Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012-2015 and 2015-2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012-2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015-2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

Gastric cancer incidence and mortality trends 2007-2016 in three European countries.

BACKGROUND : Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. METHODS : Data on 41 138 gastric cancers diagnosed in 2007-2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007-2011 vs. 2012-2016 were compared. RESULTS : Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. CONCLUSIONS : This is the first study comparing trends (2007-2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies.

Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years.

OBJECTIVE: The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years. DESIGN: Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change. RESULTS: We retrieved data on 143.7 million people aged 20-49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20-29 years from 2004 to 2016. The increase in the age group of 30-39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40-49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20-29 years, and 10-20 years later in those aged 30-39 and 40-49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30-39 years and 40-49 years, respectively. CONCLUSION: CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.

The contribution of second primary cancers to the mortality of patients with a gastric first primary cancer.

OBJECTIVES: Gastric first primary cancers (FPCs) have an increased risk of developing second primary cancers (SPCs). However, their effect on mortality remains poorly understood. Thus, we aimed to estimate the contribution of SPCs to the mortality of gastric FPCs. PATIENTS AND METHODS: A population-based cohort of gastric FPCs diagnosed in 2000-2006 was followed for SPCs (31 December 2012) and vital status (31 December 2017). SPCs (138 synchronous and 205 metachronous, ≤1 and >1 year after the FPC, respectively) were matched (1 : 3, by sex, 5-year age group, and year of FPC diagnosis) with those without an SPC and alive when the corresponding SPC was diagnosed. RESULTS: In synchronous SPCs, the hazard ratio (95% confidence interval) for death was 1.07 (0.81-1.40) in males and 0.86 (0.58-1.28) in females; the corresponding estimates for metachronous SPCs were 1.89 (1.49-2.41) and 2.08 (1.42-3.05). In synchronous SPCs, the 10-year cumulative mortality was similar to that of FPCs only; the estimates were higher in lung SPCs. The 10-year cumulative mortality was 75.5% in males and 65.5% in females with metachronous SPCs, which is more than 20% higher than for FPCs only. CONCLUSION: Among patients with gastric FPCs who survive long enough for metachronous SPCs, the latter substantially increases mortality over 10 years, whereas the effect of synchronous SPCs is generally smaller.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations.

OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

Second primary cancers and survival in patients with gastric cancer: association with prediagnosis lifestyles.

To quantify the association between prediagnosis lifestyles with the risk of second primary cancers (SPCs) and survival of patients with gastric first primary cancer (FPC). We recruited 574 gastric patients from two major public hospitals in North Portugal (2001-2006). Smoking, alcohol and dietary habits in the year before FPC diagnosis were evaluated. Patients were followed up to 31 December 2011 for an SPC and to 31 May 2017 for vital status. Cox proportional hazards regression was used to estimate adjusted hazard ratios for incidence of an SPC or death. During follow-up, SPCs were diagnosed in five women and 23 men, and 409 patients died, corresponding to an estimated 10-year cumulative incidence of 5.2% for SPC and an estimated 15-year cumulative mortality of 72.1%. A significantly higher hazard ratio (95% confidence interval) for SPCs was observed in patients reporting a higher consumption of red and processed meat versus the lowest third (4.49: 1.31-15.37), and for mortality in those with heavy alcohol intake versus never drinkers (1.73: 1.00-2.99) and excess weight versus normal weight (1.31: 1.04-1.65); no other significant associations were observed according to prediagnosis lifestyle. Prediagnosis lifestyles may affect the occurrence of an SPC and survival among gastric FPC survivors in the long term.

Western long-term accuracy of serum pepsinogen-based gastric cancer screening.

BACKGROUND: Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas. AIM: The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer. PARTICIPANTS AND METHODS: A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI≤70 ng/ml and PGI/PGII≤3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]. RESULTS: Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were 'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6]. Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58% (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups was over 24 months. CONCLUSION: The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.

Prostate cancer incidence and mortality in Portugal: trends, projections and regional differences.

There is a large geographical variability in prostate cancer incidence and mortality trends, mostly because of heterogeneity in control efforts across regions. We aimed to describe the time trends in prostate cancer incidence and mortality in Portugal, overall and by region, and to estimate the number of incident cases and deaths in 2020. The number of cases and incidence rates in 1998-2009 were collected from the Regional Cancer Registries. The number of deaths and mortality rates were obtained from the WHO mortality database (1988-2003 and 2007-2013) and Statistics Portugal (2004-2006; 1991-2013 by region). JoinPoint analyses were used to identify significant changes in trends in age-standardized incidence and mortality rates. Incidence and mortality predictions for 2020 were performed using Poisson regression models and population projections provided by Statistics Portugal. In Portugal, prostate cancer incidence has been increasing since 1998 (1.8%/year), with the exception of the North Region, with a decrease since 2006 (-3.2%/year). An overall mortality decline has been observed since 1997 (-2.2%/year), although there were two patterns of mortality variation at the regional level: one with an inflection point or significant variation in the rates and the other without significant variation. If these trends are maintained, ∼8600 incident cases and 1700 deaths may be expected to occur in Portugal in 2020. Despite the overall increasing incidence and decreasing mortality, there is a large heterogeneity across regions. Future studies should address regional differences in the trends of prostate specific antigen screening and in the effective management of prostate cancer.

Consistency and inconsistency in testing biomarkers in breast cancer. A GRELL study in cut-off variability in the Romance language countries.

PURPOSE: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries. METHODS: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers. RESULTS: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%). CONCLUSIONS: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.

Incidence rates and trends of lip, oral and oro-pharyngeal cancers in Portugal.

OBJECTIVES: To analyse the trends and patterns of lip, oral and oro-pharyngeal cancer incidence in Portugal between 1998 and 2007. PATIENTS AND METHODS: Data on lip, oral and oro-pharyngeal cancers was collected from the databases maintained at the three main Regional Cancer Registries of Portugal (1998-2007). The data were analysed by gender, age and by site. Incidence rates were age standardized by the direct method, and joinpoint regression was used to estimate trends in incidence. RESULTS: During this 10-year period, a total of 9623 cases of lip, oral and oropharynx cancers were reported, 7565 (78.6%) in males and 2058 (21.4%) in females. There was an increase in the age-standardized incidence of oral cancers by 1.96% per year for both sexes grouped together and an increase of 4.34% per year for the female group. Oro-pharyngeal cancer showed an increase incidence trend of 3.49% per year for both sexes grouped together and an increase of 3.49% per year for male group among the sites analysed. Lip cancer showed a decrease in its incidence rate. CONCLUSION: In view of rising trends, it is necessary to implement policies on oral cancer control by initiating campaigns on oral cancer awareness and screening and to harness political measures on tobacco and alcohol control for the Portuguese population.