Robin Schaffar

Trends in incidence and predictions of cutaneous melanoma across Europe up to 2015

Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they are generally not easily accessible.

Lung cancer mortality risk among breast cancer patients treated with anti-estrogens†‡

The Womens Health Initiative randomized clinical trial reported that menopausal hormone therapy increases lung cancer mortality risk. If this is true, use of anti‐estrogens should be associated with decreased lung cancer mortality risk. The authors compared lung cancer incidence and mortality among breast cancer patients with and without anti‐estrogen therapy.

Impact of socioeconomic status on prostate cancer diagnosis, treatment, and prognosis†

The objective of the current study was to evaluate the impact of socioeconomic disparities on prostate cancer presentation, treatment, and prognosis in Geneva, Switzerland, in which healthcare costs, medical coverage, and life expectancy are considered to be among the highest in the world.

Importance and determinants of Gleason score undergrading on biopsy sample of prostate cancer in a population-based study

BackgroundIn this population-based study, we investigated the degree of concordance between Gleason scores obtained from prostate biopsies and those obtained from prostatectomy specimens, as well as the determinants of biopsy understaging.MethodsWe considered for this study all 371 prostate cancer patients recorded at the Geneva Cancer Registry diagnosed from 2004 to 2006 who underwent a radical prostatectomy. We used the kappa statistic to evaluate the Gleason score concordance from biopsy and prostatectomy specimens. Logistic regression was used to determine the parameters that predict the undergrading of the Gleason score in prostate biopsies.ResultsThe kappa statistic between biopsy and prostatectomy Gleason score was 0.42 (p < 0.0001), with 67% of patients exactly matched, and 26% (n = 95) patients with Gleason score underestimated by the biopsy. In a multi-adjusted model, increasing age, advanced clinical stage, having less than ten biopsy cores, and longer delay between the two procedures, were all independently associated with biopsy undergrading. In particular, the proportion of exact match increased to 72% when the patients had ten or more needle biopsy cores. The main limitation of the study is that both biopsy and prostatectomy specimens were examined by different laboratories.ConclusionsThe data show that concordance between biopsy and prostatectomy Gleason scores lies within the classic clinical standards in this population-based study. The number of biopsy cores appears to strongly impact on the concordance between biopsy and radical prostatectomy Gleason score.

Accuracy of cause of death data routinely recorded in a population-based cancer registry: impact on cause-specific survival and validation using the Geneva cancer registry

BackgroundInformation on the underlying cause of death of cancer patients is of interest because it can be used to estimate net survival. The population-based Geneva Cancer Registry is unique because registrars are able to review the official cause of death. This study aims to describe the difference between the official and revised cause-of-death variables and the impact on cancer survival estimates.MethodsThe recording process for each cause of death variable is summarised. We describe the differences between the two cause-of-death variables for the 5,065 deceased patients out of the 10,534 women diagnosed with breast cancer between 1970 and 2009. The Kappa statistic and logistic regression are applied to evaluate the degree of concordance. The impact of discordance on cause-specific survival is examined using the Kaplan Meier method.ResultsThe overall agreement between the two variables was high. However, several subgroups presented a lower concordance, suggesting differences in calendar time and less attention given to older patients and more advanced diseases. Similarly, the impact of discordance on cause-specific survival was small on overall survival but larger for several subgroups.ConclusionEstimation of cancer-specific survival could therefore be prone to bias when using the official cause of death. Breast cancer is not the more lethal cancer and our results can certainly not be generalised to more lethal tumours.

Prognostic value of axillary lymph node status after neoadjuvant chemotherapy. Results from a multicentre study

BACKGROUND The prognostic value of lymph node involvement after neoadjuvant chemotherapy for breast cancer is not straightforward. We evaluated whether lymph node involvement is associated with overall survival in patients treated with neoadjuvant chemotherapy and whether Lymph Node Ratio (LNR--ratio of the positive to excised axillary lymph nodes) is a superior prognosticator when compared to ypN status (according to the pTNM classification). METHODS Three hundred and fourteen patients receiving neoadjuvant chemotherapy in Geneva, Singapore or Kuala Lumpur were pooled for analysis. We evaluate the prognostic value of the LNR [zero, low (>0 and <0.2), intermediate (0.2-0.65) and high risk (>0.65)] and ypN staging [ypN0, ypN1, ypN2 and ypN3] with multivariate Cox regression analysis. RESULTS When using the LNR classification, 88 patients were categorised as zero, 91 as low, 82 as intermediate and 53 as high risk. For classic ypN staging, 88 were ypN0, 126 ypN1, 58 ypN2 and 42 ypN3. Compared to the low risk category, LNR zero corresponded to an adjusted hazard ratio [HRadj] of 0.4 (95%CI, 0.2-0.9), intermediate risk LNR to a HRadj of 1.2 (0.7-2.2) and high risk LNR to a HRadj of 2.7 (1.5-5.0). Similarly, the ypN0 category corresponded to a HRadj of 0.3 (0.2-0.7), ypN2 to a HRadj 1.1 (0.6-2.0) and ypN3 to a HRadj 2.2 (1.3-3.8) compared to ypN1 patients. CONCLUSION Lymph node status after neoadjuvant chemotherapy predicts overall survival. In patients treated with neoadjuvant chemotherapy, LNR does not seem to be superior to classic ypN staging.

Cause-specific or relative survival setting to estimate population-based net survival from cancer? An empirical evaluation using women diagnosed with breast cancer in Geneva between 1981 and 1991 and followed for 20 years after diagnosis

BACKGROUND Both cause-specific and relative survival settings can be used to estimate net survival, the survival that would be observed if the only possible underlying cause of death was the disease under study. Both resulting net survival estimators are biased by informative censoring and prone to biases related to the data settings within which each is derived. We took into account informative censoring to derive theoretically unbiased estimators and examine which of the two data settings was the most robust against incorrect assumptions in the data. PATIENTS AND METHODS We identified 2489 women in the Geneva Cancer Registry, diagnosed with breast cancer between 1981 and 1991, and estimated net survival up to 20-years using both cause-specific and relative survival settings, by tackling the informative censoring with weights. To understand the possible origins of differences between the survival estimates, we performed sensitivity analyses within each setting. We evaluated the impact of misclassification of cause of death and of using inappropriate life tables on survival estimates. RESULTS Net survival was highest using the cause-specific setting, by 1% at one year and by up to around 11% twenty years after diagnosis. Differences between both sets of net survival estimates were eliminated after recoding between 15% and 20% of the non-specific deaths as breast cancer deaths. By contrast, a dramatic increase in the general population mortality rates was needed to see the survival estimates based on relative survival setting become closer to those derived from cause-specific setting. CONCLUSION Net survival estimates derived using the cause-specific setting are very sensitive to misclassification of cause of death. Net survival estimates derived using the relative-survival setting were robust to large changes in expected mortality. The relative survival setting is recommended for estimation of long-term net survival among patients with breast cancer.

Antiestrogen Therapy for Breast Cancer Modifies the Risk of Subsequent Cutaneous Melanoma

Increased risk of secondary melanoma after breast cancer has been reported. Several lines of evidence suggest that elevated estrogen levels may be implicated in melanoma etiology. Accordingly, use of antiestrogens should be associated with decreased risk of melanoma. We compared melanoma incidence among a cohort of breast cancer patients with and without antiestrogen therapy, with data from the Geneva Cancer Registry. The cohort consisted of 7,360 women diagnosed with breast cancer between 1980 and 2005. About 54% of these patients received antiestrogens. All women were followed until December 2008. We compared cutaneous melanoma incidence rates among patients with and without antiestrogens with those expected in the general population by age and period standardized incidence ratios (SIR). A total of 34 women developed a melanoma during the follow-up period. Compared with the general population, the risk of melanoma was higher for patients who did not receive antiestrogens (SIR: 1.60, 95% CI: 1.08–2.12, P = 0.02). On the contrary, the risk was close to 1 (SIR: 0.98, 95% CI: 0.40–1.56, P = 0.57) for patients who received antiestrogen therapy. This study suggests that antiestrogen therapy modifies the risk of melanoma after breast cancer. Although our results are in agreement with the hypothesis that estrogens could play a role in melanoma occurrence, they need to be replicated in a larger study with data on potential confounders. Cancer Prev Res; 5(1); 82–88. ©2011 AACR.

P1-11-01: Strong Socioeconomic Disparities in Breast Cancer Quality of Care in Switzerland.

Background Despite substantial research on socioeconomic disparities in breast cancer prognosis, important gaps remain concerning the causes of over mortality among socially deprived patients. In this population-based study, we identify disparities by socioeconomic status (SES) in diagnosis assessment and management of breast cancer in Geneva, Switzerland, where the average income and the health care system cost are among the highest in the world. Methods We included in the study all 1110 women reported with invasive breast cancer at the Geneva Cancer Registry between 2003 and 2005. SES was regrouped in three levels: low (manual employees, skilled and unskilled workers), middle (nonmanual employees and administrative staff) and high (professionals, executive administrators, entrepreneurs) based on the patient9s last occupation or, if unemployed, that of the spouse. We compared patients, tumour, treatment characteristics, surgeon caseload and delay of diagnosis as well as some of the management quality indicators established by the European School of Mastology among SES classes by heterogeneity tests. To assess the independent effect of each factor we used multivariate logistic regression, comparing women of high vs. low SES. Results Compared with patients of high SES, low SES patients were older, more often born outside Switzerland and treated in the public system. Low SES women had less often screen detected cancers (29% vs. 41%; OR multi-adjusted for breast self-examination vs. mammography: 1.7, 95%CI: 1.1−2.6, p=0.020), and less frequently magnetic resonance imaging to assess tumour size/focality (4% vs. 15%; OR multi-adjusted for breast MRI vs. ultrasound: 0.2, 95%CI: 0.1−0.5, p=0.001). They had more often a delay longer than 4 weeks between diagnosis and treatment (53.8% vs. 32.7%; OR multi-adjusted for 4 weeks and more vs. less: 2.6, 95%CI: 1.7−4.1, p multi-adjusted for surgeon9s caseload of 5–15 vs. multi-adjusted for negative vs. positive margins: 0.4, 95% CI 0.2−1.0, p=0.057) and lower access to anti-aromatase treatments (29.6% vs. 43.6%). In particular, the probability to receive anastrozole vs. tamoxifen was 70% lower (OR multi-adjusted for anastrozole vs. tamoxifen: 0.3, 95%CI: 0.2−0.6, p Conclusions: This study shows strong SES differences all along the continuum of breast cancer management, even in the highly medicalized county of Geneva. Only by improving the quality of care provided to women of low SES we will be able to prevent the excess breast cancer mortality observed among these women. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-01.

Abstract P3-07-09: Trends and determinants of breast cancer survival among unscreened women: A population-based study

Background: Breast cancer mortality has been declining in many western countries, including Switzerland,since the late 1980s. This has largely been credited to mammography screening and improved treatment. However, mortality trends are also decreasing among unscreened women, though most breast cancer deaths still occur in that population. Objective: The objective of this study was to analyse trends in,and factors affecting the survival of, women whose breast cancer was not detected by screening in the Geneva female population from 1990 to 2007. In Geneva an organized screening programme started in 2001 while opportunistic screening has existed since the beginning of the 1990s. Methods: The study population comprised1696 women aged 50-69 years oldwith invasive breast cancer that was not detected by screening and that was recorded at the population-based Geneva cancer registry. We studied tumour characteristics and prognostic factors across 6 time periods through chi square and trend tests. To assess whether breast cancer specific survival had improved over time, we calculated 5-year specific survival and performed multivariate Cox proportional hazard models to assess independent determinants of mortality. Results:Median age of the women at diagnosis was 59 years. During the 18 year study periodthere was a decrease in the proportion of diagnoses among women of low social class (25.8% in 1990-92 vs 17.3% in 2005-07, p=0.001). No change in the distribution of stage at diagnosisor hormone receptor status was observed, while between the first and last period there was an increase in cancers with lobular morphology (6.8% vs. 19.0%, p Five year breast cancer-specific survival was 82% in 1990-92 (95% Confidence Intervals [95%CI] 77-87) and 89% in 2005-07 (95% CI: 83-92; log rank test=8.68, p=0.122). In the Cox multivariate model there was a trend towards improved survival, but it was only statistically significant when comparing the period 2005-07 to the first period (Hazard Ratio 0.47, 95%CI: 0.22-0.98). Increasing age, stage, and grade, hormone receptor–negative disease, and not receiving BCS or endocrine therapy were all independently associated with a worse breast cancer–specific survival. Conclusions:We observed an improvement in survival only in recent years among women whose breast cancers were not detected by screening; this appears to be associated with improved treatment. This suggests that the breast cancer mortality reduction observed in Switzerland since the late 1980s is not likely attributable to changes in treatment before 2005, but rather to the generalization of screening. Citation Format: Elisabetta Rapiti, Thomas Agoritsas, Massimo Usel, Robin Schaffar, Hyma Schubert, Christine Bouchardy. Trends and determinants of breast cancer survival among unscreened women: A population-based study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-09.