Evaluation of pathways for progression of heterogeneous breast tumors

Sontag, Laura; Axelrod, David E.

doi:10.1016/j.jtbi.2004.08.002

Cited by 60 publications

(45 citation statements)

References 24 publications

(32 reference statements)

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“…This approach is supported by studies indicating that DCIS and invasive breast cancer can develop independently (23,24). However, because the natural history of DCIS is poorly understood (9, 10), we also carried out two sensitivity analyses.…”

Section: Discussionmentioning

confidence: 89%

Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women

Kabat

Kim

Shikany

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Observational studies have commonly linked higher alcohol consumption with a modest increase in invasive breast cancer risk, but cohort studies have not examined alcohol intake in relation to ductal carcinoma in situ (DCIS).Methods: The association between adulthood alcohol consumption assessed at baseline and subsequent DCIS risk was examined in a cohort of postmenopausal women participating in the Women's Health Initiative clinical trials, in which mammography was protocol-mandated. Alcohol intake was assessed by a semiquantitative food-frequency questionnaire. Reported DCIS cases were verified by central pathology report review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.Results: The cohort consisted of 63,822 women with information on alcohol intake, among whom 489 cases of DCIS were ascertained after a median follow-up of 8.0 years. For the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date of diagnosis of invasive breast cancer. After adjustment for covariates, the hazard ratio for DCIS among women who consumed 14 or more servings of alcohol per week, relative to nondrinkers, was 0.87 (95% confidence interval, 0.50-1.51). In addition, alcohol intake was not associated with risk of either high-grade or low-/moderate-grade DCIS.Conclusions: In this large cohort study of postmenopausal women, alcohol consumption was not associated with risk of DCIS.Impact: If other studies confirm our findings, this would suggest that alcohol may have an effect later in the carcinogenic process. Cancer Epidemiol Biomarkers Prev; 19(8); 2066-72. ©2010 AACR.

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Section: Discussionmentioning

confidence: 89%

Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women

Kabat

Kim

Shikany

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Previous mathematical and computational models of DCIS have focused on a single breast duct and have been successful in recapitulating certain features of the spatio-temporal dynamics of proliferating and motile tumor cells at this microscale [18][19][20][21][22][23][24][25][26][27][28][29], and have even, in some cases, been capable of extrapolating their results to predictions of macroscopic growth features [24] or invasive potentials as a function of grade [29]. Here we adopt a multiscale approach to predict growth and size of the volume of breast containing ducts with DCIS based on molecular measurements from histopathology of individual patient tumors.…”

Section: Methodsmentioning

confidence: 99%

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Edgerton

Chuang

Macklin

et al. 2011

Analytical Cellular Pathology

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Abstract. We introduce a novel "mathematical pathology" approach, founded on a biophysical model, to identify robust patientspecific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in-situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected by in-situ tumors at the time of diagnosis will be closely approximated by a modelderived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinoma in situ for mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R 2 = 0.74-0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R 2 = 0.08-0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery.

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“…Although DCIS is considered a nonobligate precursor to invasive breast cancer, mathematical models of progression suggest that DCIS and IDC may develop through separate but parallel pathways from a common progenitor (27). Different models that have accurately incorporated progression data collectively suggest multiple pathways of progression (28).…”

Section: Intralesional Heterogeneity Of Premalignant Lesionsmentioning

confidence: 99%

Premalignant Breast Neoplasia: A Paradigm of Interlesional and Intralesional Molecular Heterogeneity and Its Biological and Clinical Ramifications

Berman

Gauthier

Tlsty

2010

Cancer Prevention Research

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As is well established in invasive breast disease, it is becoming increasingly clear that molecular heterogeneity, both between and within lesions, is a prevalent, distinct phenotype of premalignant lesions of the breast. Key pathways of tumorigenesis modulate critical features of premalignant lesions such as proliferation, differentiation, stress response, and even the generation of diversity. Current studies show that evaluation of these lesions may provide clinically useful information on future tumor formation as well as biological insights into the origin and functional significance of this distinct phenotype. Cancer Prev Res; 3(5); 579-87. ©2010 AACR.

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Evaluation of pathways for progression of heterogeneous breast tumors

Cited by 60 publications

References 24 publications

Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women

Alcohol Consumption and Risk of Ductal Carcinoma In situ of the Breast in a Cohort of Postmenopausal Women

A Novel, Patient-Specific Mathematical Pathology Approach for Assessment of Surgical Volume: Application to Ductal Carcinomain situof The Breast

Premalignant Breast Neoplasia: A Paradigm of Interlesional and Intralesional Molecular Heterogeneity and Its Biological and Clinical Ramifications

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