Lung Cancer Rates in Women on the Rise - a Q & A with Patricia Thistlethwaite, first female program director of thoracic surgery in the nation
Historically, lung cancer has been viewed as a disease of men. Over the past 50 years, however, there has been a dramatic increase in the incidence of lung cancer in women – even as lung cancer rates in men have declined. Lung cancer is now the most common cause of cancer death in American women, accounting for more than one-quarter of all cancer deaths. In 2010, there were 105,770 new cases of lung cancer in women, with more than 71,080 deaths – more than breast, uterine and ovarian cancer deaths combined. 
The rise in female lung cancer incidence has long been attributed to more women using tobacco, but 20 percent of women who develop lung cancer have never smoked.  In the United States, 15 to 20 percent of lung cancers occur in people who have never smoked, but interestingly, 70 to 80 percent of “never-smokers” with lung cancer are women.
We asked Patricia Thistlethwaite, MD, PhD, a cardiothoracic surgeon at the University of California, San Diego and the first female program director of thoracic surgery in the nation, to shed more light on what the U.S. Surgeon General’s office has called a “contemporary epidemic.”
Q: Does anything explain the rise in cases of lung cancer in women, but not men?
A: Several factors may be contributing to the increased prevalence.
First, before 1940 few women in the United States smoked, but the integration of women into the workplace during World War II led to an increase in tobacco consumption. The prevalence of smoking in American women peaked in 1965 at 33 percent and remains at 22 percent today.  In contrast, more than half of American men smoked before 1965, but the prevalence has decreased to 23 percent today.  Thus, over time, there has been a more marked decrease in smoking in men compared to women. Second, there has been a significant increase in two types of lung cancer in women: bronchoalveolar carcinoma and adenocarcinoma, which has not been seen in the male population in this country. Both of these types of lung cancer occur in younger, non-smoking individuals, particularly women. The cause for the huge increase is not known and is being studied.
Third, there are important molecular differences in lung cancers that are suspected to be responsible for increased susceptibility in women. Women exhibit decreased DNA repair capability and increased mutations in specific cancer genes such as p53, epidermal growth factor receptor (EGFR), and K-ras. Mutations in these genes are found at a much higher frequency in adenocarcinomas, particularly in women.
Finally, one of the most obvious biologic differences between men and women is hormonal and related to estrogen, a recognized factor in the development of other types of cancer. The role of estrogen and synthetic estrogens in lung cancer in women is under investigation and somewhat controversial.  Estrogens have been shown to stimulate growth of lung cancer cells in tissue culture, yet clinical studies suggest that estrogen-progesterone supplementation probably promotes lung cancer rather than just estrogen alone.
Q: Are there significant biological differences in how lung cancer manifests itself in men and women? Or in how it is treated in women compared to men? A: We know that: 1) women are younger at the time of diagnosis of lung cancer than men; 2) the proportion of adenocarcinoma and bronchoalveolar carcinoma is higher in women than in men; and 3) women are less likely to have a smoking history.
Lung cancer presents in a similar way in men and women.  A typical presentation for lung cancer would be the development of a chronic cough that does not go away with antibiotic treatment and rest. Sometimes symptoms of lung cancer include coughing up blood, chest pain, and weight loss. Women tend to seek less medical treatment than men, so lung cancer may present at a more advanced stage in females than in males.
Lung cancer treatment is the same for men and women. Early stage disease is treated with surgery, while intermediate stage disease is treated with a combination of chemotherapy, radiation, and surgery. Advanced lung cancers are usually treated with chemotherapy alone.
There are ongoing clinical trials in San Diego hospitals, including the UC San Diego Moores Cancer Center, to study better ways to treat and cure lung cancer. These studies provide patients with a way to potentially benefit from state-of-the-art drugs and technologies, and to help the fight against lung cancer. Within the last several years, for example, a major advance in the field of lung cancer treatment has been the identification of specific genetic mutations, associated with lung cancers. These “molecular fingerprints” make each patient’s tumor unique.  Drugs that target mutations in EGFR, ALK, and EML4-ALK are being used now to treat patients with lung cancer, with good success.  The discovery of these mutations and the design of drugs to combat tumors harboring these mutations is the result of clinical trials funded both by the National Institutes of Health and private agencies.   
Q: Lung cancer is the leading cause of cancer death in the nation. It kills nearly twice as many women as breast cancer every year and three times as many men as prostate cancer. Yet, lung cancer receives measurably less research funding than either prostate or breast ($221 million in categorical funding from the National Institutes of Health in 2011 compared to $284 million for prostate and $715 million for breast). Why do you think that is?
A: Lung cancer has been tremendously underfunded compared to other types of cancer.  This is because lung cancer has traditionally been considered a “smoker’s disease.”  In other words, the patient is blamed for getting the disease.
With the awareness that lung cancer is increasing in women non-smokers, it is imperative that funding is made available to study the biology of lung cancer and to design effective cures.  The fact that lung cancer remains the number one cause of cancer death in both men and women the United States speaks for itself. 
During my lifetime, I have witnessed the dramatic decrease in deaths from many forms of cancer, particularly breast cancer.  This has been due, in part, to grass-roots efforts of individuals who have been affected by breast cancer, either directly or by knowing someone with the disease.  Awareness and advocacy leads to raising money for research, sharing a common goal to cure cancer, and a common voice to stimulate the National Institutes of Health to allocate funding for particular forms of lung cancer.  As a physician and surgeon who treats patients with lung cancer, I strongly believe that more funding for prevention and research is needed to combat this deadly disease.
Finally, gender-based differences in lung cancer make it imperative that both men and women are included in clinical trials and that gender stratification is used.  Better elucidation of female-male differences will suggest new avenues of research to benefit both men and women at risk for lung cancer.

Lung Cancer Rates in Women on the Rise - a Q & A with Patricia Thistlethwaite, first female program director of thoracic surgery in the nation

Historically, lung cancer has been viewed as a disease of men. Over the past 50 years, however, there has been a dramatic increase in the incidence of lung cancer in women – even as lung cancer rates in men have declined.
 
Lung cancer is now the most common cause of cancer death in American women, accounting for more than one-quarter of all cancer deaths. In 2010, there were 105,770 new cases of lung cancer in women, with more than 71,080 deaths – more than breast, uterine and ovarian cancer deaths combined. 

The rise in female lung cancer incidence has long been attributed to more women using tobacco, but 20 percent of women who develop lung cancer have never smoked.  In the United States, 15 to 20 percent of lung cancers occur in people who have never smoked, but interestingly, 70 to 80 percent of “never-smokers” with lung cancer are women.

We asked Patricia Thistlethwaite, MD, PhD, a cardiothoracic surgeon at the University of California, San Diego and the first female program director of thoracic surgery in the nation, to shed more light on what the U.S. Surgeon General’s office has called a “contemporary epidemic.”

Q: Does anything explain the rise in cases of lung cancer in women, but not men?

A: Several factors may be contributing to the increased prevalence.

First, before 1940 few women in the United States smoked, but the integration of women into the workplace during World War II led to an increase in tobacco consumption. The prevalence of smoking in American women peaked in 1965 at 33 percent and remains at 22 percent today.  In contrast, more than half of American men smoked before 1965, but the prevalence has decreased to 23 percent today.  Thus, over time, there has been a more marked decrease in smoking in men compared to women.
 
Second, there has been a significant increase in two types of lung cancer in women: bronchoalveolar carcinoma and adenocarcinoma, which has not been seen in the male population in this country. Both of these types of lung cancer occur in younger, non-smoking individuals, particularly women. The cause for the huge increase is not known and is being studied.

Third, there are important molecular differences in lung cancers that are suspected to be responsible for increased susceptibility in women. Women exhibit decreased DNA repair capability and increased mutations in specific cancer genes such as p53, epidermal growth factor receptor (EGFR), and K-ras. Mutations in these genes are found at a much higher frequency in adenocarcinomas, particularly in women.

Finally, one of the most obvious biologic differences between men and women is hormonal and related to estrogen, a recognized factor in the development of other types of cancer. The role of estrogen and synthetic estrogens in lung cancer in women is under investigation and somewhat controversial.  Estrogens have been shown to stimulate growth of lung cancer cells in tissue culture, yet clinical studies suggest that estrogen-progesterone supplementation probably promotes lung cancer rather than just estrogen alone.

Q: Are there significant biological differences in how lung cancer manifests itself in men and women? Or in how it is treated in women compared to men?
 
A: We know that: 1) women are younger at the time of diagnosis of lung cancer than men; 2) the proportion of adenocarcinoma and bronchoalveolar carcinoma is higher in women than in men; and 3) women are less likely to have a smoking history.

Lung cancer presents in a similar way in men and women.  A typical presentation for lung cancer would be the development of a chronic cough that does not go away with antibiotic treatment and rest. Sometimes symptoms of lung cancer include coughing up blood, chest pain, and weight loss. Women tend to seek less medical treatment than men, so lung cancer may present at a more advanced stage in females than in males.

Lung cancer treatment is the same for men and women. Early stage disease is treated with surgery, while intermediate stage disease is treated with a combination of chemotherapy, radiation, and surgery. Advanced lung cancers are usually treated with chemotherapy alone.

There are ongoing clinical trials in San Diego hospitals, including the UC San Diego Moores Cancer Center, to study better ways to treat and cure lung cancer. These studies provide patients with a way to potentially benefit from state-of-the-art drugs and technologies, and to help the fight against lung cancer. Within the last several years, for example, a major advance in the field of lung cancer treatment has been the identification of specific genetic mutations, associated with lung cancers. These “molecular fingerprints” make each patient’s tumor unique.  Drugs that target mutations in EGFR, ALK, and EML4-ALK are being used now to treat patients with lung cancer, with good success.  The discovery of these mutations and the design of drugs to combat tumors harboring these mutations is the result of clinical trials funded both by the National Institutes of Health and private agencies.   

Q: Lung cancer is the leading cause of cancer death in the nation. It kills nearly twice as many women as breast cancer every year and three times as many men as prostate cancer. Yet, lung cancer receives measurably less research funding than either prostate or breast ($221 million in categorical funding from the National Institutes of Health in 2011 compared to $284 million for prostate and $715 million for breast). Why do you think that is?

A: Lung cancer has been tremendously underfunded compared to other types of cancer.  This is because lung cancer has traditionally been considered a “smoker’s disease.”  In other words, the patient is blamed for getting the disease.

With the awareness that lung cancer is increasing in women non-smokers, it is imperative that funding is made available to study the biology of lung cancer and to design effective cures.  The fact that lung cancer remains the number one cause of cancer death in both men and women the United States speaks for itself. 

During my lifetime, I have witnessed the dramatic decrease in deaths from many forms of cancer, particularly breast cancer.  This has been due, in part, to grass-roots efforts of individuals who have been affected by breast cancer, either directly or by knowing someone with the disease.  Awareness and advocacy leads to raising money for research, sharing a common goal to cure cancer, and a common voice to stimulate the National Institutes of Health to allocate funding for particular forms of lung cancer.  As a physician and surgeon who treats patients with lung cancer, I strongly believe that more funding for prevention and research is needed to combat this deadly disease.

Finally, gender-based differences in lung cancer make it imperative that both men and women are included in clinical trials and that gender stratification is used.  Better elucidation of female-male differences will suggest new avenues of research to benefit both men and women at risk for lung cancer.

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