Invasive local recurrence increased after radiation therapy for ductal carcinoma in situ

Guerra, Lisa; Smith, Robina M.; Kaminski, Anna; Lagios, Michael D.; Silverstein, Melvin J.

doi:10.1016/j.amjsurg.2008.06.008

Cited by 13 publications

(7 citation statements)

References 12 publications

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“…The invasive foci which appear in the first years after surgical removal of DCIS must be initiated by TCD and grow in parallel with DCIS. Nonetheless, BC specific death within the first 10 years is rare for all IBTR regardless of malignancy and corresponds with a BC growth of more than 10 years the presented estimations [95].…”

Section: Field Cancerizationmentioning

confidence: 86%

True local recurrences do not metastasize

Hölzel

Emeny

Engel

2011

Cancer Metastasis Rev

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Generally, the limits of local tumor control are in part connected with the term "field cancerization" and are known from oral, lung, prostate, or mammary cancer. With the example of breast cancer (BC), the problem of ipsilateral breast tumor recurrences (IBTR) after breast-conserving surgery will be reviewed. Three types of local recurrences are distinguished: true recurrences, new primaries, or residual tumors. Good data for BC allow the description of the time-dependent risk of these three types, relative to the diagnosis of the primary tumor, because the time of initiation and the growth duration of the IBTR can be estimated. Two hypotheses explain the data: first, local recurrences may be initiated years before the diagnosis of a primary tumor (PT) and can then appear as multifocal PT at diagnosis, and second, true local recurrences probably do not metastasize. The generalizability of these hypotheses for other tumors will be discussed.

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Section: Field Cancerizationmentioning

confidence: 86%

True local recurrences do not metastasize

Hölzel

Emeny

Engel

2011

Cancer Metastasis Rev

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“…Exposure to IR can induce epithelial-to-mesenchymal transition (EMT) and activate pro-invasive pathways involving focal adhesion kinas (FAK), extracellular signal-regulated kinases (ERK1/2), mechanistic target of rapamycin (mTOR) and the transmembrane receptor c-MET. 21,26,[40][41][42] However, the effect of radiation regimen (AIR versus FIR) on radiation-induced invasion has not been previously investigated. We did not observe a significant difference in the expression of vimentin and E-cadherin at 24h following AIR compared to FIR (Fig.…”

Section: Modulation Of Pro-invasive Proteins By Airmentioning

confidence: 99%

Differential response to ablative ionizing radiation in genetically distinct non-small cell lung cancer cells

Oweida

Sharifi

Halabi

et al. 2016

Cancer Biology & Therapy

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Stereotactic ablative radiotherapy (SABR) has emerged as a highly promising treatment for medically inoperable early-stage non-small cell lung cancer patients. Treatment outcomes after SABR have been excellent compared to conventional fractionated radiotherapy (CFRT). However, the biological determinants of the response to ablative doses of radiation remain poorly characterized. Furthermore, there's little data on the cellular and molecular response of genetically distinct NSCLC subtypes to radiation. We assessed the response of 3 genetically distinct lung adenocarcinoma cell lines to ablative and fractionated ionizing radiation (AIR and FIR). We studied clonogenic survival, cell proliferation, migration, invasion, apoptosis and senescence. We also investigated the effect of AIR and FIR on the expression of pro-invasive proteins, epithelial-to-mesenchymal transition (EMT), extracellular signal-regulated kinases (ERK1/2) and the transmembrane receptor cMET. Our findings reveal that AIR significantly reduced cell proliferation and clonogenic survival compared to FIR in A549 cells only. This differential response was not observed in HCC827 or H1975 cells. AIR significantly enhanced the invasiveness of A549 cells, but not HCC827 or H1975 cells compared to FIR. Molecular analysis of pathways involved in cell proliferation and invasion revealed that AIR significantly reduced phosphorylation of ERK1/2 and upregulated cMET expression in A549 cells. Our results show a differential proliferative and invasive response to AIR that is dependent on genetic subtype and independent of intrinsic radioresistance. Further examination of these findings in a larger panel of NSCLC cell lines and in pre-clinical models is warranted for identification of biomarkers of tumor response to AIR.

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“…In fact, in the NSABP-17 and B-24 trials, the radiated group suffered a slight increase in mortality after 15 years follow-up compared with the patients who received no radiation therapy 29 , 30 . Furthermore, additional long-term follow up on the women in the Silverstein study 26 , 33 has now shown a greater risk of recurrences in the radiation arm of that cohort and that these recurrences are more commonly invasive 33 . Of further concern, is the fact that the median time to local recurrence for irradiated patients was more than twice as long when compared with non-irradiated patients.…”

Section: Discussionmentioning

confidence: 99%

Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up

et al. 2015

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Opportunities to study the natural history of ductal carcinoma in situ are rare. A few studies of incompletely excised lesions in the premammographic era, retrospectively recognized as ductal carcinoma in situ, have demonstrated a proclivity for local recurrence in the original site. The authors report a follow-up study of 45 women with low grade ductal carcinoma in situ treated by biopsy only, recognized retrospectively during a larger review of surgical pathology diagnoses and original histologic slides for 26,539 consecutive breast biopsies performed at Vanderbilt, Baptist, and St. Thomas Hospitals in Nashville, TN from 1950–1989. Long-term follow-up was previously reported on 28 of these women. Sixteen women (36%) developed invasive breast carcinoma, all in the same breast and quadrant as their incident ductal carcinoma in situ. Eleven invasive breast carcinomas were diagnosed within 10 years of the ductal carcinoma in situ biopsy. Subsequent cases were diagnosed at 12, 23, 25, 29 and 42 years. Seven women, including one who developed invasive breast cancer 29 years after her ductal carcinoma in situ biopsy, developed distant metastasis, resulting in death 1 to 7 years post diagnosis of invasive breast carcinoma. The natural history of low-grade ductal carcinoma in situ may extend more than four decades, with invasive breast cancer developing at the same site as the index lesion. This protracted natural history differs markedly from that of patients with high grade ductal carcinoma in situ or any completely delimited ductal carcinoma in situ excised to negative margins. This study reaffirms the importance of complete margin evaluation in women treated with breast conservation for ductal carcinoma in situ as well as balancing recurrence risk with possible treatment-related morbidity forolder women.

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Invasive local recurrence increased after radiation therapy for ductal carcinoma in situ

Cited by 13 publications

References 12 publications

True local recurrences do not metastasize

True local recurrences do not metastasize

Differential response to ablative ionizing radiation in genetically distinct non-small cell lung cancer cells

Continued observation of the natural history of low-grade ductal carcinoma in situ reaffirms proclivity for local recurrence even after more than 30 years of follow-up

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