scholarly journals ctDNA in Breast Milk for Early Detection of Pregnancy Associated Breast Cancer

Author(s):  
Miriam Sanso ◽  
Cristina Saura ◽  
Carolina Ortiz ◽  
Enrique Arenas Lahuerta ◽  
Judit Matito ◽  
...  

Abstract Pregnancy associated breast cancer (PABC) is an overall poor prognosis group compared to non-PABC breast cancer (BC), mainly due to late diagnosis. Effective screening approaches for early detection may improve its outcome. For the first time, we demonstrate the presence of cell-free tumor DNA (ctDNA) in the breast milk serum (sBM) of PABC in patients with early-stage disease and its ability to recapitulate somatic mutations present in the primary tumor. Moreover, our results demonstrate that sBM robustly surpasses plasma for tumor genetic profiling due to a prevalent shedding of ctDNA into the sBM in localized disease, as well as increased total cell-free DNA (cfDNA) abundance and integrity. Thus, we propose sBM as a potential new non-invasive liquid biopsy for a prompt detection of PABC.

2018 ◽  
Vol 4 (Supplement 3) ◽  
pp. 34s-34s ◽  
Author(s):  
Lydia E. Pace ◽  
Nancy L. Keating ◽  
Jean-Marie Vianney Dusengimana ◽  
Vedaste Hategekimana ◽  
Vestine Rugema ◽  
...  

Purpose In low-income countries, most women with breast cancer present with advanced-stage disease. To facilitate earlier diagnoses of symptomatic disease, feasible and effective early detection strategies are needed. We assessed health care use and patient outcomes from a randomized pilot study of an early detection program in Burera, a rural Rwandan district, where the Butaro Cancer Center of Excellence (BCCOE) is located. Methods The intervention included training for community health workers in breast health, training for health center (HC) nurses in the evaluation of breast concerns, and weekly breast clinics at HCs and BCCOE. Twelve of 18 eligible HCs were randomly assigned to receive the intervention—seven beginning in April and May 2015, and five in November and December 2015—and six served as controls for the entire study period. We abstracted HC and hospital records of patients seen between April 2015 and April 2017 and used generalized linear models to compare the incidence of biopsies, breast cancer diagnoses, and early-stage diagnoses in the geographic sectors served by intervention versus control HCs. Results Overall, 276,282 person-years were in intervention sectors and 302,856 in control sectors. Of patients, 1,500 patients sought care at intervention HCs for breast concerns versus 600 at control HCs. Three hundred eighteen patients that were referred from intervention HCs were evaluated at BCCOE compared with 62 from control HCs. The biopsy rate was 36.6 per 100,000 person-years from intervention sectors versus 8.9 per 100,000 from control sectors ( P < .001). Breast cancer was diagnosed in 19 of 101 patients from intervention HCs who underwent biopsy (18.8%) compared with 10 (37.0%) of 27 patients from control HCs. Breast cancer incidence was 6.9 per 100,000 in intervention sectors versus 3.3 per 100,000 in control sectors ( P = .35). Nine patients from intervention HCs had early-stage disease (47.4%) versus two from control HCs (20.0%). The incidence rate of early-stage breast cancer was 3.7 per 100,000 in intervention sectors versus 0.7 per 100,000 in control sectors ( P = .08). Conclusion Over 2 years, our early detection program was associated with more patients referred for hospital-level evaluation and requiring biopsies. Most patients referred by intervention HCs had benign conditions; however, there was a trend toward a higher incidence of early-stage breast cancer among patients from intervention regions. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Lydia E. Pace Stock or Other Ownership: Firefly Health


2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 49-49
Author(s):  
Euridice R. Irving ◽  
Dennis R. A. Mans ◽  
Els Th. M. Dams ◽  
Maureen Y. Lichtveld

PURPOSE Delays across the entire cancer care continuum are not uncommon. This cross-sectional study explored the health care trajectories of Surinamese women with breast cancer and identified predictors of timely diagnosis and treatment initiation. METHODS One hundred women age 30 years or older who were newly diagnosed with breast cancer in 2017 to 2018 were recruited from all 4 hospitals in Paramaribo. Data on their demographics, lifestyle, reproductive and medical history, health status, and family history of breast cancer and other malignancies were collected using a validated semistructured questionnaire. Using Anderson’s Model of Pathways to Treatment, we defined a patient interval (from detection to first consultation), diagnostic interval (from consultation to histopathologic diagnosis), and treatment interval (from diagnosis to first treatment). Log-transformed data were analyzed using linear regression, and variables with P ≤ .05 were considered statistically significant predictors of intervals. RESULTS All participants had health insurance and access to health care. Eighty-five percent of patients presented with early-stage disease. Ninety percent of patients had self-detected their disease, with 70% finding a lump. Average age was 55.6 years (± 11.8 years). Median durations of patient, diagnostic, and treatment intervals were 13 days (interquartile, range, 4-63 days), 40 days (IQR, 21-57 days), and 18 days (IQR, 8-38 days), respectively. Median duration of the entire interval was 95 days (IQR, 59-272 days). Patient-related factors associated with the intervals were religion (β = −530; P = .003), being employed (β = 149.4; P = .007), and age 50 years and older (β = −195.8; P = .037). Disease-related factors were lump as first symptom (β = −175.6; P = .038) and late-stage disease at diagnosis (β = 213.5; P = .004). CONCLUSION Given the limited-resource setting, delays in Suriname’s health care can be minimized by programs aimed at increasing breast cancer awareness and education; however, delays may have been underestimated as a result of the over-representation of early-stage disease and recall bias regarding the first symptom detected.


2019 ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Fadwa Abdel Rahman ◽  
Hanan Al-Masri ◽  
Hazem Abdulelah ◽  
Mahmoud Abu Nasser ◽  
...  

Abstract Background : Less than 10% of newly diagnosed breast cancer in our region are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and have poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in such patients. Methods : Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients’ characteristics and treatment outcomes. Results : A total of 553 patients, median age 70 (range: 65-91) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), GIII in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P<0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P=0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P=0.048). Conclusions : Older Jordanian women with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Because of comorbidities and poor performance status, some patients were not aggressively treated.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3704
Author(s):  
Jedrzej J. Jaworski ◽  
Robert D. Morgan ◽  
Shivan Sivakumar

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1526-1526
Author(s):  
R. Haque ◽  
J. E. Schottinger ◽  
M. H. Kanter ◽  
C. C. Avila ◽  
R. Contreras ◽  
...  

1526 Background: Kaiser Permanente Southern California (KPSC) led the nation in screening women for breast cancer (BCa) with a mammography rate of nearly 90% in 2007 according to 2008 Healthcare Effectiveness Data and Information Set (HEDIS) measures. Despite successes in improving screening rates in this health plan that serves 3+ million diverse members, the percentage of women diagnosed with late stage BCa (stage III, IV) remained stable, varying from 12.9% (N∼323) in 2003 to 10.8% (N∼270) in 2007. To identify patient and health care factors associated with late stage diagnosis and the impact of its enhanced screening implementation guidelines, KPSC undertook this study. Methods: This cross-sectional study included a cohort of 10,580 BCa patients from 2003–2007. We compared women diagnosed with late stage disease versus those with early stage disease (stages I, II). P values (2-sided) were based on the chi-square distribution. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. Results: Factors that were positively associated with late stage diagnosis in the univariate analyses included age, lack of recent mammography screening, worse tumor features, 80+ years of age, minority race, lower geocoded household income, increased healthcare visits, and use of Pap testing (P < 0.01 for all variables). Factors significantly associated with late stage diagnosis in the multivariate model included only lack of recent mammography screening (OR = 1.35, 95% CI: 1.14–1.58) and worse tumor features including high grade (grade 3, OR = 2.58, 95% CI: 1.96–3.40), positive lymph nodes (OR = 53.49, 95% CI: 39.90–71.72), and HER-2+ tumors (OR = 1.40, 95% CI: 1.13–1.72). Conclusions: Targeting older women, those with lower utilization, and women who did not have a recent mammogram may help further lower the prevalence of late stage diagnoses. However, given the extent of the health plan's previous efforts to enhance BCa screening rates, a ceiling effect may limit additional benefit. Additional efforts to decrease the rate of advanced tumor stage at diagnosis may include improving interpretation of mammograms or earlier detection of aggressive tumors by enhanced BRCA genetic testing. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 209-209
Author(s):  
Mats Lambe ◽  
Paul Lambert ◽  
Irma Fredriksson ◽  
Anna Plym

209 Background: More than half of all women with breast cancer are diagnosed during working age. We present a new measure of clinical and public health relevance to estimate the loss in working years after a breast cancer diagnosis. Methods: Women of working age diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N = 19,661), together with a breast cancer-free comparison cohort (N = 81,303). Women were followed until permanent exit from the labour market (defined as receipt of disability pension, old-age retirement or death) or censoring. Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and women without breast cancer. Results: The loss in working years was most pronounced in women of younger ages and in women with advanced stage disease. Women aged 50 years at diagnosis with stage I disease lost on average 0.6 years (95% CI, 0.4-0.8) of their remaining working time; the corresponding estimates were 1.2 years (1.0-1.5) in stage II, 3.2 years (2.7-3.7) in stage III, and 8.8 years (7.9-9.8) in stage IV disease. Type of treatment was a clear determinant in women with early stage disease, with a higher loss in working years among women treated with axillary surgery, mastectomy and chemotherapy. Conclusions: Our measure provides a new perspective of the burden of breast cancer in women of working age. The modest loss in working years in women with early stage disease is reassuring, although the economic consequences on a population-level are likely to be high given the large number of women diagnosed with breast cancer every year.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Aisling Barry ◽  
Anthony Fyles

Stereotactic ablative body radiotherapy (SABR) has a role as definitive therapy in many tumor sites; however, its role in the treatment of breast cancer is less well explored. Currently, SABR has been investigated in the neoadjuvant and adjuvant setting with a number of ongoing feasibility studies. However, its use comes with a number of radiobiological and technical challenges that require further evaluation. We have learned much from other extracranial disease sites such as lung, brain, and spine, where definitive treatment with SABR has shown encouraging outcomes. In women with breast cancer, SABR may eliminate the need for invasive surgery, reducing healthcare costs and hospital stays and providing an additional curative option for early-stage disease. This poses the following question: is there a role for SABR as a definitive therapy in breast cancer?


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