome of breast cancer patients receiving neoadjuvant therapy − Combined results from the GBG (German Breast Group) and the EORTC cohorts C. Fontanella1 , L. Slaets2 , P. Neven3 , S. Loibl1 , M. Vanoppen3 , J. Bogaerts2 , G. von Minckwitz1 , D. Cameron4 , M. Untch5 , H. Bonnefoi6 . 1 German Breast Group, Medicine and Research, Neu-Isenburg, Germany; 2 EORTC, Headquarters, Brussels, Belgium; 3 Katholieke Universiteit Leuven, Multidisciplinary Breast Centre and Gynecological Oncology, Leuven, Belgium; 4 Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom; 5 Helios Klinikum ´ Breast Berlin-Buch, Breast Centre, Berlin, Germany; 6 Institut Bergonie, Centre, Bordeaux, France Background: Obesity is related to increased morbidity and mortality. A correlation with poor prognosis in breast cancer (BC) patients has been observed. However, it remains controversial if obesity affects outcome in different BC subtypes equally. Material and Methods: We retrospectively evaluated 10,727 neoadjuvant BC patients: 8,872 in 7 German Breast Group (GBG) trials and 1,855 treated in the EORTC 10994/BIG 1−00 trial. Body mass index (BMI)1 (<25 kg/m2 ), BMI2 (25–29.9 kg/m2 ), and BMI3 (30 kg/m2 ) were defined according to WHO classification. BC subtypes were defined as Luminal A/B (oestrogen [ER]/progesterone [PR] receptor-pos/HER2-neg), HER2-luminal (ER/PR-pos/HER2-pos), HER2-like (ER/PR-neg/HER2pos), and TNBC (ER/PR-neg/HER2-neg). Endpoints of the study were: distant disease-free survival (DDFS, STEEP definition, GBG cohort) and distant relapse free survival (DRFS, STEEP definition, EORTC cohort). We performed Kaplan–Meier analyses to estimate DDFS/DRFS according to BMI overall and in subgroups by BC subtype. Reported p-values correspond to the log rank test. Results: In both cohorts, median age increased with increasing BMI (GBG: BMI1 47 yrs, BMI2 52 yrs, BMI3 54 yrs, EORTC: BMI1 47 yrs, BMI2 51 yrs, BMI3 52 yrs). Survival analyses showed a significant decrease in DDFS/DRFS with increased BMI. In the GBG cohort 5-year DDFS rates were: 79.4% for BMI1, 78.4% for BM2, and 73.7% for BMI3 (p < 0.001). In the EORTC cohort 5-year DRFS rates were: 73.0% for BMI1, 64.3% for BMI2, and 62.2% for BMI3 (p < 0.001). The same relationship was found in Luminal A/B patients (GBG: 83.6% for BMI1, 84.5% for BM2, and 78.2% for BMI3; p = 0.008; EORTC: 83.0% for BMI1, 65.2% for BMI2 and 62.1% for BMI3; p < 0.001). In the GBG cohort, a significant result was observed also in TNBC (71.5% for BMI1, 69.1% for BM2, and 62.2% for BMI3; p = 0.018), not in the EORT cohort (63.4% for BMI1, 68.0% for BM2, and 64.7% for BMI3; p = 0.497). No significant result was found in HER2-luminal (GBG: p = 0.061, EORTC: p = 0.828) and HER2-like (GBG: p = 0.189, EORTC: p = 0.776) patients. In the EORTC cohort, a competing risk analysis for time to distant relapse (non-BC death as a competing risk) confirmed the DRFS results. Conclusion: In this joint study we demonstrate a decrease in DDFS/DRFS in neoadjuvant BC patients with a higher BMI compared with normal weight patients. In a subgroup analysis by BC subtype, this result
Poster Sessions applies to Luminal A/B patients in both cohorts and to TNBC patients in the GBG cohort. No conflicts of interest
Friday, 21 March 2014
10:30–11:30
EUROPA DONNA SESSION
Importance of Lifestyle Choices Before and After Breast Cancer 418 Key lifestyle choices for the prevention of breast cancer
Invited
Abstract not received 419 Key facts about preventing recurrence
Invited
A. Howell1 , M.H. Harvie2 . 1 The Christie Hospital, Department of Medical Oncology, Manchester, United Kingdom; 2 Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester, Manchester, United Kingdom The major question for this presentation is: “If a patient with early breast cancer makes appropriate lifestyle choices will this reduce her chances of relapse?”. Two randomised trials (WINS and WHEL) tested the hypothesis that the most appropriate lifestyle choice to take was to reduce fat intake and increase fruit and vegetable consumption. In the WINS study a total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups within 1 year of diagnosis. Fat intake was reduced from 51.3 to 33.3 g/day (35% reduction) and resulted in a 6 pound lower body weight in the intervention group which was associated with a significant 24% reduction in relapse after a median follow up of 60 months (Chlebowski RT et al. J Natl Cancer Inst 2006; 98: 1767). In the WHEL study 3088, women previously treated for early stage breast cancer, who were 18 to 70 years old at diagnosis, were enrolled between 1995 and 2000 and followed up through June 1, 2006. Fat intake was reduced in the treated group by 13% and vegetable, fruit and fibre intake by over 30% but there was no significant reduction in weight or relapse (Pierce JP. JAMA. 2007 July 18; 298(3): 289). The remainder of data on lifestyle after diagnosis is from observational studies. These indicate that overweight/obesity at diagnosis is consistently associated with relapse (Niraula S et al. BCRT 2012; 134: 769) but weight gain or weight loss (Caan BJ et al. CBEP 2012; 96: 123) or exercise (Beasley JM. BCRT 2012; 131: 637) are variably or not associated with relapse. New randomized studies of calorie restriction and exercise are required to test the hypothesis that there is benefit. Rack et al. in Germany (SUCCESS-C Trial. Breast Care 2010; 5: 395) have completed recruitment of 3547 women after surgery and chemotherapy for early breast cancer with a body mass index between 24 and 40 kg/m2 receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. This trial is due to report in 2014. Finally, a second randomized trial of lifestyle intervention is in progress in Italy (Villarini A et al. Tumori 2012; 98(1): 1−18). Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. The trial is due to report in 2016. The jury remains out until we have the results of these two trials. No conflicts of interest
Friday, 21 March 2014
409 Invited SNPs and haplotypes associated to gene expression in breast cancer: Can they lead us to the susceptibility markers in the GWAS quest? V. Kristensen1,2,3 . 1 K.G. Jebsen Center for Breast Cancer Research, Institute for, Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2 Department of Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, Lørenskog, Norway; 3 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. Current understanding of the genetic risk is limited to high-penetrance mutations (notably BRCA1 and BRCA2), moderate-risk alleles in genes such as ATM, CHEK2, TERT and PALB2, common lower penetrance alleles, of which more than 30 have been identified so far, principally through genomewide association studies (GWAS). The effect sizes of the newly identified loci are generally modest (the highest OR was 1.26) but the high levels of statistical significance, the consistent results in the follow up studies, the generally higher effect sizes for familial cases and the fact that most of the excess of significant associations was concentrated among SNPs selected on the basis of an association in the combined breast cancer GWAS all indicate that these are robust associations. The risk for loci already identified by GWAS is currently underestimated due to currently unknown mutations and many more disease loci remain to be found. The existing data suggest that a very large number of loci, perhaps several thousand, contribute to polygenic susceptibility to breast cancer. Phenotype stratification through molecular subclasses, expression QTLs, HLA profiles, methylation profiles, treatment responses will beinevitably important for revealing novel susceptibility. Many recent studies will be discussed to emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles. No conflicts of interest 410 Proffered paper oral Trends in breast cancer mortality in thirty European countries C. Pizot1 , M. Boniol2 , P. Boyle3 , P. Autier4 . 1 International Prevention Research Institute, Statistics, Lyon, France; 2 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, Statistics, Lyon, France; 3 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, President, Lyon, France; 4 International Prevention Research Institute and Strathclyde University Global Public Health Institute at iPRI, Research, Lyon, France Background: Since the 1980s, important changes have taken place in the detection and management of breast cancer. To help decipher factors contributing to changes in trends, we analysed breast cancer mortality in 30 European countries until 2010 and made comparisons with results obtained for the period extending until 2006. Material and Methods: Breast cancer deaths and population were extracted from the WHO database. Age-standardized rates were computed using the European standard population. Results: In 1987−89, breast cancer mortality rates were highest (41.9 per 100,000) in England and Wales and lowest (20.0 per 100,000) in Romania. In 2008−10, these rates were 25.4 and 22.0 respectively, indicating that from 1989 to 2010, mortality decreased by 40.8% in England while it increased by 11.4% in Romania. The median 22-year change in the 30 countries was 27.1%, and in 2008−10, mortality ranged from 17.8 in Spain to 28.8 in Denmark. Mortality changes were largest in women under 50 (from −71.3% to −21.4%) and smallest in women 70 and over (from −29.5 to +81.5%). Compared to previous analyses, trends in Central European countries stabilized or decreased more than 5 years ago. Declines in mortality rates were 25% steeper between 2003 and 2010 than between 1989 and 2010, and faster declines were noticeable at all ages. At the same time, mortality rates are converging, indicating that over time, breast cancer mortality will homogenize across European countries. Mortality decreases were greatest in countries with higher mortality in 1987−89, with some notable exceptions. In 1987−89, rates in Italy, France and Norway were 29.7, 28.0 and 27.4, respectively, but 22-year declines in mortality rates were 26.4%, 15.8% and 34.5%, respectively. Moreover, lowest mortality reductions in women under 50 were observed in France
Poster Discussion Session (−21.4% for a European median of −47.3%). A similar situation is observed in Finland, although less severe. Conclusions: If current conditions remain equivalent, sustained decreases in breast cancer mortality will persist in coming years. The homogenization of mortality rates is a marker of general improvement in treatment and access to care, and of shared risk factors across populations. France devotes substantial amounts of resources to cancer care and reasons why breast cancer mortality do not follow trends in surrounding countries need to be investigated. No conflicts of interest
Friday, 21 March 2014
10:30–11:30
POSTER DISCUSSION SESSION
Elderly and Lifestyle 412 Poster discussion DCIS distribution of grades in 5,126 screened and non-screened women and estimated risk of overdiagnosis in breast cancer screening: A model of progression P. van Luijt1 , E.A.M. Heijnsdijk1 , J. Fracheboud1 , M.J.M. Broeders2 , J. Wesseling3 , G.J. den Heeten2 , H.J. de Koning1 . 1 Erasmus MC University Medical Center Rotterdam, Public Health, Rotterdam, Netherlands; 2 Radboud University Medical Centre, Dept for health evidence, Nijmegen, Netherlands; 3 The Netherlands Cancer Institute, Pathology, Amsterdam, Netherlands Background: Ductal carcinoma in situ (DCIS) might represent either early detection of breast cancer destined to become invasive, lethal or be overdiagnosed. The malignant potential is dependent on grade, which can be low (I), intermediate (II), or high (III). We aimed to determine whether distribution of DCIS grade is dependent on mammography screening status and to estimate overdiagnosis rate by grade. Materials and Methods: We extracted grade from pathologic reports of 5,126 Dutch women of all ages in 2007–2009 with incident cases of DCIS, provided by PALGA: Dutch Pathology Registry. We established the incidence rate of the different DCIS grades by patients’ screening status and age. We added the distribution of the DCIS cases in our microsimulation model (MISCAN) and estimated overdiagnosis rates by DCIS grade. Results: Overall, 18.3% of DCIS were grade I, 30.9% grade II, and 50.8% grade III. This distribution did not differ by screening status. We found an inverse linear trend for grade with five-year age-groups: Higher age is associated with lower DCIS grade and vice versa. Overdiagnosis as proportion of all cancers in women of the screening age was 61% for DCIS I, 57% for DCIS II, 45% for DCIS III, and 2% for invasive cancer. For women with a grade III DCIS in the ages 50−60 this overdiagnosis rate was 21−29%, compared to 50−66% in women with grade III DCIS in the ages 60−75. Conclusions: Most DCIS are high grade. DCIS grade distribution depends on age, not on screening status. The estimated overdiagnosis rate among DCIS lesions is extremely high, except for younger women with a grade III DCIS, and calls for a non-treatment randomized controlled trial for low grade DCIS. Conflict of interest: Corporate-sponsored research: SCOR global Health 413 Poster discussion Does background enhancement at breast MRI influence diagnostic accuracy in mass versus non-mass-like lesions? N. Hansen1 , C.K. Kuhl1 , A. Barabasch1 , K. Strobel1 , S. Schrading1 . 1 RWTH Aachen University Hospital, Diagnostic and Interventional Radiology, Aachen, Germany Background: Purpose of our study was to determine the influence of background enhancement on diagnostic performance of breast MRI. Material and Methods: 335 women with 494 breasts underwent dynamic contrast-enhanced breast MRI in our institution from May 2010 to November 2012. Background enhancement in MRI was scored on a 4-point-scale from absent to strong. BIRADS diagnoses were assigned per breast. BIRADS6 lesions were excluded from analysis. Diagnoses were validated either by biopsy (BIRADS 4/5) or MRI follow-up >12 months (BIRADS 1−3). Sensitivity, specificity and PPV were calculated and compared for all classes of background enhancement and type of lesion. Fisher’s exact test was used for statistical analysis.
Poster Discussion Session
Friday, 21 March 2014
S169
Table (abstract 415): Number of women by age group who underwent specific treatments (percentage of eligible women in each age group who had treatment)
Surgery in women with Charlson comorbidity score 0 Radiotherapy following breast conserving surgery Chemotherapy given to women with Charlson comorbidity score 0
60−64
65−69
70−74
75−79
80−84
85+
Total
441 313 281 164 117
343 (86.6%) 231 (85.6%) 200 (86.6%) 94 (23.7%) 61 (22.6%)
231 (84.9%) 152 (86.9%) 108 (85.0%) 41 (15.1%) 32 (18.3%)
228 (75.8%) 121 (75.2%) 86 (78.2%) 23 (7.6%) 8 (5.0%)
117 (54.4%) 68 (65.4%) 29 (69.1%) 6 (2.8%) 2 (1.9%)
55 (26.2%) 29 (29.0%) 11 (11.0%) 2 (1.0%) 0 (0%)
1415/1888 (75.0%) 914/1165 (78.5%) 715/844 (84.7%) 330/1888 (17.5%) 220/1165 (18.9%)
(89.3%) (87.9%) (88.9%) (33.2%) (32.9%)
Results: Sensitivity of MRI in breasts categorized as MR-ACR1, 2, 3, and 4 was 98% (64/65), 100% (31/31), 100% (15/15), and 100% (5/5), respectively. Specificity was 83% (175/211), 72% (76/105), 57% (26/46), and 38% (6/16). PPV was 64% (64/100), 52% (31/60), 43% (15/35), and 33% (5/15). For mass-like lesions, specificity decreased from 26% (9/35) with MR-ACR1−2 to 25% (3/12) with MR-ACR3−4 and PPV from 70% (60/86) to 59% (13/22), respectively. For non-mass-like lesions, specificity decreased from 20% (10/49) to 16% (4/25) and PPV from 47% (35/74) to 25% (7/28). Conclusions: Background enhancement does not seem to interfere with the ability to identify invasive breast cancers and DCIS in MRI (p = 1). This, however, is achieved at the expense of specificity, which decreases significantly with MR-ACR3−4 (p < 0.05). PPV, in contrast, decreases more severely for non-mass-like lesions than for mass-like lesions (25% vs 59% with MR-ACR3−4). No conflicts of interest 414 Poster discussion Impact of comprehensive geriatric assessment on treatment decision and follow-up in older breast cancer patients 1
1
2
3
4
5
H. Bode , J. Bastin , C. Kenis , L. Decoster , J.P. Lobelle , K. Milisen , K. Van Puyvelde6 , J. Flamaing7 , H. Wildiers8 . 1 University Hospitals Leuven, General Medicine, Leuven, Belgium; 2 University Hospitals Leuven, General Medical Oncology and Geriatric Medicine, Leuven, Belgium; 3 University Hospitals Brussels, General Medical Oncology, Brussels, Belgium; 4 University Hospitals Leuven, Statistics, Leuven, Belgium; 5 University Hospitals Leuven, Centre for Health Services and Nursing Research and Department of Geriatric Medicine, Leuven, Belgium; 6 University Hospitals Brussels, Department of Geriatric Medicine, Brussels, Belgium; 7 University Hospitals Leuven, Department of Geriatric Medicine, Leuven, Belgium; 8 University Hospitals Leuven, Department of General Medical Oncology, Leuven, Belgium Background: We performed this study to investigate the impact of comprehensive geriatric assessment (CGA) on treatment decisions in a large cohort of older breast cancer patients. We also studied the functional evolution during treatment and the development of severe toxicity in patients receiving chemotherapy and we looked for predictive baseline markers of functional decline and toxicity. Patients and Methods: 379 older breast cancer patients were recruited in 2 Belgian university hospitals. Only patients aged 70 years or older with a newly diagnosed or progressive breast cancer for which treatment initiation or change was considered, were eligible. At baseline, a CGA and oncological parameters were obtained. The impact of CGA on treatment decision was assessed by offering a questionnaire to the treating physicians. At 2−3 months follow-up, functionality was reassessed and severe toxicity in patients receiving chemotherapy (n = 98) was recorded. Predictors for functional decline and toxicity were identified by multivariate analysis. Results: 79.2% of treating physicians were aware of CGA results at the time of treatment decision. CGA revealed new geriatric information in 70.5% of cases, leading to geriatric intervention in 5.4% of patients. Treatment was adapted according to age and standard clinical approach in 41.1% of cases and CGA results led to an additional change of treatment decision in 5.4%. At follow-up, 47.9% of patients was dependent on activities of daily living (ADL) (compared to 54.1% at baseline) and 64.7% was dependent on instrumental activities of daily living (IADL) (compared to 58.1% at baseline). Functional decline at 2−3 months was predicted by baseline ADL, IADL and ECOG-PS, but no markers were found to predict chemotherapy toxicity. Conclusions: CGA revealed previously unknown information in 70.5% of the older breast cancer patients. 20.8% of physicians were not aware of CGA results at time of treatment decision, while CGA led to geriatric interventions in 5.4% of cases and additionally changed treatment decision in 5.4%. A proper communication appears to be indispensible. Baseline functionality measures (ADL, IADL, ECOG-PS) were found to be predictive for functional decline at 2−3 months, but predictors for severe chemotherapy toxicity could not be identified. No conflicts of interest
415 Poster discussion A population based study of the management of older women with breast cancer taking into account levels of comorbidity A. Moran1 , S. Tabasum2 , C. Connor3 , B. Magee4 , V. Pope5 , R. Audisio6 , C. Holcombe7 , N. Bundred8 . 1 North West Knowledge and Intelligence Team, Public Health England, Manchester, United Kingdom; 2 The Christie NHS Trust, Cancer Intelligence, Manchester, United Kingdom; 3 The Christie NHS Trust, Clinical Oncology, Manchester, United Kingdom; 4 The Christie Hospital NHS Trust, Clinical Oncology, Manchester, United Kingdom; 5 Mid-Cheshire Hospitals, Department of Breast Surgery, Crew, United Kingdom; 6 St Helens and Knowsley NHS Trust, Department of Breast Surgery, St Helens, United Kingdom; 7 Royal Liverpool University Hospital, Department of Breast Surgery, Liverpool, United Kingdom; 8 University Hospital of South Manchester, Department of Breast Surgery, Manchester, United Kingdom Background: Several studies and audits have reported that many older women with breast cancer do not receive ‘standard treatment’, including a study of women diagnosed in 1999 in the same population (Lavelle K, et al.; BJC (2007) 96, 1197–1203). However, it is not clear how much of this is due to increasing levels of comorbidity in older age groups. Methods: All women resident in Greater Manchester, Merseyside or Cheshire diagnosed in 2009 with breast cancer at age 60 or older were identified from the North West Cancer Registry. Details on patient and tumour variables and patient management were abstracted from hospital notes. A Charlson comorbidity score was calculated. Of the 2314 women identified on the registry database, 1888 (82%) were included in the study. Results: The table shows a large decrease with age in the use of surgery, radiotherapy following breast conserving surgery and chemotherapy. Older women with a Charlson comorbidity score of 0 were still less likely to undergo surgery or receive chemotherapy. Conclusion: These results show lower uptake of standard treatment in older women, which is not explained by increasing levels of comorbidity with age. Though the decrease in uptake with age is not as marked as in the previous study by Lavelle, the results suggest that many older women are still under-treated. Conflict of interest: Corporate-sponsored research: The work outlined in this abstract is funded by Roche Products. I have previously received other research grants from Roche.
416 Poster discussion Effect of diabetes mellitus on early breast cancer patients receiving neoadjuvant therapy C. Fontanella1 , B. Lederer1 , J. Huober2 , B. Gerber3 , K.M. Mehta1 , V. Nekljudova1 , S. Gabe1 , G. von Minckwitz1 , M. Untch4 , S. Loibl1 . 1 German Breast Group, Medicine and Research, Neu-Isenburg, ¨ Germany; 2 Universitats-Frauenklinik, Breast Center, Ulm, Germany; 3 ¨ Universitats-Frauenklinik, Breast Center, Rostock, Germany; 4 Helios Klinikum Berlin-Buch, Breast Center, Berlin, Germany Background: Recent data suggested that diabetes mellitus (DM) may negatively affect outcome of neoadjuvant chemotherapy (NAT) of breast cancer (BC) patients. Material and Methods: From 2005 to 2011, 4,065 BC patients were enrolled in GeparQuattro and GeparQuinto trial. We evaluate the incidence of DM at the time of BC diagnosis and its impact on outcome of NAT. We defined pathological complete response (pCR) as ypT0 ypN0 and distant disease-free survival (DDFS) as time from diagnosis to recurrence of tumour or death from any cause, excluding ipsilateral BC recurrence, regional invasive recurrences, contralateral BC, and in situ carcinomas. We performed cross-tabulations and c2 -test to evaluate the effect of DM with respect to categorical variables and Cox proportional hazards regression analyses (including age, body mass index [BMI], number of comorbidities, hormone receptor and HER2 status, tumour [cT] and nodal [cN] stage, grading, histotype, adverse events [AE], and dose of chemotherapy) to
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Friday, 21 March 2014
investigate the effect of DM on DDFS. In addition, a Kaplan–Meier analysis was performed. Results: Overall 2.8% (n = 112) of patients had a diagnosis of DM; 33.9% (n = 38) of DM patients received concomitant metformin. DM patients had a median age of 61 years (36 to 78) and a median BMI of 30.3 kg/m2 (19.5 to 45.2), compared with median age 49 (21 to 78) and median BMI 24.9 (16.2 to 58.0) in non-DM patients. DM patients were diagnosed with a more advanced tumour (cT4d 17.6% vs 7.7%, p < 0.001) and nodal stage (cN2−3 14.8% vs 4.9%, p < 0.001). DM patients were more likely to have a reduction in taxane dose; 17.7% of DM patients received a median of <60 mg/m2 /cycle of docetaxel vs 7.9% of non-DM patients (p < 0.001). No significant correlation with reduction in epirubicin (<60% of planned dose: 3.8% DM vs 1.4% non-DM, p = 0.308) and cyclophosphamide dose (<60% of planned dose: 7.8% DM vs 7.8% non-DM, p = 0.196). No differences were observed in grade 3−4 both haematological (DM 86.6% vs non-DM 89.7%, p = 0.208) and non-haematological (DM 45.5% vs. non-DM 39.5%, p = 0.291) AE. No difference was observed in pCR rate (DM 18.8% vs. non-DM 19.1%, p = 0.921). DM patients had an increased risk of distant recurrence (HR 2.04, CI 1.14–3.64, p = 0.016; 5-year DDFS rate DM 68.6% vs non-DM 78.2%, p < 0.001). Conclusion: In our data, DM patients presented with a more advanced stage than non-DM patients. A detrimental impact of DM on DDFS in BC patients receiving NAT was observed. No conflicts of interest
417 Poster discussion Influence of body mass index on long-term outcome of breast cancer patients receiving neoadjuvant therapy − Combined results from the GBG (German Breast Group) and the EORTC cohorts C. Fontanella1 , L. Slaets2 , P. Neven3 , S. Loibl1 , M. Vanoppen3 , J. Bogaerts2 , G. von Minckwitz1 , D. Cameron4 , M. Untch5 , H. Bonnefoi6 . 1 German Breast Group, Medicine and Research, Neu-Isenburg, Germany; 2 EORTC, Headquarters, Brussels, Belgium; 3 Katholieke Universiteit Leuven, Multidisciplinary Breast Centre and Gynecological Oncology, Leuven, Belgium; 4 Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom; 5 Helios Klinikum ´ Breast Berlin-Buch, Breast Centre, Berlin, Germany; 6 Institut Bergonie, Centre, Bordeaux, France Background: Obesity is related to increased morbidity and mortality. A correlation with poor prognosis in breast cancer (BC) patients has been observed. However, it remains controversial if obesity affects outcome in different BC subtypes equally. Material and Methods: We retrospectively evaluated 10,727 neoadjuvant BC patients: 8,872 in 7 German Breast Group (GBG) trials and 1,855 treated in the EORTC 10994/BIG 1−00 trial. Body mass index (BMI)1 (<25 kg/m2 ), BMI2 (25–29.9 kg/m2 ), and BMI3 (30 kg/m2 ) were defined according to WHO classification. BC subtypes were defined as Luminal A/B (oestrogen [ER]/progesterone [PR] receptor-pos/HER2-neg), HER2-luminal (ER/PR-pos/HER2-pos), HER2-like (ER/PR-neg/HER2pos), and TNBC (ER/PR-neg/HER2-neg). Endpoints of the study were: distant disease-free survival (DDFS, STEEP definition, GBG cohort) and distant relapse free survival (DRFS, STEEP definition, EORTC cohort). We performed Kaplan–Meier analyses to estimate DDFS/DRFS according to BMI overall and in subgroups by BC subtype. Reported p-values correspond to the log rank test. Results: In both cohorts, median age increased with increasing BMI (GBG: BMI1 47 yrs, BMI2 52 yrs, BMI3 54 yrs, EORTC: BMI1 47 yrs, BMI2 51 yrs, BMI3 52 yrs). Survival analyses showed a significant decrease in DDFS/DRFS with increased BMI. In the GBG cohort 5-year DDFS rates were: 79.4% for BMI1, 78.4% for BM2, and 73.7% for BMI3 (p < 0.001). In the EORTC cohort 5-year DRFS rates were: 73.0% for BMI1, 64.3% for BMI2, and 62.2% for BMI3 (p < 0.001). The same relationship was found in Luminal A/B patients (GBG: 83.6% for BMI1, 84.5% for BM2, and 78.2% for BMI3; p = 0.008; EORTC: 83.0% for BMI1, 65.2% for BMI2 and 62.1% for BMI3; p < 0.001). In the GBG cohort, a significant result was observed also in TNBC (71.5% for BMI1, 69.1% for BM2, and 62.2% for BMI3; p = 0.018), not in the EORT cohort (63.4% for BMI1, 68.0% for BM2, and 64.7% for BMI3; p = 0.497). No significant result was found in HER2-luminal (GBG: p = 0.061, EORTC: p = 0.828) and HER2-like (GBG: p = 0.189, EORTC: p = 0.776) patients. In the EORTC cohort, a competing risk analysis for time to distant relapse (non-BC death as a competing risk) confirmed the DRFS results. Conclusion: In this joint study we demonstrate a decrease in DDFS/DRFS in neoadjuvant BC patients with a higher BMI compared with normal weight patients. In a subgroup analysis by BC subtype, this result
Poster Sessions applies to Luminal A/B patients in both cohorts and to TNBC patients in the GBG cohort. No conflicts of interest
Friday, 21 March 2014
10:30–11:30
EUROPA DONNA SESSION
Importance of Lifestyle Choices Before and After Breast Cancer 418 Key lifestyle choices for the prevention of breast cancer
Invited
Abstract not received 419 Key facts about preventing recurrence
Invited
A. Howell1 , M.H. Harvie2 . 1 The Christie Hospital, Department of Medical Oncology, Manchester, United Kingdom; 2 Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester, Manchester, United Kingdom The major question for this presentation is: “If a patient with early breast cancer makes appropriate lifestyle choices will this reduce her chances of relapse?”. Two randomised trials (WINS and WHEL) tested the hypothesis that the most appropriate lifestyle choice to take was to reduce fat intake and increase fruit and vegetable consumption. In the WINS study a total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups within 1 year of diagnosis. Fat intake was reduced from 51.3 to 33.3 g/day (35% reduction) and resulted in a 6 pound lower body weight in the intervention group which was associated with a significant 24% reduction in relapse after a median follow up of 60 months (Chlebowski RT et al. J Natl Cancer Inst 2006; 98: 1767). In the WHEL study 3088, women previously treated for early stage breast cancer, who were 18 to 70 years old at diagnosis, were enrolled between 1995 and 2000 and followed up through June 1, 2006. Fat intake was reduced in the treated group by 13% and vegetable, fruit and fibre intake by over 30% but there was no significant reduction in weight or relapse (Pierce JP. JAMA. 2007 July 18; 298(3): 289). The remainder of data on lifestyle after diagnosis is from observational studies. These indicate that overweight/obesity at diagnosis is consistently associated with relapse (Niraula S et al. BCRT 2012; 134: 769) but weight gain or weight loss (Caan BJ et al. CBEP 2012; 96: 123) or exercise (Beasley JM. BCRT 2012; 131: 637) are variably or not associated with relapse. New randomized studies of calorie restriction and exercise are required to test the hypothesis that there is benefit. Rack et al. in Germany (SUCCESS-C Trial. Breast Care 2010; 5: 395) have completed recruitment of 3547 women after surgery and chemotherapy for early breast cancer with a body mass index between 24 and 40 kg/m2 receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. This trial is due to report in 2014. Finally, a second randomized trial of lifestyle intervention is in progress in Italy (Villarini A et al. Tumori 2012; 98(1): 1−18). Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. The trial is due to report in 2016. The jury remains out until we have the results of these two trials. No conflicts of interest