Improved Breast Cancer Survival Research Articles

Greater Survival Improvement in African American vs. Caucasian Women with Hormone Negative Breast Cancer.

Background: African American women have not benefited equally from recently improved breast cancer survival. We investigated if this was true for all subsets.Methods: We identified 395,170 patients with breast adenocarcinoma from the SEER database from 1990 to 2011 with designated race, age, stage, grade, ER and PR status, marital status and laterality, as control. We grouped patients into two time periods, 1990-2000 and 2001-2011, three age categories, under 40, 40-69 and ≥ 70 years and two stage categories, I-III and IV. We used the Kaplan-Meier and logrank tests to compare survival curves. We stratified data by patient- and tumor-associated variables to determine co-variation among confounding factors using the Pearson Chi-square test and Cox proportional hazards regression to determine hazard ratios (HR) to compare survival.Results: Stage I-III patients of both races ≥ 70 years old, African American widowed patients and Caucasians with ER- and PR- tumors had worse improvements in survival in 2001-2011 than younger, married or hormone receptor positive patients, respectively. In contrast, African Americans with ER- (Cox HR 0.70 [95% CI 0.65-0.76]) and PR- (Cox HR 0.67 [95% CI 0.62-0.72]) had greater improvement in survival in 2001-2011 than Caucasians with ER- (Cox HR 0.81 [95% CI 0.78-0.84]) and PR- disease (Cox HR 0.75 [95% CI 0.73-0.78]). This was not associated with changes in distribution of tumor or patient attributes.Conclusions: African American women with stage I-III ER- and PR- breast cancer had greater improvement in survival than Caucasians in 2001-2011. This is the first report of an improvement in racial disparities in survival from breast cancer in a subset of patients.

The Impact of Neighborhood Economic and Racial Inequalities on the Spatial Variation of Breast Cancer Survival in New Jersey

Mapping breast cancer survival can help cancer control programs prioritize efforts with limited resources. We used Bayesian spatial models to identify whether breast cancer survival among patients in New Jersey (NJ) varies spatially after adjusting for key individual (age, stage at diagnosis, molecular subtype, race/ethnicity, marital status, and insurance) and neighborhood measures of poverty and economic inequality [index of concentration at the extremes (ICE)]. Survival time was calculated for all NJ women diagnosed with invasive breast cancer between 2010 and 2014 and followed to December 31, 2015 (N = 27,078). Nonlinear geoadditive Bayesian models were used to estimate spatial variation in hazard rates and identify geographic areas of higher risk of death from breast cancer. Significant geographic differences in breast cancer survival were found in NJ. The geographic variation of hazard rates statewide ranged from 0.71 to 1.42 after adjustment for age and stage, and were attenuated after adjustment for additional individual-level factors (0.87-1.15) and neighborhood measures, including poverty (0.9-1.11) and ICE (0.92-1.09). Neighborhood measures were independently associated with breast cancer survival, but we detected slightly stronger associations between breast cancer survival, and the ICE compared to poverty. The spatial models indicated breast cancer survival disparities are a result of combined individual-level and neighborhood socioeconomic factors. More research is needed to understand the moderating pathways in which neighborhood socioeconomic status influences breast cancer survival. More effective health interventions aimed at improving breast cancer survival could be developed if geographic variation were examined more routinely in the context of neighborhood socioeconomic inequalities in addition to individual characteristics.

Regional, racial, gender, and tumor biology disparities in breast cancer survival rates in Africa: A systematic review and meta-analysis.

BackgroundThe survival rates from breast cancer in Africa are poor and yet the incidence rates are on the rise. In this study, we hypothesized that, in Africa, a continent with great disparities in socio-economic status, race, tumor biology, and cultural characteristics, the survival rates from breast cancer vary greatly based on region, tumor biology (hormone receptor), gender, and race. We aimed to conduct the first comprehensive systematic review and meta-analysis on region, gender, tumor-biology and race-specific 5-year breast cancer survival rates in Africa and compared them to 20-year survival trends in the United States.MethodsWe searched MEDLINE, EMBASE, and Cochrane Library to identify studies on breast cancer survival in African published before October 17, 2018. Pooled 5-year survival rates of breast cancer were estimated by random-effects models. We explored sources of heterogeneity through subgroup meta-analyses and meta-regression. Results were reported as absolute difference (AD) in percentages. We compared the survival rates of breast cancer in Africa and the United States.FindingsThere were 54 studies included, consisting of 18,970 breast cancer cases. There was substantial heterogeneity in the survival rates (mean 52.9%, range 7–91%, I2 = 99.1%; p for heterogeneity <0.0001). Meta-regression analyses suggested that age and gender-adjusted 5-year survival rates were lower in sub-Saharan Africa compared to north Africa (AD: –25.4%; 95% CI: –34.9 - –15.82%), and in predominantly black populations compared to predominantly non-black populations (AD: –25.9%; 95% CI: 35.40 - –16.43%). Survival rates were 10 percentage points higher in the female population compared to male, but the difference was not significant. Progesterone and estrogen receptor-positive breast cancer subtypes were positively associated with survival (r = 0.39, p = 0.08 and r = 0.24, p = 0.29 respectively), but triple-negative breast cancer was negatively associated with survival. Survival rates are increasing over time more in non-black Africans (55% in 2000 versus 65% in 2018) compared to black Africans (33% in 2000 versus 40% in 2018); but, the survival rates for Africans are still significantly lower when compared to black (76% in 2015) and white (90% in 2015) populations in the United States.ConclusionRegional, sub-regional, gender, and racial disparities exist, influencing the survival rates of breast cancer in Africa. Therefore, region and race-specific public health interventions coupled with prospective genetic studies are urgently needed to improve breast cancer survival in this region.

Breast cancer survivorship in an Asian specialist centre from Malaysia: A retrospective analysis

Background: Real world data (RWD) is increasingly relevant in breast cancer (BCa) as it is the most frequently diagnosed cancer. Developed world has seen improved breast cancer survival, however, RWDon BCa survival in Malaysia is still lacking.&#x0D; Aims and Objectives: This study aims to determine characteristics and survival of BCa patients from a single institute.&#x0D; Materials and Methods: Retrospective analysis of 168 BCa patients who were treated with at least one treatment modality in Beacon International Specialist Centre (BISC) from 2008-2012 was conducted. Patient characteristicsand treatments received were analysed descriptively to survival outcome.Vital status was obtained from the National Registry of Birth and Death (NRD) records. Observed survival rates wereestimated by Kaplan-Meier method and difference between groups by log-rank.&#x0D; Results: Of 143 eligible BCa patients,28 (19.6%) died during the study period. Five-year BCa specific survival rates were 100% for Stage I and II, 79.31% for stage III and 38.89% for Stage IV disease. In the multivariate analysis, higher stage at diagnosis, triple negative breast cancer with metastases and higher grade were associated with worse survival outcomes. The overall 5-year survival rate of BCa patients in BISC from 2008-2012 compares favourably to the survival data of developed countries.&#x0D; Conclusion: In conclusion, the overall 5-year survival rate of BCa patients in BISC compares favourably to the survival data of developed countries, as well as to other institutions.

Advances in Endocrine-Based Therapies for Estrogen Receptor-Positive Metastatic Breast Cancer

Approximately 70% of breast cancers are estrogen-receptor positive. Tamoxifen and aromatase inhibitors have been the mainstay of endocrine therapy and have improved breast cancer survival. However, a large number of patients experience disease recurrence either during or following completion of endocrine therapy. Recent improvements in our understanding of the various mechanisms underlying the development of endocrine resistance have led to a dramatic change in the landscape of current endocrine treatment with the introduction of new drugs targeting molecular pathways involved in endocrine resistance. Over the past years we have witnessed the use of combination endocrine therapy with mammalian target of rapamycin antagonists, whilst most recently the introduction of cyclin-dependent kinase 4/6 inhibitors has significantly improved response to endocrine therapy. Whilst not a formal systematic review, this article will provide historical background and summarise key clinical trials and current strategies in both first-line and second-line endocrine therapy.

Liver- and Microbiome-derived Bile Acids Accumulate in Human Breast Tumors and Inhibit Growth and Improve Patient Survival.

Metabolomics is a discovery tool for novel associations of metabolites with disease. Here, we interrogated the metabolome of human breast tumors to describe metabolites whose accumulation affects tumor biology. We applied large-scale metabolomics followed by absolute quantification and machine learning-based feature selection using LASSO to identify metabolites that show a robust association with tumor biology and disease outcome. Key observations were validated with the analysis of an independent dataset and cell culture experiments. LASSO-based feature selection revealed an association of tumor glycochenodeoxycholate levels with improved breast cancer survival, which was confirmed using a Cox proportional hazards model. Absolute quantification of four bile acids, including glycochenodeoxycholate and microbiome-derived deoxycholate, corroborated the accumulation of bile acids in breast tumors. Levels of glycochenodeoxycholate and other bile acids showed an inverse association with the proliferation score in tumors and the expression of cell-cycle and G2-M checkpoint genes, which was corroborated with cell culture experiments. Moreover, tumor levels of these bile acids markedly correlated with metabolites in the steroid metabolism pathway and increased expression of key genes in this pathway, suggesting that bile acids may interfere with hormonal pathways in the breast. Finally, a proteome analysis identified the complement and coagulation cascade as being upregulated in glycochenodeoxycholate-high tumors. We describe the unexpected accumulation of liver- and microbiome-derived bile acids in breast tumors. Tumors with increased bile acids show decreased proliferation, thus fall into a good prognosis category, and exhibit significant changes in steroid metabolism.

Impact of Race and Health Insurance Status on the Outcomes of Neoadjuvant Chemotherapy and Radiation Therapy for Breast Cancer Patients

Racial inequalities in breast cancer (BC) mortality rates continue despite general improvement in BC survival.1 We seek to discern racial and socioeconomic disparities in BC outcomes in patients who received neoadjuvant chemotherapy (NAC) and adjuvant radiation therapy (RT). We evaluated how patient characteristics, tumor biology, and radiation treatment plans influence outcomes among BC patients treated with NAC. We identified BC patients treated with NAC from 2006 to 2018 at our institution. Univariable and multivariable binary logistic regression analyses were performed to estimate the effects of race, health insurance status, and other predictors on NAC treatment outcomes. Outcomes of interest included pathologic complete response (pCR), partial response (PR), and cancer recurrence. Predictors that demonstrated significant unadjusted effects were included in the multivariable models. Variables included in the final multivariable models were health insurance status, race, Ki-67, BMI, hormone receptor (HR) status, and clinical group stage. This IRB approved study included 298 BC patients who received NAC. 69 identified as African American (AA), 227 identified as non-AA, and 2 were not reported. 168 had private insurance, 111 had Medicare/Medicaid, 17 had no insurance, and 2 were not reported. There was no significant association between race and any of the treatment outcomes. Insurance status emerged as a significant predictor for any response to NAC (pCR or PR) in both univariable and multivariable analyses (p = 0.01). Odds of pCR or PR attainment were lower for patients with Medicare/Medicaid compared to patients with private insurance (OR 0.36, 95% CI: 0.18 – 0.71). Other variables significant for attainment of either pCR or PR upon multivariable analysis included BMI (p < 0.01), HR status (p = 0.01), and clinical group stage (p < 0.01). Ki-67 (p = 0.02) and HR status (p < 0.01) demonstrated significant effects on pCR alone where odds of pCR were greater for triple negative breast cancer (TNBC) compared to ER+/PR+/HER2- (OR 4.10, 95% CI: 1.50 – 11.23). While AA patients had similar treatment outcomes as non-AA patients in our study, insurance status, Ki-67, BMI, clinical stage, and HR status correlated with outcomes and can potentially serve as useful predictive factors for cancer treatment response. In particular private health insurance and TNBC were correlated with improved outcomes. Further exploration of the impact of health insurance and HR status on treatment outcomes in BC patients treated with NAC may help predict and improve outcomes in vulnerable populations.

Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer: 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01)

BackgroundAdjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS).Patients and methodsPatients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes.ResultsTwo hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226–0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371–1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176–1.222, P = 0.120; HR 0.539, 95% CI 0.228–1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369–1.725, P = 0.565; HR 0.456, 95% CI 0.156–1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005–1.045, P = 0.014).ConclusionsOur results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival.Trial registrationClinicalTrials.gov, NCT01099436, April 2010.

Barriers to timely surgery for breast cancer in Rwanda

BackgroundEnsuring 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. MethodsWe 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. ResultsFrom 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. ConclusionWe 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.

Breast cancer survival in sub-Saharan Africa by age, stage at diagnosis and human development index: A population-based registry study.

Breast cancer is the leading cancer diagnosis and second most common cause of cancer deaths in sub‐Saharan Africa (SSA). Yet, there are few population‐level survival data from Africa and none on the survival differences by stage at diagnosis. Here, we estimate breast cancer survival within SSA by area, stage and country‐level human development index (HDI). We obtained data on a random sample of 2,588 breast cancer incident cases, diagnosed in 2008–2015 from 14 population‐based cancer registries in 12 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2,311 were included for survival analyses. The 1‐, 3‐ and 5‐year observed and relative survival (RS) were estimated by registry, stage and country‐level HDI. We equally estimated the excess hazards adjusting for potential confounders. Among patients with known stage, 64.9% were diagnosed in late stages, with 18.4% being metastatic at diagnosis. The RS varied by registry, ranging from 21.6%(8.2–39.8) at Year 3 in Bulawayo to 84.5% (70.6–93.5) in Namibia. Patients diagnosed at early stages had a 3‐year RS of 78% (71.6–83.3) in contrast to 40.3% (34.9–45.7) at advanced stages (III and IV). The overall RS at Year 1 was 86.1% (84.4–87.6), 65.8% (63.5–68.1) at Year 3 and 59.0% (56.3–61.6) at Year 5. Age at diagnosis was not independently associated with increased mortality risk after adjusting for the effect of stage and country‐level HDI. In conclusion, downstaging breast cancer at diagnosis and improving access to quality care could be pivotal in improving breast cancer survival outcomes in Africa.

ABC trial (A011502): A randomized phase III double-blinded placebo controlled trial of aspirin as adjuvant therapy breast cancer.

TPS599 Background: In-vitro and in-vivo evidence suggest that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. However, the exact benefits and risks for breast cancer survivors need to be confirmed in a randomized controlled trial. Even if the clinical effect were modest, the global impact would be substantial since aspirin is inexpensive and widely available. Methods: The primary objective is to compare the effect of 300 mg daily aspirin versus placebo upon invasive disease-free survival (iDFS) in high risk HER2 negative breast cancer patients. Secondary objectives include effects on overall survival, cardiovascular disease, toxicity, and adherence. A biospecimen repository will be created for correlative analyses including tumor collection at baseline and blood and urine samples and questionnaires assessing lifestyle factors associated with inflammation (pain, sleep, stress, and depression) at baseline and 2 years. Study design: Subjects will be randomized (1:1) to aspirin 300 mg vs placebo daily for 5 years in a double-blinded fashion. Stratification factors include hormone receptor (HR) status (positive vs negative), body mass index ( &lt; or ≥ 30 kg/m2), and stage (II vs III). Subjects will be followed every 6 six months while on study drug, then annually for 10 years. Accrual goal is 2936 patients to reach 381 iDFS events. We have 80% power to detect HR 0.75 assuming 5-year iDFS on placebo of 77%. Eligibility: Eligible subjects include patients aged 18-70 diagnosed with a primary invasive HER2 negative breast cancer. If HR positive, tumors need to be node positive and diagnosed within the past 10 years. If HR negative, tumors can be node positive or T2-4N0 within 18 months of diagnosis. Subjects who are currently anticoagulated or those with a prior history of GI bleeding, atrial fibrillation, or myocardial infarction are excluded. Subjects who regularly use aspirin (defined as ≥ 5 days per week) need to stop 30 days prior to enrollment. Updated accrual numbers will be given at the time of presentation. Clinical trial information: NCT02927249.

Demographic, clinical, and geographical factors associated with lack of receipt of physician recommended chemotherapy in women with breast cancer in Texas.

Identifying demographic, clinical, and geographical factors that contribute to disparities in the receipt of physician recommended chemotherapy in breast cancer patients. The Texas Cancer Registry was used to identify women aged ≥ 18years with invasive breast cancer diagnosed from 2007 to 2011 who received a recommendation for chemotherapy. Multivariable logistic regression was performed to determine associations between demographic and clinical factors and the receipt of chemotherapy. Cox proportional regression was used to estimate the hazard ratio (HR) for overall survival. Spatial analysis was conducted using Poisson models for breast cancer mortality and receipt of chemotherapy. Age ≥ 65 years, residence in areas with > 20% poverty index, and early disease stage were associated with lack of receipt of chemotherapy (all p < 0.001). Lack of receipt of chemotherapy was associated with decreased overall survival (HR 1.33, 95% CI 1.12-1.59, p = 0.001). A 38-county cluster in West Texas had lower receipt of chemotherapy (relative risk 0.88, p = 0.02) and increased breast cancer mortality (p = 0.03) compared to the rest of Texas. Older age, increased poverty and rural geographical location are barriers to the receipt of chemotherapy. Interventions that target these barriers may reduce health disparities and improve breast cancer survival.

Abstract MS2-2: Missed opportunities - The perils of under-treatment

Abstract Although we have seen improvements in breast cancer survival over time, the pace of improvement has varied among patients with breast cancer, and disparities in breast cancer outcomes have widened for some sub-groups. In particular, black women, those without easy access to medical care, and those at the extremes of age (youngest and oldest patients), are at higher risk for sub-optimal treatment and consequent sub-optimal breast cancer outcomes. These disparities have evolved during an era of significant treatment advances in breast cancer such as hormonal therapy and HER2-directed therapy, with a concern that under-treatment has contributed to differences in breast cancer-specific survival. Though there are cases when over-treatment and over-diagnosis result in undue toxicity, worsened quality of life, and possible detrimental outcomes, there are also many cases where patients are simply under-treated. This under-treatment manifests in a number of ways, and not only in a lack of treatment receipt all together, but also in receipt of lower intensity, non-standard, delayed, or incomplete treatment, which may be most apparent in the setting of longer-term treatments such as hormonal therapy or maintenance HER2-directed therapy. The reasons for under-treatment are complex, highly variable, and may include clear and appropriate medical contraindications but also poor treatment adherence, social stressors which limit treatment completion, the high cost of care, and limited access to high-quality care. In addition, under-treatment likely occurs due to a lack of available prospective evidence to support ideal treatments in different patient sub-groups with the need to uncomfortably extrapolate and apply data from clinical trials where many subgroups are under-represented. We need to urgently improve the evidence base for populations at risk for under-treatment so that we can better understand the side effects and outcomes experienced for both standard treatments and alternative treatment strategies. We will never realize improved survival from breast cancer for all patients until we can assure that each patient is individually receiving the right therapy at the right time with the right amount and for the right duration. Citation Format: Freedman R. Missed opportunities - The perils of under-treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr MS2-2.

Abstract P1-03-01: Differential distant disease-free intervals for mammography detected vs. clinical presentation invasive breast cancer: Early detection or lead time bias?

Abstract Background: Distant recurrence metastatic breast cancer (rMBC) incidence has declined with coincident improved breast cancer (BC) survival over time. Lead time is time from screening diagnosis to diagnosis that would have been made without screening. The purpose of screening is to detect disease at an early more treatable stage. Lead time bias would indicate early detection led only to a perceived increase in survival time without affecting the course of BC progression. Our objective was to evaluate detection method and treatment changes to distant recurrence and survival over time. Methods: In a longitudinal institutional cohort 1990-2011, we reviewed primary invasive stage I-III BC patients (n = 7991) for initial BC detection method by mammography (MamD) or patient/physician (ClinP), distant recurrence (rMBC), time from initial diagnosis to distant recurrence (DDFI) and distant disease specific survival (DDSS), follow up through 2016 updated annually. 856 patients with distant recurrence were identified and confirmed by imaging, biopsy or both. Diagnosis year time periods were set to coincide with significant treatment changes over time (1990-98, 1999-2004, 2005-2011). Chi square, mean ANOVA, DDSS and Cox proportional hazards analysis were conducted. Results: 48% of the cohort were ClinP and 52% MamD with MamD BC increasing over time [1990-98 45%, 2005-2011 54%, p&amp;lt;.001]. 72% of rMBC patients were ClinP BC. ClinP BC had shorter distant recurrence time, 4.99 years vs. 6.05 MamD BC (p = .001). Mean time from rMBC diagnosis to death was 2.88 years with no significant difference by detection method. In a Cox proportional hazards model adjusted for race, reduced risk of rMBC was observed for stage I/II, recent diagnostic years, hormone receptor positive, MamD, and low histologic grade [TNM I HzR .11, 95% CI .09, .14; TNM II HzR = .36, 95% CI = .31, .43; 1990-2004 HzR = .63, 95% CI = .53, .75; 2005-2011 HzR = .49, 95% CI = .41, .58; HR+ HzR = .70, 95% CI = .59, .82; MamD HzR = .68, 95% CI = .58, .81; low histologic grade HzR = .80, 95% CI = .67, .96; age &amp;gt;40 HzR = .79, 95% CI = .65, .96]. No difference was observed for DDSS by detection method [5-year DDSS: ClinP = 22%, MamD = 21%; log rank test = .019, p = .892]. Conclusion: At initial diagnosis, the majority of rMBC cases are symptomatic, have shorter DDFI but DDSS equal to MamD BC. MamD BC cases have lower rMBC incidence and longer DDFI possibly due to more responsive earlier diagnosed initial disease, slower progression disease or as yet unidentified biologic/genomic differences. Lead time bias may partially explain lower rMBC incidence given the benefits owed to treatment of MamD invasive BC which preclude disease progression to clinically evident BC. Mammography detected/non-symptomatic and clinically detected/symptomatic BC have differential incidence of and time to distant recurrence but no difference in DDSS. Mammography detection appears to confer a distant disease risk reduction advantage independent of other known prognostic factors but the disease has the same virulence once it becomes metastatic. Our results indicate treatment changes by diagnosis year proxy and mammography detection are both associated with decreased rMBC risk. Citation Format: Kaplan HG, Malmgren JA, Atwood MK. Differential distant disease-free intervals for mammography detected vs. clinical presentation invasive breast cancer: Early detection or lead time bias? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-01.

Variations in Breast Cancer Survival Rates: A Systematic Review and Meta-Analysis of Data from the Entire Continent of Africa

Background: The survival from breast cancer in Africa is poor and yet the incidence rate is on the rise. Causes of variations in survival from breast cancer are not well understood. We aimed to do a systematic review and meta-analysis on 5-year survival rates of breast cancer on the entire continent of Africa and to examine trends over time, and investigate sources of variations across the region. Methods: We searched MEDLINE, Embase, Cochrane Library to identify studies on breast cancer survival in African men and women published before October 17, 2018, and in any language. Random-effects meta-analyses were done to investigate between-study heterogeneity in 5-year survival rates of breast cancer and meta-regression analyses to identify potential sources of variation. 5-year survival rates of breast cancer in Africa were compared with similar estimates for black and white population in the USA from the Surveillance, Epidemiology, and End Results database. Findings: 54 studies were included, which consisted of 18,970 women and men from 13 African countries, 8 of which were from sub-Saharan region. There was wide between-study heterogeneity in the survival rates (mean 52.9%, range 7-91%, I2=99.1%; p<0.0001). Age and gender adjusted 5-year survival rates were lower in sub-Saharan Africa (absolute difference [AD] from North Africa [reference group] -25.4% (95% CI: -34.97 to -15.82%), lower in predominantly black population compared to predominantly white population -25.9% lower (95% CI: -35.40 to -16.43%). Within sub-Saharan region, survival rates are lower in western and eastern region compared to southern region. Although triple negative cancer negatively correlated with survival, the correlation did not reach a statistical significance (r=-0.27, p=0.35). Survival rates are increasing over time more in white Africans compared to black Africans but the survival rates for Africans are still significantly lower when compared to the black and white populations in the USA, a high-income country. Interpretation: Region and race-specific public health interventions coupled with genetic prospective studies are urgently needed to improve breast cancer survival Africa. Funding Statement: Support was provided from the unrestricted funds from the Academic Enrichment Fund of the Department of Surgery and the David L. Nahrwold Endowment in the Penn State College of Medicine (DIS). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: For this systematic review and meta-analysis, the authors developed a study protocol based on the PRISMA guidelines.

The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis.

Background:Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined.Methods:A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis.Results:A total of 47 studies comprising 20,607 patients were included; 23 randomized controlled studies (RCTs) provided data of adverse events for bisphosphonate therapy versus without bisphosphonates. Bisphosphonates were significantly associated with influenza-like illness (RR = 4.52), fatigue (RR = 1.08), fever (RR = 1.82), dyspepsia (RR = 1.25), anorexia (RR = 1.29), and urinary tract infection (RR = 1.32). No differences were observed in other adverse events. We combined the incidence of ONJ in 24 retrospective studies to analyze the incidence of ONJ using bisphosphonates. The pooled probability of ONJ toxicity in the bisphosphonates group was 2%.Conclusions:Bisphosphonates were significantly associated with influenza-like illness, fatigue, fever, dyspepsia, anorexia, and urinary tract infection. Furthermore, bisphosphonates increase the risk of ONJ toxicity.

Trends in vitamin D supplement use in a general female and breast cancer population in Ireland: A repeated cross-sectional study.

BackgroundVitamin D has been linked with improved survival after breast cancer diagnosis but little is known about prescribing rates. This study investigates trends in vitamin D supplement use in both a general female and breast cancer population.MethodsWomen with a breast cancer diagnosis were identified from the National Cancer Registry of Ireland (n = 19870). Women who had any vitamin D claim between 2005 and 2011 were identified from pharmacy claims data (n = 8556). Prevalence rates were calculated as a proportion of all eligible women and by age (< 55 years, ≥ 55 years). Poisson regression was used to compare rates of vitamin D prescribing across years (risk ratio (RR), 95% CI).ResultsThere was a statistically significant increase in women with a claim for vitamin D between 2005–2011, with the largest increase among breast cancer patients aged ≥ 55 years (RR = 2.26; 95% CI, 2.11–2.42).ConclusionThis may have significant public health implications if associations between vitamin D and improved breast cancer survival prove to be causal.

Adjuvant dose-dense doxorubicin-cyclophosphamide versus docetaxel-doxorubicin-cyclophosphamide for high-risk breast cancer: First results of the randomised MATADOR trial (BOOG 2004-04)

BackgroundDose-dense administration of chemotherapy and the addition of taxanes to anthracycline-based adjuvant chemotherapy have improved breast cancer survival substantially. However, clinical trials directly comparing the additive value of taxanes with dose-dense anthracycline-based chemotherapy are lacking. Patients and methodsIn the multicentre, randomised, biomarker discovery Microarray Analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens (MATADOR) trial, patients with pT1-3, pN0-3 breast cancer were randomised (1:1) between six adjuvant cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks (ddAC) and six cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks (TAC). The primary objective was to discover a predictive gene expression profile for ddAC and TAC benefit. Here we report the preplanned secondary end-point recurrence-free survival (RFS) and overall survival (OS). ResultsBetween 2004 and 2012, 664 patients were randomised. At 5 years, RFS was 87% (95% confidence interval [CI] 83%–91%) in the ddAC-treated patients and 88% (84–92%) in the TAC-treated subgroup (hazard ratio [HR] 0.89, 95% CI 0.62–1.28, P = 0.53). OS at 5 years was 93% (90%–96%) in the ddAC-treated and 94% (91%–97%) in the TAC-treated patients (HR 0.89, 95% CI 0.57–1.39, P = 0.61). Anaemia was more frequent in ddAC-treated patients (62/327 patients [18.9%] versus 15/319 patients [4.7%], P < 0.001) and diarrhoea (21 [6.4%] versus 53 [16.6%], P<0.001) and peripheral neuropathy (15 [4.6%] versus 46 [14.4%], P < 0.001) were observed more often in TAC-treated patients. ConclusionsWith a median follow-up of 7 years, no significant differences in RFS and OS were observed between six adjuvant cycles of ddAC and TAC in high-risk breast cancer patients. Trial registration numbersISRCTN61893718 and BOOG 2004-04.

Early Diagnosis of Breast Cancer in the Absence of Population-Based Mammographic Screening in Asia

Asia is made up of mainly low- and middle-income countries, where the majority of breast cancer presents as late-stage disease where survival is poor even with treatment. We review methods of early diagnosis of breast cancer in countries where population-based mammographic screening is not feasible. While there is insufficient evidence that breast self-examination and clinical breast examination (CBE) lead to a reduction in breast cancer mortality, recent trials have shown that screening with CBE successfully reduces stage at diagnosis, which may translate to improved breast cancer survival with longer follow-up. CBE may have an educational component whereby women with new breast lumps may seek care earlier. Overcoming sociocultural barriers to early detection in Asia is important before any early detection programme can be implemented. Public education, together with strengthening existing public health services, is key to earlier diagnosis of breast cancer.

Male Breast Cancer: An Updated Surveillance, Epidemiology, and End Results Data Analysis

BackgroundMale breast cancer is rare and understudied compared with female breast cancer. A current comparison with female breast cancer could assist in bridging this gap. Although conflicting data have been reported on male and female survival outcomes, data from 1973 through 2005 in the Surveillance, Epidemiology, and End Results (SEER) program have demonstrated that the improvement in breast cancer survival in men has fallen behind that of women. As treatment for breast cancer has improved significantly, an updated analysis using a contemporary population is necessary. Materials and MethodsAn analysis of SEER data from patients with a diagnosis of primary breast cancer from 2005 to 2010 were included. A Cox regression model was used to examine the association between sex and breast cancer mortality after controlling for prognostic factors, including age, race, marital status, disease stage, estrogen and progesterone receptor status, lymph node involvement, tumor grade, surgery, and geography. Subgroup analyses were performed by race and stage. ResultsWe included a total of 289,673 breast cancer cases (2054 men) with a diagnosis from 2005 to 2010. The 5-year survival rate for male patients was lower than that for female patients (82.8% vs. 88.5%). After controlling for other factors, the risk of death in men was 43% greater than that in women during the follow-up period (hazard ratio, 1.43; 95% confidence interval, 1.26-1.61). Similar results were noted in the race and stage subgroup analyses. ConclusionIn recent years, male breast cancer patients have had worse survival outcomes compared with those of female patients.