Current Treatment and Clinical Trial Developments for Ductal Carcinoma In Situ of the Breast

Boughey, Judy C.; Gonzalez, Ricardo J.; Bonner, Everett; Kuerer, Henry Mark

doi:10.1634/theoncologist.12-11-1276

Cited by 60 publications

(48 citation statements)

References 66 publications

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“…approximately half of these relapses are invasive breast cancer (28). Adjuvant breast irradiation has been proposed as an additional therapy and results in a 50% decrease in the number of ipsilateral breast recurrences (29,30).…”

Section: Discussionmentioning

confidence: 99%

Serum Autoantibody Signature of Ductal Carcinoma In Situ Progression to Invasive Breast Cancer

Mangé

Lacombe

Bascoul-Mollevi

et al. 2012

Clinical Cancer Research

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Purpose: The identification of markers associated with progression to invasive breast cancer (IBC) is a major factor that can guide physicians in the initial therapeutic decision and the management of ductal carcinoma in situ (DCIS).Experimental Design: We examined autoantibody targets in 20 DCIS and 20 IBC patients using protein microarrays and identified humoral responses that can be used to distinguish the two groups. The five most differentially targeted antigens were selected to generate an autoantibody signature for the in situ to invasive breast cancer transition. This signature was next tested on 120 independent samples (61 DCIS and 59 IBC) using specific ELISA assays. The prognosis value of the autoantibody signature was finally evaluated in a cohort of DCIS patients followed for 5 years.Results: A set of five autoantibody targets (RBP-Jk, HMGN1, PSRC1, CIRBP, and ECHDC1) with the highest differential signal intensity found in the protein microarrays experiment was used to establish an autoantibody signature of the DCIS to IBC transition. Using ELISA, this signature significantly discriminated DCIS from IBC [area under the ROC curve (AUC) ¼ 0.794, 95% confidence interval (CI): 0.674-0.877]. Interestingly, our panel could highly distinguish low-grade DCIS from high-grade DCIS exhibiting an AUC of 0.749 (95% CI: 0.581-0.866). Finally, using a Kaplan-Meier analysis, the autoantibody signature could significantly divide the DCIS patients into a poor prognosis group and a good prognosis group (P ¼ 0.01).Conclusion: These results indicate the potential of autoantibody detection as a new prognostic test with possible clinical implications for the management of DCIS.

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Section: Discussionmentioning

confidence: 99%

Serum Autoantibody Signature of Ductal Carcinoma In Situ Progression to Invasive Breast Cancer

Mangé

Lacombe

Bascoul-Mollevi

et al. 2012

Clinical Cancer Research

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“…Interestingly, grade 2 response (residual ductal carcinoma in situ DCIS only) was reduced in the trastuzumab receiving arm, 6.5% versus 12% without trastuzumab in the subgroup of HER2 positive tumor patient. This has to be put in perspective with the description of higher rate of HER2 over-expression in DCIS around 60% and the possible impact of trastuzumab on DCIS; clinical trials by the MD Anderson and the NSABP are ongoing in this setting [35].…”

Section: Discussionmentioning

confidence: 99%

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

Pierga

Delaloge

Espié

et al. 2010

Breast Cancer Res Treat

101

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, et al.. A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients. Breast Cancer Research and Treatment, Springer Verlag, 2010, 122 (2), pp.429-437. <10.1007/s10549-010-0939-3>. CLINICAL TRIALA multicenter randomized phase II study of sequential epirubicin/ cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients 2 ) for four cycles followed by docetaxel (100 mg/m 2 ) for four cycles]. HER2-negative patients (N = 220) were randomized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5-8 or no additional treatment, while HER2-positive patients confirmed by FISH (N = 120) were randomized to trastuzumab concomitant to docetaxel (8 mg/kg then 6 mg/kg IV every 3 weeks) or no additional preoperative treatment. In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5 and 13% of patients treated without and with neoadjuvant Celecoxib, respectively. In the HER2 positive group, pCR rate reached 26% in those who received neoadjuvant trastuzumab versus 19% in the others. There was no unexpected toxicity, no cardiac toxicity, and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%. Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor. In HER2-positive tumor patients, trastuzumab added to ECD leads to increased pCR rates. It was the only combination to deserve further study according to the two-stage Fleming's design used in this trial.

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“…56,57 Although there are a few molecularly based systemic options for the management of DCIS either existing or under investigation, (eg, tamoxifen for ER-positive DCIS, trastuzumab for HER2-positive DCIS), a better understanding of the molecular basis of progression is needed to develop further targeted therapy for these early lesions. 58 Information from clinical studies examining pre-invasive lesions vs invasive mammary carcinoma has yielded abundant gene expression profile differences between stages of progression (ADH vs DCIS vs IMC) (eg, [11][12][13]49,50). What is lacking is the understanding of which of these differentially expressed genes may be key players regulating transition through the stages of breast progression, not only to predict which of the lesions are more likely to progress, but to provide potential novel targets for preventative therapies.…”

Section: Discussionmentioning

confidence: 99%

Human 21T breast epithelial cell lines mimic breast cancer progression in vivo and in vitro and show stage-specific gene expression patterns

Souter

Andrews

Cook

et al. 2010

Laboratory Investigation

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Early breast cancer progression involves advancement through specific morphological stages including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series. We report here that three of the 21T cell lines indeed mimic specific stages of human breast cancer progression (21PT-derived cells, ADH; 21NT-derived cells, DCIS; 21MT-1 cells, IMC) when grown in the mammary fat pad of nude mice, albeit after a year. To develop a more rapid, readily manipulatable in vitro assay for examining the biological differences between these cell lines, we have used a 3D Matrigel system. When the three cell lines were grown in 3D Matrigel, they showed characteristic morphologies, in which quantifiable aspects of stage-specific in vivo behaviors (ie, differences in acinar structure formation, cell polarization, colony morphology, cell proliferation, cell invasion) were recapitulated in a reproducible fashion. Gene expression profiling revealed a characteristic pattern for each of the three cell lines. Interestingly, Wnt pathway alterations are particularly predominant in the early transition from 21PTci (ADH) to 21NTci (DCIS), whereas alterations in expression of genes associated with control of cell motility and invasion phenomena are more prominent in the later transition of 21NTci (DCIS) to 21MT-1 (IMC). This system thus reveals potential therapeutic targets and will provide a means of testing the influences of identified genes on transitions between these stages of pre-malignant to malignant growth. KEYWORDS: breast cancer; tumor progression; expression microarray; atypical ductal hyperplasia; ductal carcinoma in situ; invasive mammary carcinoma Pathological and epidemiological evidence has led to a histological model of breast cancer evolution, in which stem cells from the terminal duct lobular unit give rise to atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia, which can then progress to ductal carcinoma in situ (DCIS) or lobular carcinoma in situ, respectively, and eventually to invasive mammary carcinomas (IMC).1-6 These histological patterns are, however, most likely only rough phenotypic indications of underlying cellular and molecular events determining progression, 7 and may not necessarily occur in a linear fashion. There is currently much interest in identifying the nature of the cellular and molecular events involved, not only for use in determining at which point a lesion is most likely to progress to malignancy, but also in hopes of finding a way to halt ...

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Current Treatment and Clinical Trial Developments for Ductal Carcinoma In Situ of the Breast

Cited by 60 publications

References 66 publications

Serum Autoantibody Signature of Ductal Carcinoma In Situ Progression to Invasive Breast Cancer

Serum Autoantibody Signature of Ductal Carcinoma In Situ Progression to Invasive Breast Cancer

A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

Human 21T breast epithelial cell lines mimic breast cancer progression in vivo and in vitro and show stage-specific gene expression patterns

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