Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Socio-economic inequalities in lung cancer mortality in Spain: a nation-wide study using area-based deprivation.

BACKGROUND: Lung cancer is the main cause of cancer mortality worldwide and in Spain. Several previous studies have documented socio-economic inequalities in lung cancer mortality but these have focused on specific provinces or cities. The goal of this study was to describe lung cancer mortality in Spain by sex as a function of socio-economic deprivation. METHODS: We analysed all registered deaths from lung cancer during the period 2011-2017 in Spain. Mortality data was obtained from the National Institute of Statistics, and socio-economic level was measured with the small-area deprivation index developed by the Spanish Society of Epidemiology, with the census tract of residence at the time of death as the unit of analysis. We computed crude and age-standardized rates per 100,000 inhabitants by sex, deprivation quintile, and type of municipality (rural, semi-rural, urban) considering the 2013 European standard population (ASR-E). We further calculated ASR-E ratios between the most deprived (Q5) and the least deprived (Q1) areas and mapped census tract smoothed standardized lung cancer mortality ratios by sex. RESULTS: We observed 148,425 lung cancer deaths (80.7% in men), with 73.5 deaths per 100,000 men and 17.1 deaths per 100,000 women. Deaths from lung cancer in men were five times more frequent than in women (ASR-E ratio = 5.3). Women residing in the least deprived areas had higher mortality from lung cancer (ASR-E = 22.2), compared to women residing in the most deprived areas (ASR-E = 13.2), with a clear gradient among the quintiles of deprivation. For men, this pattern was reversed, with the highest mortality occurring in areas of lower socio-economic level (ASR-E = 99.0 in Q5 vs. ASR-E = 86.6 in Q1). These socio-economic inequalities remained fairly stable over time and across urban and rural areas. CONCLUSIONS: Socio-economic status is strongly related to lung cancer mortality, showing opposite patterns in men and women, such that mortality is highest in women residing in the least deprived areas and men residing in the most deprived areas. Systematic surveillance of lung cancer mortality by socio-economic status may facilitate the assessment of public health interventions aimed at mitigating cancer inequalities in Spain.

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Cadmium (Cd) and Lead (Pb) topsoil levels and incidence of childhood leukemias.

There are few well-established risk factors for childhood leukemias. While the frequency of childhood leukemias might be partially attributable to some diseases (accounting for a small fraction of cases) or ionizing radiation, the role of heavy metals has not been assessed. The objective of our study was to assess the potential association between levels of cadmium (Cd) and lead (PB) in soil and childhood leukemias incidence. We conducted a population-based case-control study of childhood leukaemia in Spain, covering 2897 incident cases gathered from the Spanish Registry of Childhood Tumours and including 14 Spanish Regions with a total population of 5,307,433 children (period 1996-2015). Cd and Pb bioavailable levels at every children's home address were estimated using data from the Geochemical Atlas of Spain. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (95%CIs); we included as covariates: sex, rurality, employment rate and socioeconomic status. Metal levels were analysed according to two definitions: as continuous variable assuming linearity and as categorical variables to explore a potentially nonlinear association (quantiles). Increases in both Cd and Pb topsoil levels were associated with increased probability of childhood leukemias incidence. The results for the models with the continuous variables showed that a unit increase on the topsoil level was associated with an OR of 1.11 for Cd (95%CI 1.00-1.24) and an OR of 1.10 for Pb (95%CI 0.99-1.21). Our study may point towards a possible link between residential Cd and Pb topsoil levels and the probability of childhood leukemias incidence. Residing in a location with the highest concentrations of these heavy metals compared to those locations with the lowest could increase the risk around a 20%, for both Cd and Pb.

Lung, Breast and Colorectal Cancer Incidence by Socioeconomic Status in Spain: A Population-Based Multilevel Study.

Socioeconomic inequalities in cancer incidence are not well documented in southern Europe. We aim to study the association between socioeconomic status (SES) and colorectal, lung, and breast cancer incidence in Spain. We conducted a multilevel study using data from Spanish population-based cancer registries, including incident cases diagnosed for the period 2010-2013 in nine Spanish provinces. We used Poisson mixed-effects models, including the census tract as a random intercept, to derive cancer incidence rate ratios by SES, adjusted for age and calendar year. Male adults with the lowest SES, compared to those with the highest SES, showed weak evidence of being at increased risk of lung cancer (risk ratio (RR): 1.18, 95% CI: 0.94-1.46) but showed moderate evidence of being at reduced risk of colorectal cancer (RR: 0.84, 95% CI: 0.74-0.97). Female adults with the lowest SES, compared to those with the highest SES, showed strong evidence of lower breast cancer incidence with 24% decreased risk (RR: 0.76, 95% CI: 0.68-0.85). Among females, we did not find evidence of an association between SES and lung or colorectal cancer. The associations found between SES and cancer incidence in Spain are consistent with those obtained in other European countries.

[Study protocol on Socioeconomic and Geographic Inequalities in Cancer Incidence, Mortality and Survival in Spain: Multilevel Population-Base Study: DESOCANES study]. / Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES.

Incidence and mortality provide information on the burden of cancer morbidity and the potential years of life lost due to cancer. The Spanish Deprivation Index (SDI) has been developed as a standardized measure to study socioeconomic deprivation in Spain at the census tract level. In addition, SDI information can be combined with ecological variables at the population level and data from the High-Resolution European Studies in Cancer. The aim of this study is to characterize socioeconomic inequalities in incidence, excess mortality, premature mortality and net survival for three of the most incident cancers (lung, colon-rectum and breast) in Spain using the SDI. This national population-based study will assess the impact of socioeconomic inequalities using a multilevel modelling approach. Spatial analysis, multilevel modeling, net survival and economic impact assessment will be used. The results will be useful for supporting decision-making, planning, and management of public health interventions aimed at reducing the impact of socioeconomic inequalities in the diagnosis and prognosis of cancer patients in Spain.

Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

BACKGROUND: High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. METHODS: A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. RESULTS: We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. CONCLUSIONS: The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.

Socioeconomic Inequalities in Colorectal Cancer Survival in Southern Spain: A Multilevel Population-Based Cohort Study.

BACKGROUND: Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain. METHODS: We conducted a multilevel population-based cohort study, including CRC cases for the period 2011-2013. The study time-to-event outcome was death, and the primary exposure was CRC patients' socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation. RESULTS: Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0-110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1-2.3). CONCLUSIONS: We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups.

Deprivation gap in colorectal cancer survival attributable to stage at diagnosis: A population-based study in Spain.

OBJECTIVE: Socioeconomic inequalities in colorectal cancer (CRC) survival are a major concern of the Spanish public health system. If these inequalities were mainly due to differences in stage at diagnosis, population-based screening programs might reduce them substantially. We aimed to determine to what extent adverse stage distribution contributed to survival inequalities in a Spanish region before the implementation of a CRC screening program. METHODS: We analyzed data from a population-based cohort study that included all patients living in a region of southern Spain with CRC diagnosed between 2004 and 2013. The European Deprivation Index was used to assign each patient a socioeconomic level based on their area of residence. The role of tumor stage in survival disparities between socioeconomic groups was assessed using a causal mediation analysis. RESULTS: A total of 2802 men and 1957 women were included in the study. For men, the adjusted difference in deaths between the most deprived and the most affluent areas was 131 deaths per 1000 person-years by the first year after diagnosis. Of these deaths, 42 (per 1000 person-years) were attributable to differences in stage at diagnosis. No socioeconomic disparities in survival were detected among female patients. CONCLUSIONS: In this study, we mainly detected socioeconomic disparities in short term survival of male patients. More than two thirds of these inequalities could not be attributed to differences in stage at diagnosis. Our results suggest that in addition to a screening program, other public health interventions are necessary to reduce the deprivation gap in survival.

Risk of breast cancer in patients with lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare metastasizing pulmonary disease that shares some clinical, cellular, and molecular similarities with metastatic breast cancer to lung. LAM cells have been identified circulating in various body fluids of patients and, intriguingly, diverse evidence indicates that these cells may originate from a different organ to the lung. Following on from these observations, we hypothesized the existence of a common risk basis between LAM and breast cancer, and suggested increased risk of breast cancer among LAM patients. Here, by studying two additional LAM cohorts with more detailed epidemiological, life-style, and disease-related data, we show consistent results; a potential excess of estrogen-receptor-positive young breast cancer cases in LAM. This observation further suggests the need of prospective studies to precisely assess the association between both diseases.

Different spatial pattern of municipal prostate cancer mortality in younger men in Spain.

BACKGROUND: Prostate cancer (PC) primarily affects elderly men. However, the specific features of cases diagnosed at younger ages (<65 years) suggest that they may represent a different clinical subtype. Our aim was to assess this suggestion by contrasting the geographical PC mortality and hospital admissions patterns in Spain for all ages to those in younger men. METHODS: The Spanish National Institute of Statistics supplied data on PC mortality, hospital admission, and population data. We estimated the expected town-specific number of deaths and calculated the standardized mortality ratios. Spatial autoregressive models of Besag-York-Mollié provided smoother municipal estimators of PC mortality risk (all ages; <65 years). We computed the provincial age-standardized rate ratios of PC hospital admissions (all men; <60 years) using Spanish rates as the reference. RESULTS: A total of 29,566 PC deaths (6% among those <65 years) were registered between 2010-2014, with three high-mortality risk zones: Northwest Spain; Southwest Andalusia & Granada; and a broad band extending from the Pyrenees Mountains to the north of Valencia. In younger men, the spatial patterns shared the high risk of mortality in the Northwest but not the central band. The PC hospital discharge rates confirmed a North-South gradient but also low mortality/high admission rates in Madrid and Barcelona and the opposite in Southwest Andalusia. CONCLUSION: The consistent high PC mortality/morbidity risk in the Northwest of Spain indicates an area with a real excess of risk. The different spatial pattern in younger men suggests that some factors associated with geographical risk might have differential effects by age. Finally, the regional divergences in mortality and morbidity hint at clinical variability as a source of inequity within Spain.

Long-term trends in pancreatic cancer mortality in Spain (1952-2012).

BACKGROUND: Pancreatic cancer is acquiring increasing prominence as a cause of cancer death in the population. The purpose of this study was to analyze long-term pancreatic cancer mortality trends in Spain and evaluate the independent effects of age, death period and birth cohort on these trends. METHODS: Population and mortality data for the period 1952-2012 were obtained from the Spanish National Statistics Institute. Pancreatic cancer deaths were identified using the International Classification of Diseases ICD-6 to ICD-9 (157 code) and ICD-10 (C25 code). Age-specific and age-adjusted mortality rates were computed by sex, region and five-year period. Changes in pancreatic cancer mortality trends were evaluated using joinpoint regression analyses by sex and region. Age-period-cohort log-linear models were fitted separately for each sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. RESULTS: In men, rates increased by 4.1% per annum from 1975 until the mid-1980s and by 1.1% thereafter. In women, there was an increase of 3.6% per annum until the late 1980s, and 1.4% per annum from 1987 to 2012. With reference to the cohort effects, there was an increase in mortality until the generations born in the 1950s in men and a subsequent decline detected by the change point in 1960. A similar trend was observed in women, but the change point occurred 10 years later than in men. CONCLUSIONS: Pancreatic cancer mortality increased over the study period in both sexes and all regions. An important rise in rates -around 4% annually- was registered until the 1980s, and upward trends were more moderate subsequently. The differences among sexes in trends in younger generations may be linked to different past prevalence of exposure to some risk factors, particularly tobacco, which underwent an earlier decrease in men than in women.

Residential radon and cancer mortality in Galicia, Spain.

Residential radon exposure is a serious public health concern, and as such appears in the recommendations of European Code Against Cancer. The objective of this study was to assess the association between residential radon levels and mortality due to different types of cancer, using misaligned data analysis techniques. Mortality data (observed cases) for each of the 313 Galician municipalities were drawn from the records of the National Statistics Institute for the study period (1999-2008). Expected cases were computed using Galician mortality rates for 14 types of malignant tumors as reference, with a total of 56,385 deaths due to the tumors analyzed. The effect estimates of indoor radon (3371 sampling points) were adjusted for sociodemographic variables, altitude, and arsenic topsoil levels (1069 sampling points), using spatial/geostatistical models fitted with stochastic partial differential equations and integrated nested Laplace approximations. These models are capable of processing misaligned data. The results showed a statistical association between indoor radon and lung, stomach and brain cancer in women in Galicia. Apart from lung cancer (relative risk (RR)=1.09), in which a twofold increase in radon exposure led to a 9% rise in mortality, the association was particularly relevant in stomach (RR=1.17) and brain cancer (RR=1.28). Further analytical epidemiologic studies are needed to confirm these results, and an assessment should be made of the advisability of implementing interventions targeting such exposure in higher-risk areas.

Compositional analysis of topsoil metals and its associations with cancer mortality using spatial misaligned data.

The presence of toxic metals in soil per se, and in soil impacted by mining, industry, agriculture and urbanisation in particular, is a major concern for both human health and ecotoxicology. The dual aim of this study was: to ascertain whether topsoil composition could influence the spatial distribution of mortality due to different types of cancer and to identify possible errors committed by epidemiological studies which analyse soil composition data as a closed number system. We conducted an ecological cancer mortality study, covering 861,440 cancer deaths (27 cancer sites) in 7917 Spanish mainland towns, from 1999 to 2008. Topsoil levels of Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by ICP-MS at 13,317 sampling points. We transformed the topsoil data in two ways, i.e. log transformation and centred logratio transformation. Principal factor analysis was performed to obtain independent latent factors for the transformed variables. To estimate the effect on mortality of topsoil factor loadings, we fitted Besag, York and Mollié models embedded in geostatistical-spatial models. This model included soil sample locations and town centroids (non-aligned data), fitted using the integrated nested Laplace approximation (INLA) as a tool for Bayesian inference and stochastic partial differential equations (SPDE). All results were adjusted for socio-demographic variables. The results indicated that soil composition could have an influence on the spatial distribution and mortality patterns of cancer. The analysis adjusted for socio-demographic variables showed excess male mortality due to digestive system tumours in areas with soils containing higher Cd, Pb, Zn, Mn and Cu concentrations, bladder cancer in areas with soils containing higher Cd concentrations, and brain cancer in areas with soils containing As. In both sexes, cancer of oesophagus was associated with soils containing a higher lead content, while lung cancer was associated with soils containing a higher copper content. Stress should be laid on the importance of taking into account the compositional nature of the data in this type of analysis.

Association between heavy metal and metalloid levels in topsoil and cancer mortality in Spain.

Spatio-temporal cancer mortality studies in Spain have revealed patterns for some tumours which display a distribution that is similar across the sexes and persists over time. Such characteristics would be common to tumours that shared risk factors, including the geochemical composition of the soil. The aim of this study was to assess the possible association between heavy metal and metalloid levels in topsoil (upper soil horizon) and cancer mortality in mainland Spain. Ecological cancer mortality study at a municipal level, covering 861,440 cancer deaths (27 different tumour locations) in 7917 Spanish mainland towns, from 1999 to 2008. The elements included in this analysis were Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Topsoil levels (partial extraction) were determined by ICP-MS at 13,317 sampling points. For the analysis, the data on the topsoil composition have been transformed by the centred logratio (clr-transformation). Principal factor analysis was performed to obtain independent latent factors for the transformed variables. To estimate the effect of heavy metal levels in topsoil composition on mortality, we fitted Besag, York and Mollié models, which included each town's factor scores as the explanatory variable. Integrated Nested Laplace Approximation (INLA) was used as a tool for Bayesian inference. All results were adjusted for sociodemographic variables. The results showed an association between trace contents of heavy metals and metalloids in topsoil and mortality due to tumours of the digestive system in mainland Spain. This association was observed in both sexes, something that would support the hypothesis that the incorporation of heavy metals into the trophic chain might be playing a role in the aetiology of some types of cancer. Topsoil composition and the presence of potentially toxic elements in trace concentrations might be an additional component in the aetiology of some types of cancer, and go some way to determine the ensuing geographic differences in mortality in Spain. The results support the interest of inclusion of heavy metal levels in topsoil as a hypothesis in analytical epidemiological studies using biological markers of exposure to heavy metals and metalloids.

Arsenic and chromium topsoil levels and cancer mortality in Spain.

Spatio-temporal cancer mortality studies in Spain have revealed patterns for some tumours which display a distribution that is similar across the sexes and persists over time. Such characteristics would be common to tumours that shared risk factors, including the chemical soil composition. The objective of the present study is to assess the association between levels of chromium and arsenic in soil and the cancer mortality. This is an ecological cancer mortality study at municipal level, covering 861,440 cancer deaths in 7917 Spanish mainland towns from 1999 to 2008. Chromium and arsenic topsoil levels (partial extraction) were determined by ICP-MS at 13,317 sampling points. To estimate the effect of these concentrations on mortality, we fitted Besag, York and Mollié models, which included, as explanatory variables, each town's chromium and arsenic soil levels, estimated by kriging. In addition, we also fitted geostatistical-spatial models including sample locations and town centroids (non-aligned data), using the integrated nested Laplace approximation (INLA) and stochastic partial differential equations (SPDE). All results were adjusted for socio-demographic variables and proximity to industrial emissions. The results showed a statistical association in men and women alike, between arsenic soil levels and mortality due to cancers of the stomach, pancreas, lung and brain and non-Hodgkin's lymphomas (NHL). Among men, an association was observed with cancers of the prostate, buccal cavity and pharynx, oesophagus, colorectal and kidney. Chromium topsoil levels were associated with mortality among women alone, in cancers of the upper gastrointestinal tract, breast and NHL. Our results suggest that chronic exposure arising from low levels of arsenic and chromium in topsoil could be a potential risk factor for developing cancer.

Study of breast cancer incidence in patients of lymphangioleiomyomatosis.

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.