Breast cancer family history leads to early breast cancer detection and optimal management.

PURPOSE: We investigated whether the relationship between family history (FH) of breast cancer and survival of women with breast cancer is related to the quality of care received, once adjusted for other prognostic variables using data from the Geneva population-based cancer registry and quality of care indicators defined by the European Society of breast cancer specialists (EUSOMA). METHODS: We included non-metastatic malignant breast tumor patients who had their surgery between 2001 and 2010. We assessed the association between FH and patient and tumor characteristics on one hand, and each quality of care indicator and an overall score of quality of care, on the other hand, through logistic regression. We assessed the impact of FH and the quality of care-score on 5-year survival with Cox regression adjusting for patient and tumor characteristics. RESULTS: 2,672 patients were included in the study. Women with a positive FH were younger, more likely from Switzerland, screen detected, had positive estrogen and progesterone receptor status, and had smaller and ductal tumors. A positive FH was also associated with better management for several quality indicators. Women with a positive FH had a better crude survival (Hazard Ratio 0.61, p = 0.006). This association was not substantially affected when adjusting for quality of care. However, the effect of FH did not persist when also adjusting for patient and tumor characteristics. CONCLUSIONS: A positive FH of breast cancer is associated with earlier breast cancer diagnosis, better tumor features, and higher quality of care. These factors explain the better survival observed among breast cancer women with a positive FH as compared to women without positive FH.

Opportunities for improving triple-negative breast cancer outcomes: results of a population-based study.

Triple-negative breast cancer (TNBC) is associated with a poor prognosis. Surgery, radiotherapy, chemotherapy, and referral for genetic counseling are the standard of care. We assessed TNBC prevalence, management, and outcome using data from the population-based Geneva cancer registry. 2591 women had a first invasive stage I-III breast cancer diagnosed between 2003 and 2011. We compared TNBC to other breast cancers (OBC) by χ2 -test and logistic regression. Kaplan-Meier survival curves, up to 31-12-2014, were compared using log-rank test. TNBC risk of mortality overall (OS) and for breast cancer (BCSS) was evaluated through Cox models. Linkage with the Oncogenetics and Cancer Prevention Unit (OCPU) database of the Geneva University Hospitals provided genetic counseling information. TNBC patients (n = 192, 7.4%) were younger, more often born in Africa or Central-South America than OBC, had larger and more advanced tumors. 18% of TNBC patients did not receive chemotherapy. Thirty-one (17%) TNBC women consulted the OCPU, 39% among those aged <40 years. Ten-year survival was lower in TNBC than OBC (72% vs. 82% for BCSS; P < 0.001; 80% vs. 91% for OS; P < 0.001). The mortality risks remained significant after adjustment for other prognostic variables. The strongest determinants of mortality were age, place of birth, and lymph node status. A substantial proportion of TNBC patients in Geneva did not receive optimal care. Over 60% of eligible women did not receive genetic counseling and 18% did not receive chemotherapy. To improve TNBC prognosis, comprehensive care as recommended by standard guidelines should be offered to all patients.

The incidence of colon cancer among patients diagnosed with left colonic or sigmoid acute diverticulitis is higher than in the general population.

BACKGROUND: Considering the low incidence of colon cancer after an initial episode of colonic diverticulitis in some categories of patients, some authors suggested to exempt them from colonoscopy. However, this incidence has never been compared to that of a reference population, and predictors of cancer are still poorly investigated. We aimed to determine the 1-year incidence of colon cancer at the site of diverticulitis in patients diagnosed with left colonic or sigmoid acute diverticulitis, to compare this incidence to a reference population to state whether endoscopy is required or not, and to identify predicting factors of cancer to better target subpopulations needing that examination. METHODS: All patients admitted at the University Hospitals of Geneva for left colonic or sigmoid acute diverticulitis were included. Patients with a previous history of colon cancer or non-available for follow-up were excluded. Demographic data, haemoglobin values, and the Hinchey score were documented. This cohort was matched with the Geneva Cancer Registry to look for cancer occurrence at the site of diverticulitis within 1 year. Predictors of cancer were assessed using univariate logistic regression and the risk of cancer by comparing observed cases to a reference population using standardized incidence ratios. RESULTS: The final cohort included 506 patients. Eleven (2.2 %) had a diagnosis of cancer at the site of diverticulitis within 1 year. The mean age was significantly different between patients with cancer and others. No predictor of cancer could be identified, except a trend for an increased risk with advancing age (p = 0.067). The standardized incidence ratios showed a 44-fold increased risk of cancer among the cohort compared to the reference population. CONCLUSIONS: Colonoscopy should be continued after an initial diagnosis of left colonic or sigmoid acute diverticulitis, irrespective of the clinical or radiological presentations.

Determinants and effects of positive surgical margins after prostatectomy on prostate cancer mortality: a population-based study.

BACKGROUND: The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. METHODS: We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. RESULTS: Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in the prostate were significantly associated to positive margins. Ten-year prostate cancer-specific survival was 96.6% for the negative margins group and 92.0% for the positive margins group (log rank p = 0.008). In the Cox survival analysis adjusted for tumour characteristics, surgical margin status per se was not an independent prognostic factor while age, pathological T, PSA level and Gleason score remained associated with prostate cancer-specific survival. CONCLUSIONS: More aggressive tumour characteristics were strong determinants for positive margins. Furthermore, surgical margin status per se was not an independent prognostic factor for prostate cancer-specific survival after adjusting by the gravity of the disease in the multivariate analysis.

Planning for the future: cancer incidence projections in Switzerland up to 2019.

BACKGROUND: Projections of the national burden of cancer play a key role in planning cancer control programmes and investments. We present projections of cancer incidence rates and cases for the period up to 2015-2019 in Switzerland. METHODS: Projections were based on cancer incidence data estimated from cancer registries for the 1989-2009 periods and demographic projections of the Federal Statistical Office. Age-specific incidence rates were modelled as a function of age, period-birth cohort using NORDPRED. RESULTS: Up to 2019 the incidence of all cancers combined is expected to decrease slightly for both sexes. Nevertheless, the overall number of cases is predicted to increase. The number of male cancer cases will increase by 30%, from 20005 in 2005-2009 to 25910/year in 2015-2019. For females the number will increase by 20%, from 16913 to 20359/year in 2015-2019. Changes in the population size and structure will be responsible for most of the increase. Among men, the largest increase is observed for melanoma (+54%), thyroid (+45%), non-Hodgkin lymphoma (+43%), and prostate (+37%). Prostate cancer will contribute with 8083 cases, colorectal cancer with 2908 and lung cancer with 2791. For women, cases of lung and oral cavity cancers will increase by +48% and +38%, respectively; those of thyroid by +45% and non-Hodgkin lymphoma by +36%. The sites with the most cancer predicted are breast (5870), colorectal and lung (over 2000 each), melanoma (1341) and corpus uteri (1040). The overall annual cancer burden predicted for 2015-19 is of 46269 new cases in Switzerland. CONCLUSIONS: Substantial investments appear to be needed in Switzerland cancer services to meet and fill absolute increased demand driven by aging population.

Risk, characteristics, and prognosis of breast cancer after Hodgkin's lymphoma.

PURPOSE: To assess breast cancer (BC) risk after Hodgkin's lymphoma (HL) and compare characteristics, risk of second BC, and prognosis of patients with these BCs with patients with first primary BC. PATIENTS AND METHODS: We considered all 9,620 women with HL recorded in the Surveillance, Epidemiology and End Results dataset in 1973-2007. We calculated age-period standardized incidence ratios of BC. We compared patient, tumor, and treatment characteristics, risk of second BC, and prognosis between patients with BC after HL (n = 316) and patients with other BCs occurring during the same period (n = 450,413) using logistic regression and Cox models adjusted for confounders. RESULTS: HL patients had a 2.4-fold higher risk for developing BC (95% confidence interval [CI], 2.2-2.7) than the general population. Age at HL diagnosis and radiation therapy influenced this risk. Compared with first primary BCs, BCs after HL were diagnosed at a younger age, at an earlier stage, were less frequently hormone receptor positive, were located more frequently in external quadrants, and were less frequently treated using radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85; 95% CI, 1.79-4.53) for developing a second BC and had a higher BC mortality risk (adjusted HR, 1.36; 95% CI, 1.05-1.76). The higher mortality risk was only partly explained by the higher occurrence rate of a second BC. CONCLUSION: HL survivors have a higher risk for developing BC, their BCs are more aggressive, they have a higher risk for a second BC occurrence, and they have a poorer prognosis. Guidelines of care should be adapted to decrease the impact of BC in these high-risk patients.

Breast cancer prognosis is inherited independently of patient, tumor and treatment characteristics.

Population-based studies have shown a concordance of breast cancer survival among first-degree relatives (FDRs), suggesting a heritable component. Reasons for such heritability remain to be elucidated. We aimed to determine whether association of breast cancer survival among FDRs is linked to shared patient and tumor characteristics or type of treatment. At the population-based Geneva Breast Cancer Registry, we identified 162 FDR pairs diagnosed with breast cancer. We categorized FDRs into poor, medium and good familial survival risk groups according to breast cancer-specific survival of their proband (mother or sister). We compared patient, tumor and treatment characteristics between categories and calculated standardized mortality ratios (SMRs) and adjusted disease-specific mortality for each group. Breast cancer patients in the poor familial survival risk group were more likely to be diagnosed at later stages than those in the good familial survival risk group. Similarly, they had higher SMRs than those in the medium and good survival risk groups (18.7, 95% confidence interval [CI]: 9.4-33.5 vs. 16.5, 95% CI: 7.5-31.3 and 9.4, 95% CI: 3.4-20.4, respectively). After adjustment for patient and tumor characteristics and type of treatment, women in the poor familial survival risk group were almost five times more likely to die of breast cancer than those in the good familial survival risk group (adjusted hazard ratio 4.8, 95% CI: 1.4-16.4). Our study shows that breast cancer prognosis clusters within families and suggests that the hereditary component is independent of patient and tumor characteristics and type of treatment.

Changing pattern of age-specific breast cancer incidence in the Swiss canton of Geneva.

Hormone replacement therapy (HRT) use declined sharply after mid-2002, when the Women's Health Initiative trial reported an association between breast cancer occurrence and HRT. Hypothesized mechanism behind this association is that HRT promotes growth of pre-existing small tumors, leading to earlier tumor detection. We evaluated the impact of the sudden decline in HRT use on age distribution of breast cancer in Geneva. We included all incident breast cancer cases recorded from 1975 to 2006 at the Geneva cancer registry. We calculated mean annual incidence rates per 100,000 for 2 year periods for three age groups and assessed temporal changes by joinpoint regression. We compared age-specific incidence curves for different periods, reflecting different prevalence rates of HRT use. After increasing constantly between 1986 and 2002 among women aged 50-69 years [annual percent change (APC): +4.4, P < 0.0001], rates declined sharply after 2003 (APC: -6.0; P = 0.0264). Age-specific breast cancer rates changed dramatically with changes in prevalence of HRT use. During low HRT prevalence, breast cancer incidence increased progressively with age, when HRT prevalence was reaching its maximum (1995-2002), higher rates were seen in 60- to 64-year-old women, with a concomitant decrease in risk among elderly. After the sudden decline in HRT use, the incidence peak diminished significantly and incidence increased again with age. Following the abrupt decline in HRT use in Geneva, breast cancer incidence rates among post-menopausal women decreased considerably with striking changes in age-specific incidence rates before, during and after the peak in HRT prevalence.

Impact of obesity on diagnosis and treatment of breast cancer.

In this population-based study, we evaluated the impact of obesity on presentation, diagnosis and treatment of breast cancer. Among all women diagnosed with invasive breast cancer in the canton Geneva (Switzerland) between 2003 and 2005, we identified those with information on body mass index (BMI) and categorized them into normal/underweight (BMI <25 kg/m(2)), overweight (BMI > or =-<30 kg/m(2)) and obese (BMI > or =30 kg/m(2)) women. Using multivariate logistic regression, we compared tumour, diagnosis and treatment characteristics between groups. Obese women presented significantly more often with stage III-IV disease (adjusted odds ratio [OR(adj)]: 1.8, 95% CI: 1.0-3.3). Tumours > or =1 cm and pN2-N3 lymph nodes were significantly more often impalpable in obese than in normal/underweight patients (OR(adj) 2.4, [1.1-5.3] and OR(adj) 5.1, [1.0-25.4], respectively). Obese women were less likely to have undergone ultrasound (OR(adj) 0.5, [0.3-0.9]) and MRI (OR(adj) 0.3, [0.1-0.6]) and were at increased risk of prolonged hospital stay (OR(adj) 4.7, [2.0-10.9]). This study finds important diagnostic and therapeutic differences between obese and lean women, which may impair survival of obese women with breast cancer. Specific strategies are needed to optimize the care of obese women with or at risk of breast cancer.

Young patients with endometrial cancer: how many could be eligible for fertility-sparing treatment?

OBJECTIVES: To assess the characteristics of young women with endometrial carcinoma, and evaluate those potentially eligible for conservative therapy. METHODS: We identified women diagnosed with endometrial cancer between 1970 and 2005 at the population-based Geneva Cancer Registry (n=1365). We classified patients into two age groups (< or =45 and >45 years old). Differences in demographic, tumor, diagnostic and treatment characteristics were tested with chi square. Kaplan-Meier analysis was used to calculate survival from endometrial cancer and the log-rank test to analyze differences in survival between the two groups. RESULTS: The young group comprised 44 (3.2%) women and the old group 1321 (96.8%) women. Synchronous ovarian malignancies were found in six patients (14%) in the young group, compared with 23 (2%) in the old group (P<0.001). Tumor stage was also different between the two groups, principally because of more stage II among the young (P=0.012). Histological tumor type, grade and specific endometrial cancer 5-year survival did not significantly differ between the two groups. According to final histopathologic evaluation, eight patients from the young group had FIGO stage IA, grade I disease, i.e. may have been eligible for fertility-sparing treatment, corresponding to an incidence rate of 0.3/100,000. CONCLUSION: No significant difference regarding tumor characteristics and survival between young and older patients was observed, except stage of disease and rate of synchronous ovarian malignancy. Conservative approach is a meaningful quality of life goal for patients with cancer, but only suitable for a limited number of patients.

Lymph node ratio as an alternative to pN staging in node-positive breast cancer.

PURPOSE: In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. PATIENTS AND METHODS: From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. RESULTS: Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION: LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.

Increased risk of second cancer among patients with ovarian borderline tumors.

OBJECTIVES: Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. METHODS: We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. RESULTS: The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. CONCLUSION: Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.