Christine Bouchardy

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.

Older Female Cancer Patients: Importance, Causes, and Consequences of Undertreatment

Despite increased interest in treatment of senior cancer patients, older patients are much too often undertreated. This review aims to present data on treatment practices of older women with breast and gynecologic cancers and on the consequences of undertreatment on patient outcome. We also discuss the reasons and validity of suboptimal care in older patients. Numerous studies have reported suboptimal treatment in older breast and gynecologic cancer patients. Undertreatment displays multiple aspects: from lowered doses of adjuvant chemotherapy to total therapeutic abstention. Undertreatment also concerns palliative care, treatment of pain, and reconstruction. Only few studies have evaluated the consequences of nonstandard approaches on cancer-specific mortality, taking into account other prognostic factors and comorbidities. These studies clearly showed that undertreatment increased disease-specific mortality for breast and ovarian cancers. For other gynecological cancers, data were insufficient to draw conclusions. Objective reasons at the origin of undertreatment were, notably, higher prevalence of comorbidity, lowered life expectancy, absence of data on treatment efficacy in clinical trials, and increased adverse effects of treatment. More subjective reasons were putative lowered benefits of treatment, less aggressive cancers, social marginalization, and physicians beliefs. Undertreatment in older cancer patients is a well-documented phenomenon responsible for preventable cancer deaths. Treatments are still influenced by unclear standards and have to be adapted to the older patients general health status, but should also offer the best chance of cure.

Changing patterns of cancer incidence in the early-and late-HAART periods: The Swiss HIV Cohort Study

Background:The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposis sarcoma (KS) and non-Hodgkins lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.Methods:We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20 615, 17 690, and 15 410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods.Results:Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkins lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population.Conclusions:Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

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.

Multiple ADH genes are associated with upper aerodigestive cancers

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10−10 and 10−9, respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.

Sex differences in presentation, management, and prognosis of patients with non–small cell lung carcinoma

OBJECTIVE AND METHODS To characterize gender differences in lung cancer, we conducted a retrospective analysis including all patients undergoing surgery for non-small cell lung carcinoma in a single institution over a 20-year period. RESULTS Compared with men (n = 839), women (n = 198) were more likely to be asymptomatic (32% vs 20%, P =.006), nonsmokers (27% vs 2%, P <.001), or light smokers (31 pack-years vs 52 pack-years; P <.001). Squamous cell carcinoma predominated in men (65%), and adenocarcinoma predominated in women (54%). Preoperative bronchoscopy contributed more frequently to a histologic diagnosis in men (69% vs 49% in women, P <.001), and fewer pneumonectomies were performed in women (22% vs 32% in men, P =.01). After multivariate Cox regression analysis, women survived longer than men (hazard ratio, 0.72; 95% confidence interval, 0.56-0. 92; P =.009) independently of age, presence of symptoms, smoking habits, type of operation, histologic characteristics, and stage of disease. The protective effect linked to female sex was present in early-stage carcinoma (stage I and II) and absent in more advanced-stage carcinoma (stage III and IV). CONCLUSIONS This study emphasizes strong sex differences in presentation, management, and prognosis of patients with non-small cell lung cancer.

Role of alcohol dehydrogenase 3 and cytochrome p-4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract

Alcohol is a recognized risk factor for upper aerodigestive tract (UAT) cancers, but the mechanism by which alcohol causes cancer remains obscure. Ethanol is oxidized to acetaldehyde (the suspected carcinogenic agent in alcohol) by alcohol dehydrogenases (ADHs) and cytochrome P‐4502E1 (CYP2E1), both of which exhibit great inter‐individual variability in activity. The hypothesis that these polymorphisms influence susceptibility to alcohol‐related cancers remains poorly documented. We investigated whether ADH3 and CYP2E1 DraI and RsaI genotypes modified the risk of UAT cancers among 121 oral cavity/pharyngeal cancer patients, 129 laryngeal cancer patients, and 172 controls, all French Caucasians. Cancer risks and gene–alcohol interactions were analyzed by unconditional logistic regression, accounting for potential confounders. ADH3 genotype was not associated with UAT cancer. In contrast, a 2‐fold risk of oral cavity/pharyngeal (OR = 2.0, 95% CI 1.0–3.9) and laryngeal (OR = 1.8, 95% CI 1.0–3.5) cancers was observed for carriers of the CYP2E1 DraI C variant allele compared with other individuals. The risk associated with the CYP2E1 RsaI c2 variant allele also increased for oral cavity/pharyngeal cancer (OR = 2.6, 95% CI 1.0–6.6). The effects of ADH3 or CYP2E1 genotype and alcohol or tobacco were independent. The highest risk of oral cavity/pharyngeal cancer was observed among the heaviest drinkers (>80 g/day) with the CYP2E1 DraI C allele (OR = 5.8, 95% CI 1.9–18.2) or the CYP2E1 RsaI c2 allele (OR = 7.2, 95% CI 1.4–38.2) compared with lighter drinkers with other genotypes. Our study suggests that CYP2E1 genotype modifies the risk of UAT cancers, but due to the low frequency of CYP2E1 variant alleles, large‐scale studies are needed to confirm our findings. Int. J. Cancer 87:734–740, 2000.

Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Objective:To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL) incidence in people with HIV (PHIV). Design:Follow-up of the Swiss HIV Cohort Study (SHCS). Methods:Between 1984 and 2006, 12 959 PHIV contributed a total of 75 222 person-years (py), of which 36 787 were spent under HAART. Among these PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized incidence was calculated and Cox regression was used to estimate hazard ratios (HR). Results:NHL incidence reached 13.6 per 1000 py in 1993–1995 and declined to 1.8 in 2002–2006. HAART use was associated with a decline in NHL incidence [HR = 0.26; 95% confidence interval (CI), 0.20–0.33], and this decline was greater for primary brain lymphomas than other NHL. Among non-HAART users, being a man having sex with men, being 35 years of age or older, or, most notably, having low CD4 cell counts at study enrolment (HR = 12.26 for < 50 versus ≥ 350 cells/μl; 95% CI, 8.31–18.07) were significant predictors of NHL onset. Among HAART users, only age was significantly associated with NHL risk. The HR for NHL declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI, 0.27–0.77) and was 0.12 (95% CI, 0.05–0.25) 7 to10 years afterwards. Conclusions:HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell count on NHL risk. The beneficial effect remained strong up to 10 years after HAART initiation.

Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma.

Objective:To investigate HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling for the effect of frequent coinfection with hepatitis C and B viruses. Design:A case–control study nested in the Swiss HIV Cohort Study. Methods:Twenty-six HCC patients were identified in the Swiss HIV Cohort Study or through linkage with Swiss Cancer Registries, and were individually matched to 251 controls according to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at enrolment. Odds ratios and corresponding confidence intervals were estimated by conditional logistic regression. Results:All HCC patients were positive for hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients included 14 injection drug users (three positive for hepatitis B surface antigen and 13 for antibodies against hepatitis C virus) and 12 men having sex with men/heterosexual/other (11 positive for hepatitis B surface antigen, three for antibodies against hepatitis C virus), revealing a strong relationship between HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds ratio (OR) per 100 cells/μl decrease = 1.33, 95% confidence interval (CI) 1.06–1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01–2.71) were significantly associated with HCC. The effects of CD4+ cell count were concentrated among men having sex with men/heterosexual/other rather than injecting drug users. Highly active antiretroviral therapy use was not significantly associated with HCC risk (OR for ever versus never = 0.59, 95% confidence interval 0.18–1.91). Conclusion:Lower CD4+ cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users.