Luminal (Her2 negative) prognostic index and survival of breast cancer patients

PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer.     

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

BackgroundObesity is a convincing risk factor for colorectal cancer. Genetic variants in or near FTO and MC4R are consistently associated with body mass index and other body size measures, but whether they are also associated with colorectal cancer risk is unclear.MethodsIn the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100 kb upstream and 300 kb downstream from each respective locus with risk of colorectal cancer in data from the Colon Cancer Family Registry (CCFR: 1960 cases; 1777 controls). Next, all SNPs that were nominally statistically significant (p < 0.05) in the discovery stage were included in replication analyses in data from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO: 9716 cases; 9844 controls).ResultsIn the discovery stage, 43 FTO variants and 18 MC4R variants were associated with colorectal cancer risk (p < 0.05). No SNPs remained statistically significant in the replication analysis after accounting for multiple comparisons.ConclusionWe found no evidence that individual variants in or near the obesity-related genes FTO and MC4R are associated with risk of colorectal cancer.     

Voluntary breath-hold reduces dose to organs at risk in radiotherapy of left-sided breast cancer

AimTo compare the dose to organs at risk with free breathing (FB) or voluntary breath-hold (VBH) during radiotherapy of patients with left sided breast cancer.BackgroundRadiotherapy reduces the risk of breast-cancer-specific mortality but the effects on other organs increase non-cancer-specific mortality. Radiation exposure to the heart, in particular in patients with left sided breast cancer, can be reduced by breath hold methods that increase the distance between the heart and the radiation field.Materials and MethodsThree-dimensional conformal radiotherapy (3D-CRT) dose plans for the left breast and organs at risk including the heart, left anterior descending coronary artery (LAD) and ipsilateral lung were compared with FB and VBH in ten patients with left sided breast cancer.ResultsThe mean doses to the heart and LAD were reduced by 50.4 % (p < 0.001) and 58.8 % (p = 0.006), respectively, in VBH relative to FB. The mean dose to the ipsilateral lung was reduced by 13.8 % (p = 0.11) in VBH relative to FB. The planning target volume (PTV) coverage was at least 95 % in both FB and VBH (p = 0.78).ConclusionThe VBH technique significantly reduces the dose to organs at risk in 3D-CRT treatment plans of left sided breast cancer.     

Breast cancer susceptibility loci in association with age at menarche,age at natural menopause and the reproductive lifespan

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies. Methods: The first analysis was based on a sample of 1328 women age 20–74 who participated as controls in a case–control study of breast cancer conducted in three U.S. states. We evaluated the associations between age at menarche, age at natural menopause and the reproductive lifespan with 13 previously identified breast cancer variants. Associations were also examined with a genetic score created as the sum of at-risk alleles across the 13 variants. For validation, significant results were evaluated in a second dataset comprised 1353 women age 43–86 recruited as part of a cohort study in Wisconsin. Results: Neither the genetic score nor any of the 13 variants considered individually were associated with age at menarche or reproductive lifespan. Two SNPs were associated with age at natural menopause; every increase in the minor allele (A) of rs17468277 (CASP8) was associated with a 1.12 year decrease in menopause age (p = 0.02). The minor allele (G) of rs10941679 (5p12) was associated with a 1.01 year increase in age at natural menopause (p = 0.01). The results were not replicated in the validation cohort (B = −0.61, p = 0.14 and B = −0.01, p = .0.98, respectively). Conclusions: The evaluated variants and reproductive experiences may work through separate pathways to influence breast cancer risk.     

Serum level of prostate-specific antigen (PSA) in women with breast cancer

ObjectiveTo identify the diagnostic role of total and free prostate-specific antigen (TPSA and FPSA) in breast cancer in women.MethodsBlood samples of 55 women with breast cancer were prospectively analyzed for PSA before and after breast surgery, with a control group of 82 healthy women.ResultsTotal and free PSA levels were significantly higher in women with breast cancer (preoperatively) than in healthy women (P < 0.001). Both serum TPSA and FPSA showed a significant decline in their pre-surgical values after surgical removal of the tumor (P < 0.001). A significant proportion of breast cancer patients (83.6%) had free PSA as the predominant molecular form in serum as compared to 0% of controls and 1.8% of postoperative groups (P < 0.001). TPSA and FPSA levels were significantly associated with younger age and earlier cancer stage, whereas no significant association was found between these two variables and FPSA as a predominant molecular form.ConclusionsThis study indicated a clinical significance of preoperative measurement of serum TPSA and FPSA in the diagnosis of women with breast cancer, and may be a useful marker for monitoring the response to treatment.     

Socioeconomic status,human papillomavirus,and overall survival in head and neck squamous cell carcinomas in Toronto,Canada

BackgroundDespite universal healthcare in some countries, lower socioeconomic status (SES) has been associated with worse cancer survival. The influence of SES on head and neck cancer (HNC) survival is of immense interest, since SES is associated with the risk and prognostic factors associated with this disease.Patients and methodsNewly diagnosed HNC patients from 2003 to 2010 (n = 2124) were identified at Toronto’s Princess Margaret Cancer Centre. Principal component analysis was used to calculate a composite score using neighbourhood-level SES variables obtained from the 2006 Canada Census. Associations of SES with overall survival were evaluated in HNC subsets and by p16 status (surrogate for human papillomavirus).ResultsSES score was higher for oral cavity (n = 423) and p16-positive oropharyngeal cancer (OPC, n = 404) patients compared with other disease sites. Lower SES was associated with worse survival [HR 1.14 (1.06–1.22), p = 0.0002], larger tumor staging (p < 0.001), current smoking (p < 0.0001), heavier alcohol consumption (p < 0.0001), and greater comorbidity (p < 0.0002), but not with treatment regimen (p > 0.20). After adjusting for age, sex, and stage, the lowest SES quintile was associated with the worst survival only for OPC patients [HR 1.66 (1.09–2.53), n = 832], primarily in the p16-negative subset [HR 1.63 (0.96–2.79)]. The predictive ability of the prognostic models improved when smoking/alcohol was added to the model (c-index 0.71 vs. 0.69), but addition of SES did not (c-index 0.69).ConclusionSES was associated with survival, but this effect was lost after accounting for other factors (age, sex, TNM stage, smoking/alcohol). Lower SES was associated with greater smoking, alcohol consumption, comorbidity, and stage.     

The relationship between ethnicity,social deprivation and late presentation of colorectal cancer

IntroductionTumour staging at time of presentation is an important factor in determining survival in colorectal cancer. The aim of this paper is to investigate the relationship between ethnicity and deprivation in late (Stage IV) presentation of colorectal cancer.MethodsData from the Thames Cancer Registry comprising 77,057 colorectal cancer patients between the years 2000 and 2012 were analysed.ResultsA total of 17,348 patients were identified with complete data, of which 53.9% were male. Patients from a Black Afro/Caribbean background were diagnosed with CRC at a much younger age than the White British group (median age 67 compared with 72, p < 0.001). In multiple regression, ethnicity, deprivation and age were positive predictors of presenting with advanced tumour stage at time of diagnosis. Black patients were more likely to present with Stage IV tumours than white patients (OR 1.37, 95% CI 1.18–1.59, p < 0.001). Social deprivation was also a predictor of Stage IV cancer presentation, with the most deprived group (Quintile 5) 1.26 times more likely to be diagnosed with Stage IV cancer compared with the most affluent group (CI 1.13–1.40, p < 0.001). Sub-group analyses demonstrated that Black & Affluent patients were still at greater risk of Stage IV CRC than their White & Affluent counterparts (OR 1.24, 95% CI 1.11–1.45, p = 0.023). Patients with rectal cancer were less likely to present with Stage IV CRC (OR 0.66, 95% CI 0.61–0.71, p < 0.001).ConclusionRacial and age related disparities exist in tumour presentation in the United Kingdom. Patients from black and socially deprived backgrounds as well as the elderly are more likely to present with advanced tumours at time of diagnosis.     

Patterns of HER2 testing in the management of primary breast cancer

Background: Women with invasive breast cancer should be tested for human epidermal growth factor receptor-2 (HER2) status at the time of diagnosis. To date, no population-based patterns of use studies have examined demographic and clinicopathologic factors associated with decisions by clinicians to test patients. Methods: We reviewed summary pathology reports submitted to the Connecticut Tumor Registry for all Black/African American (B/AA) women (n = 644) and a 7% random sample (n = 720) of White women diagnosed in 2000–2003 with primary invasive breast carcinoma. Receipt of a HER2 test (yes vs. no) was examined in relation to patient race, age, socioeconomic status, year of diagnosis, estrogen receptor (ER) status, tumor grade, lymph node status, size and stage at diagnosis. Results: A greater proportion of tumors from B/AA patients were tested compared to those of White women (69.5% vs. 61.9%, p < 0.05). Tumors of patients under the age of 60 were 1.50-times more likely than older women to have been tested, and B/AA women were 1.40-times more likely than White patients to be tested. HER2 testing was more likely to be observed when information also was reported about ER status (OR = 15.9, p < 0.001), tumor grade (OR = 2.28, p < 0.05), tumor size (OR = 2.16, p < 0.05), and lymph node status (OR = 2.06, p < 0.05). Conclusions: Variation in which breast cancer patients received HER2 testing appears to reflect expectations about a woman's prognosis. Discrepancies in receipt of testing deserve further study as current guidelines call for all tumors to be assessed in order to adequately characterize prognosis and determine eligibility for HER2-targeted therapy.     

Cancer incidence in ethnic German migrants from the Former Soviet Union in comparison to the host population

AimTo investigate cancer incidence patterns among ethnic German migrants (Aussiedler) from the Former Soviet Union, a large migrant group in Germany, in comparison to autochthonous Saarland population over a 20 year observation period.MethodsData were obtained from a cohort of Aussiedler residing in the federal state of Saarland (n = 18,619). Cancer incidence and vital status were ascertained through record linkage with the Saarland Cancer Registry and local population registries.ResultsDuring the follow up period from 1990 to 2009 we observed 638 incident diagnoses of malignant neoplasms (except non-melanoma skin cancer). The overall standardized incidence ratio (SIR) was 0.98 (95% confidence interval 0.92, 1.04). However, site-specific SIRs revealed great variation. Stomach cancer incidence was significantly higher among Aussiedler. Lung cancer was elevated for males, but lower among females. Additionally, diagnoses for colorectal cancer among males were significantly lower. Age-standardized rates (ASRs) over time show not all cancer rates of Aussiedler attenuate as expected to Saarland rates. For example, lung and prostate cancer incidence rates show increasing disparity from Saarland rates and female breast cancer incidence develops in parallel. Furthermore, ASR for overall cancer incidence of Aussiedler shows a yearly decrease (p = 0.06) whereas Saarland rates remain stable.DiscussionAussiedler incidence rates reflect incidence pattern observed in their countries of origin.     

Survival of hepatocellular carcinoma patients is significantly improving: a population-based study from southern Switzerland

BackgroundDuring the last 20 years, relevant diagnostic procedures and advanced treatments have been progressively introduced in the management of hepatocellular carcinoma (HCC).The aim of the present study was to assess up-to-date survival trends for HCC in southern Switzerland, a region with one of the highest incidence rates in the country.MethodsHCCs diagnosed in 1996–2009 were selected by the Ticino Cancer Registry. Cancer-specific survival (CSS) analysis was performed using the Kaplan–Meier method by calendar period: 1996–2000, 2001–2005 and 2006–2009. The log-rank test was used to detect differences in survival curves. Simultaneous assessment of prognostic factors was performed by a multivariate analysis using the Cox proportional-hazards regression model.Results619 HCCs were analysed. There was a significant increase of patients undergoing transarterial chemoembolisation (TACE), whereas patients undergoing curative or palliative supportive treatments remained unchanged (p < 0.0001). No shift to earlier stages was detected. Significant differences in CCS were observed by age-group (p < 0.0001), diagnosis period (p < 0.0001), diagnosis technique (p = 0.0035), Barcelona-Clinic liver cancer stage (p < 0.0001), treatment (p < 0.0001). Multivariate analysis confirmed the independent impact on CSS of factors above mentioned, not including the diagnosis technique. Death risk was higher for patients diagnosed in 1996–2000 (HR: 1.32; 95% CI: 1.03; 1.68) and 2001–2005 (HR: 1.33; 95% CI: 1.05; 1.67) in comparison with 2006–2009 (reference group).ConclusionsThe current population-based report describes a major increase in HCC survival. Simultaneously an increased use of TACE has been detected, probable cofactor of the observed survival increase. Possibly additional efforts could be made to decrease the HCC stage at diagnosis through active surveillance of cirrhotic patients to allow an increase in curative treatments. For sure efforts should be made to comply with a standardised staging system for HCC, particularly for comparative population-based issues.     

Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments?

Background and purposeTomoDirect (TD) can only operate in free-breathing. The purpose of this study is to compare TD with breath-hold 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) techniques for left breast treatments, and to determine if the lack of respiratory gating is a handicap for cardiac sparing.Materials and methods15 patients treated for left breast had two computed tomography simulation, in free breathing (FB) and in deep-inspiration breath-hold (DIBH). Four treatments were planned: TD-FB, 3DCRT-FB, 3DCRT-DIBH and IMRT-DIBH. Dose to PTV, heart, lungs, right breast and patient were compared.ResultsA slightly lower cardiac mean dose is found for 3DCRT-DIBH than for TD-FB group (1.99 Gy Vs 2.89 Gy, p = 0.0462), while no statistical difference is found for heart V₂₀. TD-FB plans show the best PTV dose homogeneity (0.053, p < 0.001) and the lowest left lung mean dose (5.16 Gy, p < 0.001). No major differences are found for the other organs.ConclusionsTomoDirect and breath-hold 3DCRT are complementary techniques for left breast treatments: for a minority of patients, respiratory gating is mandatory to lower cardiac dose; for the remaining majority of patients, TomoDirect achieves better PTV homogeneity and reduced left lung dose, with cardiac dose equivalent to 3DCRT-DIBH.     

Peri-operative blood transfusion for resected colon cancer: Practice patterns and outcomes in a population-based study

Background & objectivesLiterature suggests that peri-operative blood transfusion among patients with resected colon cancer may be associated with inferior long-term survival. The study objective was to characterize this association in our population.MethodsThis is a retrospective cohort study using the population-based Ontario Cancer Registry (2002–2008). Pathology reports were obtained for a 25% random sample of all cases and constituted the study population. Log binomial regression was used to identify factors associated with transfusion. Cox proportional hazards model explored the association between transfusion and cancer specific survival (CSS) and overall survival (OS).ResultsThe study population included 7198 patients: 18% stage I, 36% stage II, 40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused. Factors independently associated with transfusion included advanced age (p < 0.001), female sex (p < 0.001), greater comorbidity (p < 0.001), more advanced disease (p < 0.001) and open surgical resection (p < 0.001). Transfusion was associated with inferior CSS (HR 1.51, 95% CI 1.38–1.65) and OS (HR 1.52, 95% CI 1.41–1.63), after adjusting for important confounders.ConclusionsPeri-operative transfusion rates among patients with colon cancer have decreased over time. Transfusion is associated with inferior long-term CSS and OS.     

Analysis of O6-methylguanine-DNA methyltransferase methylation status in sporadic colon polyps

Background/aimThe aim of our study was to check how MGMT methylation status together with known factors influenced the risk of colon cancer development.Materials and methodsWe examined patients with colon polyps. Information concerning gender, age, lifestyle, diet, anthropometry and medical information, including cancer and family history of cancer, was analyzed. Polymorphism variety of MGMT gene was investigated in another study. Genetic analysis for MGMT methylation assessment was performed for polyp tissue samples from 143 patients.ResultsPositive methylation MGMT status was found in 55 patients. There was no correlation between gender and MGMT methylation status (p = 0.43). We did not find correlation between patients younger and older than 60 (p = 0.87). There was no correlation between smoking and MGMT methylation status (p = 0.36). We did not find correlation between BMI and MGMT methylation status (p = 0.86). We did not find correlation between MGMT methylation status and colon cancer in familial history (p = 0.45).ConclusionOur study showed no correlations between methylation status of MGMT polymorphisms and clinical features like age, gender, polyp localization, smoking status, or obesity. It has been shown previously that MGMT methylation status may show nonspecific methylation in colon polyps. Gene methylation status in adenoma tissues has also been associated by other authors with the adenoma's size, histology, and degree of atypia. In our study, we evaluated the gene methylation status in colon polyps and found no association with adenoma characteristics. The present study showed no correlation for MGMT methylation in polyps in different regions of colon.     

Does consanguinity lead to decreased incidence of breast cancer?

Background: In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend. Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors. Aim: The aim of this study was to examine the possible effect of consanguinity on the risk of breast cancer in a population with a high rate of consanguinity and find the associated risk-modifying factors. Subjects and methods: The study included 167 Qatari and other Arab expatriates women with breast cancer and 341 age and ethnicity matched control women. A questionnaire that included the socio-demographic information, type of consanguinity, medical history, life style habits, dietary intake and tumor grade was designed to collect, the information of cases and controls. A total number of 214 breast cancer patients were approached and 167 cases completed the questionnaires with a response rate of 78%. Of the 417 healthy women who agreed to participate in this study, 341 responded to the questionnaire (81.8%). Results: The study revealed that the rate of parental consanguinity was lower in breast cancer patients (24%) than in controls (32.3%) (p = 0.062). Female controls were slightly younger (46.5 ± 11.9) than breast cancer patients (48.4 ± 10.7). Breast cancer incidence was significantly higher in Qatari women (34.1%) compared to other Arab women (65.9%) (p = 0.034). A significant difference was noted only in occupation of the studied women between cases and controls (p < 0.001). Overweight (46.7%) and obesity (32.9%) were significantly higher in female breast cancer patients compared to controls (p = 0.028). Overall, the mean coefficient of consanguinity was lower in breast cancer patients (0.014) than in controls (0.018) (p = 0.0125). Family history of breast cancer was significantly more often in breast cancer patients (14.4%) than in controls (6.2%) (p = 0.002). However, the family history of breast cancer was more often positive in cases of non-consanguineous parents (15.7%) than cases of consanguineous parents (10.0%). Conclusion: The present study revealed the lack of association between of breast cancer and the parental consanguinity in Arab women residing in Qatar. The family history of breast cancer and the body mass index (BMI) are highly associated with breast cancer.     

Comparison of quadrant-specific breast cancer incidence trends in the United States and England between 1975 and 2013

BackgroundUK breast cancer incidence rates suggest that upper outer quadrant (UOQ) cancers have risen disproportionately compared with other areas over time. We aimed to provide a comparison of the trend in quadrant-specific breast cancer incidence between the United States (US) and England, and determine whether a disproportionate UOQ increase is present.MethodsSurveillance Epidemiology and End Results (SEER) cancer registry data were obtained on 630,007 female breast cancers from 1975 to 2013. English cancer registry data were obtained on 1,121,134 female breast cancers from 1979 to 2013. Temporal incidence changes were analysed using negative binomial regression. Interaction terms determined whether incidence changes were similar between sites.ResultsEnglish breast cancer incidence in the UOQ rose significantly from 13% to 28% from 1979 to 2013 whereas no significant increase was observed among SEER data. The significant interaction between quadrant and year of diagnosis (p < 0.001) in both SEER and English data indicates that breast cancer incidence in each quadrant changed at a different rate. Incidence in the UOQ rose disproportionately compared to the nipple (SEER IRR = 0.81, p < 0.001; England IRR = 0.78, p < 0.001) and axillary tail (SEER IRR = 0.87, p = 0.018; England IRR = 0.69, p < 0.001) in both SEER and England. In addition, incidence rose disproportionately in the UOQ compared to non-site-specific tumours in England (Overlapping lesions IRR = 0.81, p = 0.002; NOS IRR = 0.78, p < 0.001). The proportion of non-site-specific tumours was substantially higher in England than SEER throughout the study period (62% in England; 39% in SEER).ConclusionsBreast cancer incidence in the UOQ increased disproportionately compared to non-site-specific tumours in England but not in SEER, likely due to the decrease in non-site-specific tumours observed in England over time. There may be real differences in incidence between the two countries, possibly due to differences in aetiology, but is much more likely to be an artefact of changing data collection methods and improvements in site coding in either country.     

Clinical examples of 3D dose distribution reconstruction,based on the actual MLC leaves movement,for dynamic treatment techniques

AimTo present practical examples of our new algorithm for reconstruction of 3D dose distribution, based on the actual MLC leaf movement.BackgroundDynaLog and RTplan files were used by DDcon software to prepare a new RTplan file for dose distribution reconstruction.Materials and methodsFour different clinically relevant scenarios were used to assess the feasibility of the proposed new approach: (1) Reconstruction of whole treatment sessions for prostate cancer; (2) Reconstruction of IMRT verification treatment plan; (3) Dose reconstruction in breast cancer; (4) Reconstruction of interrupted arc and complementary plan for an interrupted VMAT treatment session of prostate cancer. The applied reconstruction method was validated by comparing reconstructed and measured fluence maps. For all statistical analysis, the U Mann–Whitney test was used.ResultsIn the first two and the fourth cases, there were no statistically significant differences between the planned and reconstructed dose distribution (p = 0.910, p = 0.975, p = 0.893, respectively). In the third case the differences were statistically significant (p = 0.015). Treatment plan had to be reconstructed.ConclusionDeveloped dose distribution reconstruction algorithm presents a very useful QA tool. It provides means for 3D dose distribution verification in patient volume and allows to evaluate the influence of actual MLC leaf motion on the dose distribution.     

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction

AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking.BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed.Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis.ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis.ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.     

Clinical outcomes of female breast cancer according to BRCA mutation status

BackgroundTo investigate breast cancer prognosis (disease-free (DFS) and overall survival (OS)) among carriers of germline BRCA mutations (BRCAm) in Denmark.MethodsWe identified all women in Central and Northern Denmark diagnosed with breast cancer during 2004–2011. We retrieved information on germline BRCAm testing from Clinical Genetics departments and clinical/treatment characteristics from population-based medical registries. Follow-up for recurrence, new primary cancer, and mortality extended from 180 days after diagnosis until 31/12/2012. We estimated median DFS and OS and five-year cumulative incidence and incidence rates (IR/1000 person-years), and 95% confidence intervals (95% CI), for each outcome.ResultsAmong 9874 patients, 523 (5%) underwent BRCA testing—90 were BRCAm carriers, 433 were BRCA wildtype (BRCAwt). Compared with BRCAwt women, BRCAm carriers were younger, had lower stage, and ER- and HER2- tumors. Median time from diagnosis to BRCA testing was 0.91 years and 1.3 years in BRCAm and BRCAwt women; median follow-up to first event was 3.9 and 3.4 years, respectively. Five-year DFS and OS were higher in BRCAm than BRCAwt women: 88% (95%CI = 78.3–93.5) vs. 75.3% (95%CI = 70.2–79.6) and 97.8% (95%CI = 91.4–99.4) vs 92.2% (95%CI = 88.5–94.7), respectively. Five-year IRs of recurrence were 36.7/1000 person-years (95%CI = 15.8–72.2) in the BRCAm cohort vs. 58.4 (95%CI = 42.9–77.6) in the BRCAwt cohort.ConclusionsBRCAm carriers may have a better prognosis than BRCAwt women. However, limited testing conducted mainly during follow-up, yielded low numbers for precise estimations, and may be attributable to selection bias.     

Patterns of metachronous metastases after curative treatment of colorectal cancer

BackgroundThis study aimed to provide information on timing, anatomical location, and predictors for metachronous metastases of colorectal cancer based on a large consecutive series of non-selected patients.MethodsAll patients operated on with curative intent for colorectal cancer (T_anyN_anyM₀) between 2003 and 2008 in the Dutch Eindhoven Cancer Registry were included (N = 5671). By means of active follow-up by the Cancer Registry staff within ten hospitals, data on development of metastatic disease were collected. Median follow-up was 5.0 years.ResultsOf the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases. Most common affected sites were the liver (60%), lungs (39%), extra-regional lymph nodes (22%), and peritoneum (19%). 86% of all metastases was diagnosed within three years and the median time to diagnosis was 17 months (interquartile range 10–29 months). Male gender (HR = 1.2, 95%CI 1.03–1.32), an advanced primary T-stage (T4 vs. T3 HR = 1.6, 95%CI 1.32–1.90) and N-stage (N1 vs. N0 HR = 2.8, 95%CI 2.42–3.30 and N2 vs. N0 HR = 4.5, 95%CI 3.72–5.42), high-grade tumour differentiation (HR = 1.4, 95%CI 1.17–1.62), and a positive (HR = 2.1, 95%CI 1.68–2.71) and unknown (HR = 1.7, 95%CI 1.34–2.22) resection margin were predictors for metachronous metastases.ConclusionsDifferent patterns of metastatic spread were observed for colon and rectal cancer patients and differences in time to diagnosis were found. Knowledge on these patterns and predictors for metachronous metastases may enhance tailor-made follow-up schemes leading to earlier detection of metastasized disease and increased curative treatment options.     

Haplotype analysis of p53 polymorphisms: Arg72Pro,Ins16bp and G13964C in Tunisian patients with familial or sporadic breast cancer

Background: The p53 polymorphisms have been extensively studied as putative breast cancer susceptibility variants. The present study was undertaken to investigate the association of p53 Arg72Pro, Ins16bp and G13964C polymorphisms and their haplotypes with breast cancer risk in Tunisian women. Methods: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 159 patients and 132 controls. Results: The G13964C intronic variant was significantly associated with familial breast cancer risk (p = 0.0018) while the genotypic distribution was similar for p53 Arg72Pro and Ins16bp in patients and controls. Moreover, the (NoIns-C), (Arg-C) and (NoIns-Arg-C) haplotypes were significantly associated with familial breast cancer risk (p = 0.0021, p = 0.0096 and p = 0.0084, respectively) while there was a trend of association between the (Ins-Arg) and (Ins-Arg-G) haplotypes and the risk of sporadic breast cancer. Only the G/C genotype as well as the (NoIns-C) haplotype remained significant after correction for multiple testing. Conclusion: Our data revealed an association between the G/C genotype and the (NoIns-C) haplotype and the risk of familial breast cancer in Tunisian women. However, these observations need to be confirmed due to the limited statistical power of our study and the small number of cases.