Overdiagnosis and Overtreatment in Cancer

Esserman, Laura J.; Thompson, Ian M.; Reid, Brian J.

doi:10.1001/jama.2013.108415

Cited by 433 publications

(397 citation statements)

References 7 publications

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“…Patients on surveillance can experience varying degrees of anxiety regarding the potential of their cancers to progress [48]. Additional studies are needed to determine whether GPS might also be used to identify men who may be candidates for less intense surveillance and perhaps some whose tumor characteristics are so indolent that they may be spared a diagnosis of ''cancer'' or converted to a program of watchful waiting, a less intensive alternative to AS [49,50].…”

Section: Discussionmentioning

confidence: 99%

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

et al. 2014

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Section: Discussionmentioning

confidence: 99%

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

et al. 2014

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“…Nonetheless, a small but significant percentage of PTCs (5-10%) behave aggressively, developing metastases and possibly leading to patient's death (2,3,29). The identification of prognostic markers able to discriminate aggressive PTCs from those with an indolent course would be of great relevance to better tailor the therapeutic approach and the long-term surveillance, avoiding overtreatment (34). The relative rarity of aggressive PTCs and the slow course of this disease make it difficult to collect large cohorts of tumors with distant metastases, which is necessary to obtain a more exhaustive comprehension of the genetic and biological processes at the basis of the metastatic spreading of these tumors and to improve the current prognostic capacity in the diagnosis of PTCs.…”

Section: Discussionmentioning

confidence: 99%

TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

Gandolfi

Ragazzi

Frasoldati³

et al. 2015

European Journal of Endocrinology

111

125

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Objective: Transcriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency of TERT promoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior. Design: We analyzed the frequency of TERT promoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation between TERT promoter mutations and BRAF V600E mutation was also investigated. Methods: TERT promoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations. Results: In the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in the TERT promoter. Noticeably, 33% of DM-PTCs were mutated in the TERT promoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E and TERT C228T mutations in the cohort of DM-PTCs. Conclusions: These results indicate that TERT promoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

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“…The detection of these tumors may represent examples of overdiagnosis. 36,37 And, if these patients had undergone surveillance rather than surgery, the clinically relevant tumors could likely have been identified at a later date at a point at which they would still be curable. In the two cases with 38 and 52 mm of ductal carcinoma in situ, less than 50% of the mammographic abnormalities were removed by core biopsy.…”

Section: Discussionmentioning

confidence: 99%

“…In an era of increasing recognition of overdiagnosis and overtreatment of breast lesions detected by screening mammography, the clinical value of detecting the upgrades in these patients could be challenged. 36,37 Disclosure/conflict of interest…”

Section: Discussionmentioning

confidence: 99%

Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies

et al. 2015

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Flat epithelial atypia of the breast commonly co-exists with atypical ductal hyperplasia, lobular neoplasia, and indolent forms of invasive carcinomas such as tubular carcinoma. Most patients with pure flat epithelial atypia on core biopsy undergo surgical excision to evaluate for carcinoma in the adjacent breast tissue. Studies to date have reported varying upgrade rates with most recommending follow-up excision. These studies have often lacked detailed radiographic correlation, central review by breast pathologists and information regarding the biology of the carcinomas identified upon excision. In this study, we report the frequency of upgrade to invasive carcinoma or ductal carcinoma in situ in excision specimens following a diagnosis of pure flat epithelial atypia on core biopsy. Radiographic correlation is performed for each case and grade/receptor status of detected carcinomas is reported. Seventy-three (73) core biopsies containing pure flat epithelial atypia were identified from our files, meeting inclusion criteria for the study. In the subsequent excision biopsies, five (7%) cases contained invasive carcinoma or ductal carcinoma in situ and seventeen (23%) contained atypical ductal hyperplasia or lobular neoplasia. All of the ductal carcinoma in situ cases with estrogen receptor results were estrogen receptor positive and intermediate grade. The invasive tumors were small (pT1a) hormone receptorpositive, HER2-negative, low-grade invasive ductal or tubular carcinomas with negative sentinel lymph-node biopsies. No upgrades were identified in the 14 patients who had all of their calcifications removed by the stereotactic core biopsy. Our rate of upgrade to carcinoma, once cases with discordant imaging are excluded, is at the lower end of the range reported in the literature. Given the low upgrade rate and indolent nature of the carcinomas associated with flat epithelial atypia, case management may be individualized based on clinical and radiographic findings. Excision may not be necessary for patients without remaining calcifications following core biopsy.

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Overdiagnosis and Overtreatment in Cancer

Cited by 433 publications

References 7 publications

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

Management of flat epithelial atypia on breast core biopsy may be individualized based on correlation with imaging studies

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