What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer?

Barrios, Carlos H.; Sampaio, Carlos Eduardo Peres; Vinholes, J.; Caponero, Ricardo

doi:10.1093/annonc/mdn756

Cited by 41 publications

(28 citation statements)

References 59 publications

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“…This is the most common BC subtype, and has a specific course of progression (21,22). This subtype requires endocrine therapy but in some cases not chemotherapy in an adjuvant setting, and requires various treatment strategies in a metastatic setting (23,24). A survival analysis of metastatic disease according to BC subtype could help in choosing an optimal treatment strategy in the patient population (25).…”

Section: Discussionmentioning

confidence: 99%

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer

Yamamura

Kamigaki

Fujita

et al. 2018

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Abstract. Background Breast cancer (BC) is the most common malignancy diagnosed in women, and leads to cancer mortality worldwide (1, 2). The majority of BC patients are diagnosed at an early disease stage, receive surgery and adjuvant treatment, and become long-term survivors who can be classified as disease-free (3-5). However, patients that develop metastatic disease during or after standard of care are generally incurable. In these cases a primary treatment goal is symptom palliation (6, 7). Patients with distant metastasis at initial diagnosis are classified as de novo stage IV metastatic patients and can be viewed as a distinct subgroup (8, 9), and these patients could be considered a poor prognostic group with incurable disease. However, a previous report suggested that de novo BC patients tend to have a better prognosis relative to recurrent BC patients (10). De novo BC patients may have a better response to systemic therapy due to their treatment-naïve status, while recurrent BC patients are more likely to show therapeutic resistance to systemic therapy after undergoing adjuvant treatment. There could also be biological differences other than the therapeutic factors between de novo and recurrent BC patients (11-13). Metastatic BC patients could form heterogeneous groups and present with varying metastatic patterns and prognostic outcomes, therefore requiring distinct treatment approaches based on BC subtype (14, 15). Treatment strategies have continuously advanced thanks to improved understanding of the heterogeneity of metastatic disease, which can have distant patterns of recurrence and varying prognostic impacts (15, 16). These approaches, which include endocrine therapies, targeted therapies, and various types of chemotherapies, are selected according to metastatic and prognostic patterns or BC subtypes based on immunohistochemical or molecular classifications (17). Although the difference in metastatic patterns and survival outcomes between de novo and recurrent BC patients is still unclear, these patients have often been treated with the same strategies. The objective of this retrospective study is to examine the prognostic outcomes between these groups of patients, both with the hormone receptor positive (HR+), and HER2-negative (HER2-) subtype. A better understanding of the metastatic course and prognostic factors for these patients 353

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Section: Discussionmentioning

confidence: 99%

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer

Yamamura

Kamigaki

Fujita

et al. 2018

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“…FK866, which is a highly specific noncompetitive inhibitor of NAMPT [5] has been shown to have beneficial effects in triple-negative breast cancer cells [16]. In the management of ER- and human epidermal growth factor receptor 2-positive breast cancers, endocrine therapy is most likely considered as the first-line of therapy [17]. However, ER-positive breast cancers with poor prognoses require more aggressive therapies and are recommended to be treated with chemotherapy, even in the case of ER-positive diseases [18].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nicotinamide Phosphoribosyltransferase Induces Apoptosis in Estrogen Receptor-Positive MCF-7 Breast Cancer Cells

et al. 2017

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PurposeTumor cells have increased turnover of nicotinamide adenine dinucleotide (NAD+), the main coenzyme in processes including adenosine diphosphate-ribosylation, deacetylation, and calcium mobilization. NAD+ is predominantly synthesized in human cells via the salvage pathway, with the first component being nicotinamide. Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme in this pathway, and its chemical inhibition by FK866 has elicited antitumor effects in several preclinical models of solid and hematologic cancers. However, its efficacy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2-positive breast cancer cells has not been previously investigated. In this study, we aimed to deplete the NAD+ content of MCF-7 cells, a model cell line for ER-positive breast cancer, by inhibiting NAMPT in order to evaluate downstream effects on p53 and its acetylation, p21 and Bcl-2-associated X protein (BAX) expression, and finally, apoptosis in MCF-7 breast cancer cells.MethodsMCF-7 cells were cultured and treated with FK866. NAD+ levels in cells were determined colorimetrically. Levels of p53 and its acetylated form were determined by Western blotting. Expression of p21 and BAX was determined by real-time polymerase chain reaction. Finally, levels of apoptosis were assessed by flow cytometry using markers for annexin V and propidium iodide.ResultsFK866 treatment was able to increase p53 levels and acetylation, upregulate BAX and p21 expression, and induce apoptosis in MCF-7 cells. Addition of exogenous NAD+ to cells reversed these effects, suggesting that FK866 exerted its effects by depleting NAD+ levels.ConclusionResults showed that FK866 could effectively inhibit NAD+ biosynthesis and induce programmed cell death in MCF-7 cells, suggesting that NAMPT inhibitors may be useful for the treatment of ER-positive breast cancers.

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“…Approximately 70% of primary breast cancers are positive for ER, which predicts a favorable initial tumor response to ER‐targeted endocrine therapy and is associated with better tumor differentiation and a more indolent natural history 1, 2. For ER‐positive, non‐life‐threatening metastatic breast cancer, endocrine manipulation represents a major option for initial treatment 3. ER status is usually determined in an invasive breast carcinoma at the time of initial diagnosis by immunohistochemical (IHC) staining, and the information is used mainly for selection of adjuvant therapy.…”

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confidence: 99%

Stability of estrogen receptor status in breast carcinoma

Gong

Han

Guo

et al. 2010

Cancer

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BACKGROUND:The purposes of this study were to address a persistent controversy as to whether the ER status of a primary tumor remains stable during progression to metastasis and to evaluate the influence of disease course and prior systemic therapy on ER status. METHODS: Breast carcinomas from 227 women with known ER status in both primary tumor and paired metastasis were retrospectively reviewed. ER status was compared between primary and metastatic tumors with respect to metastatic site, interval between two ER assays, and intervening chemotherapy and endocrine therapy. Semiquantitative comparison of ER values was performed for 92 tumor pairs. RESULTS: ER status agreed in 210 (92.5%) patients, including 147 positive and 63 negative. Of the 17 patients (7.5%) with discordant ER status, both negative to positive conversion (n ¼ 7) and positive to negative conversion (n ¼ 10) were observed. ER discordance was not significantly associated with metastatic site (locoregional vs distant), time interval between assays (<5 years vs. 5 years), or intervening chemotherapy and endocrine therapy. Semiquantitative levels of ER expression were similar between primary and metastatic tumors. In discordant cases, variations in testing methods and marginal scores were common. CONCLUSIONS: ER status in breast carcinoma is generally stable during progression to metastasis. Preanalytical and analytical variability may contribute to discordance in some cases. Given the importance of ER status for clinical management, ER testing in metastatic breast carcinoma should be repeated, especially for patients whose clinical courses are not compatible with stated ER status. Cancer 2011;117:705-13.

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What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer?

Cited by 41 publications

References 59 publications

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer

Inhibition of Nicotinamide Phosphoribosyltransferase Induces Apoptosis in Estrogen Receptor-Positive MCF-7 Breast Cancer Cells

Stability of estrogen receptor status in breast carcinoma

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