The influence of obesity on survival in early,high-risk breast cancer: results from the randomized SUCCESS A trial

Introduction

Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear.

Methods

This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0–29.9), slightly obese (BMI 30.0–34.9), moderately obese (BMI 35.0–39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors.

Results

Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71–4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63–4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes.

Conclusions

Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02181101","term_id":"NCT02181101"}}NCT02181101. Registered September 2005.     

The Relationship Between Body Composition and Response to Neoadjuvant Chemotherapy in Women with Operable Breast Cancer

Introduction.

Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes.

Objectives.

To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m².

Methods.

Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black''s nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC.

Results.

BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue.

Conclusions.

Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.     

Efficacy of adjuvant aromatase inhibitor in hormone receptor-positive postmenopausal breast cancer patients according to the body mass index

Background:

Increased adiposity may trigger signalling pathways that induce aromatase expression. As aromatase inhibitors exert their effects by blocking the aromatase enzyme, higher body mass index (BMI) can reduce the effect of aromatase inhibitors. Thus, we aimed to investigate retrospectively the effect of BMI on the efficacy of aromatase inhibitors in hormone receptor-positive postmenopausal patients with breast cancer.

Methods:

Newly diagnosed hormone receptor-positive breast cancer patients who were postmenopausal and non-metastatic were enrolled to the study. Patients with BMI ranging between 18.5 and 24.9 kg m⁻² were considered as normal weight patients (Arm A, n=102), and patients with a BMI ranging ⩾25 kg m⁻² were grouped as overweight and obese patients (Arm B, n=399).

Results:

In both normal weight and overweight patients, the baseline clinico-pathologic properties and the treatment history with radiotherapy and chemotherapy were similar, and with no statistically significant difference. In normal weight patients disease-free survival (DFS) rate was 93.7% and 77.6%, whereas in overweight and obese patients DFS rate was 96.8% and 85.5% in the first and third years, respectively, (P=0.08). Three year survival rate in Arm A patients was 98.3%, whereas in Arm B was 98.0% (P=0.57). When anastrozole was compared with letrozole in the subgroup analysis no difference with regard to DFS and overall survival was detected.

Conclusion:

These results, contradictory to the prior results, show that BMI has no worse effect on outcomes of aromatase inhibitors in postmenopausal hormone receptor-positive breast cancer patients. In the subgroup analysis, letrozole and anastrozole had similar survival outcomes.     

Validation of nutritional risk index method against patient-generated subjective global assessment in screening malnutrition in colorectal cancer patients

Objective：To validate malnutrition screening tool of nutrition risk index （NRI） against patent-generated subjective global assessment （PG-SGA） as a gold standard tool in colorectal cancer patients before radiotherapy.Methods：Nutritional status of 52 volunteer colorectal cancer patients with a mean age of 54.1±16.8 years who referred to radiotherapy center were assessed by PG-SGA （gold standard method） and NRI.Serum albumin levels of patients were determined by colorimetric method.A contingency table was used to determine the sensitivity,specificity,and predictive value of the NRI in screening patients at risk of malnutrition,in comparison with the PG-SGA in patients before radiotherapy.Results：The findings of PG-SGA and NRI showed that 52％ and 45％ of patients in our study were moderately or severely malnourished respectively.The NRI had a sensitivity of 66％ and a specificity of 60％ against PG-SGA.The positive predictive value was 64％ and the negative predicative value was 62％.The agreement between NRI and PG-SGA was statistically insignificant （kappa =0.267; P＞0.05）.Conclusions：The findings of present study showed that the prevalence of malnutrition was high in patients with colorectal cancer.Moreover,NRI method had low sensitivity and specificity in assessing nutritional status of patients with cancer.It seems that the combination of anthropometric,laboratory parameters and a subjective scoring system may be helpful tools in screening of malnutrition in cancer patients.     

The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial

Background:

We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment.

Methods:

The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety.

Results:

In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07).

Conclusion:

Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.     

The impact of BMI on subgroups of uterine cancer

Background:

Obesity increases the risk of uterine cancer, but results by histological type have differed.

Methods:

We followed 36 755 women for 17.8 years for uterine cancers.

Results and conclusion:

Body mass index (BMI) was positively associated with uterine cancers as a whole, particularly for endometrioid adenocarcinomas, for which the relative risk for very obese women (BMI: ⩾40 kg m⁻²) compared with lean (BMI: 20–24 kg m⁻²) women, was 11.1 (95% confidence interval: 5.2–23.8).     

Long-term and baseline recreational physical activity and risk of endometrial cancer: the California Teachers Study

Background:

Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size.

Methods:

Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995–1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size.

Results:

Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (P_trend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95% CI, 0.63–0.92). This inverse association was observed among overweight/obese women (body mass index ≥25 kg m⁻²; P_trend=0.006), but not among thinner women (P_trend=0.12). Baseline moderate activity was associated with lower risk among overweight/obese women.

Conclusion:

Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.     

Tumor necrosis is an important hallmark of aggressive endometrial cancer and associates with hypoxia,angiogenesis and inflammation responses

Aims

Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions.

Methods and Results

By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB.

Conclusions

Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis.     

Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways

Introduction

Obesity has been associated with increased incidence and mortality of breast cancer. While the precise correlation between obesity and breast cancer remains to be determined, recent studies suggest that adipose tissue and adipose stem cells (ASCs) influence breast cancer tumorigenesis and tumor progression.

Methods

Breast cancer cells lines were co-cultured with ASCs (n = 24), categorized based on tissue site of origin and body mass index (BMI), and assessed for enhanced proliferation, alterations in gene expression profile with PCR arrays, and enhanced tumorigenesis in immunocompromised mice. The gene expression profile of ASCs was assess with PCR arrays and qRT-PCR and confirmed with Western blot analysis. Inhibitory studies were conducted by delivering estrogen antagonist ICI182,780, leptin neutralizing antibody, or aromatase inhibitor letrozole and assessing breast cancer cell proliferation. To assess the role of leptin in human breast cancers, Oncomine and Kaplan Meier plot analyses were conducted.

Results

ASCs derived from the abdominal subcutaneous adipose tissue of obese subjects (BMI > 30) enhanced breast cancer cell proliferation in vitro and tumorigenicity in vivo. These findings were correlated with changes in the gene expression profile of breast cancer cells after co-culturing with ASCs, particularly in estrogen receptor-alpha (ESR1) and progesterone receptor (PGR) expression. Analysis of the gene expression profile of the four groups of ASCs revealed obesity induced alterations in several key genes, including leptin (LEP). Blocking estrogen signaling with ICI182,780, leptin neutralizing antibody, or letrozole diminished the impact of ASCs derived from obese subjects. Women diagnosed with estrogen receptor/progesterone receptor positive (ER⁺/PR⁺) breast cancers that also expressed high levels of leptin had poorer prognosis than women with low leptin expression.

Conclusion

ASCs isolated from the abdomen of obese subjects demonstrated increased expression of leptin, through estrogen stimulation, which increased breast cancer cell proliferation. The results from this study demonstrate that abdominal obesity induces significant changes in the biological properties of ASCs and that these alterations enhance ER⁺/PR⁺ breast cancer tumorigenesis through estrogen dependent pathways.     

Men with cancer change their health behaviour: a prospective study from the Danish diet, cancer and health study

Background:

Health behaviour changes may improve the quality of life and survival among cancer survivors. We prospectively examined changes in health behaviour among and between men with prostate cancer (PC), men with cancers other than PC and cancer-free men.

Methods:

We analysed data for 20 914 men (50–65 years), 426 with cancer, and 20 488 persons who were cancer-free between baseline (1993–1997) and follow-up (2000–2002) in multiple linear regression models to determine differences in changes in body mass index (BMI) and in alcohol and tobacco consumption.

Results

Body mass index and tobacco and alcohol consumption decreased significantly (P<0.001) between baseline and follow-up among both men with cancer and cancer-free men. Men with cancers other than PC significantly decreased their BMI (β=−058; 95% confidence interval (CI): −0.77, −0.40) and tobacco consumption (β=−1.36; 95% CI: −2.22, −0.49) compared with cancer-free men and were significantly more likely to quit smoking and lose weight.

Conclusion:

Men with cancers other than PC decreased their tobacco consumption and BMI significantly more than cancer-free men. Men with cancer do change their health behaviour; clinicians should take this into account in planning follow-up care for cancer survivors.     

Serum triglyceride concentrations and cancer risk in a large cohort study in Austria

Background:

Blood lipid levels as part of the metabolic syndrome are thought to be linked to cancer risk. Few epidemiological studies have addressed the association between serum triglyceride (STG) concentrations and cancer risk.

Methods:

Serum triglyceride concentrations were collected in a health investigation (1988–2003). The analyses included 156 153 subjects (71 693 men and 84 460 women), with 5079 incident cancers in men and 4738 cancers in women, and an average of 10.6 years of follow-up. All malignancies were ascertained from the population cancer registry. Multivariate Cox proportional hazard models stratified by age and sex were used to determine adjusted cancer risk estimates and 95% confidence interval (95% CI).

Results:

In men and women combined, higher STG concentrations were associated with increased risk of lung (4th vs 1st quartile: HR, 1.94; 95% CI, 1.47–2.54), rectal (HR, 1.56; 95% CI, 1.00–2.44), and thyroid cancer (HR, 1.96; 95% CI, 1.00–3.84). Serum triglyceride concentrations were inversely associated with non-Hodgkin''s lymphoma. In men, STG concentrations were inversely associated with prostate cancer and positively with renal cancer. In women, STG concentrations were positively associated with gynaecological cancers. Stratification by BMI revealed a higher risk of gynaecological cancers in overweight than in normal weight women. No other associations were found.

Conclusions:

Our findings support the hypothesis that STG concentrations are involved in the pathogenesis of lung, rectal, thyroid, prostate, and gynaecological cancers.     

Joint effects of nulliparity and other breast cancer risk factors

Background:

Pregnancy may reduce breast cancer risk through induction of persistent changes of the mammary gland that make the breast less susceptible to carcinogenic factors. It is not known to what extent the effects of parity are independent of other breast cancer risk factors.

Methods:

In a Norwegian cohort of 58 191 women (2890 breast cancers), we assessed whether the effects of parity on postmenopausal breast cancer risk may be modified by menstrual and anthropometric factors. We calculated attributable proportions due to interaction as a measure of synergism.

Results:

Parity, height, body mass index (BMI), age at menarche and menopause were all associated with breast cancer risk in the expected directions. For BMI, follow-up was stratified into two age groups because of non-proportional hazards. We found that nulliparity and overweight may amplify each other''s effect on breast cancer risk among women after 70 years of age (attributable proportion 0.21, 95% confidence interval 0.04–0.39). There was some indication that parity and age at menopause may antagonise each other''s effect. Effects of parity were largely unaffected by age at menarche and height.

Conclusion:

Nulliparity and overweight may have a synergistic effect on breast cancer risk in elderly women. If confirmed by others, the findings may help disentangle the interplay of different causes of breast cancer.     

Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement

Background:

This study was performed to test the hypothesis that expression of small heat shock protein Hsp-27 is, at diagnosis, a reliable predictive biomarker of clinically aggressive prostate cancer.

Methods:

A panel of tissue microarrays constructed from a well-characterised cohort of 553 men with conservatively managed prostate cancer was stained immunohistochemically to detect Hsp-27 protein. Hsp-27 expression was compared with a series of pathological and clinical parameters, including outcome.

Results:

Hsp-27 staining was indicative of higher Gleason score (P<0.001). In tissue cores having a Gleason score >7, the presence of Hsp-27 retained its power to independently predict poor clinical outcome (P<0.002). Higher levels of Hsp-27 staining were almost entirely restricted to cancers lacking ERG rearrangements (χ² trend=31.4, P<0.001), although this distribution did not have prognostic significance.

Interpretation:

This study has confirmed that, in prostate cancers managed conservatively over a period of more than 15 years, expression of Hsp-27 is an accurate and independent predictive biomarker of aggressive disease with poor clinical outcome (P<0.001). These findings suggest that apoptotic and cell-migration pathways modulated by Hsp-27 may contain targets susceptible to the development of biologically appropriate chemotherapeutic agents that are likely to prove effective in treating aggressive prostate cancers.     

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study

Purpose

The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed.

Methods

Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006.

Results

The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses).

Conclusion

Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.     

High BMI is significantly associated with positive progesterone receptor status and clinico-pathological markers for non-aggressive disease in endometrial cancer

Background:

Endometrial cancer incidence is increasing in industrialised countries. High body mass index (BMI, kg m⁻²) is associated with higher risk for disease. We wanted to investigate if BMI is related to clinico-pathological characteristics, hormone receptor status in primary tumour, and disease outcome in endometrial cancer.

Patients and methods:

In total, 1129 women primarily treated for endometrial carcinoma at Haukeland University Hospital during 1981–2009 were studied. Body mass index was available for 949 patients and related to comprehensive clinical and histopathological data, hormone receptor status in tumour, treatment, and follow-up.

Results:

High BMI was significantly associated with low International Federation of Gynaecology and Obstetrics (FIGO) stage, endometrioid histology, low/intermediate grade, and high level of progesterone receptor (PR) mRNA by qPCR (n=150; P=0.02) and protein expression by immunohistochemistry (n=433; P=0.003). In contrast, oestrogen receptor (ERα) status was not associated with BMI. Overweight/obese women had significantly better disease-specific survival (DSS) than normal/underweight women in univariate analysis (P=0.035). In multivariate analysis of DSS adjusting for age, FIGO stage, histological subtype, and grade, BMI showed no independent prognostic impact.

Conclusion:

High BMI was significantly associated with markers of non-aggressive disease and positive PR status in a large population-based study of endometrial carcinoma. Women with high BMI had significantly better prognosis in univariate analysis of DSS, an effect that disappeared in multivariate analysis adjusting for established prognostic markers. The role of PR in endometrial carcinogenesis needs to be further studied.     

Mammographic density and survival in interval breast cancers

Introduction

Mammographic density (MD) is the strongest risk factor for breast cancer. It is also strongly associated with interval cancers (ICs) due to decreased screening sensitivity and possibly by also giving rise to more aggressive tumors. With this information as background, we compared survival in interval and screen-detected cancers, taking MD into consideration.

Methods

The patients were postmenopausal women ages 50 to 74 years who were diagnosed with breast cancer in Sweden between 1993 and 1995. A total of 1,115 women with screen-detected cancers and 285 with ICs had available mammograms. Cox proportional hazards models were used to compare breast cancer-specific survival between interval and screen-detected cancers stratified on MD.

Results

Hazard rates for breast cancer-specific survival were approximately three times higher in ICs than in screen-detected cancers, independent of MD. After adjustment for tumor size, a proxy for time to diagnosis, ICs in nondense breasts still had a statistically significantly increased hazard rate compared to screen-detected cancers in nondense breasts (5-yr survival hazard ratio (HR) 2.43, P = 0.001). In dense breasts, however, there was no longer evidence of a difference in survival between ICs and screen-detected cancers (5-yr survival HR 1.41, P = 0.486).

Conclusions

In nondense breasts, ICs seem to be truly more aggressive than screen-detected cancers. In dense breasts, the poorer prognosis of ICs compared to that of screen-detected cancers may be attributable at least partially to later detection. However, to the best of our knowledge, this study is the first to investigate these relationships, and further studies are warranted to confirm our results.     

The impact of body mass index on complication and survival in resected oesophageal cancer: a clinical-based cohort and meta-analysis

Background:

Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial.

Methods:

In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m⁻²) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication.

Results:

Patients with higher BMI had more postoperative complication (P=0.002), such as anastomotic leakage (P=0.016) and cardiovascular diseases (P<0.001), but less incidence of chylous leakage (P=0.010). Logistic regression analysis showed that BMI (P=0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70–0.92, P=0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) (P<0.001), oesophageal adenocarcinoma (EA) (P=0.034), never-smoking (P=0.035), ever-smoking (P=0.035), never alcohol consumption (P=0.005), weight loss (P=0.003) and advanced pathological stage (P<0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02–1.06, P=0.001), wound infection (RR=1.03, 95% CI: 1.00–1.05, P=0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00–1.05, P=0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96–0.99, P<0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71–0.85, P<0.001).

Conclusion:

Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer.     

Associations between BRCA Mutations in High-Risk Breast Cancer Patients and Familial Cancers Other than Breast or Ovary

Purpose

We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.

Methods

Patients with breast cancer who had at least one of the following risk factors were enrolled: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender. Genetic testing for BRCA mutation and questionnaires about personal and family histories of malignancies were performed.

Results

Among the 238 eligible patients, 49 (20.6%) patients had BRCA1/2 mutations, which were more frequent in patients with multiple risk factors (p<0.0001). There were 271 members of 156 (65.5%) families who had histories of other primary cancer. The distribution of the families was 119 (63.0%) and 37 (75.5%) in the BRCA-negative and positive group, respectively (p=0.0996). Multiple familial cancers occurred in 70 families, which were significantly more frequent in BRCA-positive families (p=0.0034). By ordinal logistic regression, the occurrence of multiple familial cancers was associated with BRCA mutations (p=0.0045), not with other risk factors. The most common site of disease was the stomach, which is the most common in nationwide. And the proportional incidence of pancreatic cancer (6.8%) was significantly higher than that of nationwide cancer statistics (2.4%, p=0.0137).

Conclusion

BRCA mutations in high-risk breast cancer patients were associated with multiple risk factors and multiple family members with other primary cancers. Genetic counseling based on accurate information should be provided to families with BRCA mutation carriers.     

Influence of Body Mass Index on Survival in Veterans With Multiple Myeloma

Purpose.

We investigated the association between body mass index (BMI) at the time of multiple myeloma (MM) diagnosis and overall survival in a cohort of patients within the Veterans Health Administration system. We also evaluated the association between weight loss in the year prior to diagnosis and survival.

Patients and Methods.

Prospective analysis was performed on a retrospectively assembled cohort of 2,968 U.S. veterans diagnosed and treated for MM between September 1, 1999, and September 30, 2009, with follow-up information through October 22, 2011. Cox modeling controlling for patient- and disease-related prognostic variables was used to analyze the data.

Results.

Underweight patients (BMI <18.5 kg/m²) had increased mortality, whereas patients who were overweight (BMI 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²) had lower mortality compared with healthy-weight patients (BMI 18.5–24.9 kg/m²). Weight loss ≥10% of baseline in the year before diagnosis was also associated with increased mortality and made the association between increased BMI and survival nonsignificant.

Conclusion.

Disease-related weight loss may be an important and heretofore unknown indicator of poor prognosis in MM. Assessment of weight loss prior to MM diagnosis should become a standard component of the clinical history in patients with newly diagnosed MM. Further research may identify relationships between disease-related weight loss and currently used prognostic factors in MM, further defining the role of this clinical factor in prognostic stratification.     

KRAS mutation profile differences between rectosigmoid localized adenocarcinomas and colon adenocarcinomas

Background

Colorectal cancer has a heterogeneous nature that is influenced by the tumour site. Many improvements have been made in identifying and characterizing the genetic alterations between colon and rectal cancers. However, there is not enough information about KRAS mutational differences between rectosigmoid and colon cancers arising elsewhere in the large bowel. The aim of this study was to determine the differences in the frequency of KRAS genetic alterations between rectosigmoid cancers and colon cancers.

Methods

Eighty-four patients diagnosed with colorectal cancer were included in this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumour tissue sections. KRAS mutation analysis which was designed to detect the seven most common KRAS gene mutations (Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp) was performed. Chi-square test was used to test the association between mutation status and other variables.

Results

This study represents the first KRAS mutational results from Turkish rectosigmoid cancer patients. The KRAS mutation frequency of rectosigmoid tumours is higher (34.3%, 12/35) than that of colon-localized tumours (30.6%, 15/49). However, there is no significant correlation between the KRAS mutation status and tumour location (rectosigmoid and colon).

Conclusions

KRAS mutation analysis has a predictive and prognostic value in identifying tumours that may be resistant to treatment. Our study shows that differences in the biological behaviour of rectosigmoid and colon cancers should be considered. This finding highlights the importance of personalized cancer management, which could be assisted by cancer genotyping tools.