Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

Screening Programs for Breast Cancer: Toward Individualized, Risk-Adapted Strategies of Early Detection.

Early detection of breast cancer (BC) comprises two approaches: screening of asymptomatic women in a specified target population at risk (usually a target age range for women at average risk), and early diagnosis for women with BC signs and symptoms. Screening for BC is a key health intervention for early detection. While population-based screening programs have been implemented for age-selected women, the pivotal clinical trials have not addressed the global utility nor the improvement of screening performance by utilizing more refined parameters for patient eligibility, such as individualized risk stratification. In addition, with the exception of the subset of women known to carry germline pathogenetic mutations in (high- or moderately-penetrant) cancer predisposition genes, such as BRCA1 and BRCA2, there has been less success in outreach and service provision for the unaffected relatives of women found to carry a high-risk mutation (i.e., "cascade testing") as it is in these individuals for whom such actionable information can result in cancers (and/or cancer deaths) being averted. Moreover, even in the absence of clinical cancer genetics services, as is the case for the immediate and at least near-term in most countries globally, the capacity to stratify the risk of an individual to develop BC has existed for many years, is available for free online at various sites/platforms, and is increasingly being validated for non-Caucasian populations. Ultimately, a precision approach to BC screening is largely missing. In the present chapter, we aim to address the concept of risk-adapted screening of BC, in multiple facets, and understand if there is a value in the implementation of adapted screening strategies in selected women, outside the established screening prescriptions, in the terms of age-range, screening modality and schedules of imaging.

Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study.

BACKGROUND: Comprehensive breast cancer management is essential to achieve high breast cancer survival; however, detailed reports of the treatment regimens received by patients are scarce in sub-Saharan Africa where survival is low. We aimed to examine treatment initiation, guideline concordance, and abandonment in patients with non-metastatic breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort. METHODS: The ABC-DO prospective cohort study recruited women (aged ≥18 years) with newly diagnosed invasive breast cancer in eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, Uganda, South Africa, and Zambia). We analysed treatments received by women who were classified as non-metastatic (M0) at the initial presentation. Data on surgery, radiotherapy, and systemic therapies were obtained from medical records and a self-reported follow-up questionnaire at 6 months after the diagnosis, follow-up calls every 3 months, and a baseline questionnaire. Initiation, completion, and abandonment of treatment modalities and combined therapy regimens were examined overall, by country-specific groups, and by clinical factors relevant for guideline-based treatment. FINDINGS: Of 2313 women recruited into the ABC-DO study between Sept 10, 2014, and Dec 31, 2017, 2226 had histologically or clinically confirmed breast cancer. Of these 2226 women, 510 were excluded from the present analysis because 378 had metastatic disease, 37 were prevalent cases (defined as those previously diagnosed with breast cancer >2 years before baseline), 82 had unknown TNM stage, and 13 were White or Asian women in South Africa (number was too small for analysis). After a median follow-up of 5·2 years (IQR 4·6-5·9), 1163 (68%) of 1716 women underwent breast cancer surgery. Surgery and systemic therapy (ie, multimodality treatment) with radiotherapy was initiated in 370 (36%) of 1028 women with localised tumours versus 156 (23%) of 688 women with locally advanced tumours, whereas multimodality treatment without radiotherapy was initiated in 386 (38%) versus 167 (24%) women, respectively. Of 1530 patients requiring chemotherapy (which excludes 105 who died within 6 months after baseline), 1013 (66%) initiated treatment of neoadjuvant chemotherapy or surgery within 3 months after baseline, which was adequately completed by 359 (35%) of 1013 women, marginally completed by 284 (28%), abandoned by 200 (20%), and unknown in 151 (15%). 19 (2%) women died within 6 months after chemotherapy initiation. Of 1375 women in whom endocrine therapy was indicated, this treatment was initiated in 920, and lasted at least 3 years in 367 (40%) women. Treatment disparities between country-specific groups were substantial for all therapy regimens. INTERPRETATION: A high proportion of patients with non-metastatic breast cancer did not initiate, did not fully complete, or abandoned treatment with surgery, systemic therapy, radiotherapy, or an appropriate combination of these, highlighting the need for improved treatment access and completion in sub-Saharan Africa to potentially prevent premature breast cancer deaths. FUNDING: National Institutes of Health (National Cancer Institute), Susan G Komen, and the International Agency for Research on Cancer.

Implementation of a large-scale breast cancer early detection program in a resource-constrained setting: real-world experiences from 2 large states in India.

BACKGROUND: The Breast Health Initiative (BHI) was launched to demonstrate a scalable model to improve access to early diagnosis and treatment of breast cancer. METHODS: A package of evidence-based interventions was codesigned and implemented with the stakeholders, as part of the national noncommunicable disease program, through the existing primary health care system. Data from the first 18 months of the BHI are presented. RESULTS: A total of 108,112 women received breast health education; 48% visited the health facilities for clinical breast examination (CBE), 3% had a positive CBE result, and 41% were referred to a diagnostic facility. The concordance of CBE findings between health care providers and adherence to follow-up care improved considerably, with more women visiting the diagnostic facilities and completing diagnostic evaluation within 1 month from initial screening, and with only 9% lost to follow-up. The authors observed a clinically meaningful decrease in time to complete diagnostic evaluation with biopsy, from 37 to 9 days. CONCLUSIONS: The results demonstrate the feasibility and effectiveness of implementing a large-scale, decentralized breast cancer early detection program delivered through the existing primary health care system in India.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer.

PURPOSE: Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured. METHODS: Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1-6 and 27-35; low oestrogen and low progesterone) or W2 (days 7-26; high oestrogen and high or low progesterone). RESULTS: The invasion module score of RS was lower (- 10.9%; p = 0.098), whereas the ER (+ 16.6%; p = 0.046) and proliferation (+ 7.3%; p = 0.13) module scores were higher in W2. PGR expression was significantly increased in W2 (+ 81.4%; p = 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (r = 0.72-0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%. CONCLUSION: There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.

Comparing models of delivery for cancer genetics services among patients receiving primary care who meet criteria for genetic evaluation in two healthcare systems: BRIDGE randomized controlled trial.

BACKGROUND: Advances in genetics and sequencing technologies are enabling the identification of more individuals with inherited cancer susceptibility who could benefit from tailored screening and prevention recommendations. While cancer family history information is used in primary care settings to identify unaffected patients who could benefit from a cancer genetics evaluation, this information is underutilized. System-level population health management strategies are needed to assist health care systems in identifying patients who may benefit from genetic services. In addition, because of the limited number of trained genetics specialists and increasing patient volume, the development of innovative and sustainable approaches to delivering cancer genetic services is essential. METHODS: We are conducting a randomized controlled trial, entitled Broadening the Reach, Impact, and Delivery of Genetic Services (BRIDGE), to address these needs. The trial is comparing uptake of genetic counseling, uptake of genetic testing, and patient adherence to management recommendations for automated, patient-directed versus enhanced standard of care cancer genetics services delivery models. An algorithm-based system that utilizes structured cancer family history data available in the electronic health record (EHR) is used to identify unaffected patients who receive primary care at the study sites and meet current guidelines for cancer genetic testing. We are enrolling eligible patients at two healthcare systems (University of Utah Health and New York University Langone Health) through outreach to a randomly selected sample of 2780 eligible patients in the two sites, with 1:1 randomization to the genetic services delivery arms within sites. Study outcomes are assessed through genetics clinic records, EHR, and two follow-up questionnaires at 4 weeks and 12 months after last genetic counseling contactpre-test genetic counseling. DISCUSSION: BRIDGE is being conducted in two healthcare systems with different clinical structures and patient populations. Innovative aspects of the trial include a randomized comparison of a chatbot-based genetic services delivery model to standard of care, as well as identification of at-risk individuals through a sustainable EHR-based system. The findings from the BRIDGE trial will advance the state of the science in identification of unaffected patients with inherited cancer susceptibility and delivery of genetic services to those patients. TRIAL REGISTRATION: BRIDGE is registered as NCT03985852 . The trial was registered on June 6, 2019 at clinicaltrials.gov .

Patient Interactions With an Automated Conversational Agent Delivering Pretest Genetics Education: Descriptive Study.

BACKGROUND: Cancer genetic testing to assess an individual's cancer risk and to enable genomics-informed cancer treatment has grown exponentially in the past decade. Because of this continued growth and a shortage of health care workers, there is a need for automated strategies that provide high-quality genetics services to patients to reduce the clinical demand for genetics providers. Conversational agents have shown promise in managing mental health, pain, and other chronic conditions and are increasingly being used in cancer genetic services. However, research on how patients interact with these agents to satisfy their information needs is limited. OBJECTIVE: Our primary aim is to assess user interactions with a conversational agent for pretest genetics education. METHODS: We conducted a feasibility study of user interactions with a conversational agent who delivers pretest genetics education to primary care patients without cancer who are eligible for cancer genetic evaluation. The conversational agent provided scripted content similar to that delivered in a pretest genetic counseling visit for cancer genetic testing. Outside of a core set of information delivered to all patients, users were able to navigate within the chat to request additional content in their areas of interest. An artificial intelligence-based preprogrammed library was also established to allow users to ask open-ended questions to the conversational agent. Transcripts of the interactions were recorded. Here, we describe the information selected, time spent to complete the chat, and use of the open-ended question feature. Descriptive statistics were used for quantitative measures, and thematic analyses were used for qualitative responses. RESULTS: We invited 103 patients to participate, of which 88.3% (91/103) were offered access to the conversational agent, 39% (36/91) started the chat, and 32% (30/91) completed the chat. Most users who completed the chat indicated that they wanted to continue with genetic testing (21/30, 70%), few were unsure (9/30, 30%), and no patient declined to move forward with testing. Those who decided to test spent an average of 10 (SD 2.57) minutes on the chat, selected an average of 1.87 (SD 1.2) additional pieces of information, and generally did not ask open-ended questions. Those who were unsure spent 4 more minutes on average (mean 14.1, SD 7.41; P=.03) on the chat, selected an average of 3.67 (SD 2.9) additional pieces of information, and asked at least one open-ended question. CONCLUSIONS: The pretest chat provided enough information for most patients to decide on cancer genetic testing, as indicated by the small number of open-ended questions. A subset of participants were still unsure about receiving genetic testing and may require additional education or interpersonal support before making a testing decision. Conversational agents have the potential to become a scalable alternative for pretest genetics education, reducing the clinical demand on genetics providers.

Designing a resource-stratified, phased implementation strategy for breast health care services in India.

BACKGROUND: Breast cancer is the most common cancer among women in India. Jhpiego, a not-for-profit health organization, is providing technical assistance for developing an evidence-based model of breast health care in the states of Uttar Pradesh and Jharkhand in India. METHODS: A situational assessment of breast health care services using validated tools was conducted in the 2 states. RESULTS: Findings of the assessment were presented to the Breast Health Technical Advisory Committee comprised of subject experts and government functionaries. The committee, guided by Breast Health Global Initiative resource-stratified guidelines, developed a conceptual framework for integration of breast health services into the existing health system. This conceptual framework was presented to the Technical Advisory Groups (TAGs) of the respective state governments. Each TAG then developed an operationally feasible, contextually appropriate implementation plan in alignment with the national guidelines for noncommunicable diseases. This implementation plan guided the rollout of the breast health care program in the Lucknow (Uttar Pradesh) and Ranchi (Jharkhand) districts. CONCLUSIONS: Early results from the implementation suggest that it is feasible to integrate the breast health care pathway with the ongoing National Cancer Control Program of India.

The Breast Health Global Initiative 2018 Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation: Methods and overview.

BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

Breast cancer early detection: A phased approach to implementation.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Estimating child mortality associated with maternal mortality from breast and cervical cancer.

BACKGROUND: Large-scale population studies demonstrate an association between mothers' deaths and child mortality in both lower and higher income countries. The authors estimated children's deaths in association with mothers' deaths from breast or cervical cancer, 2 common cancers in low-income and middle-income countries affecting women of reproductive age, to develop a comprehensive assessment of the death burden of these cancers. METHODS: A Monte Carlo simulation model was devised whereby women were at risk of dying from breast cancer, cervical cancer, or another cause. Compared with children who have living mothers, children of women who die before they reached age 10 years have an elevated risk of death from all causes. Therefore, simulations were conducted, and the impact of mothers' deaths from cervical and breast cancer on associated child mortality was quantified for Bangladesh, Burkina Faso, and Denmark (benchmark analysis), then the analyses were extended to all African countries. RESULTS: Benchmark estimates of child deaths associated with mothers' deaths from breast and cervical cancer resulted in an increment in cancer-related mortality of approximately 2% in Bangladesh, 14% in Burkina Faso, and less than 1% in Denmark. The model predicted an increment in comprehensive cancer deaths when including child death estimates by as high as 30% in certain African countries. CONCLUSIONS: To the authors' knowledge, this is the first study to estimate the impact of a mother's death from cancer on child mortality. The model's estimates call for further investigation into this correlation and underscore the relevance of adequate access to prevention and treatment among women of childbearing age.

Predictors of mammographic density among women with a strong family history of breast cancer.

BACKGROUND: Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. METHODS: We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. RESULTS: Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. CONCLUSIONS: In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.

Breast cancer in women living with HIV: A first global estimate.

There is a growing population of older women living with HIV/AIDS (WLWHA). Breast cancer is a common cancer in women worldwide, but the global number of breast cancers in WLWHA is not known. We estimated, for each UN sub-region, the number and age distribution of WLWHA who were diagnosed with breast cancer in 2012, by combining IARC-GLOBOCAN estimates of age-country specific breast cancer incidence with corresponding UNAIDS HIV prevalence. Primary analyses assumed no HIV-breast cancer association, and a breast cancer risk reduction scenario was also considered. Among 16.0 million WLWHA aged 15+ years, an estimated 6,325 WLWHA were diagnosed with breast cancer in 2012, 74% of whom were in sub-Saharan Africa, equally distributed between Eastern, Southern and Western Africa. In most areas, 70% of HIV-positive breast cancers were diagnosed under age 50. Among all breast cancers (regardless of HIV status), HIV-positive women constituted less than 1% of the clinical burden, except in Eastern, Western and Middle Africa where they comprised 4-6% of under age 50 year old breast cancer patients, and in Southern Africa where this patient subgroup constituted 26 and 8% of breast cancers diagnosed under and over age 50 respectively. If a deficit of breast cancer occurs in WLWHA, the global estimate would reduce to 3,600. In conclusion, worldwide, the number of HIV-positive women diagnosed with breast cancer was already substantial in 2012 and with an expected increase within the next decade, early detection and treatment research targeted to this population are needed.

Interventions to close the divide for women with breast and cervical cancer between low-income and middle-income countries and high-income countries.

Breast and cervical cancers are the commonest cancers diagnosed in women living in low-income and middle-income countries (LMICs), where opportunities for prevention, early detection, or both, are few. Yet several cost-effective interventions could be used to reduce the burden of these two cancers in resource-limited environments. Population- wide vaccination against human papillomavirus (HPV) linked to cervical screening, at least once, for adult women has the potential to reduce the incidence of cervical cancer substantially. Strategies such as visual inspection with acetic acid and testing for oncogenic HPV types could make prevention of cervical cancer programmatically feasible. These two cancers need not be viewed as inevitably fatal, and can be cured, particularly if detected and treated at an early stage. Investing in the health of girls and women is an investment in the development of nations and their futures. Here we explore ways to lessen the divide between LMICs and high-income countries for breast and cervical cancers.

Changing global policy to deliver safe, equitable, and affordable care for women's cancers.

Breast and cervical cancer are major threats to the health of women globally, particularly in low-income and middle-income countries. Radical progress to close the global cancer divide for women requires not only evidence-based policy making, but also broad multisectoral collaboration that capitalises on recent progress in the associated domains of women's health and innovative public health approaches to cancer care and control. Such multisectoral collaboration can serve to build health systems for cancer, and more broadly for primary care, surgery, and pathology. This Series paper explores the global health and public policy landscapes that intersect with women's health and global cancer control, with new approaches to bringing policy to action. Cancer is a major global social and political priority, and women's cancers are not only a tractable socioeconomic policy target in themselves, but also an important Trojan horse to drive improved cancer control and care.