Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?

Pons‐Tostivint, Elvire; Alouani, Emily; Kirova, Youlia; Vaysse, Charlotte

doi:10.1016/j.critrevonc.2020.103146

Cited by 13 publications

(15 citation statements)

References 107 publications

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“…Recent large, real-world databases from Europe and the USA (reviewed in ref. 81 ) have shown that ~40% of women undergo LRT in the context of dnMBC. Numerous meta-analyses have attempted to summarize data in the attempt to overcome several biases deriving from the relevant heterogeneity but drawbacks in the studies included affect the conclusions.…”

Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

“…Numerous meta-analyses have attempted to summarize data in the attempt to overcome several biases deriving from the relevant heterogeneity but drawbacks in the studies included affect the conclusions. 81 The majority of the retrospective studies examined did not include information on tumour subtypes, therefore limiting the application of findings in current clinical practice. 81 Other important biases are timing bias, for example, different timing of patient inclusion at diagnosis of dnMBC or after a systemic therapy, which could have selected for patients with a better prognosis; patient selection bias, for example, the trend to propose LRT to younger and healthier patients and with oligometastatic disease; and treatment-related biases, for example, the lack of information on response to systemic therapy, the long recruitment period, which encompasses different available therapies, and the heterogeneity of treatments (systemic or LRT).…”

Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

“…81 The majority of the retrospective studies examined did not include information on tumour subtypes, therefore limiting the application of findings in current clinical practice. 81 Other important biases are timing bias, for example, different timing of patient inclusion at diagnosis of dnMBC or after a systemic therapy, which could have selected for patients with a better prognosis; patient selection bias, for example, the trend to propose LRT to younger and healthier patients and with oligometastatic disease; and treatment-related biases, for example, the lack of information on response to systemic therapy, the long recruitment period, which encompasses different available therapies, and the heterogeneity of treatments (systemic or LRT). 81 One of the most recent and largest meta-analyses assessing the role of LRT in dnMBC included 42 studies retrospective and 5 prospective studies with more than 210,000 patients.…”

Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

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HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

Torrisi¹,

Jacobs²,

Miggiano³

et al. 2023

DIC

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De novo metastatic breast cancer (dnMBC) accounts for ~6-10% of all breast cancers and for ~30% of MBC with increasing incidence over time. Hormone receptor-positive/ human epidermal growth factor receptor 2-negative (HR + /HER2 -) tumours are the most frequent subtype with a similar incidence to that observed amongst recurrent MBC (rMBC). Higher frequency of PI3KCA and ARID2 mutations and a lower frequency of ESR1 mutations and of genes involved in DNA damage, as compared with rMBC, have been reported in HR + /HER2 -dnMBC; however, these are not correlating with prognosis, whilst tumour mutational burden is inversely correlated with outcome. Bone represents the most frequent metastatic site, being the single site in up to 60% of patients with dnMBC. HR + /HER2 -dnMBC has been generally reported to have better outcomes than rMBC, with a median overall survival ranging from 26 months to nearly 5 years in patients with favourable features such as age <40 years and bone-only disease, but not when compared with patients with late recurring disease (≥2-5 years). Analyses of the de novo cohorts within randomized clinical trials and large real-world series report a better outcome after treatment with CDK4/6 inhibitors and endocrine agents as compared to rMBC. Despite the limitations of retrospective studies and controversial results of the randomized trials, locoregional treatment of the primary tumour after response to systemic therapy appears to confer a survival benefit, particularly in patients with favourable prognostic factors. Altogether genomic, biological and clinical findings highlight HR + /HER2 -dnMBC as a peculiar entity as compared with rMBC and deserve a dedicated treatment algorithm.

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Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

Section: Evidence From Retrospective Studiesmentioning

confidence: 99%

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HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

Torrisi¹,

Jacobs²,

Miggiano³

et al. 2023

DIC

View full text Add to dashboard Cite

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“…Patients with clinical T1/2 disease more often received breast-conserving operations compared to patients with T3/4 disease; thus, the decrease in LRR might be more dramatic in group 1 than that in group 2. A recent review proposed a decision algorithm to select the optimal candidates for LRT in dnMBC and reported that LRT could be an option for ER/PR or HER2-positive patients [ 24 ]. Although most previous RCTs on LRT for dnMBC failed to demonstrate the benefit of LRT, future studies focusing on patients with these favorable IHC subtypes may demonstrate improved survival through LRT including PORT.…”

Section: Discussionmentioning

confidence: 99%

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02)

Kim

et al. 2022

Cancer Res Treat

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To investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT. Materials and MethodsThis study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively. ResultsThe median follow-up time was 53.7 months (range, 3. 1-194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 stage, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.50-0.82, p <0.001), in addition to T1/2 stage, ≤5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups [Group 1, T1/2 and non-TNBC (n=193); Group 2, T3/4 and non-TNBC (n=171); and Group 3, TNBC (n=49)], and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in Group 1 and 2, not in Group 3. ConclusionPORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 stage and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

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“…Most patients were treated in an adjuvant setting due to noncomplete pathological response after neoadjuvant chemotherapy. Locoregional treatment in de novo metastatic breast cancers might potentially prolong survival 16,17 and patients in this situation were consequently eligible; however, none were included due to lack of recruitment.…”

Section: Discussionmentioning

confidence: 99%

Combination of Olaparib with radiotherapy for triple‐negative breast cancers: One‐year toxicity report of the RADIOPARP Phase I trial

Loap

Loirat

Berger

et al. 2021

Intl Journal of Cancer

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Triple-negative breast cancer (TNBC) cells are sensitive to PARP1 inhibitors in vitro.The combination of Olaparib and radiotherapy for TNBC is currently evaluated in the Phase I RADIOPARP trial. RADIOPARP is a monocentric prospective open-label Phase I dose-escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50, 100, 150 or 200 mg twice a day [BID]); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. Twenty-four TNBC patients were enrolled between September 2017 and November 2019. Olaparib was escalated to 200 mg BID without dose-limiting toxicities. At 1-year follow-up, no treatment-related grade ≥3 toxicity was observed. One patient (4.2%) had persistent grade 2 adverse events (breast pain, fibrosis and deformity). There was no cardiac, pulmonary or digestive toxicity related to treatment. The 1-year follow-up report of the RADIOPARP Phase I trial, evaluating Olaparib associated with breast radiotherapy in TNBC patients, consequently demonstrated an excellent toxicity profile of this combination with few low-grade adverse events.

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Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?

Cited by 13 publications

References 107 publications

HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

HR+/HER2– de novo metastatic breast cancer: a true peculiar entity?

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02)

Combination of Olaparib with radiotherapy for triple‐negative breast cancers: One‐year toxicity report of the RADIOPARP Phase I trial

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