The effect of adjuvant chemotherapy on survival in Korean patients with node negative T1c, triple negative breast cancer

Lim, Seung Taek; Park, Chan Heun; Kim, Sung Yong; Nam, Seok Jin; Kang, Eun Young; Moon, Byung In; Lee, Hyouk Jin; Jeon, Ye Won; Gwak, Hongki; Suh, Young Jin

doi:10.1371/journal.pone.0197523

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…However, we found no significant difference in survival between patients treated with this intensive regimen and those receiving other less intensive regimens including CMF, anthracycline-based and taxane-based regimens. This result is in keeping with several other retrospective reports 17,23,31 and the current study results provide a basis for the design of future prospective trials. Therefore, it is reasonable to consider less intensive chemotherapy for patients with T1cN0M0 TNBC, which is consistent with current guidelines.…”

Section: Discussionsupporting

confidence: 93%

“…Some studies have demonstrated poor outcomes for patients with T1N0M0 TNBC who are treated without chemotherapy, and adjuvant chemotherapy significantly improved survival accordingly. [22][23][24] By contrast, other studies could not prove the benefit of adjuvant chemotherapy. [14][15][16]19,20 One of the important reasons for this disparity might be the difference in the definition of "small" tumors used in these studies.…”

Section: Discussionmentioning

confidence: 93%

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Adjuvant chemotherapy for small, lymph node–negative, triple‐negative breast cancer: A single‐center study and a meta‐analysis of the published literature

Lei

Huang

et al. 2020

Cancer

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BACKGROUND: Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node-negative, triple-negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes. METHODS: The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat-Sen University Cancer Center. For the meta-analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population. RESULTS: Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence-free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/ bN0M0) were included in the meta-analysis. The meta-analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease. CONCLUSIONS: Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta-analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 93%

Adjuvant chemotherapy for small, lymph node–negative, triple‐negative breast cancer: A single‐center study and a meta‐analysis of the published literature

Lei

Huang

et al. 2020

Cancer

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“…According to clinical trials, the TNBC subtype is more sensitive to chemotherapy and has higher pathologic complete response (pCR) rates than non-TNBC subtypes [6]. A real-world study revealed that chemotherapy significantly increased the overall survival rate (adjusted HR = 0.58, 95% CI = 0.46-0.73) and breast cancer-specific survival rate (adjusted HR = 0.65, 95% CI = 0.48-0.89) of TNBC patients during the 8.2-year median follow-up [7,8]. However, a sustained response can only be observed in a small proportion of TNBC patients and chemoresistance eventually develops in most patients.…”

Section: Introductionmentioning

confidence: 99%

CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR

Wang

Chen

et al. 2022

J Hematol Oncol

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Background Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown. Methods By using RNA high-throughput sequencing technology, qRT-PCR and in situ hybridization assays, we screened dysregulated circRNAs in breast cancer and TNBC tissues. Then in vitro assays, animal models and patient-derived organoids (PDOs) were utilized to explore the roles of the candidate circRNA in TNBC. To investigate the underlying mechanisms, RNA pull-down, RNA immunoprecipitation (RIP), co immunoprecipitation (co-IP) and Western blotting assays were carried out. Results In this study, we demonstrated that circRNA-CREIT was aberrantly downregulated in doxorubicin resistant triple-negative breast cancer (TNBC) cells and associated with a poor prognosis. The RNA binding protein DHX9 was responsible for the reduction in circRNA-CREIT by interacting with the flanking inverted repeat Alu (IRAlu) sequences and inhibiting back-splicing. By utilizing in vitro assays, animal models and patient-derived organoids, we revealed that circRNA-CREIT overexpression significantly enhanced the doxorubicin sensitivity of TNBC cells. Mechanistically, circRNA-CREIT acted as a scaffold to facilitate the interaction between PKR and the E3 ligase HACE1 and promoted proteasomal degradation of PKR protein via K48-linked polyubiquitylation. A reduced PKR/eIF2α signaling axis was identified as a critical downstream effector of circRNA-CREIT, which attenuated the assembly of stress granules (SGs) to activate the RACK1/MTK1 apoptosis signaling pathway. Further investigations revealed that a combination of the SG inhibitor ISRIB and doxorubicin synergistically inhibited TNBC tumor growth. Besides, circRNA-CREIT could be packaged into exosomes and disseminate doxorubicin sensitivity among TNBC cells. Conclusions Our study demonstrated that targeting circRNA-CREIT and SGs could serve as promising therapeutic strategies against TNBC chemoresistance.

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“…However, the benefits seen in survival may be attributed to the selection of healthier individuals. Radiation was more likely to be omitted in elderly patients with a higher number of comorbidities [ 13 , 14 , 18 , 19 , 20 ]. In our study, we examined BCSS as opposed to OS due to the competing risk of mortality from associated comorbidities and age.…”

Section: Discussionmentioning

confidence: 99%

Cancer-Specific Outcomes in the Elderly with Triple-Negative Breast Cancer: A Systematic Review

et al. 2021

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Triple-negative breast cancer (TNBC) is more common among young women, although it frequently presents in older patients. Despite an aging population, there remains a paucity of data on the treatment of TNBC in elderly women. We conducted a systematic review of the peer-reviewed and unpublished literature that captures the management and breast-cancer-specific survival (BCSS) of women ≥70 years old with TNBC. Out of 739 papers, five studies met our inclusion criteria. In total, 2037 patients with TNBC treated between 1973 and 2014 were captured in the analysis. Women ≥70 years old were less likely to undergo surgical resection compared to those <70 (92.8% vs. 94.6%, p = 0.002). Adjuvant therapy, including radiation and chemotherapy, was also less likely to be utilized in women ≥70 years of age. These treatment differences were associated with more than a doubling of cancer-specific mortality in the elderly cohort (5.9% vs. 2.7% in ≤70 years old, p < 0.0001). Two of the five studies showed improved BCSS with adjuvant treatment while others showed no difference. Our systemic review questions the appropriateness of therapeutic de-escalation in this cohort and highlights the significant gap in our understanding of the optimal management for elderly patients with TNBC. Until more data are available, multidisciplinary treatment decision-making should carefully balance the available clinical evidence as well as the patient’s predicted life expectancy and goals-of-care preferences.

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The effect of adjuvant chemotherapy on survival in Korean patients with node negative T1c, triple negative breast cancer

Cited by 6 publications

References 19 publications

Adjuvant chemotherapy for small, lymph node–negative, triple‐negative breast cancer: A single‐center study and a meta‐analysis of the published literature

Adjuvant chemotherapy for small, lymph node–negative, triple‐negative breast cancer: A single‐center study and a meta‐analysis of the published literature

CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR

Cancer-Specific Outcomes in the Elderly with Triple-Negative Breast Cancer: A Systematic Review

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