Dataset Information

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

ABSTRACT:

Objective

To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR).

Methods

Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1-4, L1-4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response.

Results

Sixteen patients completed the trial. The %TC ranged 20%-80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7-0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to <0.00001). Post-SABR %HM of tumor habitat H4 demonstrated the largest change, increasing 13% (P = 0.039). Conversely, combined %HM for H1-3 decreased 17% (P = 0.006). This change correlated with %TC (P < 0.00001) and distinguished pathologic partial responders (≤70 %TC) from nonresponders with 94% accuracy, 93% sensitivity, 100% specificity, 100% positive predictive value, and 67% negative predictive value.

Conclusion

In patients undergoing preoperative SABR treatment for ER/PR+ HER2- breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.

SUBMITTER: Weinfurtner RJ

PROVIDER: S-EPMC9851176 | biostudies-literature | 2022 May-Jun

REPOSITORIES: biostudies-literature

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Publications

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Weinfurtner R Jared RJ Abdalah Mahmoud M Stringfield Olya O Ataya Dana D Williams Angela A Mooney Blaise B Rosa Marilin M Lee Marie C MC Khakpour Nazanin N Laronga Christine C Czerniecki Brian B Diaz Roberto R Ahmed Kamran K Washington Iman I Latifi Kujtim K Niell Bethany L BL Montejo Michael M Raghunand Natarajan N

Journal of breast imaging 20220407 3

<h4>Objective</h4>To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR).<h4>Methods</h4>Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enh ...[more]

PMID: 36686407

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Project description:PurposePreoperative radiation therapy (RT) for pancreatic adenocarcinoma reduces positive surgical margin rates, and when delivered to an ablative dose range it may improve local control and overall survival for patients with unresectable disease. Use of stereotactic body RT to achieve a higher biologically effective dose has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by stereotactic magnetic resonance image guided adaptive radiation therapy (SMART).Methods and materialsWe describe our single-institution experience of high biologically effective dose SMART before resection of localized pancreatic adenocarcinoma. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (V 5.0). Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria.ResultsWe analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received ablative dose SMART (A-SMART) followed by surgical resection. Median age at diagnosis was 68 years (range, 34-86). Most patients received chemotherapy (80.8%) before RT. All patients received A-SMART to a median dose of 50 (range, 40-50) Gy in 5 fractions. Toxicity data were collected prospectively and there were no acute grade 2+ toxicities associated with RT. The median time to resection was 50 days (range, 37-115), and the procedure types included Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Pathologic response was observed in 88% of cases. The time from RT to surgery was associated with tumor regression grade (P = .0003). The median follow-up after RT was 16.5 months (range, 3.9-26.2). The derived median progression-free survival from RT was 13.2 months.ConclusionsThe initial surgical and pathologic outcomes after A-SMART are encouraging. Preoperative A-SMART was associated with low toxicity rates and no surgical or RT-associated mortality. The surgical morbidity was comparable to historic rates after upfront resection. These data also suggest that the time from stereotactic body RT to surgical resection is associated with pathologic response.

Project description:Background: Extensive amounts of archived formalin fixed paraffin embedded (FFPE) human tumor tissues are the ultimate resource to investigate signaling network underlying tumorigenesis in human. Yet, their usage is severely limited for lacking of suitable protein techniques. In this study, a quantitative, objective, absolute, and high throughput immunoblot method, quantitative dot blot (QDB), was explored to address this issue by investigating the putative relationship between estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) pathways in breast cancer tumorigenesis. Methods: In this descriptive observational retrospective study, ER, PR, Her2, and Ki67 protein levels were measured absolutely and quantitatively in 852 FFPE breast cancer tissues using the QDB method. ER, PR, and Her2 levels were charted on the X, Y, and Z-axes to observe samples distribution in a 3D scatterplot. Results: A "seesaw" relationship between ER/PR and Her2 pathways was observed in ER-PR-Her2 space, characterized by the expression levels of these 3 proteins. Specimens with strong expressions of ER/PR proteins were found spreading along the ER/PR floor while those with strong Her2 expression were found wrapping around the Her2 axis. Those lacking strong expressions of all 3 proteins were found accumulating at the intersection of the ER, PR, and Her2 axes. Few specimens floated in the ER-PR-Her2 space to suggest the lack of co-expression of all 3 proteins simultaneously. Ki67 levels were found to be significantly reduced in specimens spreading in the ER-PR space. Conclusions: The unique distribution of specimens in ER-PR-Her2 space prior to any clinical intervention provided visual support of bidirectional talk between ER/PR and Her2 pathways in breast cancer specimens. Clinical interventions to suppress these 2 pathways alternatively warrant further exploration for breast cancer patients accordingly. Our study also demonstrated that the QDB method is an effective tool to analyze archived FFPE cancer specimens in biomedical research.

Project description:AimsThe available research on the association between estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-/PR+ status, and the occurrence of lung cancer subsequent to breast cancer in patients (referred to as BC-LuC) had been limited. Consequently, there is a need to examine whether ER, PR, HER2, and ER-/PR+ have independent correlations with the risk and outcomes of BC-LuC, while appropriately adjusting for other potential covariates.MethodsThe present study employed a cohort design and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program spanning from 2010 to 2015. The study population consisted of 683,336 individuals who were diagnosed with breast cancer (referred to as BC). Various covariates were assessed at baseline, including age, sex, race, marital status, CS tumor size, laterality, radiation, chemotherapy, months from diagnosis to treatment, breast subtype, AJCC 7th edition (2010-2015), and combined summary stage (2004+). The primary objective of this study was to investigate the association between ER, PR, HER2, ER-/PR+ status, and the risk of developing BC-LuC. Logistic regression analysis was employed to assess this association. Furthermore, multivariable Cox regression analyses were conducted to calculate adjusted hazard ratios (HRs) along with their respective 95% confidence intervals (CIs). Kaplan-Meier plots and log-rank tests were utilized to estimate the outcomes, specifically overall survival (OS), disease-specific survival (DSS), and metastasis.ResultsThe average age of 198,972 selected participants was 59.8 ± 13.1 years, and about 99.3% of them were female. Result of fully adjusted binary logistic regression showed PR+ and HER2+ were positively associated with lower risk BC-LuC after adjusting confounders (ORs = 0.84, 95% CI: 0.73-0.96, p = 0.011 and ORs = 0.83, 95% CI: 0.72-0.96, p = 0.012, respectively). ER+ and ER-/PR+ were detected no significant relationship with BC-LuC (ORs = 1.03, 95% CI: 0.87-1.22, p = 0.718 and ORs = 1.02, 95% CI: 0.61-1.72, p = 0.936, respectively). In subgroups analyses, the results remain stable. Multivariable Cox regression showed that BC-LuC patients with ER and PR were significantly associated with OS and DSS. However, ER, PR, HER2, and ER-/PR+ were significantly associated with OS and DSS in breast cancer patients. The relationship between ER, PR, HER2, and ER-/PR+ and metastasis in breast cancer patients was different.ConclusionThe results of this study indicated a potential correlation between PR- and HER2- status and a risk of developing BC-LuC. Furthermore, it appears that the prognosis of BC-LuC may be influenced by the presence of ER+ and PR+. Therefore, additional research is warranted to fully investigate and validate this association.

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Project description:BackgroundGenetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing.Methods/principal findingsWe retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. aUPD was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus.Conclusions/significanceWe conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclude that a genome-wide scale analysis of aUPD regions for homozygous sequence alterations can provide valuable insights into breast tumorigenesis.

Dataset Information

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective

Methods

Results

Conclusion

Publications

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Similar Datasets

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