Comparative diagnostic accuracy of &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT for breast cancer recurrence

Piva, Roberto; Ticconi, Flavia; Ceriani, Valentina; Scalorbi, Federica; Fiz, Francesco; Capitanio, Selene; Bauckneht, Matteo; Cittadini, Giuseppe; Sambuceti, Gianmario; Morbelli, Silvia

doi:10.2147/bctt.s111098

Cited by 17 publications

(14 citation statements)

References 88 publications

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“…This underlines the potential importance of other glucose transporters and the glycolysis inhibitor sensitivity of breast cancer cells in vitro [ 28 ]. The intense effect of the glycolytic inhibitor (3BP) can be attributed to the in vitro glucose dependence of cell cultures, which is not a universal in vivo feature of breast cancer cells (e.g., PET-CT-negative cases exist [ 29 ]). LDHA and LDHB expression (representing Warburg- and reverse-Warburg-effects, respectively) showed individual alterations, displaying the most remarkable differences among glycolytic markers.…”

Section: Discussionmentioning

confidence: 99%

In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy

Petővári

Dankó

Tőkés

et al. 2020

Cancers

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In spite of tremendous developments in breast cancer treatment, the relatively high incidence of relapsing cases indicates a great need to find new therapeutic strategies in recurrent, metastatic and advanced cases. The bioenergetic needs of growing tumours at the primary site or in metastases—accumulating genomic alterations and further heterogeneity—are supported by metabolic rewiring, an important hallmark of cancer. Adaptation mechanisms as well as altered anabolic and catabolic processes balance according to available nutrients, energy, oxygen demand and overgrowth or therapeutic resistance. Mammalian target of rapamycin (mTOR) hyperactivity may contribute to this metabolic plasticity and progression in breast carcinomas. We set out to assess the metabolic complexity in breast cancer cell lines and primary breast cancer cases. Cellular metabolism and mTOR-related protein expression were characterised in ten cell lines, along with their sensitivity to specific mTOR and other metabolic inhibitors. Selected immunohistochemical reactions were performed on ~100 surgically removed breast cancer specimens. The obtained protein expression scores were correlated with survival and other clinicopathological data. Metabolic and mTOR inhibitor mono-treatments had moderate antiproliferative effects in the studied cell lines in a subtype-independent manner, revealing their high adaptive capacity and survival/growth potential. Immunohistochemical analysis of p-S6, Rictor, lactate dehydrogenase A, glutaminase, fatty acid synthase and carnitine palmitoyltransferase 1A in human samples identified high mTOR activity and potential metabolic plasticity as negative prognostic factors for breast cancer patients, even in subtypes generally considered as low-risk. According to our results, breast cancer is characterised by considerable metabolic diversity, which can be targeted by combining antimetabolic treatments and recent therapies. Alterations in these pathways may provide novel targets for future drug development in breast cancer. We also propose a set of immunostainings for scoring metabolic heterogeneity in individual cases in order to select patients who may benefit from more accurate follow-up and specific therapies.

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Section: Discussionmentioning

confidence: 99%

In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy

Petővári

Dankó

Tőkés

et al. 2020

Cancers

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“…In these patients, its positive predictive value and accuracy of detection of distant metastases are 97% and 83–86%, respectively [11, 12]. Moreover, PET/CT can be useful for identifying the site of relapse when traditional imaging is equivocal or conflicting [13].…”

Section: Discussionmentioning

confidence: 99%

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

Corso¹,

Gilardi²,

Girardi³

et al. 2020

Oncology

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Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5-43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0-108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4-10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9-30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

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“…However, 18 F-FDG PET-CT is an expensive procedure and false-positive outcomes, caused for example by inflammatory processes, physiological muscle uptake, or old fracture sites, could result in unnecessary additional procedures as well [ 7 ]. False-negative results can occur due to low FDG uptake in some conditions, such as invasive lobular carcinoma, ongoing endocrine therapy, and small highly sclerotic skeletal lesions with low rate of actively replicating cells [ 14 ]. The clinical role of 18 F-FDG PET-CT remains controversial [ 15 ], since there is no evidence of the impact of 18 F-FDG PET-CT on patients’ outcomes.…”

Section: Introductionmentioning

confidence: 99%

Screening for distant metastases in patients with ipsilateral breast tumor recurrence: the impact of different imaging modalities on distant recurrence-free interval

Poodt

Schipper

Bta

et al. 2019

Breast Cancer Res Treat

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Purpose In patients with ipsilateral breast tumor recurrence (IBTR), the detection of distant disease determines whether the intention of the treatment is curative or palliative. Therefore, adequate preoperative staging is imperative for optimal treatment planning. The aim of this study is to evaluate the impact of conventional imaging techniques, including chest X-ray and/or CT thorax-(abdomen), liver ultrasonography(US), and skeletal scintigraphy, on the distant recurrence-free interval (DRFI) in patients with IBTR, and to compare conventional imaging with 18 F-FDG PET-CT or no imaging at all. Methods This study was exclusively based on the information available at time of diagnoses of IBTR. To adjust for differences in baseline characteristics between the three imaging groups, a propensity score (PS) weighted method was used. Results Of the 495 patients included in the study, 229 (46.3%) were staged with conventional imaging, 89 patients (19.8%) were staged with 18 F-FDG PET-CT, and in 168 of the patients (33.9%) no imaging was used ( N = 168). After a follow-up of approximately 5 years, 14.5% of all patients developed a distant recurrence as first event after IBTR. After adjusting for the PS weights, the Cox regression analyses showed that the different staging methods had no significant impact on the DRFI. Conclusions This study showed a wide variation in the use of imaging modalities for staging IBTR patients in the Netherlands. After using PS weighting, no statistically significant impact of the different imaging modalities on DRFI was shown. Based on these results, it is not possible to recommend staging for distant metastases using 18 F-FDG PET-CT over conventional imaging techniques. Electronic supplementary material The online version of this article (10.1007/s10549-019-05205-z) contains supplementary material, which is available to authorized users.

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Comparative diagnostic accuracy of <sup>18</sup>F-FDG PET/CT for breast cancer recurrence

Cited by 17 publications

References 88 publications

In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy

In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy

How Useful Are Tumor Markers in Detecting Metastases with FDG-PET/CT during Breast Cancer Surveillance?

Screening for distant metastases in patients with ipsilateral breast tumor recurrence: the impact of different imaging modalities on distant recurrence-free interval

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