Aromatase Levels Predict Survival in Women With Lung Cancer

Aromatase, which is an enzyme that naturally makes estrogen from another hormone called androgen, has been linked to more aggressive disease and lower survival rates in women over 65 with stage I or II lung cancer. This discovery not only gives physicians a possible new tool to predict survival but may also provide a target for therapy using aromatase inhibitors, already approved for the treatment of breast cancer.

Scientists from University of California in Los Angeles' (UCLA) Jonsson Cancer Center (Los Angeles, CA, USA) labs knew that estrogen played a role in lung cancer growth, much as it does in breast cancer. In animal models, they showed that either estrogen or aromatase triggered the growth of human lung cancer tumors. They then looked retrospectively at lung cancer tumor samples from more than 750 men and women seen at UCLA or the University of Texas M.D. Anderson Cancer Center (Houston, TX, USA) using a novel high-throughput technology called tissue microarray. Aromatase levels were measured and correlated with disease aggression and survival rates. In women 65 and over, higher aromatase levels were associated with more aggressive disease and a greater risk of death.

"All indications suggest that this is a very powerful prognostic marker that lets us predict which patients have a higher likelihood of prolonged survival versus death from lung cancer,” said the study's senior author, Dr. Lee Goodglick, an associate professor in the UCLA department of pathology and laboratory medicine (Los Angeles, CA, USA) and a Jonsson Cancer Center scientist. "If doctors know that a woman has a higher probability of longer-term survival, they may choose a more strategic course of action, compared to a woman with a more aggressive form of lung cancer, where doctors might choose a more aggressive course of therapy. Another notable finding from this study is that we are able to predict survival at a relatively early stage of the disease, when we have more treatment options.”

Dr. Goodglick reported that it is important to understand why aromatase levels work as predictors only in women and why they work best in those over 65. It does not appear to be related to menopause, because the average age of onset is about 51. Instead, it may be related to levels of another family of hormones, androgens, which steadily decrease in women over 65. Aromatases use certain androgens as starting material to make estrogen. The cancer may be devising ever-changing strategies to, in effect, feed itself so it can grow and spread more rapidly.

"We need to figure out all the strategies that a lung cancer cell uses to trigger and amplify the estrogen pathway,” Dr. Goodglick said. "In women over 65, one trick the cancer cells appear to use is increasing aromatase. It remains an interesting mystery what strategy the cancer cells are using in women under 65 and in men. Identifying which branch of the estrogen pathway is hijacked by cancer cells will allow us to specifically attack that branch on a person-by-person basis. I think this study is one important step in that direction.”

The next step for scientists will be to continue their work with an even larger patient population at multiple cancer centers nationwide. This will help determine the framework by which physicians might use this test effectively in the clinic. Defining the role that estrogen and the estrogen pathway play in lung cancer and devising ways to intervene at each step, tailored to a specific patient, will also be the goal, Dr. Goodglick noted.

"It remains an interesting mystery what strategy the cancer cells are using in women under 65 and in men. Identifying which branch of the estrogen pathway is hijacked by cancer cells will allow us to specifically attack that branch on a person-by-person basis. I think this study is one important step in that direction,” Dr. Goodglick added.


Related Links:
University of California in Los Angeles Jonsson Cancer Center
University of Texas' M.D. Anderson Cancer Center
UCLA Department of Pathology and Laboratory Medicine