Women Vs Men Comparison info

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ASK THE DOCTOR

By Chandra P. Belani, MD, and Suresh Ramalingam, MD

Q. Is lung cancer a common problem in women?

A. Lung cancer is the most common cause of cancer-related deaths in women. More than 70,000 women die from lung cancer each year in the United States. In fact, lung cancer kills more women than breast cancer. The incidence of lung cancer in women has increased rapidly and has outpaced the incidence in men over the past three decades. This change is likely related to the change in smoking practices among women because more women began smoking during this period.

Q. Are women affected by lung cancer differently than men?

A. The differences in lung cancer between men and women are being increasingly recognized in recent years, and some interesting information is beginning to emerge.

Women appear to be more susceptible to the carcinogenic effects of cigarette smoking. Compared with men, women who develop lung cancer tend to be younger and have smoked fewer cigarettes than men who develop the disease. The reasons behind the increased carcinogenic effect are not entirely clear. Studies have suggested that women are more prone to DNA damage caused by the carcinogens in tobacco.

There are also inherent differences in the biological behavior of lung cancer in women. Women with lung cancer have an overall better outcome than men do. They are generally more likely to experience tumor shrinkage when treated with standard therapies, and they survive longer than men.

In addition, there are differences between men and women in the overall side-effect profile of chemotherapy. Women have decreased DNA repair capacity, which may account not only for their increased susceptibility to lung cancer but also for the increased toxicity and the improved survival found when they are treated with platinum-based chemotherapy.

Q. What factors are responsible for the different behaviors of lung cancer in women?

A. It is not entirely clear why lung cancer behaves differently in women than men, but the answers to this question are beginning to emerge. The role of estrogen hormones is an important factor that has been studied only over the past few years.

Estrogen appears to promote the growth of lung cancer cells in the experimental setting. It also appears that tumors that overexpress estrogen receptors tend to have more-aggressive behavior and are associated with overall inferior survival. Based on these observations, clinical trials are evaluating the utility of blocking the estrogen receptor to treat lung cancer in women.

A small study conducted in postmenopausal women demonstrated the feasibility of this approach, with promising preliminary results, prompting a larger trial by the University of California at Los Angeles and at the University of Pittsburgh Cancer Institute to evaluate it further. If these studies validate the observed clinical and preclinical benefits with total estrogen blockade with or without other proven systemic therapies, individualized therapy for lung cancer based on gender would be the next step.

Q. Are there differences in the way lung cancer is treated in women compared with men?

A. Until recently, women with lung cancer were treated along similar lines as men. With the development of newer drugs, it appears that gender-related differences can be exploited to improve the outcome for women with lung cancer. For example, the epidermal growth factor receptor (EGFR) pathway is a proven therapeutic target for lung cancer. Women with lung cancer are more likely to harbor mutations in the EGFR tyrosine-kinase domain, which increases the likelihood of responding to drugs that block the EGFR pathway—such as Tarceva® (erlotinib) and Iressa® (gefitinib). Female gender and adenocarcinoma histology are the two important clinical characteristics that have clearly demonstrated a correlation with EGFR tyrosine-kinase inhibitor efficacy.

Another drug that appears to be suited for gender-specific therapy is polyglutamated paclitaxel (PPX). This novel formulation of paclitaxel is given intravenously and is metabolized to its active form, a step that is mediated by an enzyme called cathepsin B. It appears that estrogen hormone induces the expression of cathepsin B. Based on this, women would be more likely to have higher intracellular concentrations of the active paclitaxel when treated with PPX. Retrospective analysis of three large clinical trials that were completed recently suggests better outcomes in women treated with PPX when compared with men.

This exciting phenomenon is now being tested in a large randomized clinical trial for women with lung cancer. In this trial women with lung cancer are treated with PPX or paclitaxel. The study is open to both premenopausal and postmenopausal women who have a performance status of 2 (limited functional status). If proven effective, this will be the first test of gender-specific therapy for advanced non–small cell lung cancer.

Clearly, the cause and the biology of lung cancer are multifaceted and require an improved understanding of the interplay among gender, genetics, and environmental factors. With increased awareness of how all of these factors are related, researchers are continuing to examine how the application of targeted and individualized therapies can help patients today and what treatments will bring hope for the future.

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