Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer

Han, Yunwei; Yu, Zuwei; Wen, Shaoyan; Zhang, Bin; Cao, Xuchen; Wang, Xin

doi:10.1007/s10549-011-1799-1

Cited by 63 publications

(61 citation statements)

References 42 publications

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“…However, in a multivariate analysis only the number of affected lymph nodes, tumor size, progesterone receptor status, surgical procedure, age and adjuvant tamoxifen therapy retained prognostic significance, whereas the leukocyte nadir count did not. Han et al [7] CAFt and CMF are no longer commonly used in the adjuvant setting for the treatment of breast cancer. Recently, anthracycline and taxane based cytotoxic regimens have been adopted as standard regimens for the adjuvant treatment of locally advanced and operable breast cancer.…”

Section: Breast Cancermentioning

confidence: 99%

“…Recently, interest in the impact of neutropenia on survival during administration of cytotoxic chemotherapy in solid tumors has been under investigation [2] . Several published articles have described a positive impact of chemotherapy-induced neutropenia on survival [3][4][5][6][7][8] . Conversely, other studies illustrated no effect, or an adverse impact on survival [9,10] .…”

Section: Introductionmentioning

confidence: 99%

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Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Eskander

Tewari

2012

J Hemat Malig

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Background: Recent advances in chemotherapy administration, including targeted therapies and dose-dense scheduling have led to an increased incidence of neutropenia. Chemotherapy-induced neutropenia has been shown to be associated with improved treatment outcomes in various solid tumor types. We looked to summarize the relationship between chemotherapy-induced neutropenia and survival in patients with breast, ovarian and cervical cancer and describe future directions of research. Methodology/Principle findings:A comprehensive PUBMED literature search was conducted using the key words "solid tumor", "breast cancer", "ovarian cancer", "cervical cancer", "endometrial cancer", in combination with "chemotherapy", "neutropenia", "survival", "disease recurrence" and "prognosis". The search was also guided through a review of the reference lists of original and review articles. Published papers included in the review met the following criteria: patients with breast, ovarian, endometrial or cervical cancer treated with chemotherapy; prospective and retrospective studies, both randomized and cohort designs, evaluating impact of neutropenia or leukopenia on disease outcome. Eleven studies met the inclusion criteria. Sample size ranged from 103-750 subjects. The majority of included studies were conducted in breast cancer patients (7 of 11). No studies related to endometrial cancer were identified. Outcome measures included overall survival, progression free survival and distant disease free survival. All studies were retrospective in nature. Of the 11 identified studies, 9 suggested that the occurrence of chemotherapy-induced neutropenia was associated with improvement in oncologic outcome.Conclusions/Significance: Evaluation of the impact of chemotherapy-induced neutropenia on outcomes in patients with breast, ovarian and cervical cancer is warranted utilizing prospectively collected data from patients enrolled in clinical trials.

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Section: Breast Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Eskander

Tewari

2012

J Hemat Malig

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“…Interestingly, chemotherapy-induced neutropenia is associated with improved survival in patients with non-small cell lung, breast, gastric or colorectal cancer [182][183][184][185] . This beneficial association may be explained by two reasons, one of which is neutrophil-independent and the other neutrophil-dependent.…”

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confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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“…In these prostate tumors, infiltrating neutrophils secrete IL1RA to counteract cancer cell senescence and activate proliferation. Clinical support for a role of neutrophils in chemotherapy response comes from observations in a variety of cancer patients, such as breast and non-small cell lung cancer patients, where chemotherapyinduced neutropenia is associated with better patient prognosis [46,47]. We and others have established a metastasis-promoting role for neutrophils in breast and melanoma models [48][49][50].…”

Section: Innate Immune Cellsmentioning

confidence: 91%

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Coffelt

Visser

2015

Trends in Immunology

125

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SummaryConventional anti-cancer therapies, such as chemotherapy, radiotherapy and targeted therapy, are designed to kill cancer cells. Yet, the efficacy of anti-cancer therapies is not only determined by their direct effects on cancer cells, but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit a number of changes in immune-related parameters including the composition, phenotype and function of immune cells. In this review, we discuss the impact of innate and adaptive immune cells on the success of anti-cancer therapy, we examine the opportunities to exploit host immune responses to boost tumor clearing and we highlight the challenges facing the treatment of advanced metastatic disease. Then and now: The link between the immune system and anti-cancer therapiesThe relationship between anti-cancer therapies and the immune system is as old as the invention of anti-cancer therapies themselves. After the use of mustard gas in the trenches of World War I, a seminal observation was made that some exposed soldiers displayed severe loss of bone marrow and lymph node cells [1]. This observation then spurred the idea that the anti-proliferative capacity of mustard gas may also slow the growth of cancer cells.Experiments carried out in mice transplanted with lymphoid tumors were convincing enough to treat a lymphoma patient [2], and these events initiated the standardized treatment of cancer patients with chemotherapy [3,4].Fast forward 100 years later. The influence of immune cells on tumor progression and metastasis is well established [5], and an appreciation for the immune system's impact during conventional anti-cancer therapy treatment is growing. Recent seminal advances indicate that immune cells can shape the outcome of various anti-cancer therapies. As such, 2 immune cells and their molecular mediators have evolved into bona vide targets of therapeutic manipulation in cancer patients. The recent breakthrough of immunotherapeutics that inhibit negative immune regulatory pathways, such as anti-CTLA4 and anti-PD1, has initiated a new era in the treatment of cancer [6]. In parallel, immunomodulatory strategies aimed at dampening pro-tumor functions of immune cells are currently being tested in cancer patients [7]. Immune cells also function as reliable biomarkers, since their abundance or activation status often predicts how well patients respond to a particular treatment regimen.Here, we review these novel experimental and clinical insights, highlighting potential implications for the development of synergistic therapies designed to combat primary tumors and, more importantly, metastatic disease. The pros and cons of experimental mouse modelsResearch questions aimed at understanding the role of immune cells during anti-cancer therapy require models that mirror the complex interactions between the immune system and diverse forms of human cancers. Transplantable cancer cell line models and carcinogeninduced cancer models are the most frequently used for these purposes. However...

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Prognostic value of chemotherapy-induced neutropenia in early-stage breast cancer

Cited by 63 publications

References 42 publications

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Neutrophils in cancer: neutral no more

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

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