Richard Love

Breast cancer: a neglected disease for the majority of affected women worldwide.

Abstract:  Recent progress with declines in mortality in some high‐income countries has obscured the fact that for the majority of women worldwide who are newly diagnosed, breast cancer is a neglected disease in the context of other numerically more frequent health problems. For this growing majority, it is also an orphan disease, in that detailed knowledge about tumor characteristics and relevant host biology necessary to provide even basic care is absent. With the possible exception of nutritional recommendations, current international cancer policy and planning initiatives are irrelevant to breast cancer. The progress that has occurred in high‐income countries has come at extraordinary fiscal expense and patient toxicity, which of themselves suggest nonrelevance to women and healthcare practitioners in middle‐ and low‐income countries. The implications of these circumstances appear clear: if the promise of the now 60‐year‐old Declaration of Human Rights that the fruits of medical science accrue to all mankind is to be realized with respect to breast cancer, a basic and translational global research initiative should be launched.

The International Cancer Expert Corps: a unique approach for sustainable cancer care in low and lower-middle income countries

The growing burden of non-communicable diseases including cancer in low- and lower-middle income countries (LMICs) and in geographic-access limited settings within resource-rich countries requires effective and sustainable solutions. The International Cancer Expert Corps (ICEC) is pioneering a novel global mentorship–partnership model to address workforce capability and capacity within cancer disparities regions built on the requirement for local investment in personnel and infrastructure. Radiation oncology will be a key component given its efficacy for cure even for the advanced stages of disease often encountered and for palliation. The goal for an ICEC Center within these health disparities settings is to develop and retain a high-quality sustainable workforce who can provide the best possible cancer care, conduct research, and become a regional center of excellence. The ICEC Center can also serve as a focal point for economic, social, and healthcare system improvement. ICEC is establishing teams of Experts with expertise to mentor in the broad range of subjects required to establish and sustain cancer care programs. The Hubs are cancer centers or other groups and professional societies in resource-rich settings that will comprise the global infrastructure coordinated by ICEC Central. A transformational tenet of ICEC is that altruistic, human-service activity should be an integral part of a healthcare career. To achieve a critical mass of mentors ICEC is working with three groups: academia, private practice, and senior mentors/retirees. While in-kind support will be important, ICEC seeks support for the career time dedicated to this activity through grants, government support, industry, and philanthropy. Providing care for people with cancer in LMICs has been a recalcitrant problem. The alarming increase in the global burden of cancer in LMICs underscores the urgency and makes this an opportune time fornovel and sustainable solutions to transform cancer care globally.

CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer

BackgroundWhile tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.FindingsIn an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case–control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease.We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.ConclusionsThis exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.

Serum Metabolomic Profiles Identify ER-Positive Early Breast Cancer Patients at Increased Risk of Disease Recurrence in a Multicenter Population

Purpose: Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)–negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, premenopausal women with EBC who were enrolled in an international phase III trial. Experimental Design: Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic. Results: In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score. Conclusions: In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors. Clin Cancer Res; 23(6); 1422–31. ©2017 AACR.

Transforming Science, Service, and Society

Battling cancer in developing countries requires partnerships between cancer-care mentors from high-income countries and local community health workers. Management of the cancer burden in low- and lower-middle–income countries requires global partnerships between cancer-care mentors from high-income countries and community health workers familiar with the local circumstances.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer

In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described.

e-ESAS: improving quality of life for breast cancer patients in developing countries

In this paper, we present e-ESAS, a mobile phone based remote monitoring tool for patients with palliative care need, carefully designed for developing countries. Most of the current remote monitoring systems are complex, obtrusive and expensive resulting in a system unsuitable to deploy in low-income countries. We here describe evolution and performance of e-ESAS within the contexts of breast cancer patients as these patients require management of pain and other symptoms. Edmonton Symptom Assessment Scale (ESAS) was developed to capture the important parameters where patients themselves report their level of ten symptoms. Our e-ESAS improves the current system by reducing visits by patients to clinics, providing more flexibility to both doctors and patients, improving the quality of data, accommodating doctors to fine tune interventions, and providing a convenient representation of data to doctors. User interface was designed according to feedbacks from users resulting in a UI with better performance. The system is intended to provide a platform for future research as large amount of real data is being accumulated from the deployment. The system demonstrates the feasibility of accessing quality health care through cell phones by rural, poor patients in developing countries. The system enables doctors to serve more patients as it saves time for doctors, requiring less time to view patient information.

e-ESAS: Evolution of a participatory design-based solution for breast cancer (BC) patients in rural Bangladesh

Abstract Healthcare facility is scarce for rural women in the developing world. The situation is worse for patients who are suffering from diseases that require long-term feedback-oriented monitoring such as breast cancer. Lack of motivation to go to the health centers on patients’ side due to sociocultural barriers, financial restrictions and transportation hazards results in inadequate data for proper assessment. Fortunately, mobile phones have penetrated the masses even in rural communities of the developing countries. In this scenario, a mobile phone-based remote symptom monitoring system (RSMS) with inspirational videos can serve the purpose of both patients and doctors. Here, we present the findings of our field study conducted on 39 breast cancer patients in rural Bangladesh. Based on the results of extensive field studies, we have categorized the challenges faced by patients in different phases of the treatment process. As a solution, we have designed, developed and deployed e-ESAS—the first mobile-based RSMS in rural context. Along with the detail need assessment of such a system, we describe the evolution of e-ESAS and the deployment results. We have included the unique and useful design lessons that we learned as e-ESAS evolved through participatory design process. The findings show how e-ESAS addresses several challenges faced by patients and doctors and positively impact their lives.

Feasibility Study of Case-Finding for Breast Cancer by Community Health Workers in Rural Bangladesh

BACKGROUND Mortality from breast cancer is high in low- and middle-income countries, in part because most patients have advanced stage disease when first diagnosed. Case-finding may be one approach to changing this situation. MATERIALS AND METHODS We conducted a pilot study to explore the feasibility of population-based case finding for breast cancer by community health workers (CHWs) using different data collection methods and approaches to management of women found to have breast abnormalities. After training 8 CHWs in breast problem recognition, manual paper data collection and operation of a cell-phone software platform for reporting demographic, history and physical finding information, these CHWs visited 3150 women >age 18 and over they could find--from 2356 households in 8 villages in rural Bangladesh. By 4 random assignments of villages, data were collected manually (Group 1), or with the cell-phone program alone (Group 2) or with management algorithms (Groups 3 and 4), and women adjudged to have a serious breast problem were shown a motivational video (Group 3), or navigated/accompanied to a breast problem center for evaluation (Group 4). RESULTS Only three visited women refused evaluation. The manual data acquisition group (1) had missing data in 80% of cases, and took an average of 5 minutes longer to acquire, versus no missing data in the cell phone-reporting groups (2,3 and 4). One woman was identified with stage III breast cancer, and was appropriately treated. CONCLUSIONS Among very poor rural Bangladeshi women, there was very limited reluctance to undergo breast evaluation. The estimated rarity of clinical breast cancer is supported by these population-based findings. The feasibility and efficient use of mobile technology in this setting is supported. Successor studies may most appropriately be trials focusing on improving the suggested benefits of motivation and navigation, on increasing the numbers of cases found, and on stage of disease at diagnosis as the primary endpoint.

Symptom Levels in Care-Seeking Bangladeshi and Nepalese Adults With Advanced Cancer

Purpose Three-fourths of patients with advanced cancer are reported to suffer from pain. A primary barrier to provision of adequate symptom treatment is failure to appreciate the intensity of the symptoms patients are experiencing. Because data on Bangladeshi and Nepalese patients’ perceptions of their symptomatic status are limited, we sought such information using a cell phone questionnaire. Methods At tertiary care centers in Dhaka and Kathmandu, we recruited 640 and 383 adult patients, respectively, with incurable malignancy presenting for outpatient visits and instructed them for that single visit on one-time completion of a cell phone platform 15-item survey of questions about common cancer-associated symptoms and their magnitudes using Likert scales of 0 to 10. The questions were taken from the Edmonton Symptom Assessment System and the Brief Pain Inventory instruments. Results All but two Bangladeshi patients recruited agreed to study participation. Two-thirds of Bangladeshi patients reported usual pain levels ≥ 5, and 50% of Nepalese patients reported usual pain levels ≥ 4 (population differences significant at P < .001). Conclusion Bangladeshi and Nepalese adults with advanced cancer are comfortable with cell phone questionnaires about their symptoms and report high levels of pain. Greater attention to the suffering of these patients is warranted.