Hyma Schubert

Diagnostic changes as a reason for the increase in papillary thyroid cancer incidence in Geneva, Switzerland

Objective: Several studies have reported upward incidence trends of papillary thyroid cancer. It is unclear whether these trends reflect a real risk increase, by some attributed to iodine supplementation, or an artificial one, due to increased diagnostic activity or changed histological criteria. This study examines if these artificial factors explain the increased papillary thyroid cancer incidence in the Swiss canton of Geneva. Methods: All thyroid carcinomas (n = 436) recorded between 1970 and 1998 at the Geneva Cancer Registry were considered. European age-adjusted incidence trends were estimated using linear regression analysis. For papillary cancers we evaluated diagnostic modalities and way of presentation (in particular microcarcinoma < 1 cm or silent carcinoma). In addition, we reviewed the histological slides of follicular carcinomas. Results: Papillary thyroid cancer incidence increased significantly from 0.7 to 1.8/100,000 for men and from 3.1 to 4.3/100,000 for women between 1970–74 and 1995–98. The proportion of microcarcinomas and silent carcinomas increased from 17% to 24% between 1970–79 and 1990–98. At histological review, follicular cancers were more often reclassified as papillary cancer for cases diagnosed between 1970 and 1979 than for cases diagnosed between 1990 and 1998 (45% vs 25%, p = n.s.). Conclusions: The increasing papillary thyroid cancer incidence seems mainly due to changes in histological diagnostic criteria and, to a lesser extent, to increased diagnostic activity. If confirmed, the results of this study indicate that fears of increasing incidence rates of papillary thyroid cancer should not prevent implementation of adequate programs of iodine supplementation in the many areas where iodine deficiency still prevails.

Important increase of invasive lobular breast cancer incidence in Geneva, Switzerland

A recent paper from the United States reported a sharp and unexplained increase in invasive lobular breast cancer incidence since 1977 (Li et al., Cancer 2000;88:2561–9). We investigated if this trend was also present in Geneva, Switzerland, where breast cancer incidence is one of the highest in Europe. We analyzed trends in breast cancer incidence according to histologic subtype, age and stage, to clarify the pattern. Our population‐based study includes all histologically confirmed invasive breast carcinomas (n = 6,247) recorded between 1976 and 1999 at the Geneva Cancer Registry. Breast histology was classified as ductal carcinoma, lobular carcinoma and other. Incidence trends were studied by log‐linear regression analyses. Models including effects of age, period and birth cohorts were used to describe rising incidence trends. The incidence of ductal carcinoma increased 1.2% per year (ptrend < 0.001) from 85.2 to 110.1/100,000. This increase concerned women aged 50–69 years and early‐stage tumors. Lobular cancer incidence increased disproportionately (14.4% per year, ptrend < 0.01) and rose from 2.9 to 20.5/100,000. This increase affected all age categories and both localized and advanced stages. In addition, a strong age‐cohort effect was present (p < 0.05), and women aged 50–59 years born after 1944 experienced the most marked increase. Our study shows a disproportionate increase of lobular breast cancer incidence compared to ductal cancer incidence. Contrary to ductal cancer, trends for lobular cancer are unlikely to be explained by increased use of screening mammography. Other explanations must be researched, in particular the role played by hormone replacement therapy.

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.

Reduced Lung Cancer Mortality Risk among Breast Cancer Patients Treated with Anti-Estrogens.

Background: The Women Health Initiative study recently reported that women on hormone replacement therapy (HRT) were at increased risk of dying from lung cancer. If exposure to estrogens can worsen lung cancer outcome, we hypothesized that anti-estrogens may, on the contrary, improve its prognosis. We compared lung cancer incidence and mortality among breast cancer patients with and without anti-estrogen therapy. Methods: All 6715 patients recorded with a breast cancer in the population-based Geneva Cancer registry in the period 1980-2003 were included in the study. Forty-six percent of these women (3066) received anti-estrogen therapy (tamoxifen in large majority). Age, sex and year-specific population data were used to calculate standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs), to compare the study population to the general female population of Geneva canton. For each woman we computed person-years at risk from the date of diagnosis of breast cancer to the date of diagnosis of invasive lung cancer cancer, date of death, date lost to follow-up, or end of the study period (December 31, 2007). Results: The cohort yielded a total of 57,100 person-years.During the study period we observed a total of 40 cases of metachronous lung cancers (diagnosed at least six months after the breast cancer). Compared with the general population, the risk of developing a lung cancer among women who received anti-estrogens was 0.63 (95% Confidence Intervals [CI]: 0.33-1.10) and among women without anti-estrogens was 1.12 (95% CI: 0.74-1.62). Lung cancer mortality rate was 31.44/100,000. The mortality rate were 9.23/100,000 for women with anti-estrogens and 44.97/100,000 for women without anti-estrogens.Compared to the general population the SMR for lung cancer was 0.13 (95% CI: 0.02-0.47) among women who took anti-estrogens (p Discussion: Women who received anti-estrogens as breast cancer treatment have a significantly decreased risk of dying from lung cancer. This result further supports the role of estrogens in lung cancer prognosis and suggests that exposure to anti-estrogens may offer some protection against tumor mortality. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 35.

Patients' Refusal of Surgery Strongly Impairs Breast Cancer Survival

Objective:To compare patient and tumor characteristics and survival between women who refused and women who accepted surgery for breast cancer. Summary Background Data:Surgery represents the central component of curative breast cancer treatment, but some women decide not to undergo surgery. Recent studies on the prognosis of non operated breast cancer are nonexistent. Patients and Methods:This study included all 5339 patients aged < 80 years with nonmetastatic breast cancer recorded at the Geneva Cancer Registry between 1975 and 2000. We consulted the clinical files of all nonoperated women to identify those who refused surgery. Patients who refused surgery were compared with those accepting surgery using logistic regression. The effect of refusal of surgery on breast cancer mortality was evaluated by Cox proportional hazards analysis. Results:Seventy patients (1.3%) refused surgery. These women were older, more frequently single, and had larger tumors. Overall, 37 (53%) women had no treatment, 25 (36%) hormone-therapy alone, and 8 (11%) other adjuvant treatments alone or in combination. Five-year specific breast cancer survival of women who refused surgery was lower than that of those who accepted (72%, 95% confidence interval, 60%–84% versus 87%, 95% confidence interval, 86%–88%, respectively). After accounting for other prognostic factors including tumor characteristics and stage, women who refused surgery had a 2.1-fold (95% confidence interval, 1.5–3.1) increased risk to die of breast cancer compared with operated women. Conclusions:Women who refuse surgery for breast cancer have a strongly impaired survival. This information might help patients who are hesitant toward surgery make a better informed decision.

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.

Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias

BACKGROUND Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. PATIENTS AND METHODS We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeons affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. RESULTS Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). CONCLUSIONS This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortality.

Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer

BACKGROUND Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival. METHODS We included 46 patients with known information on the family history of breast or ovarian cancer recorded at the Geneva Cancer Registry between 1970 and 2009. We compared patients with and without a family history with chi-square of heterogeneity, risk of second cancer with standardised incidence ratios (SIRs), and overall survival by Kaplan-Meier methods. RESULTS Approximately 20% of men with breast cancer had a positive family history. No differences were observed between men with and without familial risk except that patients with increased risk were more likely to receive radiotherapy and hormone therapy when compared with patients without familial risk. This more complete therapy is likely to be explained by the heightened awareness of cancer treatment among breast cancer patients with affected family members. Six men developed a second cancer. SIRs for second cancer were not significantly increased among patients with or without familial risk (1.93, 95% confidence interval [CI] 0.23-6.97 and 1.04, 95% CI 0.28-2.66, respectively). Overall survival was not significantly different between the two groups. CONCLUSIONS Prognosis was similar among patients with or without familial risk. Our results are however based on small numbers and larger registry-based cohorts of males with precise data on familial risk are still warranted.

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.