Elsevier

Lung Cancer

Volume 76, Issue 3, June 2012, Pages 280-285
Lung Cancer

Characteristics of lung cancer in women: Importance of hormonal and growth factors

https://doi.org/10.1016/j.lungcan.2011.11.023Get rights and content

Abstract

Based on epidemiological, clinical, and preclinical data, lung carcinogenesis can be distinctive in women, suggesting that women should be treated differently depending on the expression of various specific biomarkers. We aimed to describe the hormonal and genetic profile of lung cancer in both men and women to identify gender specificities. Primary lung-tumor tissues from surgically treated patients, (50 men, 50 women) were analyzed and compared for expression of estrogen receptors (ER) α and β, progesterone receptors (PR), epidermal growth-factor receptor (EGFR), and HER2 (for EGFR and K-Ras mutations). These data were combined with clinical and outcome data. Fewer women with lung cancer were smokers (p = 0.001) and they smoked fewer cigarettes (p = 0.001). We observed a higher rate of EGFR mutations (p = 0.02) and ERα expression (p = 0.006) in women. ERβ and EGFR were also expressed more frequently in women (p = 0.29 and p = 0.16). HER2 was overexpressed regardless of gender in three men and two women. K-Ras was mutated in 16% of both men and women. Interestingly, there was a positive link between EGFR expression and expression of ERα (p = 0.028) and ERβ (p = 0.047) in both men and women. Expression of ERα was associated with improved disease-free survival (p = 0.007). Our findings provide further evidence on the specificities of lung cancer in women. The differential expression of specific biomarkers, which could be targeted by therapy, favors the development of gender-based treatment guided by biomarker expression.

Introduction

The incidence of lung cancer is increasing dramatically in women. It is now the leading cause of death from cancer among women in the USA and is the second cause in Europe [1]. Many studies have reported gender differences in clinical presentation and the biology of lung cancer, suggesting that lung cancer in women should be considered a specific entity [2]. In particular, its epidemiology is different in women, with tobacco explaining only 70% of its incidence. The prevalence of adenocarcinoma in women has also been demonstrated. Moreover, both prognosis and response to treatment appear to be different compared to men. In line with these findings, lung carcinogenesis is, at least in part, distinct in women [3].

Two main mechanisms have emerged from recent findings in the field of lung carcinogenesis in women: the increased involvement of genetic alterations, such as EGFR (epidermal growth-factor) mutations [4], [5], and the potential impact of hormonal factors [6]. EGFR appears to be more frequently mutated in women than in men, leading to a better response rate to EGFR tyrosine-kinase-inhibitor (EGFR-TKI) therapy. A recent study reported that, among a population of 217 patients positive for the EGFR mutation, 72.8% were women and that erlotinib was associated with improved progression-free survival (PFS) and overall survival (OS) [7]. Many recent epidemiological and clinical studies have also provided evidence of a role for estrogens in the genesis and progression of lung cancer, especially non-small-cell lung tumors [6], [8]. Many hormonal receptors, such as ERα, ERβ (estrogen receptors α and β) and PR (progesterone receptors) have been isolated in lung-cancer tissues. ERs have been shown to be involved in the onset of lung cancer in cells and animal models [9]. Lastly, the interaction of ERs with growth-factor-receptor signaling is an emerging area of investigation. Estrogen can directly stimulate the transcription of estrogen-responsive genes and can also transactivate growth-factor-signaling pathways, such as the EGFR pathway [10]. A direct correlation between both pathways has been suggested by two recent studies [11], [12].

We hypothesize that improved knowledge of lung cancer in women will permit identification of specific genetic alterations or hormonal profiles that may serve as new therapeutic targets. Most of the studies focusing on this population, report isolated data concerning either epidemiological, radiological or mono-markers characteristics. We thus aim in our study to analyze a homogenous population of surgically treated lung cancer patients and to compare the immuno-histochemical expression of hormonal receptors and growth factors, and the status of EGFR and K-Ras mutations, to define specific profiles and to pave the way for gender-based targeted.

Section snippets

Patients and tissues

Patients underwent surgery at the Thoracic Oncology Department (Toulouse University Hospital, France) and samples were analyzed in the Pathology Department. Diagnoses were assessed by a lung-cancer pathologist by applying the latest WHO classification [13], and the clinicopathological stage was assigned according to the tumor-node-metastasis classification [14]. Patients were treated and followed-up at our Institution to ensure collection of clinical data. All patients signed an informed

Clinico-pathological characteristics of lung cancer in women

We did not found any significant differences between men and women regarding age, tumor-stage, or surgical procedure. In contrast, we found a significantly higher rate of non-smokers in women with lung cancer compared to men (30% vs. 0%, p < 0.001) and less tobacco consumption (30 vs. 40 pack-year, p = 0.0004). A majority of women were menopausal. Only a minority of women were receiving hormonal treatment at the time of diagnosis, so we were not able to examine the impact of contraceptive or

Discussion

The purpose of this study was to establish a profile of molecular markers (EGFR and K-Ras gene mutations, hormonal receptors, EGFR and HER2 protein expression) in specimens obtained from surgically treated non-small-cell lung-cancer (NSCLC) patients and to identify specificities of lung cancer in women.

We first looked at the clinico-pathological characteristics of lung cancer and found that less women with lung cancer smoked. This finding is in agreement with published data [16], [20], [21] and

Conflict of interest statement

None.

Acknowledgement

The authors acknowledge “La Ligue Régionale Contre le Cancer” for supporting the study.

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