1,750 research outputs found
Abstract P5-22-22: Breast tumor location in <i>BRCA</i> mutation carriers and implications for prevention
No full textAbstract
Introduction:
Close to 65% of BRCA mutation carriers do not choose prophylactic mastectomy, despite their high breast cancer risk. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk and can be modified to target specific areas of the breast. We wondered if a majority of tumors in BRCA mutation carriers would be confined to one quadrant, allowing for the use of targeted cosmetic mammoplasty as a novel method of risk reduction.
Methods:
We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning &gt;1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squaredtest.
Results:
Mean age at breast cancer diagnosis was 44 years with mean tumor size of 2.2 cm (0.1-7cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant whether or not multicentric tumors were included in the analysis (p&lt;0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p=0.021).
Conclusions:
More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that removing this quadrant through breast reduction mammoplasty could significantly reduce breast cancer risk. For women who are not ready for prophylactic mastectomy, this data supports an intermediate risk reduction step instead of only offering surveillance.
Citation Format: Hosseini A, Esserman LJ, Wallace AM, Au A, Mukhtar RA. Breast tumor location in BRCA mutation carriers and implications for prevention [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-22.</jats:p
Abstract P5-12-04: The impact of bariatric surgery on mammographic breast density
No full textAbstract
Background:
Bariatric surgery decreases breast cancer risk, but its impact on mammographic findings is not well understood. Obesity and breast density both increase breast cancer risk, but paradoxically are inversely related. We investigated how mammographic density changes after bariatric surgery, and whether or not that change is related to amount of weight loss.
Methods:
We reviewed records for 349 prospectively collected patients who underwent bariatric surgery between 2013-2015, and identified 45 women with pre- and post-operative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), Breast Imaging-Reporting and Data System density, and calculated excess BMI loss. Data were analyzed in Stata 14.2.
Results:
Average age was 54 years, mean pre-operative BMI was 44 (range 36-72), and mean percentage excess BMI lost was 73% at 1.3 years. One third had a change in mammographic breast density, which increased 93% of the time (p&lt;0.001). Amount of weight loss was not associated with density change; in fact, weight loss was lower in those with a density change than in those without a density change (68% versus 75% excess BMI lost).
Conclusions:
The majority of women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Interestingly, the amount of weight loss was not associated with change in breast density. These findings suggest the metabolic effects of bariatric surgery have an effect on breast cancer risk independent of BMI reduction. Future work will include studying mammographic changes associated with non-surgical weight loss.
Citation Format: Hosseini A, Khoury AL, Carter J, Wong JM, Alvarado MD, Ewing C, Esserman LJ, Mukhtar RA. The impact of bariatric surgery on mammographic breast density [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-12-04.</jats:p
Abstract PD3-05: Effect of MR imaging contrast kinetic thresholds for prediction of neoadjuvant chemotherapy response in breast cancer subtypes – Results from ACRIN 6657 / I-SPY 1 trial
No full textAbstract
Background: Breast MRI has the potential to non-invasively measure response to neoadjuvant chemotherapy (NACT). We studied the effect of varying two analytic parameters used to define MRI-measured tumor volume in the prediction of pathologic complete response (pCR) to NACT and to determine if optimization of these parameter thresholds would improve the prediction of pCR.
Methods: Women with locally advanced breast cancer (tumor size ≥ 3cm) were enrolled in the ACRIN 6657 / I-SPY 1 TRIAL. Each patient had up to four dynamic contrast-enhanced MRI examinations: before NACT (MR1), after one cycle of NACT (MR2), between the anthracycline-based regimen and taxane (MR3), and after NACT and prior to surgery (MR4). Breast cancer was stratified by subtypes of hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2) status: HR+/HER2, HER2+, and triple negative ((TN) HR-/HER2-). MRI-measured functional tumor volume (FTV) and change in FTV (ΔFTV) were investigated as predictors of the outcome pCR. FTV is defined as the image volume with enhancement kinetics exceeding both an early percentage enhancement threshold (PEt) and a signal enhancement ratio threshold (SERt). Primary study analysis used empirically determined values. For this study PEt was varied from 30% to 200% in 10% intervals, and SERt was varied from 0.0 to 2.0 in 0.2 unit intervals. FTV was measured at each examination (FTV1, FTV2, FTV3, FTV4). ΔFTV was measured relative to the first examination (ΔFTV2, ΔFTV3, ΔFTV4). For each pair of varied PEt and SERt thresholds, the absolute and relative FTVs were re-measured and analyzed for discrimination of pCR using the area under the curve (AUC) of the receiver operating characteristic curve.
Results: A total of 116 patients were included from the ACRIN 6657 / I-SPY 1 TRIAL who had complete data on all four MRI visits, HR/HER2 status, and pCR outcome. Mean age was 48 years old (range 29-69). The full cohort of 116 patients was divided into subgroups: 45 (39%) HR+/HER2-; 39 (34%) HER2+; and 30 (26%) TN. When stratified by subtypes, lower AUCs with less variation were observed in patients with HER2+ cancer than patients with HR+/HER2- and TN breast cancer. When examining prediction by visit, maximum AUCs were found at later time points in all patient cohorts. Specifically, maximum AUC was observed for the full cohort at ΔFTV3 with AUC of 0.78 (CI: 0.69–0.87) when PEt=130% and SERt=0; for HR+/HER2- subtype at ΔFTV3 with AUC of 0.9 (CI: 0.84–0.97) when PEt=130% and SERt=0 were the same as in the full cohort; for HER2+ subtype at FTV3 with AUC of 0.77 (CI: 0.62–0.92) when PEt=70%/SERt=1.4; for triple negative at FTV4 with AUC of 0.89 (CI: 0.76–1) when PEt=40%/SERt=2.0.
Conclusion: This analysis suggests that the thresholds of MRI quantitative DCE measurements may need to be adjusted by breast cancer subtype to improve the predictive performance. The PEt threshold may need to be set higher in HR+/HER2- than other subtypes, which may be due to higher background parenchymal enhancement among HR+ patients. SER threshold may need to be set at higher level for triple negative subtype. A validation is underway in I-SPY 2, with a larger patient population.
Citation Format: Li W, Arasu V, Jones EF, Newitt DC, Wilmes LJ, Kornak J, Esserman LJ, Hylton NM. Effect of MR imaging contrast kinetic thresholds for prediction of neoadjuvant chemotherapy response in breast cancer subtypes – Results from ACRIN 6657 / I-SPY 1 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD3-05.</jats:p
Abstract CSF1-2: Controversies in Screening for Breast Cancer
No full textAbstract
Over the last 10 years, we have learned a great deal about breast cancer. We now know that all breast cancers are not the same. Whether defined by receptor status or molecular subtype, we now know that there is a range of growth rates and associated risk of metastases for each breast cancer subtype. It stands to reason then that the impact of screening is likely to be different for each breast cancer subtype. And of course, every woman is not the same, and consideration of both genetic predisposition and the context of competing health risks should play a role in optimizing screening strategies for women. The goal of this talk is to integrate these considerations with the observations on breast cancer incidence over the past 25 years since the advent of screening. The rise in the incidence of early stage disease, particularly for women over the age of 50, has not been accompanied by a commensurate decline in the incidence of regional cancers. Regional or more locally advanced cancers are more likely to present at younger ages, and as interval cancers. On the other hand, indolent disease is more likely to appear in women of older age. This knowledge helps us to understand how to better personalize screening recommendations and better understand the screening trial data and the differential impact by age as well as the US Preventive Services Task Force screening guidelines. The screening trials also reflect an era when systemic treatment was quite different than it is today. Moreover, recent data suggest that the impact of optimal systemic treatment reduces the impact of screening. Finally, we must take into account the fact that screening is more likely to detect indolent cancers (IDLE tumors) when they are present. These insights present opportunities to improve our approach to screening which may in turn reduce the burden of cancer and cancer diagnosis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr CSF1-2.</jats:p
»LJ« Artist book
No full textThe thesis paper deals with the artist book, an art form that has become a part of the university curriculum since the beginning of my university studies. It is most closely connected with the fields of sketch and photography. Both personl sketch and the field of photography have been of particular interest to me during my university years and I prepared an exhibition on the subject, presented by Faculty of Education Gallery. This thesis covers the historical and theoretical background of the artist book and maps the creation of my own artist book, an artistic superaddition titled LJ.
Some of the pioneers of the artist book are also mentioned, including Ed Ruscha, the author of the Twenty Six Gasoline Stations. He was one of the first artist to draw attention to the various artistic possibilities of this art form intertwining different graphic components including sketch, photography, font, paper characteristic, and other visual effects. Franc zagoričnik is presented as a native artist interested in the art form. He was a member of the OHO group, which reached the same conclusions as Ruscha in the 1970s.
The thesis places the artist book within the field of education, since this particular pedagogical approach has been shown to give the pupil freedom of choice and thus enrich his sensibilty to artistic expression. Pratical reasearch was conducted at a high school in Koper, while theoretical research heavily relied on the MGLC library, which is the only Slovene library to carry contemporary literature on this particular art form
Correction to: Photoacoustic Measurements of the Thermal and Elastic Properties of n-Type Silicon Using Neural Networks (Silicon, (2020), 12, 6, (1289-1300), 10.1007/s12633-019-00213-6)
No full textThe original version of the article unfortunately contained an error. © 2020, Springer Nature B.V.
The author name ‘Кatarina Lj. Djordjevic’ was inadvertently
captured twice. The correct author group is shown above.Link to the corrected article: [https://vinar.vin.bg.ac.rs/handle/123456789/8759
Episodic encoding is more than the sum of its parts: An fMRI investigation of multifeatural contextual encoding
No full textEpisodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced
Abstract PD7-02: Identification of breast cancers with an indolent disease course: 70 gene indolent threshold validation in a Swedish randomized trial of tamoxifen vs. not, with 20 year outcomes
No full textAbstract
Importance: The frequency of cancers with indolent behavior has increased with screening. We asked whether an ultralow risk threshold on a multigene classifier would identify women whose cancers had an indolent course over 2 decades of follow-up, and which features were most predictive of outcome.
Methods: An ultralow risk threshold of the FDA-cleared MammaPrint 70-gene expression score was set to predict long-term absence of breast cancer-specific mortality in the absence of systemic therapy. The Stockholm Tamoxifen (STO) trial conducted between 1976 and 1990, where postmenopausal women with clinically detected node-negative breast cancers &lt;3cm were randomized to receive tamoxifen versus not, was used for validation. Immunohistochemistry markers (n=727) and Agilent microarrays for MammaPrint risk scoring (n=652) were performed from formalin-fixed paraffin-embedded primary tumor blocks. Recursive partitioning was performed using the rpart package in R to select variables and construct a regression tree that best predicts 20-year breast cancer specific survival. Input variables include: age, period of diagnosis, grade, hormone receptor status, HER2 and Ki69 status, 70-gene risk categories (high, low but not ultra, or ultralow), treatment arm and tumor size; and cross-validation was used to select the final regression tree model.
Results: In this trial conducted in the era before mammographic screening, 58% and 42% were MammaPrint low and high risk, respectively, while 15% were above the ultralow threshold. In the tamoxifen treated arm, women with tumors above the ultralow threshold had no deaths at 15 years and their 20-year disease-specific survival rates of 97%; whereas if untreated, their survival rates were 94%. Recursive partitioning identified the ultralow threshold classification as the first primary split in the model. Once the indolent tumors were partitioned out, among women with tumors below the ultralow threshold, the next most prognostic feature was size, where patients with tumors &gt;20mm have worse breast cancer specific survival. The last split in the model divides the patients with tumors ≤20mm into 70-gene high risk vs low but not ultralow risk groups.
Conclusions and Relevance: A threshold of the 70-gene MammaPrint assay can identify patients with indolent disease whose long-term risk of death from breast cancer after surgery alone is exceedingly low. This threshold emerged as the most prognostic variable, followed by tumor size, and mammaprint high vs. low but not ultralow in our recursive partitioning analysis. This suggests that finding indolent tumors early at a small size may not have much impact on patient outcome. Determining the presence of an ultralow risk breast cancer may prevent overtreatment. Conversely, once the indolent tumors are taken out of consideration, both biology and size impact outcome, and finding these tumors at a small size is likely still important and supports screening in this postmenopausal node negative population.
Citation Format: Esserman LJ, Yau C, Thompson CK, van't Veer LJ, Borowsky AD, Hoadley KA, Tobin NP, Nordenskjöld B, Fornander T, Stål O, Benz CC, Lindström LS. Identification of breast cancers with an indolent disease course: 70 gene indolent threshold validation in a Swedish randomized trial of tamoxifen vs. not, with 20 year outcomes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-02.</jats:p
Abstract P2-09-23: Diffusion-weighted MRI improves imaging prediction of response in the I-SPY 2 trial
No full textAbstract
Background: The I-SPY 1 TRIAL demonstrated that functional tumor volume (FTV) measured by dynamic contrast-enhanced (DCE) MRI during neoadjuvant chemotherapy (NAC) predicts both pathologic complete response (pCR) and recurrence free survival1. In addition to DCE, the I-SPY 2 TRIAL is testing whether diffusion weighted MRI (DWI), a non-contrast method that characterizes water mobility and cellularity by measuring the apparent diffusion coefficient (ADC), acquired during the same MRI exam as DCE, can provide valuable distinct information about tumor response. We hypothesize that combining FTV and ADC can improve the predictive performance of breast MRI.
Methods: I-SPY 2 includes women with stage II or III breast cancer with tumor size ≥ 2.5 cm. A sub-cohort of I-SPY 2 patients from 2 graduated experimental drug arms2,3 (N=115 of 263): veliparib-carboplatin (VC, N=38), neratinib (N=37) and their controls (treated with paclitaxel or paclitaxel + trastuzumab, N=40), were included in this study: 148 patients were excluded due to missing imaging data or poor DWI quality. Each patient had four MRI exams: pre-treatment (T1), early treatment (after 3 weekly cycles of experimental drugs, T2), between regimen (T3), and pre-surgery (T4). FTV and ADC were measured for the whole tumor at T1, T2, and T3. Percent change of FTV (ΔFTV) and ADC (ΔADC) at T2 and T3 compared to T1 were analyzed as predictors of pCR. The predictive performance of ΔFTV, ΔADC and their combination was evaluated using a logistic regression model treating pCR as the binary outcome. Odds ratios were estimated for each 10% decrease of ΔFTV and 10% increase of ΔADC to reach pCR. The likelihood ratio test was used to evaluate the effect of variables in the logistic model. The statistical significance level for all testing was set at 0.05.
Results: Out of 115 patients included in this analysis, 36 (31%) reached pCR. The combined model using ΔFTV+ΔADC showed statistically significant improvement over the single predictor ΔFTV alone (p=0.038 for the period T1 to T2 and p&lt;0.001 for the period T1 to T3). The odds ratio estimates represent a 27% increase in odds for each 10% increase in ΔADC after accounting for ΔFTV at T2 and 38% increase at T3 (see Table 1).
Table 1 The odds ratio of ΔFTV and ΔADC with 95% confidence intervalTreatment time pointΔFTV aloneΔADC aloneΔADC adjusted for ΔFTVEarly treatment (T2)1.19 (1.05, 1.36)1.33 (1.06, 1.70)1.27 (1.01, 1.63)Bwteeen regimen (T3)1.41 (1.12, 1.98)1.44 (1.24, 1.71)1.38 (1.18, 1.64)
Conclusion: The addition of ADC to standard FTV MRI may help refine the prediction of treatment response. Evaluation of the method by cancer subtype in a larger cohort is ongoing.
References
1. Hylton NM, Gatsonis CA, Rosen MA, et al. Neoadjuvant Chemotherapy for Breast Cancer: Functional Tumor Volume by MR Imaging Predicts Recurrence-free Survival-Results from the ACRIN 6657/CALGB 150007 I-SPY 1 TRIAL. Radiology. 2016;279(1):44-55.
2. Rugo HS, Olopade OI, DeMichele A, et al. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 2016;375(1):23-34.
3. Park JW, Liu MC, Yee D, et al. Adaptive Randomization of Neratinib in Early Breast Cancer. N Engl J Med. 2016;375(1):11-22.
Citation Format: Li W, Wilmes LJ, Newitt DC, Jones EF, Gibbs J, Poon M, Li E, Partridge SC, Kornak J, Esserman LJ, Hylton NM. Diffusion-weighted MRI improves imaging prediction of response in the I-SPY 2 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-23.</jats:p
Abstract P2-05-03: Intra-tumor heterogeneity of the estrogen receptor predicts less benefit from tamoxifen therapy and poor long-term breast cancer patient survival – Retrospective analyses of the STO-3 randomized trial
No full textAbstract
Background
We and others have shown that the clinically used breast cancer markers alter their expression throughout tumor progression, influencing patient survival (Lindström et al, JCO 2012). What are the likely explanations to our findings? Here, we aimed to determine whether breast cancer intra-tumor heterogeneity of the estrogen receptor (ER) is a marker of tumor aggressiveness and benefit of tamoxifen therapy in a large randomized trial.
Material and methods
The Stockholm Tamoxifen (STO-3) trial enrolled postmenopausal lymph node negative breast cancer patients with a tumor size of less than 30 mm, between 1976 and 1990, to be randomized to receive adjuvant tamoxifen versus not. From the original randomized trial cohort approximately half of the patients (778 patients) had primary tumor formalin-fixed paraffin-embedded blocks available and were included in our study. No significant differences in age and period of diagnosis, type of surgery received, receptor status, tumor grade and size were observed between the treatment arms.
All tumor slides were immunostained in a central laboratory using the SP1 antibody. ER slides were scored by two independent breast cancer pathologists assessing the fraction of cancer cells for each ER intensity level (0, +1, +2 or +3) compared to established standards. The resulting distribution of ER stained tumor cells defines intra-tumor heterogeneity of ER (Rao's quadratic entropy (QE),Potts et al, Lab Invest 2012). Intra-tumor heterogeneity was categorized using the third tertile as cut-off for high heterogeneity (726 patients).
Analyses of long-term breast cancer specific survival (25 years) by intra-tumor heterogeneity of ER were performed using univariate Kaplan-Meier and multivariate Cox proportional hazard modeling adjusting for treatment arm, age and period of diagnoses, ER, progesterone receptor (PR), HER2, Ki-67, tumor grade, and tumor size. Further, a test of correlation was performed to investigate whether intra-tumor heterogeneity of ER was correlated to the percentage of ER positive cells, the H-Score or the Luminal A and B subtype (PAM50).
Results
In the univariate Kaplan-Meier analyses, a statistically significant difference in long-term survival by intra-tumor heterogeneity of ER was seen for all patients (log rank, P=0.018), tamoxifen treated arm (log rank, P=0.0033), but not untreated arm (log rank, P=0.19). However in the multivariate analysis, patients with high intra-tumor heterogeneity of ER in the treated arm as well as in the untreated arm had an almost two-fold increased long-term risk of fatal breast cancer disease as compared to patients with low or intermediate heterogeneity (Treated arm: HR, 2.06; 95% CI, 1.04-4.07 and Untreated arm: HR, 1.71; 95% CI, 1.01-2.87).
No significant correlation of intra-tumor heterogeneity to the tested variables was seen.
Conclusions
Patients with high intra-tumor heterogeneity of ER had less benefit from tamoxifen therapy and an increased long-term risk of fatal breast cancer disease. Our findings should be clinically relevant since therapy benefit was evaluated in a randomized trial with long-term follow-up.
Citation Format: Lindström LS, Yau C, Czene K, Thompson CK, van't Veer LJ, Nordenskjöld B, Stål O, Fornander T, Benz CC, Borowsky AD, Esserman LJ. Intra-tumor heterogeneity of the estrogen receptor predicts less benefit from tamoxifen therapy and poor long-term breast cancer patient survival – Retrospective analyses of the STO-3 randomized trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-03.</jats:p
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