Tumor Biol. DOI 10.1007/s13277-015-3291-8
RESEARCH COMMENTARY
Atmospheric particulate matter and breast cancer survival: estrogen receptor triggered? Qiang Huo & Chang Cai & Qifeng Yang
Received: 6 December 2014 / Accepted: 25 February 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Keywords Air pollution . Breast cancer . Cancer survival . Estrogen receptor . Particulate matter
To the Editor, Recently, a study has reported the effect of ambient particulate matter (PM) on the outcome of breast cancer in the USA [1]. The authors indicated that exposure to higher PM was significantly associated with poorer survival, particularly among females diagnosed with early-stage cancer. Actually solid data and analyses given by several studies have revealed that atmospheric PM is associated with the increased morbidity and mortality of breast cancer patients [2–4]. However, to date, the underlying mechanism was not mentioned and still remains unclear. Atmospheric PM is the major air pollutant found in northern China, including Shandong Province. Our team presented an interesting report a few months ago [5], and the study has been continued. As reported, we previously recruited female patients who had resided in the same cities of Shandong Province for at least 10 years prior to their diagnosis of early-stage breast cancers [5]. Informed consent was obtained from all individual participants included in the study. We only considered PM10 (particulate matter less than 10 μm in diameter) data since previous Q. Huo : C. Cai : Q. Yang (*) Department of Breast Surgery, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan 250012, Shandong Province, China e-mail: [email protected] Q. Huo Department of Orthopaedic Surgery, Zibo Central Hospital, 54 West Gongqingtuan Road, Zibo 255036, Shandong Province, China
PM2.5 (particulate matter less than 2.5 μm in diameter) data were impossible to access: these data will not be extensively monitored in China until 2016. Nevertheless, PM2.5 data were contained within the PM10 monitoring data naturally. Moreover, we analyzed the PM10 geographical distribution pattern (Fig. 1a) and reviewed literature describing global estimates of PM2.5 concentrations from satellite-based data, indicating a high consistency of PM2.5 and PM10 geographical concentration distribution over the same time period [6]. Our cigarette-smoking status adjusted logistic regression model only included female patients who were diagnosed with invasive breast cancer (pathological tumor-node-metastasis (pTNM) stages I–III) or ductal carcinoma in situ (DCIS), and the result indicated that patients living in high-PM areas presented with more invasive cancers (p= 0.028, Fig. 1b) with higher tumor grades (p=0.028, Fig. 1c), which is consistent with Hu’s study. Interestingly, we observed a higher ratio of estrogen receptor (ER)-positive cases in patients from high-PM group (p=0.022, Fig. 1d) and noticed that the differences in tumor’s histological grade did originate from ER-positive cases (p=0.003, Fig. 1e), not ER-negative ones (p=0.663, Fig. 1f) [5]. Based on previous findings [5], we conducted survival analyses using Kaplan-Meier curves in ERpositive and ER-negative cases, respectively. All deaths caused by other diseases were considered as censored cases. Our results suggested that exposure to high PM was significantly associated with poorer recurrence-free survival (RFS) (p=0.019, Fig. 1g) and marginally associated with overall survival (OS) (p=0.083, Fig. 1h) in ER-positive patients, but not in ER-negative cases (p=0.427 for RFS, and p=0.730 for OS, Fig. 1i, j, respectively). Based on our classification method, medium-PM group included intermediate cases, a continuum set between the high- and the low-PM groups, which means that the characteristics of it may fall in between them. Focused on the subject of this study, we carefully compared the prognostic data between high- and lowPM cases only, with its limited sample size.
Tumor Biol. Fig. 1 Atmospheric PM exposure may contribute to the development and outcomes of ER-positive breast cancers. a Geographical distribution pattern of PM in Shandong Province during 2001–2006. b The proportions of invasive patients among all cases in different PM areas. c The proportions of highgrade patients among invasive cases in different PM areas. d The proportions of ER-positive patients among all cases in different PM areas. e The proportions of high-grade patients among ER-positive invasive cases in different PM areas. f The proportions of high-grade patients among ER-negative invasive cases in different PM areas. g Recurrence-free survival (RFS) in ER-positive patients. h Overall survival (OS) in ER-positive patients. i RFS in ER-negative patients. j OS in ER-negative patients
Tumor Biol.
Though previous studies have presented several hypotheses attempting to explain the association between atmospheric particulate matter and breast cancer morbidity or mortality [3, 7–9], there is no satisfactory answer for researchers to date. We observed an ER-related difference in tumor’s histopathological type, pTNM grade, and patient’s survival time between cases from high- and lowPM groups. Our investigation also suggested that atmospheric PM exposure specifically contributes to the development and outcomes of ER-positive breast cancers. On the other hand, Chen et al. demonstrated that the dilution of airborne particles could promote the proliferation of ER-positive breast cancer cells by the activation of ERα signaling and greatly inhibit E2-induced cell proliferation in vitro [10]. The authors showed that organic solvent extract of atmospheric PM demonstrated similar biological characteristics of xenoestrogens since it showed similar estrogenic and anti-estrogenic effects in vitro, which provided preliminary experimental evidence for our hypothesis. We believe that this new point of view could provide a new strategy in similar investigations to reveal the association between PM pollution and the morbidity and mortality of breast cancers. Further investigation using large-scale cohort is urgently warranted to confirm or modify the findings from this study. Acknowledgments This work was supported by the National Adolescents Science and Technology Innovation Award Foundation of China and the National Natural Science Foundation of China (No. 30772133; No. 81072150; No. 81172529; No. 81272903) and the Shandong Science and Technology Development Plan (No. 2012GZC22115). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Compliance with ethical standards Conflicts of interest None Ethics committee approval For this type of study, formal consent is not required.
Informed consent Informed consent was obtained from all individual participants included in the study.
References 1. Hu H, Dailey AB, Kan H, Xu X. The effect of atmospheric particulate matter on survival of breast cancer among US females. Breast Cancer Res Treat. 2013;139(1):217–26. doi:10.1007/s10549-013-2527-9. 2. Nie J, Beyea J, Bonner MR, Han D, Vena JE, Rogerson P, et al. Exposure to traffic emissions throughout life and risk of breast cancer: the Western New York Exposures and Breast Cancer (WEB) study. Cancer Causes Control. 2007;18(9):947–55. doi:10.1007/ s10552-007-9036-2. 3. Crouse DL, Goldberg MS, Ross NA, Chen H, Labreche F. Postmenopausal breast cancer is associated with exposure to trafficrelated air pollution in Montreal, Canada: a case–control study. Environ Health Perspect. 2010;118(11):1578–83. doi:10.1289/ehp. 1002221. 4. Bonner MR, Han D, Nie J, Rogerson P, Vena JE, Muti P, et al. Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure. Cancer Epidemiol Biomarkers Prev. 2005;14(1):53–60. 5. Huo Q, Zhang N, Wang X, Jiang L, Ma T, Yang Q. Effects of ambient particulate matter on human breast cancer: is xenogenesis responsible? PLoS One. 2013;8(10):e76609. doi:10.1371/journal.pone.0076609. 6. van Donkelaar A, Martin RV, Brauer M, Kahn R, Levy R, Verduzco C, et al. Global estimates of ambient fine particulate matter concentrations from satellite-based aerosol optical depth: development and application. Environ Health Perspect. 2010;118(6):847–55. doi:10. 1289/ehp.0901623. 7. Chameides WL. Environmental factors in cancer: focus on air pollution. Rev Environ Health. 2010;25(1):17–22. 8. Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. N Engl J Med. 2000;343(24):1742–9. doi:10.1056/NEJM200012143432401. 9. Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. J Toxicol. 2011;2011:487074. doi:10.1155/2011/487074. 10. Chen ST, Lin CC, Liu YS, Lin C, Hung PT, Jao CW, et al. Airborne particulate collected from central Taiwan induces DNA strand breaks, Poly(ADP-ribose) polymerase-1 activation, and estrogen-disrupting activity in human breast carcinoma cell lines. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng. 2013;48(2):173–81. doi:10. 1080/10934529.2012.717809.
RESEARCH COMMENTARY
Atmospheric particulate matter and breast cancer survival: estrogen receptor triggered? Qiang Huo & Chang Cai & Qifeng Yang
Received: 6 December 2014 / Accepted: 25 February 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Keywords Air pollution . Breast cancer . Cancer survival . Estrogen receptor . Particulate matter
To the Editor, Recently, a study has reported the effect of ambient particulate matter (PM) on the outcome of breast cancer in the USA [1]. The authors indicated that exposure to higher PM was significantly associated with poorer survival, particularly among females diagnosed with early-stage cancer. Actually solid data and analyses given by several studies have revealed that atmospheric PM is associated with the increased morbidity and mortality of breast cancer patients [2–4]. However, to date, the underlying mechanism was not mentioned and still remains unclear. Atmospheric PM is the major air pollutant found in northern China, including Shandong Province. Our team presented an interesting report a few months ago [5], and the study has been continued. As reported, we previously recruited female patients who had resided in the same cities of Shandong Province for at least 10 years prior to their diagnosis of early-stage breast cancers [5]. Informed consent was obtained from all individual participants included in the study. We only considered PM10 (particulate matter less than 10 μm in diameter) data since previous Q. Huo : C. Cai : Q. Yang (*) Department of Breast Surgery, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan 250012, Shandong Province, China e-mail: [email protected] Q. Huo Department of Orthopaedic Surgery, Zibo Central Hospital, 54 West Gongqingtuan Road, Zibo 255036, Shandong Province, China
PM2.5 (particulate matter less than 2.5 μm in diameter) data were impossible to access: these data will not be extensively monitored in China until 2016. Nevertheless, PM2.5 data were contained within the PM10 monitoring data naturally. Moreover, we analyzed the PM10 geographical distribution pattern (Fig. 1a) and reviewed literature describing global estimates of PM2.5 concentrations from satellite-based data, indicating a high consistency of PM2.5 and PM10 geographical concentration distribution over the same time period [6]. Our cigarette-smoking status adjusted logistic regression model only included female patients who were diagnosed with invasive breast cancer (pathological tumor-node-metastasis (pTNM) stages I–III) or ductal carcinoma in situ (DCIS), and the result indicated that patients living in high-PM areas presented with more invasive cancers (p= 0.028, Fig. 1b) with higher tumor grades (p=0.028, Fig. 1c), which is consistent with Hu’s study. Interestingly, we observed a higher ratio of estrogen receptor (ER)-positive cases in patients from high-PM group (p=0.022, Fig. 1d) and noticed that the differences in tumor’s histological grade did originate from ER-positive cases (p=0.003, Fig. 1e), not ER-negative ones (p=0.663, Fig. 1f) [5]. Based on previous findings [5], we conducted survival analyses using Kaplan-Meier curves in ERpositive and ER-negative cases, respectively. All deaths caused by other diseases were considered as censored cases. Our results suggested that exposure to high PM was significantly associated with poorer recurrence-free survival (RFS) (p=0.019, Fig. 1g) and marginally associated with overall survival (OS) (p=0.083, Fig. 1h) in ER-positive patients, but not in ER-negative cases (p=0.427 for RFS, and p=0.730 for OS, Fig. 1i, j, respectively). Based on our classification method, medium-PM group included intermediate cases, a continuum set between the high- and the low-PM groups, which means that the characteristics of it may fall in between them. Focused on the subject of this study, we carefully compared the prognostic data between high- and lowPM cases only, with its limited sample size.
Tumor Biol. Fig. 1 Atmospheric PM exposure may contribute to the development and outcomes of ER-positive breast cancers. a Geographical distribution pattern of PM in Shandong Province during 2001–2006. b The proportions of invasive patients among all cases in different PM areas. c The proportions of highgrade patients among invasive cases in different PM areas. d The proportions of ER-positive patients among all cases in different PM areas. e The proportions of high-grade patients among ER-positive invasive cases in different PM areas. f The proportions of high-grade patients among ER-negative invasive cases in different PM areas. g Recurrence-free survival (RFS) in ER-positive patients. h Overall survival (OS) in ER-positive patients. i RFS in ER-negative patients. j OS in ER-negative patients
Tumor Biol.
Though previous studies have presented several hypotheses attempting to explain the association between atmospheric particulate matter and breast cancer morbidity or mortality [3, 7–9], there is no satisfactory answer for researchers to date. We observed an ER-related difference in tumor’s histopathological type, pTNM grade, and patient’s survival time between cases from high- and lowPM groups. Our investigation also suggested that atmospheric PM exposure specifically contributes to the development and outcomes of ER-positive breast cancers. On the other hand, Chen et al. demonstrated that the dilution of airborne particles could promote the proliferation of ER-positive breast cancer cells by the activation of ERα signaling and greatly inhibit E2-induced cell proliferation in vitro [10]. The authors showed that organic solvent extract of atmospheric PM demonstrated similar biological characteristics of xenoestrogens since it showed similar estrogenic and anti-estrogenic effects in vitro, which provided preliminary experimental evidence for our hypothesis. We believe that this new point of view could provide a new strategy in similar investigations to reveal the association between PM pollution and the morbidity and mortality of breast cancers. Further investigation using large-scale cohort is urgently warranted to confirm or modify the findings from this study. Acknowledgments This work was supported by the National Adolescents Science and Technology Innovation Award Foundation of China and the National Natural Science Foundation of China (No. 30772133; No. 81072150; No. 81172529; No. 81272903) and the Shandong Science and Technology Development Plan (No. 2012GZC22115). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Compliance with ethical standards Conflicts of interest None Ethics committee approval For this type of study, formal consent is not required.
Informed consent Informed consent was obtained from all individual participants included in the study.
References 1. Hu H, Dailey AB, Kan H, Xu X. The effect of atmospheric particulate matter on survival of breast cancer among US females. Breast Cancer Res Treat. 2013;139(1):217–26. doi:10.1007/s10549-013-2527-9. 2. Nie J, Beyea J, Bonner MR, Han D, Vena JE, Rogerson P, et al. Exposure to traffic emissions throughout life and risk of breast cancer: the Western New York Exposures and Breast Cancer (WEB) study. Cancer Causes Control. 2007;18(9):947–55. doi:10.1007/ s10552-007-9036-2. 3. Crouse DL, Goldberg MS, Ross NA, Chen H, Labreche F. Postmenopausal breast cancer is associated with exposure to trafficrelated air pollution in Montreal, Canada: a case–control study. Environ Health Perspect. 2010;118(11):1578–83. doi:10.1289/ehp. 1002221. 4. Bonner MR, Han D, Nie J, Rogerson P, Vena JE, Muti P, et al. Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure. Cancer Epidemiol Biomarkers Prev. 2005;14(1):53–60. 5. Huo Q, Zhang N, Wang X, Jiang L, Ma T, Yang Q. Effects of ambient particulate matter on human breast cancer: is xenogenesis responsible? PLoS One. 2013;8(10):e76609. doi:10.1371/journal.pone.0076609. 6. van Donkelaar A, Martin RV, Brauer M, Kahn R, Levy R, Verduzco C, et al. Global estimates of ambient fine particulate matter concentrations from satellite-based aerosol optical depth: development and application. Environ Health Perspect. 2010;118(6):847–55. doi:10. 1289/ehp.0901623. 7. Chameides WL. Environmental factors in cancer: focus on air pollution. Rev Environ Health. 2010;25(1):17–22. 8. Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. N Engl J Med. 2000;343(24):1742–9. doi:10.1056/NEJM200012143432401. 9. Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. J Toxicol. 2011;2011:487074. doi:10.1155/2011/487074. 10. Chen ST, Lin CC, Liu YS, Lin C, Hung PT, Jao CW, et al. Airborne particulate collected from central Taiwan induces DNA strand breaks, Poly(ADP-ribose) polymerase-1 activation, and estrogen-disrupting activity in human breast carcinoma cell lines. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng. 2013;48(2):173–81. doi:10. 1080/10934529.2012.717809.
