Gérald Fioretta

Undertreatment Strongly Decreases Prognosis of Breast Cancer in Elderly Women

PURPOSE No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients. PATIENTS AND METHODS We reviewed clinical files of 407 breast cancer patients aged >/= 80 years recorded at the Geneva Cancer Registry between 1989 and 1999. Patient and tumor characteristics, general health status, comorbidity, treatment, and cause of death were considered. We evaluated determinants of treatment by logistic regression and effect of treatment on mortality by Cox model, accounting for prognostic factors. RESULTS Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. CONCLUSION Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patients health status, but also should offer the best chance of cure.

Complete Excision of Primary Breast Tumor Improves Survival of Patients With Metastatic Breast Cancer at Diagnosis

PURPOSE Surgery of the primary tumor usually is not advised for patients with metastatic breast cancer at diagnosis because the disease is considered incurable. In this population-based study, we evaluate the impact of local surgery on survival of patients with metastatic breast cancer at diagnosis. METHODS We included all 300 metastatic breast cancer patients recorded at the Geneva Cancer Registry between 1977 and 1996. We compared mortality risks from breast cancer between patients who had surgery of the primary breast tumor to those who had not and adjusted these risks for other prognostic factors. RESULTS Women who had complete excision of the primary breast tumor with negative surgical margins had a 40% reduced risk of death as a result of breast cancer (multiadjusted hazard ratio [HR], 0.6; 95% CI, 0.4 to 1.0) compared with women who did not have surgery (P = .049). This mortality reduction was not significantly different among patients with different sites of metastasis, but in the stratified analysis the effect was particularly evident for women with bone metastasis only (HR, 0.2; 95% CI, 0.1 to 0.4; P = .001). Survival of women who had surgery with positive surgical margins was not different from that of women who did not have surgery. CONCLUSION Complete surgical excision of the primary tumor improves survival of patients with metastatic breast cancer at diagnosis, particularly among women with only bone metastases.

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.

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.

Recent trends in prostate cancer mortality show a continuous decrease in several countries

Prostate specific antigen (PSA) screening was introduced to detect prostate cancer at an early stage and to reduce prostate cancer‐specific mortality. Until results from clinical trials are available, the efficacy of PSA screening in reducing prostate cancer mortality can be estimated by surveillance of prostate cancer mortality trends. Our study analyzes recent trends in prostate cancer mortality in 38 countries. We used the IARC‐WHO cancer mortality database and performed joinpoint analysis to examine prostate cancer mortality trends and identified 3 patterns. In USA, and to a lesser extent in Germany, Switzerland, Canada, France, Italy and Spain, prostate cancer‐specific mortality decreased to a level lower than before the introduction of PSA screening. In Australia, New Zealand, Austria, Finland, The Netherlands, Norway, United Kingdom, Hungary, Slovakia, Israel, Singapore, Sweden and Portugal, mortality from prostate cancer decreased but rates remain higher than before the introduction of PSA screening. Prostate cancer mortality continued to increase in Belgium, Denmark, Greece, Ireland, Bulgaria, Czech Republic, Belarus, Ukraine, Russian Federation, Romania, Poland, Argentina, Chile, Cuba, Mexico, Japan, China Hong Kong and the Republic of Korea. The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer.

Social class is an important and independent prognostic factor of breast cancer mortality

Reasons of the important impact of socioeconomic status on breast cancer prognosis are far from established. This study aims to evaluate and explain the social disparities in breast cancer survival in the Swiss canton of Geneva, where healthcare costs and life expectancy are among the highest in the world. This population‐based study included all 3,920 female residents of Geneva, who were diagnosed with invasive breast cancer before the age of 70 years between 1980 and 2000. Patients were divided into 4 socioeconomic groups, according to the womans last occupation. We used Cox multivariate regression analysis to identify reasons for the socioeconomic inequalities in breast cancer survival. Compared to patients of high social class, those of low social class had an increased risk (unadjusted hazard ratio [HR] 2.4, 95% CI: 1.6–3.5) of dying as a result of breast cancer. These women were more often foreigners, less frequently had screen‐detected cancer and were at more advanced stage at diagnosis. They less frequently underwent breast‐conserving surgery, hormonal therapy, and chemotherapy, in particular, in case of axillary lymph node involvement. When adjusting for all these factors, patients of low social class still had a significantly increased risk of dying of breast cancer (HR 1.8, 95% CI: 1.2–2.6). Overmortality linked to low SES is only partly explained by delayed diagnosis, unfavorable tumor characteristics and suboptimal treatments. Other factors, not measured in this study, also could play a role. While waiting for the outcome of other researches, we should consider socioeconomic status as an independent prognostic factor and provide intensified support and surveillance to women of low social class.

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.

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.

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.