Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

<p>Abstract</p> <p>Background</p> <p>Amplification of the <it>ERBB2 </it>(<it>Her-2/neu</it>) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for <it>topoisomerase II alpha </it>(<it>TOP2A</it>), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.</p> <p>Methods and patients</p> <p>Archival tissue samples from 63 breast cancer patients with <it>ERBB2 </it>amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near <it>ERBB2</it>. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available.</p> <p>Results</p> <p>Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted <it>TOP2A </it>had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. <it>TOP2A </it>deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between <it>TOP2A </it>deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).</p> <p>Conclusion</p> <p><it>TOP2A </it>deletion is associated with poor prognosis in <it>ERBB2</it>-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.</p

Disparities in breast cancer by race and ethnicity.

e18526 Background: Breast cancer is the most common female malignancy. While there have been significant advances in diagnosis and treatment of breast cancer, there are gaps in care leading to high mortality rates in low socio-economic populations and ethnic minorities. This inequality is attributed to poor access to care and later stages at diagnosis. Methods: All female breast cancer patients between 2000-2020 (N=8,444) were included. Statistical analysis was done with X2 testing for categorical variables and T-tests for continuous variables. A univariate logistic regression was used to understand impact of each characteristic. Results: Black women were more likely to have poor prognostic factors for breast cancer compared to white women: distant metastatic disease at diagnosis (4.6% vs 3.2%, p=0.02), triple negative disease (25% vs 13.6%, p&lt;0.01), high oncotype dx score &gt;25 (37.2% vs 26.1%, p=0.04), recurrence (14.9% vs 12.1%, p=0.04), and mortality rate (24.2% vs 15.6%, p&lt;0.01). Despite these high-risk factors, white women were more likely to have a mastectomy than black women (43.8% vs 35.4%, p&lt;0.01), and the average age at diagnosis was higher in black women at 59.2±13.5 years compared to white women at 57.5±12.8 years (p&lt;0.01). The most prominent poor prognostic factor in black women was having triple negative breast cancer with OR 2.13 (95% CI 1.7- 2.6) compared to others in Table. Hispanic women were more likely to have higher stage at diagnosis (OR 1.21), lymph node involvement (OR 1.03), metastatic disease (OR 1.43), and tumor size &gt;1cm (OR 1.06) than nonHispanic women, but only lymph node involvement at diagnosis was statistically significant (29.1% vs 24.5%, p=0.02). Conclusions: There is a high prevalence of racial and ethnic disparities in women with breast cancer. Black women are more likely to have poor prognostic factors including metastatic disease at diagnosis and triple negative breast cancer, leading to higher recurrence and mortality rates. Hispanic women are also more likely to have poor prognostic factors, but this data was not statistically significant due to small sample size. Efforts to improve access to health care leading to earlier diagnosis may decrease the gap in mortality rate for minority women with predisposition to high-risk malignancies.[Table: see text] </jats:p

Abemaciclib with or without fulvestrant for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer with disease progression following prior treatment with palbociclib.

e12533 Background: Abemaciclib is a selective inhibitor of CDK4 and CDK6 kinase activity. It is approved for patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, advanced or metastatic breast cancer (MBC) previously treated: in combination with fulvestrant for patients with disease progression following endocrine therapy (MONARCH 2) and as monotherapy for patients with disease progression after endocrine therapy and chemotherapy for MBC (MONARCH 1). The patients in these trials were CDK 4/6 inhibitor-naïve. It has not yet been studied in patients who previously received a CDK 4/6 inhibitor. Methods: We performed a chart review of patients with HR positive, HER2-negative MBC treated at Rush University Medical Center who progressed on palbociclib, either with an aromatase inhibitor (AI) or fulvestrant, and were subsequently treated with abemaciclib with or without fulvestrant. We documented patient demographics, prior treatment, and response to abemaciclib therapy. Results: 21 female patients, mean age 57.8 (+/- 13.2y), were included. Patients had received 1-5 prior lines of endocrine therapy and 0 – 4 prior lines of chemotherapy for MBC. All patients received prior palbociclib: 14 patients with an AI, 6 patients with fulvestrant, and 1 patient received palbociclib with an AI and then with fulvestrant. Of the 21 patients, 17 were treated with abemaciclib monotherapy and 4 received abemaciclib with fulvestrant. SD was seen in 19% of patients (4/21) and 62% had PD (13/21). The CBR was 29% (6/21) and all of these patients received abemaciclib monotherapy. Due to expected toxicities of the drug (diarrhea, neutropenia, and thrombocytopenia), 19% (4/21) of patients discontinued treatment. 4 patients continued abemaciclib monotherapy for greater than 8.3M. 3 patients were on treatment for less than 35 days; 2 stopped due to expected toxicities and one had progression of disease on physical exam. Median treatment duration was 3.1M. Conclusions: This retrospective chart review of 21 patients demonstrates that abemaciclib has limited activity as a single agent in patients previously treated with palbociclib. </jats:p

Impact of oncotype Dx score on treatment and long-term outcomes.

e12518 Background: Oncotype dx is a 21 gene breast cancer assay that helps predict benefit of chemotherapy in early-stage hormone receptor positive (HR+), HER2 negative, 0 to 3 node positive breast cancer as reported by TAILORx and RxPonder trials. Both trials found no benefit of adjuvant therapy in mid-range scores of 11-25 with the exception of some benefit in age under 50 or premenopausal status, no benefit if score was 0-10, and benefit of chemotherapy if &gt;25. Methods: All breast cancer patients between 2019-2020 were chart checked to evaluate oncotype dx scores. Patient characteristics were analyzed between oncotype dx scores of 0-10, 11-25, and &gt;25 using X square tests. 2000-2020 institutional cancer registry data was analyzed to understand recurrence and mortality in patients with oncotype dx testing. Results: 173 patients had oncotype dx testing between 2019-2020, and most were HR+, HER2-, and had 0-3 lymph nodes. There was no difference in race or ethnicity between the groups of oncotype dx scores (Table), and average age at diagnosis for all three groups was 58 years. More patients with lower oncotype dx score had hormone therapy, but this was not significant (0-10 at 93.6%, 11-25 at 90.8%, and &gt;25 at 82.1%, p=0.26). Patients with a higher oncotype score were significantly more likely to have chemotherapy (0-10 at 0%, 11-25 at 17.3%, and &gt;25 at 82.1%, p&lt;0.01). When looking at long term outcomes, the mortality rate was highest in the 11-25 score group at 9.5%, but was not significantly higher than 0-10 at 4.7% and &gt;25 at 2.1% (p=0.15). The recurrence was highest in the 0-10 group at 5.4%, but not significant compared to the 11-25 group at 4.1% and &gt;25 group at 4.2% (p=0.09). Conclusions: Race, ethnicity, and age does not impact predisposition to high oncotype dx score, which is interesting since literature shows minority women have higher mortality rates. This could be because oncotype dx looks at early-stage breast cancers and many minority women have later stages at diagnosis. There was no difference in which group received hormone therapy and there was significantly higher rate of chemotherapy administration in patients with scores &gt;25, which is consistent with prospective trial recommendations. When evaluating long term outcomes between oncotype dx groups over 20 years, there was no significant difference in recurrence of disease or mortality indicating that oncotype dx scoring accurately predicted overall benefit of chemotherapy.[Table: see text] </jats:p

Abstract A50: Is there a reverse racial/ethnic disparity in chemotherapy treatment among breast cancer patients?

Abstract Background: There is evidence that minority women are more likely than White women to receive suboptimal breast cancer care, however this may not be the case with regards to chemotherapy for which White women may be less likely than Black or Hispanic women to receive chemotherapy. In order to better understand this apparent reverse disparity, this study seeks to examine how changes in the treatment guidelines may affect the disparity observed in chemotherapy treatment. Methods: Interview and medical record data came from a population-based study of 989 breast cancer patients (397 non-Hispanic White, 411 non-Hispanic Black, 181 Hispanic) diagnosed between 2005-2008. Of these, 87% (N=849) consented to medical record abstraction, including a linkage with the Illinois State Cancer Registry (ISCR). Patients who consented to the medical record abstraction and had single primary tumors were considered for this study. Eligibility for chemotherapy (CT) was defined according to the National Comprehensive Cancer Network (NCCN) guidelines in two ways. First, CT eligibility was defined according to the 2005 guidelines and then also according to the 2006-2007 guidelines. The outcome variables included treatment recommendation, acceptance, and initiation which were derived from the interview, medical record, and ISCR data. Age-adjusted risk differences (RDs) were estimated using logistic regression (with marginal standardization) in order to report percentages. Results: The medical record consent rate was 87%. Among those with a medical record consent and single primary tumors (n=824), 460 were CT-eligible per the 2005 NCCN guidelines and 284 were CT-eligible per the 2006-2007 guidelines (eligibility could not be determined for 107 node-negative, hormone receptor-positive women because their HER2 status was unavailable). Using the 2005 NCCN guidelines, chemotherapy was recommended to 74% of CT-eligible patients and non-Hispanic White patients were less likely than minority patients to receive a recommendation (0.62 vs. 0.75, RD=13%p=0.001). However, if the 2006-2007 guidelines were used, 94% of eligible patients received a recommendation and there were no racial/ethnic differences. Of these women who received a recommendation, 98% accepted it and a resulting 100% initiated treatment. However, the overall treatment initiation was 92% and in multivariate analysis, patients with lower income (p=0.03), breast conserving surgery (p=0.01), and low grade tumors (p=0.05) were less likely to initiate chemotherapy. Conclusions: The apparent reverse racial/ethnic disparity in chemotherapy treatment may appear or disappear depending on which guideline is used to determine treatment eligibility. It is reasonable that clinicians change treatment practices ahead of published guidelines as to provide their patients with the best care. Future studies on treatment quality should consider this when defining treatment eligibility. The vast majority of CT-eligible patients are receiving chemotherapy, although patients with less aggressive appearing tumors are less likely to receive CT. Citation Format: Abigail Silva, Garth H. Rauscher, Kent Hoskins, Ruta D. Rao. Is there a reverse racial/ethnic disparity in chemotherapy treatment among breast cancer patients? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A50.</jats:p

Abstract A49: Mediators of racial/ethnic disparities in radiation treatment among breast cancer patients.

Abstract Background: Radiation after surgery can reduce recurrence and breast cancer mortality yet there is some evidence that not all women receive guideline-concordant radiation treatment. Indeed, studies that have examined the receipt of radiation among women who underwent breast-conserving surgery have found that Black and Hispanic women were less likely than White women to complete their locoregional treatment. However, little is known about the factors that may facilitate or impede treatment. In order to better understand the causes of disparities in radiation treatment, this study seeks to: 1) determine the extent to which there is a racial/ethnic disparity in radiation treatment initiation, and 2) examine patient factors and hospital characteristics that may help explain the variation. Methods: Interview and medical record data came from a population-based study of 989 breast cancer patients (397 non-Hispanic White, 411 non-Hispanic Black, 181 Hispanic) diagnosed between 2005-2008. Of these, 87% (N=849) consented to medical record abstraction, including a linkage with the Illinois State Cancer Registry (ISCR). Patients who consented to the medical record abstraction and had single invasive primary tumors were considered for this study. Radiation treatment eligibility was defined according to the 2005-2007 National Comprehensive Cancer Network (NCCN) guidelines. The outcome variables included treatment recommendation, acceptance, and initiation which were derived from the interview, medical record, and ISCR data. Risk differences (RDs) were estimated using logistic regression (with marginal standardization). Potential mediators related to radiation initiation were identified, and then assessed by rescaling model coefficients using the method of Karlson, Holm, and Breen. All models were adjusted for age and time from diagnosis to interview. Results: Among patients with single invasive primary tumors (n=614), 443 patients (72%) were eligible for radiation treatment (RT) per the NCCN guidelines. Radiation treatment was recommended to 88% of eligible patients of which 93% accepted it. Among those who accepted treatment, 97% received radiation. This translated into an overall treatment initiation of 79%. Minority patients were less likely than non-Hispanic (nH) White patients to initiate radiation (0.75 vs. 0.85, RD=10%p=0.000). Minorities were more likely to have moderate-high grade tumors and symptomatically detected tumors which in turn were less likely to receive radiation (all p-values &amp;lt;0.01). Minority women were also more likely than nH White women (p&amp;lt;0.0001) to receive chemotherapy, which in turn was associated with lower receipt of RT (p&amp;lt;0.05). Together these factors explained 46% of the disparity (p=0.002). Conclusions: Patients who are eligible for radiation and have more aggressive appearing tumors at diagnosis are more likely to receive chemotherapy but at the expense of completing their locoregional (radiation) therapy. This disproportionately affects minority patients and results in underuse of radiation in these women. Greater diffusion of gene expression profiling (e.g. Oncotype) may improve cancer care not only by reducing overuse of chemotherapy but by eliminating chemotherapy as a potential barrier to receipt of RT. Citation Format: Abigail Silva, Garth H. Rauscher, Rao D. Ruta, Kent Hoskins. Mediators of racial/ethnic disparities in radiation treatment among breast cancer patients. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A49.</jats:p