Place of Death for Israeli Cancer Patients Over a 20-Year Period: Reducing Hospital Deaths, but Barriers Remain.

BACKGROUND: Cancer remains a leading cause of mortality worldwide. While the main focus of palliative care (PC) is quality of life, the elements that comprise the quality of death are often overlooked. Dying at home, with home-hospice-care (HHC) support, rather than in-hospital, may increase patient satisfaction and decrease the use of invasive measures. We examined clinical and demographic characteristics associated with out-of-hospital death among patients with cancer, which serves as a proxy measure for HHC deaths. METHODS: Using death certification data from the Israel Central Bureau of Statistics, we analyzed 209,158 cancer deaths between 1998 and 2018 in Israel including demographic information, cause of death, and place of death (POD). A multiple logistic regression model was constructed to identify factors associated with out-of-hospital cancer deaths. RESULTS: Between 1998 and 2018, 69.1% of cancer deaths occurred in-hospital, and 30.8% out-of-hospital. Out-of-hospital deaths increased by 1% annually during the study period. Older patients and those dying of solid malignancies were more likely to die out-of-hospital (OR = 2.65, OR = 1.93, respectively). Likelihood of dying out-of-hospital varied with area of residency; patients living in the Southern district were more likely than those in the Jerusalem district to die out-of-hospital (OR = 2.37). CONCLUSION: The proportion of cancer deaths occurring out-of-hospital increased during the study period. We identified clinical and demographic factors associated with POD. Differences between geographical areas probably stem from disparity in the distribution of PC services and highlight the need for increasing access to primary EOL care. However, differences in age and tumor type probably reflect cultural changes and suggest focusing on educating patients, families, and physicians on the benefits of PC.

Coexistence of malignancies in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune intraepidermal bullous disease. PV has a major effect on morbidity as well as quality of life. There is sparse literature regarding the association between pemphigus vulgaris (PV) and comorbid malignancies. In this study we aimed to assess the risk of malignancy in a cohort of patients with PV and characterize PV-associated malignancies. Data were collected from two tertiary referral centers between the years 2008 and 2019 and compared with the national cancer registry. Of 164 patients with PV, 19 were diagnosed with malignancy: seven prior to PV diagnosis and 12 after. All cancers, solid and hematological, displayed higher incidences compared to the general population (p <0.001). In conclusion, we demonstrated higher rates of malignancies among patients with PV than in the general population. These observations suggest the need for careful assessment and follow up of patients with PV, given the possibility of associated malignancies.

Occupational Exposure to Nonionizing Radiation and Risk for Malignancy in Young Adults.

INTRODUCTION: Nonionizing radiation (NIR) is considered "possibly carcinogenic to humans," and therefore, exposure of young military personnel raises concerns regarding increased risk for cancer. The aim of our study was to compare the cancer incidence in exposed and nonexposed populations in order to gain better understanding of their risk. MATERIALS AND METHODS: A longitudinal retrospective cohort study, between 2009 and 2018, was conducted. Israel Defense Forces (IDF) aerial defense units service members, with NIR exposure (range of 2-300 GHz, below the International Commission of Non-Ionizing Radiation Protection guidelines), were compared with a similar sociodemographic group of service members without NIR exposure. Both groups were followed for cancer incidence (all-cause and specific malignancies). Kaplan-Meier analysis of cancer-free survival and univariate and multivariable logistic regressions for possible confounders and risk factors were performed. This analysis was repeated on a matched 1:1 control group. RESULTS: Exposure and comparison groups included 3,825 and 11,049 individuals, respectively. Forty-one cases diagnosed with cancer were identified during the follow-up time (mean 4.8 [±2.7] years), 13 (0.34%) of which were reported in the exposure group, and 28 (0.25%) were reported in the comparison group. The odds ratio (OR) for cancer incidence in the exposure vs. control groups was 1.34 (95%CI, 0.70-2.60), P-value = 0.3807. The results remained unchanged after adjustment for sex, age at enrollment, service length, socioeconomic status, and military occupation (adjOR = 1.38 [95%CI, 0.67-2.82], P = 0.3818). CONCLUSIONS: Our study did not find an increased short-term risk for cancer in young adults exposed to NIR radiation as compared with unexposed young adults.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study.

OBJECTIVE: To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. STUDY DESIGN: Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. RESULTS: Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). CONCLUSION: The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

An Assessment of the Completeness and Timeliness of the Israel National Cancer Registry.

BACKGROUND: The Israel National Cancer Registry (INCR) was established in 1960. Reporting has been mandatory since 1982. All neoplasms of uncertain/unknown behavior, in situ and invasive malignancies (excluding basal and squamous cell carcinomas of the skin), and benign neoplasms of the brain and central nervous system (CNS) are reportable. OBJECTIVES: To assess completeness and timeliness of the INCR for cases diagnosed or treated in 2005. METHODS: Abstractors identified cases of in situ and invasive malignancies and tumors of benign and uncertain behavior of the brain and CNS diagnosed or treated in 2005 in the files of medical records departments, pathology and cytology laboratories, and oncology and hematology institutes in 39 Israeli medical facilities. Cases were linked to the INCR database by national identity number. Duplicate cases, and those found to be non-reportable were excluded from analysis. Completeness was calculated as the percent of reportable cases identified by the survey that were present in the registry. Timeliness was calculated as the percent of reportable cases diagnosed in 2005, which were incorporated into the registry prior to 31 December 2007. RESULTS: The INCR's completeness is estimated at 93.7% for all reportable diseases, 96.8% for invasive solid tumors, and 88.0% for hematopoietic tumors. Incident cases for the calendar year 2005 were less likely to be present in the registry database than those diagnosed prior to 2005. CONCLUSIONS: Completeness and timeliness of the INCR are high and meet international guidelines. Fully automated reporting will likely improve the quality and timeliness of INCR data.

Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation-what should be expected?

OBJECTIVE: To evaluate the delivery rate and to characterize patients following ovarian tissue cryopreservation (OTCP) who did not undergo auto-transplantation. METHODS AND MATERIALS: All consecutive cancer patients admitted to our IVF unit, from January 2004 to December 2015, who underwent OTCP for the purpose of fertility preservation without autotransplantation were analyzed. The cohort included 338 patients and was linked to the National Live Birth registry of the Israel Ministry of Health in order to determine whether the women delivered following the cancer diagnosis. MAIN OUTCOME MEASURES: Delivery rate following OTCP without autotransplantation. RESULTS: During 6.4 years of follow-up, 30% of the patients delivered, with no differences in gravity, age at first diagnosis of cancer, type of malignancy, or the prevalence of relapse of malignancy between those who delivered and those who did not. Moreover, in multivariate analysis, those undergoing OTCP before the age of 30 and those suffering from breast cancer had significantly higher odds to conceive and deliver following cancer treatment without the need of autotransplantation. CONCLUSIONS: Further studies are required to elucidate the appropriate subgroup of patients with breast cancer under the age of 30 years, who will need OTCP. This information might aid both fertility specialists' counseling and their oncological patients in pursuing the appropriate fertility preservation strategy.

Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.

Trends in the incidence of primary brain, central nervous system and intracranial tumors in Israel, 1990-2015.

BACKGROUND: The association between cellphone technology and brain, central nervous system (CNS) and intracranial tumors is unclear. Analysis of trends in incidence of such tumors for periods during which cellphone use increased dramatically may add relevant information. Herein we describe secular trends in the incidence of primary tumors of the brain and CNS from 1990 to 2015 in Israel, a period during which cellphone technology became extremely prevalent in Israel. METHODS: All cases of primary brain, CNS and intracranial tumors (excluding lymphomas) diagnosed in Israel from 1990 to 2015 were identified in the Israel National Cancer Registry database and categorized by behavior (malignant; benign/uncertain behavior) and histologic type. Annual age-standardized incidence rates by sex and population group (Jews; Arabs) were computed, and the annual percent changes and 95% confidence intervals per category were calculated using Joinpoint software. RESULTS: Over 26 years (1990-2015) no significant changes in the incidence of malignant brain, CNS and intracranial tumors were observed, except for an increase in malignant glioma incidence in Jewish women up to 2008 and Arab men up to 2001, which levelled off in both subgroups thereafter. The incidence of benign/uncertain behavior brain, CNS and intracranial tumors increased in most population groups up to the mid-2000s, a trend mostly driven by changes in the incidence of meningioma, but either significantly decreased (Jews) or stabilized (Arabs) thereafter. CONCLUSIONS: Our findings are not consistent with a discernable effect of cellphone use patterns in Israel on incidence trends of brain, CNS and intracranial tumors.

Cancer surveillance in northern Africa, and central and western Asia: challenges and strategies in support of developing cancer registries.

The Global Initiative for Cancer Registry Development partnership, led by the International Agency for Research on Cancer (IARC), was established in response to an overwhelming need for high-quality cancer incidence data from low-income and middle-income countries. The IARC Regional Hub for cancer registration in North Africa, Central and West Asia was founded in 2013 to support capacity building for cancer registration in each of the countries in this region. In this Series paper, we advocate the necessity for tailored approaches to cancer registration given the rapidly changing cancer landscape for this region, and the challenges faced at a national level in developing data systems to help support this process given present disparities in resources and health infrastructure. In addition, we provide an overview of the status of cancer surveillance and activities country-by-country, documenting tailored approaches that are informing local cancer-control policy, and potentially curbing the growing cancer burden across the region.

Time Trends in the Incidence and Mortality of Ovarian Cancer in Ireland, Northern Ireland, and Israel, 1994-2013.

OBJECTIVES: The aims of this study were to compare time trends in ovarian cancer incidence and mortality in populations with (1) similar genetics but different health care systems (Ireland and Northern Ireland [NI]) and (2)different genetics but similar health care system (Israeli Jews and Arabs) and to interpret the results. METHODS: Age-standardized rates of ovarian cancer incidence and mortality for 1994-2013 in the 3 countries were obtained from national cancer registries and national statistics. Time trends in incidence, mortality, and incidence-to-mortality ratio were assessed by linear regression models applied to each country and between populations (Ireland-NI, Ireland-Israeli Jews, Israeli Jews-Arabs). Joinpoint analysis was used to calculate the annual percentage change (APC). RESULTS: Ovarian cancer incidence and mortality rates in 1994 were similar in the countries studied. Thereafter a reduction in incidence and mortality was observed in Ireland (incidence APC1994-2013 = -0.75%, P < 0.05; mortality APC1994-2013 = -0.67%, P < 0.05), NI (incidence APC1998-2013 = -1.5%, P < 0.05; mortality APC2005-2013 = -3.8%, P < 0.05), and Israeli Jews (incidence APC1994-2013 = -2.2%, P < 0.05; mortality APC1994-2013 = -1.2%, P < 0.05). Trends in Israeli Arabs remained stable. Significant incidence trend differences between Ireland and Israeli Jews (P = 0.009) and between Israeli Jews and Arabs (P = 0.004) were observed. The only significant trend difference for mortality was between Israeli Jews and Arabs (P = 0.038). Incidence-to-mortality ratios showed stable trends in all groups except for Israeli Jews (APC1994-2013 = -1.0%, P < 0.05). CONCLUSIONS: Time trends in ovarian cancer incidence (decreasing) and mortality (decreasing) were similar in Ireland, NI, and Israeli Jews, following global trends, with a more prominent incidence decline in Israeli Jews. Decreasing mortality trends are driven by falling incidence in the countries studied rather than improved survival.

Second Primary Cancers After Primary Breast Cancer Diagnosis in Israeli Women, 1992 to 2006.

PURPOSE: Improvements in early detection and treatment have resulted in improved long-term survival from breast cancer, which increases the likelihood of the occurrence of second primary cancers. We calculated the risk of second primary cancers among Israeli women receiving a first primary breast cancer diagnosis. METHODS: By using data from the Israel National Cancer Registry, we identified 46,090 women with invasive breast cancer diagnosed between 1990 and 2006 and non-breast primary cancers diagnosed subsequent to breast cancer diagnosis. We used life table analysis to calculate the risk of a second primary cancer and calculated standardized incidence ratios (SIRs) by using age-specific cancer risk in the general population of Israeli women as the standard and stratifying by diagnosis period (1992 to 1996, 1997 to 2001, 2002 to 2006) and age at diagnosis (< 50 and ≥ 50 years). RESULTS: The probability of a second malignancy was 3.6% within 5 years, 8.2% within 10 years, and 13.9% within 15 years. The SIR for any second non-breast primary cancer was 1.26 (95% CI, 1.23 to 1.30). Significantly increased risks of colorectal, uterine, lung, ovarian, and thyroid cancer and leukemia were observed for the full follow-up period, which persisted after excluding the first 6 months after index diagnosis, although increased leukemia and colorectal cancer risks were no longer statistically significant. Women younger than age 50 years at initial diagnosis had a greater excess risk than women age 50 years and older (SIR, 1.77 [95% CI, 1.63 to 1.91] and 1.20 [95% CI, 1.15 to 1.24], respectively). CONCLUSION: The findings likely reflect a combination of personal risk factors (genetics, hormonal therapy, environmental exposures) as well as the effects of the initial cancer treatment and are unlikely to be explained by enhanced surveillance alone.

Using Israel's National Cancer Registry Database to Track Progress in the War against Cancer: A Challenge for Health Services.

BACKGROUND: The number of cancer survivors has been increasing worldwide and is now approximately 32.6 million and growing. Cancer survivors present a challenge to health care providers because of their higher susceptibility to long-term health outcomes related to their primary disease and treatment. OBJECTIVES: To report on the number of cancer survivors and incident cancer cases in the period 1960-2009 in Israel, in order to provide data on the scope of the challenge Israel's health care funds face. METHODS: The Israel National Cancer Registry (INCR) database was used to identify new cancer cases diagnosed during the period 1960-2009. Lifetable analysis was used to assess changes in cumulative survival and population prevalence of cancer survivors throughout the 50 year study period. RESULTS: Almost 600,000 invasive cancer cases were diagnosed during the period 1960-2009 (overall absolute survival rate 54%). Within this time period, the number of new patients diagnosed with cancer increased fivefold and that of cancer survivors ninefold. The absolute survival of cancer patients and the prevalence of cancer survivors in the general population significantly increased with time from 34% and 0.5%, respectively (1960-1969), to 62% and 1.9%, respectively (2000-2009). Cumulative absolute survival for 5, 10 and 15 years following diagnosis increased with time as well. CONCLUSIONS: The INCR database is useful to assess progress in the war against cancer. The growing numbers of cancer survivors in Israel present a challenge to the national health and social services system.

Primary Peritoneal Serous Carcinoma in Men: A Rare and Non-BRCA-associated Entity.

BACKGROUND: Primary peritoneal serous carcinoma (PPSC) is a rare neoplasm. The paucity of reported cases among men may provide insight to the cell of origin of PPSC. MATERIALS AND METHODS: A search for the ICD 0-3 code of PPSC (C48.2) in the following datasets: the Israeli National Cancer registry (INCR), the Surveillance, Epidemiology, and End Results (SEER) database in the USA, Israeli male BRCA carriers, male high-risk and BRCA carriers in a USA study, and the Italian Study on Male Breast Cancer (MBC) were performed. RESULTS: In the INCR dataset, 220 entries for C48.2 code were noted, with only one male (male:female ratio=0.0045). In the SEER dataset for histology codes of papillary/serous/ adenocarcinoma, 2,673 cases were recorded, with five males (male:female ratio=0.0018). None of the recorded US or Italian male BRCA carriers or MBC, or Israeli male BRCA carriers was diagnosed with PPSC. CONCLUSION: PPSC is a rare neoplasm, seemingly not associated with BRCA mutations in men, and fallopian tube epithelial cell implants may contribute to its development.

Trends of Second Primary Malignancy in Patients with Thyroid Cancer: A Population-Based Cohort Study in Israel.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy. TC patients have a good prognosis and a low disease-related mortality rate. Since such patients are often young, they may be at a higher risk for a second primary malignancy (SPM). This study sought to determine the incidence, risk, and types of SPM between 1980 and 2011, and to assess SPM trends over time among Israeli TC patients. METHODS: Data were derived from the Israel National Cancer Registry. Primary TC patients diagnosed during 1980-2009 were followed up for SPM incidence until December 31, 2011. Standardized incidence ratios (SIRs) of observed to expected SPM (based on the general population rates) were calculated using Poisson regression. Analyses were stratified by time period of initial TC diagnosis (1980-1995 and 1996-2009). RESULTS: A total of 11,538 TC patients were identified. After exclusion of 107 duplicate cases, records of 1032 patients with SPM were analyzed (an SPM incidence of 8.9%). SIRs for all-site SPMs were 1.23 [confidence interval 1.08-1.35] for males and 1.19 [confidence interval 1.10-1.27] for females. SIRs for tumors of the urinary system and prostate were significantly elevated in males, as were SIRs for tumors of the brain, urinary system, breast, and lung in females. Variables associated with increased risk of developing SPMs included a younger age at TC diagnosis, a shorter latency period, being born in Asia/Africa for both sexes, and being born in Israel for females. Compared with the general population, a subanalysis by TC diagnosis during 1980-1995 and 1996-2009 disclosed a higher SPM incidence for the latter time period in males and for both time periods, with a slightly higher SIR for the latter time period in females. CONCLUSIONS: The overall risk of SPM in Israeli TC patients was significantly greater for both sexes compared with the general population, thus identifying TC patients as a high-risk group and calling for caretakers to apply specific follow-up guidelines.

Application of the double kernel density approach to the analysis of cancer incidence in a major metropolitan area.

RATIONALE: Although cancer is a main cause of human morbidity worldwide, relatively small numbers of new cancer cases are recorded annually in single urban areas. This makes the association between cancer morbidity and environmental risk factors, such as ambient air pollution, difficult to detect using traditional methods of analysis based on age standardized rates and zonal estimates. STUDY GOAL: The present study investigates the association between air pollution and cancer morbidity in the Greater Haifa Metropolitan Area in Israel by comparing two analytical techniques: the traditional zonal approach and more recently developed Double Kernel Density (DKD) tools. While the first approach uses age adjusted Standardized Incidence Ratios (SIRs) for small census areas, the second approach estimates the areal density of cancer cases, normalized by the areal density of background population in which cancer events occurred. Both analyses control for several potential confounders, including air pollution, proximities to main industrial facilities and socio-demographic attributes. RESULTS: Air pollution variables and distances to industrial facilities emerged as statistically significant predictors of lung and NHL cancer morbidity in the DKD-based models (p<0.05) but not in the models based on SIRs estimates (p>0.2). CONCLUSION: DKD models appear to be a more sensitive tool for assessing potential environmental risks than traditional SIR-based models, because DKD estimates do not depend on a priory geographic delineations of statistical zones and produce a smooth and continuous disease 'risk surface' covering the entire study area. We suggest using the DKD method in similar studies of the effect of ambient air pollution on chronic morbidity, especially in cases in which the number of statistical areas available for aggregation and comparison is small and recorded morbidity events are relatively rare.

Trends of Thyroid Cancer in Israel: 1980-2012.

OBJECTIVES: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980-2012, in light of the global trends. METHODS: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. RESULTS: In 1980-2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98-6.93, driven almost entirely by papillary carcinoma (APCs 5.75-8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980-2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC -1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. CONCLUSIONS: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends.

Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study.

It has been hypothesized that incidence of and mortality from several malignancies are increased among diabetic patients. Whether certain treatment modalities, including use of metformin, sulfonylureas, or insulins, affect cancer incidence or mortality and whether use of long-acting insulin analogues glargine and detemir may increase cancer incidence more than traditional human insulins are debated. The objective was to investigate the association between specific glucose-lowering agents and cancer incidence in diabetic members of an Israeli health maintenance organization. We studied a cohort of 36,342 diabetic patients aged at least 18 years with no history of cancer or treatment with insulin as of January 1, 2003. For the period from January 2003 to December 2007, we searched pharmacy records for purchases of glucose-lowering agents, including metformin, sulfonylureas, human insulin, and analogue insulins. Incident cancer diagnoses were identified from the health maintenance organization cancer registry. We studied the association of cancer incidence with the use of specific glucose-lowering agents, controlling for age, sex, and baseline glycohemoglobin measurement. Cancer was diagnosed in 6% of the study cohort during 164,652 person-years of follow-up time. Cancer incidence increased with age and varied with medication purchasing patterns. On multivariate analysis, age (hazard ratio [HR], 1.049; confidence interval [CI], 1.045-1.052), male sex (HR, 1.16; CI, 1.065-1.264), and number of insulin purchases (HR, 1.007; CI, 1.001-1.012) were significantly associated with increased cancer risk, whereas number of metformin purchases was associated with reduced cancer risk (HR, 0.996; CI, 0.994-0.998). Male sex, age, and human insulin purchases were associated with increased cancer incidence, whereas metformin purchases were associated with decreased cancer risk. There was a trend for increased cancer incidence associated with use of long-acting insulin analogues, but the number of long-acting insulin analogue users was too small for risk estimates to be conclusive.

Trends in breast cancer incidence associated with reductions in the use of hormone replacement therapy.

BACKGROUND: The publication of the Women's Health Initiative Study in 2002 spurred reductions in hormone replacement therapy (HRT) use worldwide. Subsequent drops in breast cancer incidence have since been reported. We used person-level data from a large Israeli health plan to study the relationship between HRT use and breast cancer incidence. METHODS: We accessed pharmacy, mammography and cancer registry data for women ages 50 and over. Using Chi-square analysis, we examined changes over time in HRT and mammography utilization and breast cancer incidence [invasive and ductal carcinoma in situ (DCIS)]. Using calendar year-specific Cox proportional hazards analyses, we estimated the hazard of recent HRT use on cancer incidence. We used locally weighted scatterplot smoothing (LOWESS) and autoregressive integrated moving average (ARIMA) modeling to further examine this association. RESULTS: The study population ranged from 118,724 in 2000 to 154,447 in 2007. Thirteen percent of study women purchased HRT in 2000, vs. 4.0% in 2007 (p<0.001). Breast cancer incidence rose from 3.8/1000 to 4.3/1000 in 2005; the proportion of women undergoing mammography rose from 8% in 2000 to a peak of 34.1% in 2005 (p<0.001). Hazard ratios for the association of HRT with breast cancer ranged from 1.2 to 2.4. ARIMA demonstrated the association of both mammography (in the same month) and HRT use (in the preceding month) with cancer incidence. CONCLUSION: This study demonstrates the competing impacts of HRT and mammography on cancer incidence. Our findings support the conclusion that changes in HRT utilization are linked to reductions in breast cancer incidence.