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Background: Butaro Cancer Center of Excellence (BCCOE) was founded to serve Rwanda's rural low-income population, providing subsidized cancer diagnosis and treatment with transport stipends for the lowest-income patients. We examined whether travel distance to BCCOE was associated with advanced-stage diagnoses and treatment completion., Methods: We conducted a retrospective cohort study using medical record data from BCCOE patients with pathologically-confirmed breast cancer from 2012-2016. Women with no prior surgery were included in the stage analysis; those with non-metastatic disease were included in the treatment analysis. We calculated travel distances using spatial analytic software and used multivariable logistic regression to examine the association of distance and other patient characteristics with late-stage diagnoses and treatment completion within one year of diagnosis., Results: The analytic cohort for stage included 426 patients; 75.1% had late-stage (stage 3 or 4) disease. In univariable analyses, patients residing in BCCOE's surrounding district had a lower proportion of late-stage diagnoses compared to those residing outside the district (57.9% v 76.8%, p = 0.02). In adjusted analyses, odds of late-stage diagnosis were 2.46 (95% CI:1.21-5.12) times higher among those in distance quartile 4 (> 135.8 km) versus 1 (< 55.7 km); the effect of distance was less strong in sensitivity analyses excluding patients from BCCOE's surrounding district. Patients from sectors with > 50% poverty had 2.33 times higher odds of late-stage diagnoses (95% CI:1.07-5.26) relative to those with poverty < 30%. In the treatment completion cohort (n = 348), 49.1% of patients completed surgery and chemotherapy within a year. In adjusted analyses, travel distance and poverty were not linearly associated with treatment completion., Conclusions: At Rwanda's first public cancer facility, sector-level poverty and longer travel distances were associated with late-stage breast cancer diagnoses, but less clearly associated with treatment completion, perhaps partly due to travel stipends provided to the lowest-income individuals undergoing treatment. Our findings support further investigation into wider use of travel stipends to facilitate early diagnosis and treatment completion., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Partners HealthCare Institutional Review Board [2012P002016] (Boston, MA), the Rwanda National Ethics Committee (No 348/RNEC/2012), and the Harvard University Institutional Review Board [IRB20-0699] (Boston, MA). The requirement for informed consent from individuals whose medical records were reviewed for the study was waived. Consent for publication: N/A. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Importance: Racial disparities in receipt of guideline-concordant care (GCC) among older patients with potentially curable breast cancer are understudied., Objective: To determine whether rates of GCC, time to treatment initiation, and all-cause mortality in stage I to III breast cancer differ by race among older adults., Design, Setting, and Participants: This cohort study used data from the National Cancer Database and included patients aged 65 years and older with stage I to III breast cancer, diagnosed between 2010 and 2019. Data analysis was conducted between July 2022 to July 2023., Exposures: Race, defined as non-Hispanic Black or non-Hispanic White., Main Outcomes and Measures: The primary outcome was nonreceipt of GCC, defined using the National Comprehensive Cancer Network guidelines, and all-cause mortality. The secondary outcome was time to treatment initiation. Univariate and multivariate regression analysis were used to determine association between exposure and outcomes. Models for GCC and all-cause mortality included age, stage, receptor status, year of diagnosis, Charlson-Deyo comorbidity index, insurance, health care setting, and neighborhood-level educational attainment and median income., Results: The analytic cohort included 258 531 participants (mean [SD] age, 72.5 [6.0] years), with 25 174 participants who identified as non-Hispanic Black (9.7%) and 233 357 participants who identified as non-Hispanic White (90.3%), diagnosed between 2010 and 2017. A total of 4563 non-Hispanic Black participants (18.1%) and 35 374 non-Hispanic White participants (15.2%) did not receive GCC. Non-Hispanic Black race, compared with non-Hispanic White race, was associated with increased odds of not receiving GCC in the multivariate analysis (adjusted odds ratio [aOR], 1.13; 95% CI, 1.08-1.17; P < .001). Non-Hispanic Black race was associated with 26.1% increased risk of all-cause mortality in the univariate analysis, which decreased to 4.7%, after adjusting for GCC and clinical and sociodemographic factors (adjusted hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .006). Non-Hispanic White race, compared with non-Hispanic Black race, was associated with increased odds of initiating treatment within 30 (OR, 1.65; 95% CI, 1.6-1.69), 60 (OR, 2.11; 95% CI, 2.04-2.18), and 90 (OR, 2.39; 95% CI, 2.27-2.51) days of diagnosis., Conclusions and Relevance: In this cohort study, non-Hispanic Black race was associated with increased odds of not receiving GCC and less timely treatment initiation. Non-Hispanic Black race was associated with increased all-cause mortality, which was reduced after adjusting for GCC and clinical and sociodemographic factors. These findings suggest that optimizing timely receipt of GCC may represent a modifiable pathway to improving inferior survival outcomes among older non-Hispanic Black patients with breast cancer.

Objectives: Narrative communication has demonstrated effectiveness in promoting positive health behaviours, delivering support and coping with complex decision-making. Formal research evaluating this intervention for cancer treatment in Africa is lacking. We aimed to develop, and assess acceptability and usability of survivor video narrative interventions for breast cancer treatment in Botswana., Design: A pilot study design., Setting: Single-centre, tertiary hospital, sub-Saharan Africa., Participants: Eight women, ≥18 years old, with stages I-III breast cancer were enrolled for the video intervention. 106 women, ≥18 years old, with stages I-IV breast cancer viewed the narrative videos and 98 completed the acceptability and usability surveys., Intervention: Survivor narrative videos were developed using the theory of planned behaviour and using a purposive sample of Batswana, Setswana-speaking, breast cancer survivors, who had completed systemic treatment and surgery with high rates of adherence to the prescribed treatment plan., Primary Outcomes: We assessed acceptability and usability among prospectively enrolled patients presenting for routine breast cancer care at Princess Marina Hospital in Botswana, using a 13-item survey., Results: Participants expressed high acceptability and usability of the videos, including 99% (97/98) who strongly agreed/agreed that the video presentations were easy to understand, 92% (90/98) who would recommend to other survivors and 94% (92/98) who wished there were more videos. Additionally, 89% (87/98) agreed or strongly agreed that the one-on-one instruction on how to use the tablet was helpful and 87% (85/98) that the video player was easy to use., Conclusion: Culturally appropriate survivor video narratives have high acceptability and usability among patients with breast cancer in Botswana. There is an opportunity to leverage this intervention in routine breast cancer care for treatment support. Future studies will test the implementation and effectiveness of narrative videos on a wider scale, including for patients being treated for other cancers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: There is urgent need for interventions to facilitate earlier diagnosis of breast cancer in low- and middle-income countries where mammography screening is not widely available. Understanding patients' experiences with early detection efforts, whether they are ultimately diagnosed with cancer or benign disease, is critical to optimize interventions and maximize community engagement. We sought to understand the experiences of patients undergoing breast evaluation in Rwanda's Women's Cancer Early Detection Program (WCEDP)., Methods: We conducted in-person semi-structured interviews with 30 patients in two districts of Rwanda participating in the WCEDP. Patients represented a range of ages and both benign and malignant diagnoses. Interviews were recorded, transcribed, translated, and thematically analyzed., Results: Participants identified facilitators and barriers of timely care along the breast evaluation pathway. Community awareness initiatives were facilitators to care-seeking, while persistent myths and stigma about cancer were barriers. Participants valued clear clinician-patient communication and emotional support from clinicians and peers. Poverty was a major barrier for participants who described difficulty paying for transport, insurance premiums, and other direct and indirect costs of hospital referrals in particular. COVID-19 lockdowns caused delays for referred patients. Although false-positive clinical breast exams conferred financial and emotional burdens, participants nonetheless voiced appreciation for their experience and felt empowered to monitor their own breast health and share knowledge with others., Conclusion: Rwandan women experienced both benefits and burdens as they underwent breast evaluation. Enthusiasm for participation was not reduced by the experience of a false-positive result. Reducing financial, logistical and emotional burdens of the breast diagnostic pathway through patient navigation, peer support and decentralization of diagnostic services could improve patients' experience., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Increased breast density augments breast cancer risk and reduces mammography sensitivity. Supplemental breast MRI screening can significantly increase cancer detection among women with dense breasts. However, few women undergo this exam, and screening is consistently lower among racially minoritized populations. Implementation strategies informed by behavioral economics ("nudges") can promote evidence-based practices by improving clinician decision-making under conditions of uncertainty. Nudges directed toward clinicians and patients may facilitate the implementation of supplemental breast MRI., Methods: Approximately 1600 patients identified as having extremely dense breasts after non-actionable mammograms, along with about 1100 clinicians involved with their care at 32 primary care or OB/GYN clinics across a racially diverse academically based health system, will be enrolled. A 2 × 2 randomized pragmatic trial will test nudges to patients, clinicians, both, or neither to promote supplemental breast MRI screening. Before implementation, rapid cycle approaches informed by clinician and patient experiences and behavioral economics and health equity frameworks guided nudge design. Clinicians will be clustered into clinic groups based on existing administrative departments and care patterns, and these clinic groups will be randomized to have the nudge activated at different times per a stepped wedge design. Clinicians will receive nudges integrated into the routine mammographic report or sent through electronic health record (EHR) in-basket messaging once their clinic group (i.e., wedge) is randomized to receive the intervention. Independently, patients will be randomized to receive text message nudges or not. The primary outcome will be defined as ordering or scheduling supplemental breast MRI. Secondary outcomes include MRI completion, cancer detection rates, and false-positive rates. Patient sociodemographic information and clinic-level variables will be examined as moderators of nudge effectiveness. Qualitative interviews conducted at the trial's conclusion will examine barriers and facilitators to implementation., Discussion: This study will add to the growing literature on the effectiveness of behavioral economics-informed implementation strategies to promote evidence-based interventions. The design will facilitate testing the relative effects of nudges to patients and clinicians and the effects of moderators of nudge effectiveness, including key indicators of health disparities. The results may inform the introduction of low-cost, scalable implementation strategies to promote early breast cancer detection., Trial Registration: ClinicalTrials.gov NCT05787249. Registered on March 28, 2023., (© 2023. The Author(s).)

Importance: Black women in the United States have higher breast cancer (BC) mortality rates than White women. The combined role of multiple factors, including body mass index (BMI), age, and tumor subtype, remains unclear., Objective: To assess the association of race and ethnicity with survival among clinical trial participants with early-stage BC (eBC) according to tumor subtype, age, and BMI., Design, Setting, and Participants: This cohort study analyzed survival data, as of November 12, 2021, from participants enrolled between 1997 and 2010 in 4 randomized adjuvant chemotherapy trials: Cancer and Leukemia Group B (CALGB) 9741, 49907, and 40101 as well as North Central Cancer Treatment Group (NCCTG) N9831, legacy groups of the Alliance of Clinical Trials in Oncology. Median follow-up was 9.8 years., Exposures: Non-Hispanic Black and Hispanic participants were compared with non-Hispanic White participants within subgroups of subtype (hormone receptor positive [HR+]/ERBB2 [formerly HER2] negative [ERBB2-], ERBB2+, and HR-/ERBB2-), age (<50, 50 to <65, and ≥65 years), and BMI (<18.5, 18.5 to <25.0, 25.0 to <30.0, and ≥30.0)., Main Outcomes and Measures: Recurrence-free survival (RFS) and overall survival (OS)., Results: Of 9479 participants, 436 (4.4%) were Hispanic, 871 (8.8%) non-Hispanic Black, and 7889 (79.5%) non-Hispanic White. The median (range) age was 52 (19.0-89.7) years. Among participants with HR+/ERBB2- tumors, non-Hispanic Black individuals had worse RFS (hazard ratio [HR], 1.49; 95% CI, 1.04-2.12; 5-year RFS, 88.5% vs 93.2%) than non-Hispanic White individuals, although the global test for association of race and ethnicity with RFS was not significant within any tumor subtype. There were no OS differences by race and ethnicity in any subtype. Race and ethnicity were associated with OS in young participants (age <50 years; global P = .008); young non-Hispanic Black participants (HR, 1.34; 95% CI, 1.04-1.71; 5-year OS, 86.6% vs 92.0%) and Hispanic participants (HR, 1.62; 95% CI, 1.16-2.29; 5-year OS, 86.2% vs 92.0%) had worse OS than young non-Hispanic White participants. Race and ethnicity were associated with RFS in participants with BMIs of 25 to less than 30, with non-Hispanic Black participants having worse RFS (HR, 1.81; 95% CI, 1.23-2.68; 5-year RFS, 83.2% vs 87.3%) than non-Hispanic White participants., Conclusions and Relevance: In this cohort study, racial and ethnic survival disparities were identified in patients with eBC receiving standardized initial care, and potentially at-risk subgroups, for whom focused interventions may improve outcomes, were found.

Objective: To evaluate whether integrating breast and cervical cancer screening in Rwanda's Women's Cancer Early Detection Program led to early breast cancer diagnoses in asymptomatic women., Methods: Launched in three districts in 2018-2019, the early detection programme offered clinical breast examination screening for all women receiving cervical cancer screening, and diagnostic breast examination for women with breast cancer symptoms. Women with abnormal breast examinations were referred to district hospitals and then to referral hospitals if needed. We examined how often clinics were held, patient volumes and number of referrals. We also examined intervals between referrals and visits to the next care level and, among women diagnosed with cancer, their initial reasons for seeking care., Findings: Health centres held clinics > 68% of the weeks. Overall, 9763 women received cervical cancer screening and clinical breast examination and 7616 received breast examination alone. Of 585 women referred from health centres, 436 (74.5%) visited the district hospital after a median of 9 days (interquartile range, IQR: 3-19). Of 200 women referred to referral hospitals, 179 (89.5%) attended after a median of 11 days (IQR: 4-18). Of 29 women diagnosed with breast cancer, 19 were ≥ 50 years and 23 had stage III or stage IV disease. All women with breast cancer whose reasons for seeking care were known (23 women) had experienced breast cancer symptoms., Conclusion: In the short-term, integrating clinical breast examination with cervical cancer screening was not associated with detection of early-stage breast cancer among asymptomatic women. Priority should be given to encouraging women to seek timely care for symptoms., ((c) 2023 The authors; licensee World Health Organization.)

Purpose: To evaluate the scope and types of cancer research projects in sub-Saharan Africa (SSA) to identify research gaps and inform future efforts., Methods: This retrospective observational study summarized information on cancer research projects in SSA from the International Cancer Research Partnership (ICRP) between 2015 and 2020, alongside 2020 cancer incidence and mortality data from the Global Cancer Observatory. SSA cancer research projects were identified as led by investigators in SSA countries, or by investigators in non-SSA countries with collaborators in SSA, or in database keyword searches. Projects from the Coalition for Implementation Research in Global Oncology (CIRGO) were also summarized., Results: A total of 1,846 projects were identified from the ICRP database, funded by 34 organizations in seven countries (only one, Cancer Association of South Africa, based in SSA); only 156 (8%) were led by SSA-based investigators. Most projects focused on virally induced cancers (57%). Across all cancer types, projects were most frequently related to cervical cancer (24%), Kaposi sarcoma (15%), breast cancer (10%), or non-Hodgkin lymphoma (10%). Gaps were observed for several cancers with higher incidence/mortality burden in SSA; for example, prostate cancer accounted for only 4% of projects but 8% of cancer-related deaths and 10% of new cases. Approximately 26% were dedicated to etiology. Treatment-related research declined over the study period (14%-7% of all projects), while projects related to prevention (15%-20%) and diagnosis/prognosis (15%-29%) increased. Fifteen CIRGO projects were identified; seven were relevant across multiple cancer types, and 12 focused either wholly or partially on cancer control (representing 50% of the total research effort)., Conclusion: This analysis shows notable discrepancies between cancer burden and research projects and identifies opportunities for future strategic investments in cancer care in SSA.

Objective: To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert ® STRAT4 assay., Methods: We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods., Findings: We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available., Conclusion: Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in sub-Saharan African laboratories, leading to improved treatment selection and better clinical outcomes., ((c) 2023 The authors; licensee World Health Organization.)

Purpose: There is limited evidence to guide incorporation of breast cancer early detection into resource-constrained health systems where mammography screening is not yet available. To inform such strategies, we sought to understand health care workers' perspectives on a breast cancer early detection initiative integrated into community, primary, and secondary levels of care in Rwanda., Methods: We conducted a qualitative study using semistructured interviews with 33 community health workers, clinicians, and administrators at health facilities participating in the Women's Cancer Early Detection Program (WCEDP), through which women received clinical breast examination if they were receiving cervical cancer screening, or had breast concerns. Through thematic analysis, we identified dynamics and patterns associated with successes and challenges of the program's breast health services., Results: Successes and challenges identified by participants corresponded with the community- and primary care-based steps of cancer early diagnosis identified by the WHO. Regarding step 1 (community awareness/access), participants noted increases in awareness and care-seeking. Challenges included difficulty overcoming stigma and engaging older women. Regarding step 2 (clinical evaluation), all participants described increased breast health knowledge, skills, and confidence. Integrating the WCEDP with other services was challenging because of inadequate staffing; offering WCEDP services on a designated day/week had advantages and disadvantages. Although participants appreciated WCEDP referral mechanisms, they desired more communication from referral facilities. Patients' poverty was the most consistently identified impediment to referral completion., Conclusion: Rwandan health care workers identified real-world successes and challenges of implementing principles of early cancer diagnosis for breast cancer early detection. Future interventions should focus on engagement of older women, community awareness, patient socioeconomic support, and optimizing integration into primary care.

Purpose: To scale up early detection of breast cancer in low- and middle-income countries, research is needed to inform the role of diagnostic breast ultrasound performed by nonradiologists in resource-constrained settings. The authors examined 2-year clinical follow-up and outcomes among women who underwent diagnostic breast ultrasound performed by nonradiologist clinicians participating in a breast ultrasound training and mentorship program at a rural Rwandan hospital., Methods: Imaging findings, management plans, and pathologic results were prospectively collected during the training using a standardized form. Data on follow-up and outcomes for patients receiving breast ultrasound between January 2016 and March 2017 were retrospectively collected through medical record review., Results: Two hundred twenty-nine breast palpable findings (199 patients) met the study's eligibility criteria. Of 104 lesions initially biopsied, 38 were malignant on initial biopsy; 3 lesions were identified as malignant on repeat biopsy. All 34 patients ultimately diagnosed with cancer received initial recommendations for either biopsy or aspiration by trainees. The positive predictive value of trainee biopsy recommendation was 34.8% (95% confidence interval, 24.8%-45.0%). The sensitivity of trainees' biopsy recommendation for identifying malignant lesions was 92.7% (95% confidence interval, 84.2%-100%). Of 46 patients who did not receive biopsy and were told to return for clinical or imaging follow-up, 37.0% did not return., Conclusions: Trained nonradiologist clinicians in Rwanda successfully identified suspicious breast lesions on diagnostic breast ultrasound. Loss to follow-up was common among patients instructed to return for surveillance, so lower biopsy thresholds, decentralized surveillance, or patient navigation should be considered for patients with low- or intermediate-suspicion lesions., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to quantify the health system cost of the first 2 years of a Breast Cancer Early Detection (BCED) programme in a rural district in Rwanda. We also aimed to estimate the cost of implementing the programme in other districts with different referral pathways and identify opportunities for enhanced cost efficiency., Design: Retrospective, cross-sectional analysis using time-driven activity-based costing, based on timed patient clinical encounters, retrospective patient data and unit costs of resources abstracted from administrative and finance records., Setting: The BCED programme focused on timely evaluation of individuals with breast symptoms. The study evaluated the health system cost of the BCED programme at seven health centres (HCs) in Burera district and Butaro Cancer Centre of Excellence (BCCOE) at Butaro District Hospital., Outcome Measures: Health system costs per patient visit and cost per cancer diagnosed were quantified. Total start-up and recurring operational costs were also estimated, as well as health system costs of different scale-up adaptations in other districts., Results: One-time start-up costswere US$36 917, recurring operational costswere US$67 711 and clinical costswere US$14 824 over 2 years. Clinical breast examinations (CBE) at HCs cost US$3.27/visit. At BCCOE, CBE-only visits cost US$13.47/visit, CBE/ultrasound US$14.79/visit and CBE/ultrasound/biopsy/pathology US$147.81/visit. Overall, clinical cost per breast cancer diagnosed was US$1482. Clinicalcost drivers were personnel at HCs (55%) and biopsy/pathology supplies at BCCOE (46%). In other districts, patients experience a longer breast evaluation pathway, adding about US$14.00/patient; this could be decreased if ultrasound services were decentralised., Conclusion: Clinical costs associated with BCED services at HCs were modest, similar to other general outpatient services. The BCED programme's start-up and operational costs were high but could be reduced by using local trainers and virtual mentorship. In other districts, decentralising ultrasound and/or biopsies to district hospitals could reduce costs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are limited data on breast surgery completion rates and prevalence of care-continuum delays in breast cancer treatment programs in low-income countries., Methods: This study analyzes treatment data in a retrospective cohort of 312 female patients with non-metastatic breast cancer in Haiti. Descriptive statistics were used to summarize patient characteristics; treatments received; and treatment delays of > 12 weeks. Multivariate logistic regressions were performed to identify factors associated with receiving surgery and with treatment delays. Exploratory multivariate survival analysis examined the association between surgery delays and disease-free survival (DFS)., Results: Of 312 patients, 249 (80%) completed breast surgery. The odds ratio (OR) for surgery completion for urban vs. rural dwellers was 2.15 (95% confidence interval [CI]: 1.19-3.88) and for those with locally advanced vs. early-stage disease was 0.34 (95%CI: 0.16-0.73). Among the 223 patients with evaluable surgery completion timelines, 96 (43%) experienced delays. Of the 221 patients eligible for adjuvant chemotherapy, 141 (64%) received adjuvant chemotherapy, 66 of whom (47%) experienced delays in chemotherapy initiation. Presentation in the later years of the cohort (2015-2016) was associated with lower rates of surgery completion (75% vs. 85%) and with delays in adjuvant chemotherapy initiation (OR [95%CI]: 3.25 [1.50-7.06]). Exploratory analysis revealed no association between surgical delays and DFS., Conclusion: While majority of patients obtained curative-intent surgery, nearly half experienced delays in surgery and adjuvant chemotherapy initiation. Although our study was not powered to identify an association between surgical delays and DFS, these delays may negatively impact long-term outcomes., (© 2022. The Author(s).)

Purpose: Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT)., Methods: This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding., Results: In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy., Conclusion: Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes., Competing Interests: Robert GrossConsulting or Advisory Role: PfizerResearch Funding: Merck (Inst) Lawrence N. ShulmanResearch Funding: Celgene (Inst), Independence Blue Cross (Inst) Surbhi GroverHonoraria: Varian Medical SystemsConsulting or Advisory Role: GenesisCareResearch Funding: Varian Medical Systems Angela DeMicheleResearch Funding: Pfizer (Inst), Genentech (Inst), Calithera Biosciences (Inst), Novartis (Inst)No other potential conflicts of interest were reported.

Background: The American College of Surgeons Commission on Cancer's (CoC) new operative standards for breast cancer, melanoma, and colon cancer surgeries will require that surgeons provide synoptic documentation of essential oncologic elements within operative reports. Prior to designing and implementing an electronic tool to support synoptic reporting, we evaluated current documentation practices at our institution to understand baseline concordance with these standards., Methods: Applicable procedures performed between 1 January 2018 and 31 December 2018 were included. Two independent reviewers evaluated sequential operative notes, up to a total of 100 notes, for documentation of required elements. Complete concordance (CC) was defined as explicit documentation of all required CoC elements. Mean percentage CC and surgeon-specific CC were calculated for each procedure. Interrater reliability was assessed via Cohen's kappa statistic., Results: For sentinel lymph node biopsy, mean CC was 66% (n = 100), with surgeon-specific CC ranging from 6 to 100%, and for axillary dissection, mean CC was 12% (n = 89) and surgeon-specific CC ranged from 0 to 47%. The single surgeon performing melanoma wide local excision had a mean CC of 98% (n = 100). For colon resections, mean CC was 69% (n = 96) and surgeon-specific CC ranged from 39 to 94%. Kappa scores were 0.77, 0.78, -0.15, and 0.78, respectively., Conclusions: We identified heterogeneity in current documentation practices. In our cohort, rates of baseline concordance varied across surgeons and procedures. Currently, documentation elements are interspersed within the operative report, posing challenges to chart abstraction with resulting imperfect interrater reliability. This presents an exciting opportunity to innovate and improve compliance by introducing an electronic synoptic documentation tool., (© 2021. Society of Surgical Oncology.)

Introduction: Systemic treatment for breast cancer in sub-Saharan Africa (SSA) is cost effective. However, there are limited real-world data on the translation of breast cancer treatment guidelines into clinical practice in SSA. The study aimed to identify provider factors associated with adherence to breast cancer guideline-concordant care at Princess Marina Hospital (PMH) in Botswana., Materials and Methods: The Consolidated Framework for Implementation Research was used to conduct one-on-one semistructured interviews with breast cancer providers at PMH. Purposive sampling was used, and sample size was determined by thematic saturation. Transcribed interviews were double-coded and analyzed in NVivo using an integrated analysis approach., Results: Forty-one providers across eight departments were interviewed. There were variations in breast cancer guidelines used. Facilitators included a strong tension for change and a government-funded comprehensive cancer care plan. Common provider and health system barriers were lack of available resources, staff shortages and poor skills retention, lack of relative priority compared with HIV/AIDS, suboptimal interdepartmental communication, and lack of a clearly defined national cancer control policy. Community-level barriers included accessibility and associated transportation costs. Participants recommended the formal implementation of future guidelines that involved key stakeholders in all phases of planning and implementation, strategic government buy-in, expansion of multidisciplinary tumor boards, leveraging nongovernmental and academic partnerships, and setting up monitoring, evaluation, and feedback processes., Discussion: The study identified complex, multilevel factors affecting breast cancer treatment delivery in Botswana. These results and recommendations will inform strategies to overcome specific barriers in order to promote standardized breast cancer care delivery and improve survival outcomes., Implications for Practice: To address the increasing cancer burden in low- and middle-income countries, resource-stratified guidelines have been developed by multiple international organizations to promote high-quality guideline-concordant care. However, these guidelines still require adaptation in order to be successfully translated into clinical practice in the countries where they are intended to be used. This study highlights a systematic approach of evaluating important contextual factors associated with the successful adaptation and implementation of resource-stratified guidelines in sub-Saharan Africa. In Botswana, there is a critical need for local stakeholder input to inform country-level and facility-level resources, cancer care accessibility, and community-level barriers and facilitators., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Purpose: The COVID-19 pandemic has posed significant pressures on healthcare systems, raising concern that related care delays will result in excess cancer-related deaths. Because data regarding the impact on patients with breast cancer are urgently needed, we aimed to provide a preliminary estimate of the impact of COVID-19 on time to treatment initiation (TTI) for patients newly diagnosed with breast cancer cared for at a large academic center., Methods: We conducted a retrospective study of patients with newly diagnosed early-stage breast cancer between January 1, 2020, and May 15, 2020, a time period during which care was affected by COVID-19, and an unaffected cohort diagnosed between January 1, 2018 and May 15, 2018. Outcomes included patient volume, TTI, and initial treatment modality. Adjusted TTI was compared using multivariable linear regression., Results: Three hundred sixty-six patients were included. There was an 18.8% decrease in patient volume in 2020 (n = 164) versus 2018 (n = 202). There was no association between time of diagnosis (pre-COVID-19 or during COVID-19) and adjusted TTI ( P = .926). There were fewer in situ diagnoses in the 2020 cohort ( P = .040). There was increased use of preoperative systemic therapy in 2020 (43.9% overall, 20.7% chemotherapy, and 23.2% hormonal therapy) versus 2018 (16.4% overall, 12.4% chemotherapy, and 4.0% hormonal therapy) ( P < .001)., Conclusion: TTI was maintained among patients diagnosed and treated for breast cancer during the COVID-19 pandemic at a single large academic center. There was a decrease in patient volume, specifically in patients with in situ disease and a shift in initial therapy toward the use of preoperative hormonal therapy., Competing Interests: Lawrence N. ShulmanResearch Funding: Celgene Ira J. BleiweissHonoraria: Bard BiopsySpeakers' Bureau: Bard Biopsy, Philips Digital Imaging Rachel C. JankowitzHonoraria: EisaiConsulting or Advisory Role: MerckNo other potential conflicts of interest were reported.

Background: Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care., Methods: For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes., Findings: We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0)., Interpretation: Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging., Funding: Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply., Design: A retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016., Setting: Princess Marina Hospital in Gaborone, Botswana., Participants: Patients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy., Primary and Secondary Outcome Measures: Frequency of delays and patterns of prescription changes for specific regimens and cancer types., Results: 167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout., Conclusions: The aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery., Competing Interests: Competing interests: SD, SG, DIS, TBR, PM, LNS and YMM have nothing to disclose. WBB reports personal fees from Genentech, outside the submitted work; Robert Gross reports grants from NIH, during the conduct of the study; personal fees from Pfizer, outside the submitted work; AD reports grants from Pfizer, grants from Novartis, grants from Genentech, grants from Calithera, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We hypothesize that in addition to specimen margin widths other clinical variables may help predict the presence of residual disease in the lumpectomy bed., Methods: Patients with Stage I-III invasive breast cancer (BC) who underwent partial mastectomy (PM) and re-excision from July 2010-June 2015 were retrospectively reviewed. Bivariate analyses were conducted using two-sample t-tests for continuous variables and Fisher's Exact tests for categorical variables. A multivariate logistic regression was then performed on significant bivariate analyses variables., Results: ne-hundred and eighty-four patients were included in our analysis; 47% had residual disease on re-excision, while 53% had no residual disease. Tumor and nodal stage, operation type, type of disease present at margin, and number of positive margins were significantly associated with residual disease. On multivariate logistic regression, DCIS alone at the margin (p = 0.02), operation type (PM with cavity margins) (p = 0.003), and number of positive margins (3 or more) (p < 0.001) remained predictive of residual disease at re-excision., Conclusion: Based on a more comprehensive review of the initial pathology, there are additional factors that can help predict the likelihood of finding residual disease and help guide the surgeon in the decision for re-excision., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Few studies have explored the relationship between body habitus and breast cancer outcomes in Caribbean women of African ancestry. This study evaluates the association between body mass index (BMI) and disease-free survival (DFS) in a retrospective cohort of 224 female Haitian patients with nonmetastatic breast cancer., Patients and Methods: BMI was obtained from the medical records and categorized as normal weight (< 25 kg/m 2 ), overweight (25-29.9 kg/m 2 ), and obese (≥ 30 kg/m 2 ). DFS was defined as time from surgical resection to disease recurrence, death, or censoring. Kaplan-Meier survival curves were generated, and the association between BMI and DFS was evaluated using Cox proportional hazard models to control for multiple confounders. Exploratory analyses were conducted on weight changes during adjuvant chemotherapy., Results: Eighty-three patients (37.1%) were normal weight, 66 (29.5%) were overweight, and 75 (33.5%) were obese. There were no statistical differences in baseline characteristics or treatments received by BMI group. Twenty-six patients died and 73 had disease recurrence. Median DFS was 41.1 months. Kaplan-Meier estimates showed no significant DFS differences by BMI categories. After controlling for confounders, normal weight patients, when compared with overweight and obese patients, had adjusted hazard ratios of 0.85 (95% CI, 0.49 to 1.49) and 0.90 (95% CI, 0.52 to 1.55), respectively. Overall, mean weight loss of 2% of body weight was noted over the course of adjuvant chemotherapy. Patients who were postmenopausal ( P = .007) and obese ( P = .05) lost more weight than other groups. However, chemotherapy-related weight changes did not have an impact on DFS., Conclusion: Baseline BMI and weight changes during adjuvant chemotherapy did not have an impact on DFS in this cohort. Future prospective studies in similar Caribbean breast cancer cohorts are needed to verify study findings.

Background: There are few studies on breast cancer outcomes in the Caribbean region. This study identified a retrospective cohort of female patients with nonmetastatic breast cancer in Haiti and conducted survival analyses to identify prognostic factors that may affect patient outcomes., Methods: The cohort included 341 patients presenting between June 2012 and December 2016. The primary endpoint was event-free survival (EFS), defined as time to disease progression, recurrence, or death. Descriptive summaries of patient characteristics and treatments were reported. Survival curves were plotted using Kaplan-Meier estimation. Multivariate survival analyses were performed using Cox proportional hazards regression., Results: Median age at diagnosis was 49 years, with 64.2% being premenopausal. Most patients (55.1%) were staged as locally advanced. One hundred and sixty patients received neoadjuvant therapy: 33.3% of patients with early stage disease and 61.2% of those with locally advanced stage disease. Curative-intent surgery was performed in 278 (81.5%) patients, and 225 patients received adjuvant therapy. Adjuvant endocrine therapy was used in 82.0% of patients with estrogen receptor-positive disease. During the follow-up period, 28 patients died, 77 had disease recurrence, and 10 had progressive disease. EFS rates at 2 years and 3 years were 80.9% and 63.4%, respectively. After controlling for multiple confounders, the locally advanced stage group had a statistically significant adjusted hazard ratio for EFS of 3.27 compared with early stage., Conclusion: Patients with nonmetastatic breast cancer in Haiti have more advanced disease, poorer prognostic factors, and worse outcomes compared with patients in high-income countries. Despite several limitations, curative treatment is possible in Haiti., Implications for Practice: Patients with breast cancer in Haiti have poor outcomes. Prior studies show that most Haitian patients are diagnosed at later stages. However, there are no rigorous studies describing how late-stage diagnosis and other prognostic factors affect outcomes in this population. This study presents a detailed analysis of survival outcomes and assessment of prognostic factors in patients with nonmetastatic breast cancer treated in Haiti. In addition to late-stage diagnosis, other unfavorable prognostic factors identified were young age and estrogen receptor-negative disease. The study also highlights that the availability of basic breast cancer treatment in Haiti can lead to promising early patient outcomes., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Purpose: The burden of cancer is growing in low- and middle-income countries (LMICs), including sub-Saharan Africa. Ensuring the delivery of high-quality cancer care in such regions is a pressing concern. There is a need for strategies to identify meaningful and relevant quality measures that are applicable to and usable for quality measurement and improvement in resource-constrained settings., Methods: To identify quality measures for breast cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda, we used a modified Delphi process engaging two panels of experts, one with expertise in breast cancer evidence and measures used in high-income countries and one with expertise in cancer care delivery in Rwanda., Results: Our systematic review of the literature yielded no publications describing breast cancer quality measures developed in a low-income country, but it did provide 40 quality measures, which we adapted for relevance to our setting. After two surveys, one conference call, and one in-person meeting, 17 measures were identified as relevant to pathology, staging and treatment planning, surgery, chemotherapy, endocrine therapy, palliative care, and retention in care. Successes of the process included participation by a diverse set of global experts and engagement of the BCCOE community in quality measurement and improvement. Anticipated challenges include the need to continually refine these measures as resources, protocols, and measurement capacity rapidly evolve in Rwanda., Conclusion: A modified Delphi process engaging both global and local expertise was a promising strategy to identify quality measures for breast cancer in Rwanda. The process and resulting measures may also be relevant for other LMIC cancer facilities. Next steps include validation of these measures in a retrospective cohort of patients with breast cancer.

Introduction: The role of sentinel lymph node biopsy (SLNB) for patients with ductal carcinoma in-situ (DCIS) is limited given the rarity of nodal metastasis in non-invasive disease. Although SLNB is typically a safe procedure, there are potential complications and associated costs. The purpose of this study is to assess national surgical practice patterns and clinical outcomes with respect to the use of SLNB for DCIS in patients undergoing breast conserving surgery (BCS)., Methods: Case-level data from the National Cancer Data Base (NCDB) was assessed to identify adult patients ≥ 18 with DCIS, who underwent BCS and SLNB. Patient demographics and hospital characteristics were grouped for analytic purposes. A multivariate analysis was performed for patient and hospital characteristics., Results: We identified 15,422 patients with DCIS undergoing BCS in 2015, of which 2,698 (18%) underwent SLNB. A multivariate analysis demonstrated a significant association between greater frequency of SLNB in patients age range of 60-69, receipt of care at a community facility, and higher nuclear grade DCIS. Positive sentinel nodes metastasis was identified in 0.9% patients undergoing BCS and SLNB for DCIS., Conclusion: The role of SLNB in patients with DCIS undergoing BCS is limited and does not routinely provide meaningful information or benefit to clinical management. Despite this, nearly one in five patients undergoing BCS for DCIS had lymph node sampling performed. Given the potential increased morbidity and financial implications, this finding represents an opportunity for further education and improvement in patient selection for SLNB., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC)., Methods: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR., Results: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis., Conclusions: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes., (© 2019 Wiley Periodicals, Inc.)

Background: Ensuring timely and high-quality surgery must be a key element of breast cancer control efforts in sub-Saharan Africa. We investigated delays in preoperative care and the impact of on-site versus off-site operation on time to operative treatment of patients with breast cancer at Butaro Cancer Center of Excellence in Rwanda., Methods: We used a standardized data abstraction form to collect demographic data, clinical characteristics, treatments received, and disease status as of November 2017 for all patients diagnosed with breast cancer at Butaro Cancer Center of Excellence in 2014 to 2015., Results: From 2014 to 2015, 89 patients were diagnosed with stage I to III breast cancer and treated with curative intent. Of those, 68 (76%) underwent curative breast operations, 12 (14%) were lost to follow-up, 7 (8%) progressed, and 2 declined the recommended operation. Only 32% of patients who underwent operative treatment had the operation within 60 days from diagnosis or last neoadjuvant chemotherapy. Median time to operation was 122 days from biopsy if no neoadjuvant treatments were given and 51 days from last cycle of neoadjuvant chemotherapy. Patients who received no neoadjuvant chemotherapy experienced greater median times to operation at Butaro Cancer Center of Excellence (180 days) than at a referral hospital in Kigali (93 days, P = .04). Most patients (60%) experienced a disruption in preoperative care, frequently at the point of surgical referral. Documented reasons for disruptions and delays included patient factors, clinically indicated treatment modifications, and system factors., Conclusion: We observed frequent delays to operative treatment, disruptions in preoperative care, and loss to follow-up, particularly at the point of surgical referral. There are opportunities to improve breast cancer survival in Rwanda and other low- and middle-income countries through interventions that facilitate more timely surgical care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Feasible and effective strategies are needed to facilitate earlier diagnosis of breast cancer in low-income countries. The goal of this study was to examine the impact of health worker breast health training on health care utilization, patient diagnoses, and cancer stage in a rural Rwandan district., Methods: We conducted a cluster randomized trial of a training intervention at 12 of the 19 health centers (HCs) in Burera District, Rwanda, in 2 phases. We evaluated the trainings' impact on the volume of patient visits for breast concerns using difference-in-difference models. We used generalized estimating equations to evaluate incidence of HC and hospital visits for breast concerns, biopsies, benign breast diagnoses, breast cancer, and early-stage disease in catchment areas served by intervention versus control HCs., Results: From April 2015 to April 2017, 1,484 patients visited intervention HCs, and 308 visited control HCs for breast concerns. The intervention led to an increase of 4.7 visits/month for phase 1 HCs ( P = .001) and 7.9 visits/month for phase 2 HCs ( P = .007) compared with control HCs. The population served by intervention HCs had more hospital visits (115.1 v 20.5/100,000 person-years, P < .001) and biopsies (36.6 v 8.9/100,000 person-years, P < .001) and higher breast cancer incidence (6.9 v 3.3/100,000 person-years; P = .28). The incidence of early-stage breast cancer was 3.3 per 100,000 in intervention areas and 0.7 per 100,000 in control areas ( P = .048)., Conclusion: In this cluster randomized trial in rural Rwanda, the training of health workers and establishment of regular breast clinics were associated with increased numbers of patients who presented with breast concerns at health facilities, more breast biopsies, and a higher incidence of benign breast diagnoses and early-stage breast cancers.

Background: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials., Materials and Methods: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012., Results: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% ( p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9-13.7) and 13.5 years (95% CI, 12.9-14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92-1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3-5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results., Conclusion: Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers . NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) IMPLICATIONS FOR PRACTICE: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Purpose: A few previous studies report a direct relationship between older age and chemotherapy-induced neuropathy. This study further evaluated this adverse event's age-based risk., Methods: CALGB 40101 investigated adjuvant paclitaxel (80 mg/m 2 once per week or 175 mg/m 2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age-based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years., Results: Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55-64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups ( p = .14). In univariate analysis, only motor neuropathy had a higher age-based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively ( p = .04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one-category improvement), showed no statistically significant age-based differences. In contrast, obesity was associated with neuropathy, and every 2-week paclitaxel was associated with trends toward neuropathy., Conclusion: Although paclitaxel-induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number . NCT00041119 (CALGB 40101)., Implications for Practice: Age alone is not an independent risk factor for paclitaxel-induced neuropathy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Purpose: In April 2015, we initiated a training program to facilitate earlier diagnosis of breast cancer among women with breast symptoms in rural Rwanda. The goal of this study was to assess the impact of the training intervention in breast cancer detection on knowledge and skills among health center nurses and community health workers (CHWs)., Methods: We assessed nurses' and CHWs' knowledge about breast cancer risk factors, signs and symptoms, and treatability through a written test administered immediately before, immediately after, and 3 months after trainings. We assessed nurses' skills in clinical breast examination immediately before and after trainings and then during ongoing mentorship by a nurse midwife. We also examined the appropriateness of referrals made to the hospital by health center nurses., Results: Nurses' and CHWs' written test scores improved substantially after the trainings (overall percentage correct increased from 73.9% to 91.3% among nurses and from 75.0% to 93.8% among CHWs ( P < .001 for both), and this improvement was sustained 3 months after the trainings. On checklists that assessed skills, nurses' median percentage of actions performed correctly was 24% before the training. Nurses' skills improved significantly after the training and were maintained during the mentorship period (the median score was 88% after training and during mentorship; P < .001). In total, 96.1% of patients seen for breast concerns at the project's hospital-based clinic were deemed to have been appropriately referred., Conclusion: Nurses and CHWs demonstrated substantially improved knowledge about breast cancer and skills in evaluating and managing breast concerns after brief trainings. With adequate training, mentorship, and established care delivery and referral systems, primary health care providers in sub-Saharan Africa can play a critical role in earlier detection of breast cancer.

Purpose: As breast cancer incidence and mortality rise in sub-Saharan Africa, it is critical to identify strategies for delivery of high-quality breast cancer care in settings with limited resources and few oncology specialists. We investigated the quality of treatments received by a cohort of patients with breast cancer at Butaro Cancer Center of Excellence (BCCOE), Rwanda's first public cancer center., Patients and Methods: We reviewed medical records of all female patients diagnosed with invasive breast cancer at BCCOE between July 2012 and December 2013. We evaluated the provision of chemotherapy, endocrine therapy, surgery, and chemotherapy dose densities. We also applied modified international quality metrics and estimated overall survival using interval-censored analysis., Results: Among 150 patients, 28 presented with early-stage, 64 with locally advanced, and 53 with metastatic disease. Among potentially curable patients (ie, those with early-stage or locally advanced disease), 74% received at least four cycles of chemotherapy and 63% received surgery. Among hormone receptor-positive patients, 83% received endocrine therapy within 1 year of diagnosis. Fifty-seven percent of potentially curable patients completed surgery and chemotherapy and initiated endocrine therapy if indicated within 1 year of biopsy. Radiotherapy was not available. At the end of follow-up, 62% of potentially curable patients were alive, 24% were dead, and 14% were lost to follow-up., Conclusion: Appropriate delivery of chemotherapy and endocrine therapy for breast cancer is possible in rural sub-Saharan African even without oncologists based on site. Performing timely surgery and ensuring treatment completion were key challenges after the opening of BCCOE. Further investigation should examine persistent quality gaps and the relationship between treatment quality and survival.

Background: Breast cancer is the most common malignancy encountered during pregnancy. However, the burden of pregnancy-associated breast cancer (PABC) and subsequent care is understudied in sub-Saharan Africa (SSA). Here, we describe the characteristics, diagnostic delays and treatment of women with PABC seeking care at a rural cancer referral facility in Rwanda., Methods: Data from female patients aged 18-50 years with pathologically confirmed breast cancer who presented for treatment between July 1, 2012 and February 28, 2014 were retrospectively reviewed. PABC was defined as breast cancer diagnosed in a woman who was pregnant or breastfeeding. Numbers and frequencies are reported for demographic and diagnostic delay variables and Wilcoxon rank sum and Fisher's exact tests are used to compare characteristics of women with PABC to women with non-PABC at the alpha = 0.05 significance level. Treatment and outcomes are described for women with PABC only., Results: Of the 117 women with breast cancer, 12 (10.3%) had PABC based on medical record review. The only significant demographic differences were that women with PABC were younger (p = 0.006) and more likely to be married (p = 0.035) compared to women with non-PABC. There were no significant differences in diagnostic delays or stage at diagnosis between women with PABC and women with non-PABC women. Eleven of the women with PABC received treatment, three had documented treatment delays or modifications due to their pregnancy or breastfeeding, and four stopped breastfeeding to initiate treatment. At the end of the study period, six patients were alive, three were deceased and three patients were lost to follow-up., Conclusions: PABC was relatively common in our cohort but may have been underreported. Although patients with PABC did not experience greater diagnostic delays, most had treatment modifications, emphasizing the potential value of PABC-specific treatment protocols in SSA. Larger prospective studies of PABC are needed to better understand particular challenges faced by these patients and inform policies and practices to optimize care for women with PABC in Rwanda and similar settings.

Breast cancer is the leading cause of cancer mortality among women in developing countries. Timely and accurate histopathological diagnosis of breast cancer is critical to delivering high-quality breast cancer care to patients in low- and middle-income countries (LMIC). The most important prognostic factors in breast cancer along with tumor size and nodal status are tumor grade, estrogen receptor status, as well as HER2 status in countries where specific targeted therapies are available. In addition, detailed and complete cancer registry data are needed to assess a country's disease burden and guide disease prioritization and allocation of resources for breast cancer treatment. Innovations in leapfrog technology and low-cost point-of-care tests for molecular evaluations are needed to provide accurate and timely pathology, with the ultimate goal of improving survival outcomes for patients with breast cancer in LMIC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Survival is considered an important indicator of the quality of cancer care, but the validity of different methodologies to measure comparative survival rates is less well understood. We explored whether the National Cancer Data Base (NCDB) could serve as a source of unadjusted and risk-adjusted cancer survival data and whether these data could be used as quality indicators for individual hospitals or in the aggregate by hospital type., Methods: The NCDB, an aggregate of > 1,500 hospital cancer registries, was queried to analyze unadjusted and risk-adjusted hazards of death for patients with stage III breast cancer (n = 116,787) and stage IIIB or IV non-small-cell lung cancer (n = 252,392). Data were analyzed at the individual hospital level and by hospital type., Results: At the hospital level, after risk adjustment, few hospitals had comparative risk-adjusted survival rates that were statistically better or worse. By hospital type, National Cancer Institute-designated comprehensive cancer centers had risk-adjusted survival ratios that were statistically significantly better than those of academic cancer centers and community hospitals., Conclusion: Using the NCDB as the data source, survival rates for patients with stage III breast cancer and stage IIIB or IV non-small-cell lung cancer were statistically better at National Cancer Institute-designated comprehensive cancer centers when compared with other hospital types. Compared with academic hospitals, risk-adjusted survival was lower in community hospitals. At the individual hospital level, after risk adjustment, few hospitals were shown to have statistically better or worse survival, suggesting that, using NCDB data, survival may not be a good metric to determine relative quality of cancer care at this level.

Purpose: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines., Methods: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS., Results: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS., Conclusions: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

Background: This study evaluated the use of axillary surgery (AS), including sentinel lymph node biopsy (SLNB), for patients with ductal carcinoma in situ (DCIS) and the factors associated with its use. To determine whether utilization of SLNB is appropriate, predictors of SLNB performance were compared with factors predictive of tumor upstaging., Methods: The National Cancer Data Base was utilized to identify patients with American Joint Committee on Cancer (AJCC) clinical stage 0 breast cancer treated from 2004 to 2013. DCIS with microinvasion was excluded. Chi square tests and logistic regression were used to examine patient, tumor, and facility features associated with SLNB and tumor upstaging., Results: Of the 218,945 total patients, 155,093 (70.8 %) underwent lumpectomy, and 63,852 (29.2 %) underwent mastectomy. SLNB was performed for 19.0 % of lumpectomy patients and 63.5 % of mastectomy patients. Multivariate analysis for 2012-2013 demonstrated that estrogen receptor (ER)-negative and grade 3 tumors were more likely to be treated with SLNB in both groups. Tumor size was significant only for the lumpectomy patients who underwent one operation. Further, 22.8 % of lumpectomy patients and 18.7 % of mastectomy patients who underwent AS were upstaged compared with 1.8 % of lumpectomy and 3.6 % of mastectomy patients who did not undergo AS. Tumor upstaging was predicted by ER-negative status (odds ratio [OR] 2.99; 95 % confidence interval [CI] 2.76-3.24) but not by higher grade or larger tumor size., Conclusions: Use of SLNB for DCIS is high with mastectomy, and nearly one fifth of the lumpectomy patients underwent SLNB. However, the performance of AS was strongly associated with the likelihood of upstaging in both groups, suggesting that surgical judgment plays an important role in this decision.

Unlabelled: : The objective of this review is to describe existing data on breast cancer incidence and mortality in low- and middle-income countries (LMICs), in particular in sub-Saharan Africa; identify the limitations of these data; and review what is known about breast cancer control strategies in sub-Saharan African countries and other LMICs. Available estimates demonstrate that breast cancer incidence and mortality are rising in LMICs, including in Africa, although high-quality data from LMICs (and particularly from sub-Saharan Africa) are largely lacking. Case fatality rates from breast cancer appear to be substantially higher in LMICs than in high-income countries. Significant challenges exist to developing breast cancer control programs in LMICs, perhaps particularly in sub-Saharan Africa, and the most effective strategies for treatment and early detection in the context of limited resources are uncertain. High-quality research on breast cancer incidence and mortality and implementation research to guide effective breast cancer control strategies in LMICs are urgently needed. Enhanced investment in breast cancer research and treatment in LMICs should be a global public health priority., Implications for Practice: The numbers of new cases of breast cancer, and breast cancer deaths per year, in low- and middle-income countries are rising. Engagement by the international breast cancer community is critical to reduce global disparities in breast cancer outcomes. Cancer specialists and institutions in high-income countries can serve as key partners in training initiatives, clinical care, protocol and program development, and research. This article provides an overview of what is known about breast cancer incidence, mortality, and effective strategies for breast cancer control in sub-Saharan Africa and identifies key gaps in the literature. This information can help guide priorities for engagement by the global cancer community., (©AlphaMed Press.)

Background: Breast cancer incidence is rising in low- and middle-income countries. Understanding the distribution of breast disease seen in clinical practice in such settings can guide early detection efforts and clinical algorithms, as well as support future monitoring of cancer detection rates and stage., Patients and Methods: We conducted a retrospective medical record review of 353 patients who presented to Butaro Cancer Center of Excellence in Rwanda with an undiagnosed breast concern during the first 18 months of the cancer program., Results: Eighty-two percent of patients presented with a breast mass. Of these, 55% were diagnosed with breast cancer and 36% were diagnosed with benign disease. Cancer rates were highest among women 50 years and older. Among all patients diagnosed with breast cancer, 20% had stage I or II disease at diagnosis, 46% had locally advanced (stage III) disease, and 31% had metastatic disease., Conclusion: After the launch of Rwanda's first public cancer referral center and breast clinic, cancer detection rates were high among patients presenting with an undiagnosed breast concern. These findings will provide initial data to allow monitoring of changes in the distribution of benign and malignant disease and of cancer stage as cancer awareness and services expand nationally., Implications for Practice: The numbers of cases and deaths from breast cancer are rising in low-income countries. In many of these settings, health care systems to address breast problems and efficiently refer patients with symptoms concerning for cancer are rudimentary. Understanding the distribution of breast disease seen in such settings can guide early detection efforts and clinical algorithms. This study describes the characteristics of patients who came with a breast concern to Rwanda's first public cancer referral center during its first 18 months. More than half of patients with a breast mass were diagnosed with cancer; most had late-stage disease. Monitoring changes in the types of breast disease and cancer stages seen in Rwanda will be critical as breast cancer awareness and services grow., (©AlphaMed Press.)

Background: Breast cancer incidence is increasing in low- and middle-income countries (LMICs). Mortality/incidence ratios in LMICs are higher than in high-income countries, likely at least in part because of delayed diagnoses leading to advanced-stage presentations. In the present study, we investigated the magnitude, impact of, and risk factors for, patient and system delays in breast cancer diagnosis in Rwanda., Materials and Methods: We interviewed patients with breast complaints at two rural Rwandan hospitals providing cancer care and reviewed their medical records to determine the diagnosis, diagnosis date, and breast cancer stage., Results: A total of 144 patients were included in our analysis. Median total delay was 15 months, and median patient and system delays were both 5 months. In multivariate analyses, patient and system delays of ≥6 months were significantly associated with more advanced-stage disease. Adjusting for other social, demographic, and clinical characteristics, a low level of education and seeing a traditional healer first were significantly associated with a longer patient delay. Having made ≥5 health facility visits before the diagnosis was significantly associated with a longer system delay. However, being from the same district as one of the two hospitals was associated with a decreased likelihood of system delay., Conclusion: Patients with breast cancer in Rwanda experience long patient and system delays before diagnosis; these delays increase the likelihood of more advanced-stage presentations. Educating communities and healthcare providers about breast cancer and facilitating expedited referrals could potentially reduce delays and hence mortality from breast cancer in Rwanda and similar settings., Implications for Practice: Breast cancer rates are increasing in low- and middle-income countries, and case fatality rates are high, in part because of delayed diagnosis and treatment. This study examined the delays experienced by patients with breast cancer at two rural Rwandan cancer facilities. Both patient delays (the interval between symptom development and the patient's first presentation to a healthcare provider) and system delays (the interval between the first presentation and diagnosis) were long. The total delays were the longest reported in published studies. Longer delays were associated with more advanced-stage disease. These findings suggest that an opportunity exists to reduce breast cancer mortality in Rwanda by addressing barriers in the community and healthcare system to promote earlier detection., (©AlphaMed Press.)

Objective: Develop and evaluate a foundational oncology-specific standard for the communication and coordination of care throughout the cancer journey, with early-stage breast cancer as the use case., Materials and Methods: Owing to broad uptake of the Health Level Seven (HL7) Consolidated Clinical Document Architecture (C-CDA) by health information exchanges and large provider organizations, we developed an implementation guide in congruence with C-CDA. The resultant product was balloted through the HL7 process and subsequently implemented by two groups: the Health Story Project (Health Story) and the Athena Breast Health Network (Athena)., Results: The HL7 Implementation Guide for CDA, Release 2: Clinical Oncology Treatment Plan and Summary, DSTU Release 1 (eCOTPS) was successfully balloted and published as a Draft Standard for Trial Use (DSTU) in October 2013. Health Story successfully implemented the eCOTPS the 2014 meeting of the Healthcare Information and Management Systems Society (HIMSS) in a clinical vignette. During the evaluation and implementation of eCOPS, Athena identified two practical concerns: (1) the need for additional CDA templates specific to their use case; (2) the many-to-many mapping of Athena-defined data elements to eCOTPS., Discussion: Early implementation of eCOTPS has demonstrated successful vendor-agnostic transmission of oncology-specific data. The modularity enabled by the C-CDA framework ensures the relatively straightforward expansion of the eCOTPS to include other cancer subtypes. Lessons learned during the process will strengthen future versions of the standard., Conclusion: eCOTPS is the first oncology-specific CDA standard to achieve HL7 DSTU status. Oncology standards will improve care throughout the cancer journey by allowing the efficient transmission of reliable, meaningful, and current clinical data between the many involved stakeholders., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Breast cancer diagnosed in young women may be more aggressive, with higher rates of local and distant recurrence compared to the disease in older women. Epidemiologic evidence suggests that Korean women have a lower incidence of breast cancer than women in the United States, but that they present at a younger age than their American counterparts. We sought to compare risk factors and management of young women with breast cancer in Boston, Massachusetts (US) with those in Seoul, South Korea (KR)., Materials and Methods: A retrospective review was performed of consecutive patients less than 35 years old with a diagnosis of breast cancer at academic cancer centers in the US and KR from 2000-2005. Patient data were obtained by chart review. Demographic, tumor and treatment characteristics were compared utilizing Pearson's chi- square or Wilcoxon rank-sum tests where appropriate. All differences were assessed as significant at the 0.05 level., Results: 205 patients from the US and 309 from KR were analyzed. Patients in US were more likely to have hormone receptor positive breast cancer, while patients in KR had a higher rate of triple negative lesions. Patients in US had a higher mean body mass index and more often reported use of birth control pills, while those in the KR were less likely to have a sentinel node procedure performed or to receive post mastectomy radiation., Conclusions: Patients under 35 diagnosed with breast cancer in the US and KR differ with respect to demographics, tumor characteristics and management. Although rates of breast conservation and mastectomy were similar, US patients were more likely to receive post mastectomy radiation. The lower use of sentinel node biopsy is explained by the later adoption of the technique in KR. Further evaluation is necessary to evaluate recurrence rates and survival in the setting of differing disease subtypes in these patients.

Peripheral neuropathy is a common dose-limiting toxicity for patients treated with paclitaxel. For most individuals, there are no known risk factors that predispose patients to the adverse event, and pathogenesis for paclitaxel-induced peripheral neuropathy is unknown. Determining whether there is a heritable component to paclitaxel-induced peripheral neuropathy would be valuable in guiding clinical decisions and may provide insight into treatment of and mechanisms for the toxicity. Using genotype and patient information from the paclitaxel arm of CALGB 40101 (Alliance), a phase III clinical trial evaluating adjuvant therapies for breast cancer in women, we estimated the variance in maximum grade and dose at first instance of sensory peripheral neuropathy. Our results suggest that paclitaxel-induced neuropathy has a heritable component, driven in part by genes involved in axon outgrowth. Disruption of axon outgrowth may be one of the mechanisms by which paclitaxel treatment results in sensory peripheral neuropathy in susceptible patients.

Purpose: Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity., Patients and Methods: Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported., Results: With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T., Conclusion: This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC., (© 2014 by American Society of Clinical Oncology.)

Introduction: Breast cancer is the most common type of cancer among women, and the leading cause of cancer deaths worldwide. Among early detection methods, screening by mammography has been used in most developed countries as gold standard. The goal of this study was to evaluate the difficulties and opportunities in implementing breast cancer screening in Brazil, with an emphasis on the diagnostic methods used according to stage distribution., Methods: Between 2007 and 2009, 248 women were diagnosed with breast cancer in the Barretos region. Most of these were interviewed in their homes using a questionnaire with sociodemographic and preventive breast cancer screening questions. All other data were obtained from Barretos Cancer Hospital (BCH) medical records., Results: The screening program conducted by BCH was responsible for 46.1% of diagnosed cases, with 30.1% of these referred from the private system and 23.8% from the public system. Among asymptomatic women screened by the BCH Screening Program 70.8% had clinical stage 0-I disease, compared with 58.1% in the private and 50% in the public systems. Monthly breast self-examination was reported by 48.5% of the women. Clinical breast examinations were regularly performed by 88.9% of gynecologists in the private and 40.7% in the public health systems. Only 5.6% of the women reported difficulty in accessing mammography and this was most frequently due to fear of the disease or lack of knowledge about mammography in asymptomatic women., Conclusion: This breast cancer screening program resulted in a substantial number of patients presenting with clinical stage (CS) 0-I disease. The success of this program was due to intensive community interventions, free mammography, and the availability of health care and mammography close to patients' homes.

Purpose: We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results., Experimental Design: A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis., Results: We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel., Conclusions: The enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients., (©2012 AACR.)