Lung Cancer in Women
Lung Cancer in Women
Excluding nonmelanoma cutaneous malignancies, LC is the most common cancer worldwide and the most common cause of cancer-related death in women in the United States, killing >430,000 women globally in 2008. The American Cancer Society estimated that physicians diagnosed approximately 109,000 new cases, and that >72,000 deaths occurred from cancers of the lung and bronchus in American women during 2012, despite the fact that mortality has declined marginally in this population. Non-Hispanic white women have slightly higher incidences and mortality rates, whereas these are significantly lower in Native American, Hispanic, and Asian or Pacific Islander women. Among African American women, incidence parallels that of the entire female LC population, and the mortality rate is just below the overall LC population rate.
Cigarette smoking clearly remains the most significant risk factor for the development of LC among women, with 85% to 90% of all cases in American women related to tobacco use. Although women are still generally considered to have a lower risk of developing the disease than men, this view is evolving as the incidence of LC continued to increase during the past two decades in women but not increasing in men. It is uncertain whether this trend is a result of the number of cigarettes smoked, the types of cigarettes smoked, or the age of smoking initiation. One meta-analysis of 48 studies demonstrated a steeper dose-response curve for intensity of smoking among women than among men, suggesting that the narrowing gap in LC incidence between men and women may indeed be the result of a trend among women smokers during the last half of the 20th century to consume more cigarettes. Prospective cohorts have not confirmed this finding.
What has garnered even more attention with regard to sex is the incidence among never smokers who have demonstrated an increased response to molecularly targeted therapy. Although Thun et al found no sex differences in their pooled analysis of data from eight large cohort studies of never smokers, a review by Sun and colleagues revealed that never smokers comprise 6% of LC cases in men but 15% of cases in women. Wakelee et al identified age-adjusted incidence rates of 14.4 to 20.8/100,000 person-years in women compared to 4.8 to 13.7/100,000 person-years in men. Whether these differences are the result of a greater genetic predisposition among women in general has not been firmly established, although evidence for the presence of genetic polymorphisms that make women more susceptible to LC has been published. Factors associated with an increased risk of LC in never-smoking women are well described (Table 1) and these findings affect treatment decisions.
Closely tied to never-smoking status, both with regard to LC incidence and treatment, is tumor cell type. Smoking history associates with all cell types, but to a greater degree with both squamous cell and small cell LC than with adenocarcinoma. Although adenocarcinoma has long been the most common cell type among women and among all adults who have never smoked (women having a greater risk than men among never smokers), during the past 2 decades it has also overtaken squamous cell as the most common cell type of all pulmonary malignancies. This pattern change in histology of tumors has been attributed by some to the advent of filtered cigarettes, but there is no substantiated evidence to suggest that this change has had a differential bearing on disease incidence in women versus men. Rather, the incidence of adenocarcinoma has risen in both sexes. This has created an even greater difference than was present 4 decades ago between adenocarcinoma and squamous cell or small cell LC in women. Differences in cell type drive present treatment strategies.
Another potential LC risk factor specific to women and far more heavily studied in breast and gynecologic tumors is HT. The evidence is equivocal to initial data suggesting that HT conferred a 2.5-fold increased risk of pulmonary adenocarcinoma on female smokers. In addition, data demonstrate associations between HT and both younger age at LC diagnosis and decreased median survival among victims. Contrasting this are epidemiological studies suggesting that HT may protect against lung malignancies, as well as a large British cohort study failing to demonstrate an association between HT and LC. Data are insufficient to comment upon the advisability of HT when considering LC risk.
Lung tumors also have been examined for the presence of human papillomavirus (HPV), particularly subtypes 16 and 18, which are highly prevalent in cervical cancer specimens. The presence of HPV has ranged widely, from 0% to 80%, implying that more investigation with reliable methodology is necessary. As in head and neck cancer, there is evidence to suggest that the presence of HPV 16 and HPV 18 may predict improved treatment outcomes.
Epidemiology
Excluding nonmelanoma cutaneous malignancies, LC is the most common cancer worldwide and the most common cause of cancer-related death in women in the United States, killing >430,000 women globally in 2008. The American Cancer Society estimated that physicians diagnosed approximately 109,000 new cases, and that >72,000 deaths occurred from cancers of the lung and bronchus in American women during 2012, despite the fact that mortality has declined marginally in this population. Non-Hispanic white women have slightly higher incidences and mortality rates, whereas these are significantly lower in Native American, Hispanic, and Asian or Pacific Islander women. Among African American women, incidence parallels that of the entire female LC population, and the mortality rate is just below the overall LC population rate.
Cigarette smoking clearly remains the most significant risk factor for the development of LC among women, with 85% to 90% of all cases in American women related to tobacco use. Although women are still generally considered to have a lower risk of developing the disease than men, this view is evolving as the incidence of LC continued to increase during the past two decades in women but not increasing in men. It is uncertain whether this trend is a result of the number of cigarettes smoked, the types of cigarettes smoked, or the age of smoking initiation. One meta-analysis of 48 studies demonstrated a steeper dose-response curve for intensity of smoking among women than among men, suggesting that the narrowing gap in LC incidence between men and women may indeed be the result of a trend among women smokers during the last half of the 20th century to consume more cigarettes. Prospective cohorts have not confirmed this finding.
What has garnered even more attention with regard to sex is the incidence among never smokers who have demonstrated an increased response to molecularly targeted therapy. Although Thun et al found no sex differences in their pooled analysis of data from eight large cohort studies of never smokers, a review by Sun and colleagues revealed that never smokers comprise 6% of LC cases in men but 15% of cases in women. Wakelee et al identified age-adjusted incidence rates of 14.4 to 20.8/100,000 person-years in women compared to 4.8 to 13.7/100,000 person-years in men. Whether these differences are the result of a greater genetic predisposition among women in general has not been firmly established, although evidence for the presence of genetic polymorphisms that make women more susceptible to LC has been published. Factors associated with an increased risk of LC in never-smoking women are well described (Table 1) and these findings affect treatment decisions.
Closely tied to never-smoking status, both with regard to LC incidence and treatment, is tumor cell type. Smoking history associates with all cell types, but to a greater degree with both squamous cell and small cell LC than with adenocarcinoma. Although adenocarcinoma has long been the most common cell type among women and among all adults who have never smoked (women having a greater risk than men among never smokers), during the past 2 decades it has also overtaken squamous cell as the most common cell type of all pulmonary malignancies. This pattern change in histology of tumors has been attributed by some to the advent of filtered cigarettes, but there is no substantiated evidence to suggest that this change has had a differential bearing on disease incidence in women versus men. Rather, the incidence of adenocarcinoma has risen in both sexes. This has created an even greater difference than was present 4 decades ago between adenocarcinoma and squamous cell or small cell LC in women. Differences in cell type drive present treatment strategies.
Another potential LC risk factor specific to women and far more heavily studied in breast and gynecologic tumors is HT. The evidence is equivocal to initial data suggesting that HT conferred a 2.5-fold increased risk of pulmonary adenocarcinoma on female smokers. In addition, data demonstrate associations between HT and both younger age at LC diagnosis and decreased median survival among victims. Contrasting this are epidemiological studies suggesting that HT may protect against lung malignancies, as well as a large British cohort study failing to demonstrate an association between HT and LC. Data are insufficient to comment upon the advisability of HT when considering LC risk.
Lung tumors also have been examined for the presence of human papillomavirus (HPV), particularly subtypes 16 and 18, which are highly prevalent in cervical cancer specimens. The presence of HPV has ranged widely, from 0% to 80%, implying that more investigation with reliable methodology is necessary. As in head and neck cancer, there is evidence to suggest that the presence of HPV 16 and HPV 18 may predict improved treatment outcomes.
