Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study

Gong, Yue; Liu, Yi-Rong; Ji, Peng; Hu, Xin; Shao, Zhi Ming

doi:10.1038/srep45411

Cited by 161 publications

(177 citation statements)

References 37 publications

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“…The molecular heterogeneity of breast cancer is well established (1), but breast cancer is still approached clinically as three large therapeutic subgroups: hormone receptor-positive (HRþ), human epidermal growth factor receptor 2-amplified (HER2þ), and the so-called triple-negative breast cancer (TNBC), defined by the lack of hormone receptors and HER2 amplification/overexpression. Approximately 65% of breast cancers fall into the HRþ/HER2À category (2,3). The standard treatment for these patients has been hormonal blockadebased therapies directed at inhibiting the estrogen/estrogen receptor (ER) signaling pathway by various modalities (4).…”

Section: Introductionmentioning

confidence: 99%

Biomarker Analyses of Response to Cyclin-Dependent Kinase 4/6 Inhibition and Endocrine Therapy in Women with Treatment-Naïve Metastatic Breast Cancer

Finn

Liu

Zhu

et al. 2020

Clinical Cancer Research

125

136

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Purpose: Preclinical data identified the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib as synergistic with antiestrogens in inhibiting growth of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HRþ/HER2À) human breast cancer models. This observation was validated clinically in the randomized, placebo-controlled, phase III PALOMA-2 study. Experimental Design: To determine markers of sensitivity and resistance to palbociclib plus letrozole, we performed comprehensive biomarker analyses, investigating the correlation with progression-free survival (PFS), on baseline tumor tissues from PALOMA-2. Results: Despite a broad biomarker search, palbociclib plus letrozole demonstrated consistent PFS gains versus placebo plus letrozole, with no single biomarker or cassette of markers associated with lack of benefit from combination treatment. Palbociclib plus letrozole confers efficacy on both luminal A and B patients. Higher CDK4 levels were associated with endocrine resistance which was mitigated by the addition of palbociclib, whereas lower PD-1 levels were associated with greater palbociclib plus letrozole benefit. Tumors with more active growth factor signaling, as exemplified by increased expression of FGFR2 and ERBB3 mRNA, appeared to be associated with greater PFS gain from the addition of palbociclib. Conclusions: These data underscore the importance of CDK4/ 6 signaling in HRþ/HER2À breast cancer and suggest that the interplay between steroid hormone and peptide growth factor signaling could drive dependence on CDK4/6 signaling. See related commentary by Anurag et al., p. 3

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Section: Introductionmentioning

confidence: 99%

Biomarker Analyses of Response to Cyclin-Dependent Kinase 4/6 Inhibition and Endocrine Therapy in Women with Treatment-Naïve Metastatic Breast Cancer

Finn

Liu

Zhu

et al. 2020

Clinical Cancer Research

125

136

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“…1,2 Despite a favourable prognosis relative to other subtypes of metastatic breast cancer, outcomes of hormone-receptor-positive, HER2-negative metastatic breast cancer remain poor, with a median overall survival of 36 months. 2,3 The oestrogen receptor signalling pathway is the main driver of cancer cell growth and survival in these tumours, so endocrine-based therapies are considered the most effective treatments. 2 In the past decade, randomised controlled trials have led to the introduction of several innovative therapeutic strategies into clinical practice, consisting of new targeted therapies combined with hormone treatments, both in endocrinesensitive and endocrine-resistant metastatic breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

Giuliano

Schettini

Rognoni

et al. 2019

The Lancet Oncology

133

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Background Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. Methods We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as firstline or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. Findings We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0•42; 95% credible interval [CrI] 0•25-0•70), ribociclib plus letrozole (0•43; 0•24-0•77), abemaciclib plus anastrozole or letrozole (0•42; 0•23-0•76), palbociclib plus fulvestrant (0•37; 0•23-0•59), ribociclib plus fulvestrant (0•48; 0•31-0•74), abemaciclib plus fulvestrant (0•44; 0•28-0•70), everolimus plus exemestane (0•42; 0•28-0•67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0•39; 0•22-0•66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8•95; 95% CrI 1•03-76•92). Interpretation In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free surv...

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“…Patients with HR‐positive breast cancer are at increased risk for the development of bone metastases, whereas bone metastases are less frequent in cases of triple‐negative tumors 15, 16, 17, 18, 19, 20, 21. Previous studies also indicated that tumor subtype is an important prognostic factor for the survival of patients with bone metastases, where worse survival was seen in patients with triple‐negative breast cancer 22, 23…”

Section: Introductionmentioning

confidence: 99%

Incidence proportions and prognosis of breast cancer patients with bone metastases at initial diagnosis

Gong

Zhang

et al. 2018

Cancer Medicine

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IntroductionPopulation‐based data on the incidence and prognosis of bone metastases at diagnosis of breast cancer are currently limited. Hence, we conducted this study to analyze the incidence proportions and prognostic factors of patients with breast cancer and bone metastases at the time of cancer diagnosis.Materials and methodsPatients with primary invasive breast cancer and bone metastases at initial diagnosis between 2010 and 2014 were identified using the Surveillance, Epidemiology, and End Results (SEER) dataset and Fudan University Shanghai Cancer Center (FUSCC) cohort. Multivariable logistic regression was performed to identify predictors of the presence of bone metastases at diagnosis. Univariate and multivariate analyses were performed to determine the effects of each variable on survival.ResultsOf 229, 195 patients from SEER database included in the analysis, 8295 patients had bone metastases at initial diagnosis, reflecting 3.6% of the entire study population, and 65.1% of the subset with metastatic disease to any distant site. Patients with hormone receptor (HR)‐positive human epidermal growth factor receptor 2 (HER2)‐negative represented the highest incidence proportions among patients with metastatic disease (73.9%). Among entire cohort, multivariable logistic regression identified eight factors as predictors of the presence of bone metastases at diagnosis. Median OS for the patients with bone metastases in SEER and FUSCC cohorts was 30.0 and 68.2 months, respectively. Patients with HR‐positive HER2‐positive subtype had the longest median OS, and patients with triple‐negative subtype showed the shortest median OS. Multivariable Cox model in SEER cohort confirmed age, histology, grade, tumor subtype, extraosseous metastatic sites, history of primary surgery, insurance status, marital status, and income as independent prognostic factors for both OS and BCSS.ConclusionsThe findings of this study provide population‐based estimates of the incidence and prognosis for patients with bone metastases at initial diagnosis of breast cancer.

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Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study

Cited by 161 publications

References 37 publications

Biomarker Analyses of Response to Cyclin-Dependent Kinase 4/6 Inhibition and Endocrine Therapy in Women with Treatment-Naïve Metastatic Breast Cancer

Biomarker Analyses of Response to Cyclin-Dependent Kinase 4/6 Inhibition and Endocrine Therapy in Women with Treatment-Naïve Metastatic Breast Cancer

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

Incidence proportions and prognosis of breast cancer patients with bone metastases at initial diagnosis

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