De novo Metastatic Breast Cancer Arising in Young Women: Review of the Current Evidence

Conte, Benedetta; Soldato, Davide; Razeti, Maria Grazia; Fregatti, Piero; Azambuja, Evandro de; Schettini, Francesco; Prat, Aleix; Mastro, Lucia Del; Lambertini, Matteo

doi:10.1016/j.clbc.2021.10.001

Cited by 7 publications

(7 citation statements)

References 95 publications

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“…There are many reasons for this. First, our study confirmed that younger patients have fewer comorbidities (24), while older patients have decreased physiologic function and an increased risk of non-cancer death. Younger patients were more likely to receive treatment (surgery and chemotherapy), consistent with previous studies (18).…”

Section: Discussionsupporting

confidence: 73%

Metastasis patterns and prognosis in young breast cancer patients: A SEER database analysis

Zhang

Wu²,

Liu³

et al. 2022

Front. Oncol.

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BackgroundThere are few studies on young patients with metastatic breast cancer (MBC). This study aims to explore the metastasis pattern and prognosis of young patients with MBC.MethodsA total of 6,336 MBC patients diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were selected. They were divided into two age groups: the younger group (≤40 years old) and the older group (>40 years old). χ2 test was used to compare clinicopathological characteristics. Survival differences were compared by Kaplan–Meier analysis. Cox regression models were used to determine the prognostic factors affecting survival. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences.ResultsFinally, 494 patients (7.8%) who are ≤40 years old and 5,842 patients (92.2%) who are >40 years old were included. In the younger group, the proportion of liver metastasis was significantly higher than that in the older group; the proportion of lung metastasis was significantly lower than that of the older group. Kaplan–Meier analysis showed that the younger group had the best prognosis and the older group had the worst. Youth is an independent protective factor for overall survival (OS). In the younger group, liver metastasis had the best prognosis among all metastatic sites, and the HER2-enriched subtype had the best prognosis among all subtypes.ConclusionsThe disease in young MBC patients is more aggressive but has a better prognosis, especially in liver metastases and the HER2-enriched subtypes.

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Section: Discussionsupporting

confidence: 73%

Metastasis patterns and prognosis in young breast cancer patients: A SEER database analysis

Zhang

Wu²,

Liu³

et al. 2022

Front. Oncol.

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“…dnMBC represents 1-7% of all MBC diagnosed in women aged ≤40 years. 7 Conflicting evidence on the relative incidence of dnMBC amongst young women as compared with older women is available. 7 In HR + /HER2tumours, age-related genomic differences have been reported, with young women showing features of increased endocrine resistance, with a higher proportion of GATA3 mutations, hypermethylation of ESR1 and increased activation of EGFR, though no specific data for dnMBC is available.…”

Section: Young Women (Age ≤40 Years)mentioning

confidence: 99%

“…7 Conflicting evidence on the relative incidence of dnMBC amongst young women as compared with older women is available. 7 In HR + /HER2tumours, age-related genomic differences have been reported, with young women showing features of increased endocrine resistance, with a higher proportion of GATA3 mutations, hypermethylation of ESR1 and increased activation of EGFR, though no specific data for dnMBC is available. 7 In the analysis of the large SEER database including ~19,400 women with dnMBC, young age (<40 years) was associated with improved outcomes particularly when compared with elderly patients (mOS 43 versus 18 months).…”

Section: Young Women (Age ≤40 Years)mentioning

confidence: 99%

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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“…Studies have shown that BCYW is generally more aggressive with a poorer prognosis than BC in older patients [ 16 , 17 , 18 ]. A high prevalence of TNBC, basal-like tumors, and luminal B exists in BCYW [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, the effect of cancer subtypes on the genome of women with BC aged ≤40 years remains poorly studied.…”

Section: Resultsmentioning

confidence: 99%

“…The range of clinical characteristics exhibited in BCYW is distinct from that exhibited in older premenopausal and postmenopausal women with BC; thus, BCYW could be considered a subset of premenopausal diseases. BCYW exhibits more aggressive cancer subtypes (such as TNBC/basal, HER2-positive, and luminal B) than BC in older patients [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The prognosis of BCYW is generally worse than that of BC in older patients, presumably due to its aggressive subtypes, detection at an advanced stage, and a high recurrence rate [ 1 , 6 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Delineation of Pathogenomic Insights of Breast Cancer in Young Women

Paul

George

Saini

et al. 2022

Cells

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The prognosis of breast cancer (BC) in young women (BCYW) aged ≤40 years tends to be poorer than that in older patients due to aggressive phenotypes, late diagnosis, distinct biologic, and poorly understood genomic features of BCYW. Considering the estimated predisposition of only approximately 15% of the BC population to BC-promoting genes, the underlying reasons for an increased occurrence of BCYW, at large, cannot be completely explained based on general risk factors for BC. This underscores the need for the development of next-generation of tissue- and body fluid-based prognostic and predictive biomarkers for BCYW. Here, we identified the genes associated with BCYW with a particular focus on the age, intrinsic BC subtypes, matched normal or normal breast tissues, and BC laterality. In young women with BC, we observed dysregulation of age-associated cancer-relevant gene sets in both cancer and normal breast tissues, sub-sets of which substantially affected the overall survival (OS) or relapse-free survival (RFS) of patients with BC and exhibited statically significant correlations with several gene modules associated with cellular processes such as the stroma, immune responses, mitotic progression, early response, and steroid responses. For example, high expression of COL1A2, COL5A2, COL5A1, NPY1R, and KIAA1644 mRNAs in the BC and normal breast tissues from young women correlated with a substantial reduction in the OS and RFS of BC patients with increased levels of these exemplified genes. Many of the genes upregulated in BCYW were overexpressed or underexpressed in normal breast tissues, which might provide clues regarding the potential involvement of such genes in the development of BC later in life. Many of BCYW-associated gene products were also found in the extracellular microvesicles/exosomes secreted from breast and other cancer cell-types as well as in body fluids such as urine, saliva, breast milk, and plasma, raising the possibility of using such approaches in the development of non-invasive, predictive and prognostic biomarkers. In conclusion, the findings of this study delineated the pathogenomics of BCYW, providing clues for future exploration of the potential predictive and prognostic importance of candidate BCYW molecules and research strategies as well as a rationale to undertake a prospective clinical study to examine some of testable hypotheses presented here. In addition, the results presented here provide a framework to bring out the importance of geographical disparities, to overcome the current bottlenecks in BCYW, and to make the next quantum leap for sporadic BCYW research and treatment.

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De novo Metastatic Breast Cancer Arising in Young Women: Review of the Current Evidence

Cited by 7 publications

References 95 publications

Metastasis patterns and prognosis in young breast cancer patients: A SEER database analysis

Metastasis patterns and prognosis in young breast cancer patients: A SEER database analysis

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

Delineation of Pathogenomic Insights of Breast Cancer in Young Women

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