The Diverse Distribution of Risk Factors between Breast Cancer Subtypes of ER, PR and HER2: A 10-Year Retrospective Multi-Center Study in China

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Abstract

Introduction

Hormone receptors, human epidermal growth factor receptor 2 and some risk factors determine therapies and prognosis of breast cancer. The risk factors distributed differently between patients with receptors. This study aimed to investigate the distribution of risk factors between subtypes of breast cancer by the 3 receptors in Chinese native women with a large sample size.

Methods

The multi-center study analyzed 4211 patient medical records from 1999 to 2008 in 7 regions of China. Data on patients’ demographic information, risk factors (menopausal status, parity, body mass index) and receptor statuses were extracted. Breast cancer subtypes included ER (+/−), PR (+/−), HER2 (+/−), 4 ER/PR and 4 molecular subtypes. Wilcoxon and Chi-square tests were used to estimate the difference. The unconditional logistic regression model was used for analysis, and presented p-value after Bonferroni correction in the results.

Results

Compared to patients with negative progesterone receptor, the positive patients were younger at diagnosis, and reported less likely in postmenopausal status and lower parity ( p<0.05). Comparing with the subtype of ER+/PR+, ER+/PR− subtype were 4-year older at diagnosis (OR = 1.02), more likely to be postmenopausal (OR = 1.91) and more likely to have >1 parity (OR = 1.36) ( p<0.05); ER−/PR− subtype were more likely to be postmenopausal (OR = 1.33) and have >1 parity (OR = 1.19) ( p<0.05). In contrast to the luminal A subtype, triple negative subtype had a lower BMI (OR = 0.96) and ORs of overweight and obesity reduced by >20% ( p<0.05).

Conclusion

In this study, it was found that Chinese female patients did have statistically significant differences of age, menopausal status, parity and body mass index between breast cancer subtypes. Studies are warranted to further investigate the risk factors between subtypes, which was meaningful for prevention and treatment among Chinese females.

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Most cited references 18

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Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients

Lisa K Dunnwald, Mary Rossing, Christopher Li (2007)

Background Breast cancer patients with tumors that are estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive have lower risks of mortality after their diagnosis compared to women with ER- and/or PR-negative disease. However, few studies have evaluated variations in the risks of breast cancer-specific mortality across ER/PR status by either demographic or clinical characteristics. Methods Using data from 11 population-based cancer registries that participate in the SEER (Surveillance, Epidemiology, and End Results) program, 155,175 women at least 30 years old with a primary diagnosis of invasive breast carcinoma from 1990 to 2001 were included in the study. Associations between joint hormone receptor status and breast cancer mortality risk within categories of diagnosis age, diagnosis year, race/ethnicity, histologic tumor type, stage, grade, size, and axillary lymph node status were evaluated using the Cox proportional hazards model. Results Compared to ER+/PR+ cases, elevations in risk of mortality were observed across all subcategories of age at diagnosis, ranging from 1.2- to 1.5-fold differences for ER+/PR- cases, 1.5- to 2.1-fold differences for ER-/PR+ cases, and 2.1- to 2.6-fold differences for ER-/PR- cases. Greater differences were observed in analyses stratified by grade; among women with low-grade lesions, ER-/PR- patients had a 2.6-fold (95% confidence interval [CI] 1.7 to 3.9) to 3.1-fold (95% CI 2.8 to 3.4) increased risk of mortality compared to ER+/PR+ patients, but among women with high-grade lesions, they had a 2.1-fold (95% CI 1.9 to 2.2) to 2.3-fold (95% CI 1.8 to 2.8) increased risk. Conclusion Compared to women with ER+/PR+ tumors, women with ER+/PR-, ER-/PR+, or ER-/PR- tumors experienced higher risks of mortality, which were largely independent of the various demographic and clinical tumor characteristics assessed in this study. The higher relative mortality risks identified among ER-/PR- patients with small or low-grade tumors raise the question of whether there may be a beneficial role for adjuvant chemotherapy in this population.

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Etiology of hormone receptor-defined breast cancer: a systematic review of the literature.

Jennifer H Fergenbaum, Michelle Althuis, Louise Brinton … (2004)

Breast cancers classified by estrogen receptor (ER) and/or progesterone receptor (PR) expression have different clinical, pathologic, and molecular features. We examined existing evidence from the epidemiologic literature as to whether breast cancers stratified by hormone receptor status are also etiologically distinct diseases. Despite limited statistical power and nonstandardized receptor assays, in aggregate, the critically evaluated studies (n = 31) suggest that the etiology of hormone receptor-defined breast cancers may be heterogeneous. Reproduction-related exposures tended to be associated with increased risk of ER-positive but not ER-negative tumors. Nulliparity and delayed childbearing were more consistently associated with increased cancer risk for ER-positive than ER-negative tumors, and early menarche was more consistently associated with ER-positive/PR-positive than ER-negative/PR-negative tumors. Postmenopausal obesity was also more consistently associated with increased risk of hormone receptor-positive than hormone receptor-negative tumors, possibly reflecting increased estrogen synthesis in adipose stores and greater bioavailability. Published data are insufficient to suggest that exogenous estrogen use (oral contraceptives or hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks associated with breast-feeding, alcohol consumption, cigarette smoking, family history of breast cancer, or premenopausal obesity did not differ by receptor status. Large population-based studies of determinants of hormone receptor-defined breast cancers defined using state-of-the-art quantitative immunostaining methods are needed to clarify the role of ER/PR expression in breast cancer etiology.

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A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

Jing-Jing Li, Bao-Ning Zhang, Jin-Hu Fan … (2011)

Background According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer. Methods This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study. Results Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)). Conclusions The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.

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Author and article information

Contributors

Qing-Yi Wei: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 20 August 2013

Volume: 8

Issue: 8

Electronic Location Identifier: e72175

Affiliations

[1 ]Departments of Epidemiology, Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

[2 ]Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, China

[3 ]Department of Breast Surgery, Liaoning Cancer Hospital, Shenyang, China

[4 ]Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, China

[5 ]Department of Breast-thyroid Surgery, Xiangya Second Hospital, Central South University, Changsha, China

[6 ]Department of Oncosurgery, The First Affiliated Hospital of Medical College, Xi’an JiaoTong University, Xi’an, China

[7 ]Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Gungzhou, China

[8 ]Department of Breast Surgery, The Second People’s Hospital of Sichuan Province, Chengdu, China

The University of Texas MD Anderson Cancer Center, United States of America

Author notes

* E-mail: qiaoy@ 123456cicams.ac.cn

Competing Interests: The study was funded by Pfizer and had nothing to declare relating to employment,consultancy, patents, products in development or marketed products.This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Analyzed the data: QKS RH SZ YLQ. Contributed reagents/materials/analysis tools: JL RH JHF BZ HJY ZHT JJH XMX HL JYL YLQ. Wrote the paper: QKS RH. Collected the data: JL RH JHF BZ HJY ZHT JJH XMX HL JYL.

Article

Publisher ID: PONE-D-13-03232

DOI: 10.1371/journal.pone.0072175

PMC ID: 3748061

PubMed ID: 23977244

SO-VID: cbb56a06-4bcc-45d2-98c8-98397d785ac3

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 16 January 2013

Date accepted : 10 July 2013

Page count

Pages: 7

Funding

The study was funded by Pfizer ( www.pfizer.com). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The Diverse Distribution of Risk Factors between Breast Cancer Subtypes of ER, PR and HER2: A 10-Year Retrospective Multi-Center Study in China

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Abstract

Introduction

Methods

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Conclusion

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PLOS Climate

Most cited references 18

Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients

Etiology of hormone receptor-defined breast cancer: a systematic review of the literature.

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

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