ABC3 Consensus Commented from the Perspective of the German Guidelines

Untch, Michael; Augustin, Doris; Ettl, Johannes; Haidinger, Renate; Harbeck, Nadia; Lück, H.-J.; Lüftner, Diana; Marmé, Frederik; Müller, Lothar; Overkamp, Friedrich; Ruckhäberle, Eugen; Thill, Marc; Thomssen, Christoph; Wuerstlein, Rachel; Marschner, Norbert

doi:10.1055/s-0042-101168

Cited by 6 publications

(6 citation statements)

References 14 publications

(4 reference statements)

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“…We therefore sought to augment the effect of KIFC1 depletion by combining it with a clinically relevant therapy capable of further induction of centrosome amplification in tumor cells. Platinum-based chemotherapies are currently considered one of the standard of care treatments for advanced TNBCs 37 and cisplatin is known to cause centrosome amplification by decoupling the centrosome duplication cycle from the DNA replication cycle 38 . We found that MDA-MB-231 cells show an increase in centrosome amplification when treated with increasing concentrations of cisplatin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer

et al. 2018

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Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies and validates gene addictions in TNBCs. CNAs and gene expression alterations are integrated and genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these genes using RNAi in breast cancer and non-malignant cells, validating malignant cell selective dependence upon 37 of 130 genes. Further analysis reveals a cluster of 13 TNBC addiction genes frequently co-upregulated that includes genes regulating cell cycle checkpoints, DNA damage response, and malignant cell selective mitotic genes. We validate the mechanism of addiction to a potential drug target: the mitotic kinesin family member C1 (KIFC1/HSET), essential for successful bipolar division of centrosome-amplified malignant cells and develop a potential selection biomarker to identify patients with tumors exhibiting centrosome amplification.

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Section: Resultsmentioning

confidence: 99%

Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer

et al. 2018

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“…In current clinical practice, approximately half of the patients with de novo stage IV disease were treated with local surgery, because it was associated with better local control and longer survival times in retrospective studies (19,25,26). The consensus from the Third International Consensus Conference for Advanced Breast Cancer suggests that surgery to the primary site can be considered in selected patients, particularly to improve the quality of life (27). However, the survival benefit of radiotherapy in these patients has been rarely investigated (13,20,21).…”

Section: Introductionmentioning

confidence: 99%

Aggressive Local Treatment Improves Survival in Stage IV Breast Cancer With Synchronous Metastasis

et al. 2020

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Introduction To investigate the effect of local treatment strategy on survival outcome in de novo stage IV breast cancer patients who received chemotherapy. Methods We identified stage IV breast cancers that presented with synchronous metastasis from the Surveillance, Epidemiology, and End Results database. Binomial logistic regression, Kaplan–Meier survival curves, propensity score matching (PSM), and multivariate Cox regression model were used for statistical analyses. Results We identified 5,374 patients in total, including 2,319 (43.2%), 2,137 (39.8%), and 918 (17.1%) patients who received surgery alone, surgery+radiotherapy, and radiotherapy alone, respectively. The probability of patients receiving surgery alone decreased over time, and the probability of patients receiving radiotherapy alone increased over time. However, no significant difference was observed in the probability of patients receiving postoperative radiotherapy (P = 0.291). The 3-year breast cancer-specific survival (BCSS) in patients treated with surgery alone, radiotherapy alone, and surgery+radiotherapy was 57.1, 35.9, and 63.9%, respectively (P < 0.001). The local treatment strategy was the independent prognostic factor related to BCSS. Using surgery alone as the reference, radiotherapy alone was related to lower BCSS (P < 0.001), while additional radiotherapy after surgery improved BCSS (P < 0.001). Similar results were observed using PSM. Conclusions Compared to radiotherapy alone, surgery to the primary site may confer a survival benefit in stage IV breast cancer with synchronous metastasis, and additional postoperative radiotherapy further improves outcome after primary tumor removal. Local treatment can only be an option in highly selected patients with de novo stage IV disease in the treatment guidelines. More prospective studies are needed to investigate the role of local management for this patient subset.

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“…Approximately 70-80% of patients with breast cancer are diagnosed with hormone receptor (HR)-positive luminal A or luminal B subtype. Endocrine therapy is an important treatment approach for hormone receptor-positive patients; yet, some patients may develop primary and secondary resistance (2)(3)(4). Endocrine resistance seems to be associated with the activation of multiple growth factor signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer

Zhang¹,

Zhou²,

Zhang³

et al. 2021

Ann Transl Med

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Background: To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)negative metastatic breast cancer using real-world clinical data.Methods: Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated.Results: A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy.The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed.Conclusions: Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

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ABC3 Consensus Commented from the Perspective of the German Guidelines

Cited by 6 publications

References 14 publications

Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer

Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer

Aggressive Local Treatment Improves Survival in Stage IV Breast Cancer With Synchronous Metastasis

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer

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