Symptom Assessment and Early Access to Supportive and Palliative Care for Patients With Advanced Solid Tumors in Mexico.

BACKGROUND: Early specialized palliative care improves quality of life of patients with advanced cancer, and guidelines encourage its integration into standard oncology care. However, many patients fail to obtain timely palliative/supportive care evaluations, particularly in limited-resource settings. We aimed to determine the proportion of patients with advanced cancer who received an assessment of symptoms and were referred to supportive and palliative care services during the first year after diagnosis in a Mexican hospital. METHODS: Individuals with newly diagnosed advanced solid tumors and 1 year of follow-up at the oncology clinics in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City from October 2015 to April 2016 were included in this retrospective study. RESULTS: Seventy-seven patients were included. Forty-two (54.5%) were referred to the various supportive care services during the first year after diagnosis, and 23 (29.8%) were referred to the palliative care clinic. The most commonly assessed symptoms by oncologists were pain (77.9%), anorexia (74.0%), fatigue (68.8%), and nausea (55.8%), while depression/anxiety were evaluated in 10 (12.9%) patients. The oncologist offered to clarify treatment goals in 39 (50.6%) cases and evaluated the understanding of diagnosis/illness and prognosis in 22 (28.5%). CONCLUSION: Palliative and supportive care services were widely underutilized, which may be related to a lack of standardized symptom assessments and poor end-of-life communication. Novel strategies are needed to improve the implementation of tools for systematic symptom assessment and to optimize the integration of supportive care interventions into oncology care in developing countries.

Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.

PURPOSE: A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients. METHODS: 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed. RESULTS: An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk. CONCLUSIONS: In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.

Disparities in Breast, Lung, and Cervical Cancer Trials Worldwide.

PURPOSE: As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown. METHODS: We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank. RESULTS: Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs ( P < .001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P = .66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work. CONCLUSION: There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences.

Barriers to Primary Debulking Surgery for Advanced Ovarian Cancer in Latin America.

Ovarian cancer is gynecologic tumor with particularly high mortality because it is usually diagnosed in advanced stages. In Latin America and the Caribbean, it is the eighth most common malignancy in women, with an estimated 18,000 new cases and 11,500 deaths annually. Standard of care for women diagnosed with advanced ovarian cancer (AOC) is primary cytoreductive surgery followed by systemic chemotherapy using a combination of paclitaxel plus carboplatin. To pursue upfront surgery, highly specialized and well-trained gynecologic oncologists are required, in addition with well-equipped hospitals. Neoadjuvant chemotherapy (NACT) has been gaining greater acceptance in the past decade for patients with AOC. Two phase III randomized clinical trials have demonstrated that NACT is noninferior to primary cytoreductive surgery for women with stages III and IV epithelial ovarian cancer, and since publication of these results, NACT is more commonly used. Apart from medical reasons of inoperability and unresectability, there may be nonmedical barriers to upfront debulking surgery in clinical practice. These barriers include inadequate expertise of the surgeon, inadequate resources, and/or barriers to access. The aim of this article was to discuss patterns of care and barriers to upfront ovarian debulking surgery, as well as a possible shift toward overuse of NACT as the primary approach for patients with AOC (stages III and IV) in Latin America.

End-of-Life Care in Latin America.

Cancer has become a global pandemic with disproportionately higher mortality rates in low- and middle- income countries, where a large fraction of patients present in advanced stages and in need of end-of-life care. Globally, the number of adults needing end-of-life care is greater than 19 million, and up to 78% of these patients are living in low- and middle- income countries. In the Americas alone, more than one million people are in need of end-of-life care, placing an enormous burden on local health systems, which are often unprepared to meet the challenge presented by this complex patient population. In Latin America, cancer care is characterized by the presence of vast inequalities between and within countries, and the provision of end-of-life care is no exception. Disparities in access to advanced care planning, with a lack of provision of adequate palliative care and pain medication, are common in the region. These shortcomings are related in large part to inadequate or inappropriate legislation, lack of comprehensive national palliative care plans, insufficient infrastructure, lack of opportunities for clinical training, unreliable reporting of data, and cultural barriers. This report reviews the current status of end-of-life care in Latin America, focusing on identifying existing deficiencies and providing a framework for improvement.

Improving access to high-cost cancer drugs in Latin America: Much to be done.

Lack of access to high-cost medications is a complex issue at the intersection of economics, medicine, politics, and ethics, and it poses a significant threat to global health care. The problem is even more significant in low- and middle-income countries, such as those in Latin America, where governments and individuals struggle to pay for products that are priced at several times the level of their per capita gross domestic product. In this review, we examine the determinants for increasing drug costs and how Latin American countries face this burgeoning crisis. We emphasize that a number of opportunities and strategies to reduce costs and improve access exist and should be identified and implemented, ideally within a regional approach with multiple stakeholders involved and based on systematic and transparent cost-effectiveness analyses. Cancer 2017;123:1313-1323. © 2016 American Cancer Society.

Assessment of the prognostic and predictive utility of the Breast Cancer Index (BCI): an NCIC CTG MA.14 study.

BACKGROUND: Biomarkers that can be used to accurately assess the residual risk of disease recurrence in women with hormone receptor-positive breast cancer are clinically valuable. We evaluated the prognostic value of the Breast Cancer Index (BCI), a continuous risk index based on a combination of HOXB13:IL17BR and molecular grade index, in women with early breast cancer treated with either tamoxifen alone or tamoxifen plus octreotide in the NCIC MA.14 phase III clinical trial (ClinicalTrials.gov Identifier NCT00002864; registered 1 November 1999). METHODS: Gene expression analysis of BCI by real-time polymerase chain reaction was performed blinded to outcome on RNA extracted from archived formalin-fixed, paraffin-embedded tumor samples of 299 patients with both lymph node-negative (LN-) and lymph node-positive (LN+) disease enrolled in the MA.14 trial. Our primary objective was to determine the prognostic performance of BCI based on relapse-free survival (RFS). MA.14 patients experienced similar RFS on both treatment arms. Association of gene expression data with RFS was evaluated in univariate analysis with a stratified log-rank test statistic, depicted with a Kaplan-Meier plot and an adjusted Cox survivor plot. In the multivariate assessment, we used stratified Cox regression. The prognostic performance of an emerging, optimized linear BCI model was also assessed in a post hoc analysis. RESULTS: Of 299 samples, 292 were assessed successfully for BCI for 146 patients accrued in each MA.14 treatment arm. BCI risk groups had a significant univariate association with RFS (stratified log-rank p = 0.005, unstratified log-rank p = 0.007). Adjusted 10-year RFS in BCI low-, intermediate-, and high-risk groups was 87.5 %, 83.9 %, and 74.7 %, respectively. BCI had a significant prognostic effect [hazard ratio (HR) 2.34, 95 % confidence interval (CI) 1.33-4.11; p = 0.004], although not a predictive effect, on RFS in stratified multivariate analysis, adjusted for pathological tumor stage (HR 2.22, 95 % CI 1.22-4.07; p = 0.01). In the post hoc multivariate analysis, higher linear BCI was associated with shorter RFS (p = 0.002). CONCLUSIONS: BCI had a strong prognostic effect on RFS in patients with early-stage breast cancer treated with tamoxifen alone or with tamoxifen and octreotide. BCI was prognostic in both LN- and LN+ patients. This retrospective study is an independent validation of the prognostic performance of BCI in a prospective trial.

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer.

PURPOSE: The identification of patients with metastatic triple-negative breast cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of interest. We conducted a single-arm phase II clinical trial of single-agent platinum for mTNBC with biomarker correlates. PATIENTS AND METHODS: Patients with mTNBC received first- or second-line cisplatin (75 mg/m(2)) or carboplatin (area under the concentration-time curve 6) by physician's choice once every 3 weeks. Coprimary end points were objective response rate (RR) and response prediction by p63/p73 gene expression. Secondary and exploratory end points included toxicity assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined subgroups, including BRCA1/2 mutation carriers. RESULTS: Patients (N = 86; 69 as first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was 25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%) than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2 mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory analyses showed that a BRCA-like genomic instability signature (n = 32) discriminated responding and nonresponding tumors (mean homologous recombination deficiency-loss of heterozygosity/homologous recombination deficiency-large-scale state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively), whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five of the six long-term responders alive at a median of 4.5 years lacked germline BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores. CONCLUSION: Platinum agents are active in mTNBC, especially in patients with germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify patients without mutations who could benefit from platinum therapy agents. Prospective controlled confirmatory trials are warranted.

Challenges to effective cancer control in China, India, and Russia.

Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement.

Outcomes of breast cancer in Brazil related to health care coverage: a retrospective cohort study.

BACKGROUND: Breast cancer is the most common malignancy in women in Brazil. Differences between patients with public versus private healthcare coverage about general characteristics, disease presentation, treatment of primary tumors, and clinical outcomes have not been fully investigated. METHODS: A national, retrospective cohort of 3,142 patients drawn from a representative sample of Brazilian medical centers was selected. Clinical and demographic data and type of healthcare coverage were retrieved by chart review. Groups were compared using the χ(2) test. The log-rank test was used for comparison of disease-free survival (DFS), postrelapse, and overall survival (OS). Multivariate Cox regression modeling with adjustment for patient characteristics and stage at diagnosis was performed. All P values are two sided. RESULTS: Patients with public health coverage presented with more advanced disease at diagnosis (P < 0.001). DFS and OS for patients presenting with stage 0-II disease did not differ according to the type of healthcare coverage, whereas a significant difference in outcomes was seen for stage III-IV patients (P = 0.002 and P = 0.008, respectively). In a Cox multivariate analysis, no association was found for the type of health coverage with either DFS or OS, but there was an association for postrelapse survival (P < 0.001). CONCLUSION: In Brazil, patients with breast cancer with public health coverage present with more advanced disease, and this possibly explains worse DFS and OS when compared with those with private coverage. IMPACT: Earlier diagnosis and treatment of breast cancer could improve outcomes of women with public health coverage in Brazil.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.

Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer.

Breast cancer in Mexico: a growing challenge to health and the health system.

Breast cancer is a major public health issue in low-income and middle-income countries. In Mexico, incidence and mortality of breast cancer have risen in the past few decades. Changes in health-care policies in Mexico have incorporated programmes for access to early diagnosis and treatment of this disease. This Review outlines the status of breast cancer in Mexico, regarding demographics, access to care, and strategies to improve clinical outcomes. We identify factors that contribute to the existing disease burden, such as low mammography coverage, poor quality control, limited access to diagnosis and treatment, and insufficient physical and human resources for clinical care.

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective.

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women.

PURPOSE: To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. METHODS: Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. RESULTS: Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). CONCLUSION: Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.