By Susan Dudley, PhD, Renee Y. Carter, MD, Tiffanie Hammond, and Amrita Ford, MA
Risk Factors for Lung Cancer
Non-Smokers and the Possible Role of Estrogen
Surviving Lung Cancer
Racial and Ethnic Differences in Lung Cancer
Symptoms of Lung Cancer
Lung Cancer Detection and Treatment
Advances in Treatment but They are High-Cost and Only for Some Patients
Funding for Lung Cancer Research
Lung cancer is the #1 cause of cancer death among women in the United States. Lung cancer used to be thought of as a man’s disease, but women now account for almost half of new cases and deaths from lung cancer. In 2014, 48% of the almost 216,000 people diagnosed with lung cancer were women, and 45% of the 155,526 who died from lung cancer were women.1
Lung cancer deaths in women began quickly rising in 1960, and by 1987, the number of female deaths from lung cancer exceeded the number of deaths from breast cancer. Today the number of deaths in women from lung cancer surpasses those from all gynecological cancers combined.2 While the rate of lung cancer deaths among men has been steadily decreasing since the 1990s, the lung cancer death rate among women did not start to go down until a decade later (2003-2007).3 The decline of lung cancer deaths among women, however, may not be as rapid as it has been in men: women born around 1960 with a high rate of smoking are just now entering the age when lung cancer diagnosis is most common.
Everyone knows that smoking is the leading cause of lung cancer. It is responsible for 90% of lung cancer deaths in men and 80% in women. Beginning in the 1940’s during World War II, smoking became more acceptable for American women.4 As more women began to smoke, the number of deaths from lung cancer increased very dramatically among women — by more than 600% between 1950 and 1997. When a woman stops smoking, her risk of developing lung cancer decreases, but not as much as many women may think. Twenty years after stopping, the risk of developing lung cancer drops only by half. In addition, exposure to second-hand smoke at home, work, or other environments—including childhood exposures—can cause lung cancer in women who have never smoked themselves.5
Although smoking increases the risk of lung cancer dramatically, 1 in 5 women diagnosed with lung cancer have never smoked, whereas among men who develop lung cancer, only 1 in 12 have never smoked.46 Of all the types of lung cancer, women are more likely to develop adenocarcinoma, a type of non-small cell lung cancer (NSCLC), which is also the type of lung cancer more commonly found in non-smokers.
It is unclear why non-smoking women are at greater risk for developing lung cancer than non-smoking men. Studies indicate that biological and genetic differences between men and women play a role in susceptibility to lung cancer and the risk of dying from it. Some research shows that estrogen, a hormone found in both men and women but much higher in women, may help certain lung cancer cells to grow and spread throughout the lungs. For example, a 2009 study based on the Women’s Health Initiative showed that post-menopausal women who took estrogen and progesterone combined hormone therapy had an increased risk of dying from lung cancer, regardless of whether they had never smoked, stopped smoking, or were currently smoking (although current and former smokers were at the highest risk for death).7 A 2010 study indicated that post-menopausal women who took hormone therapy for more than 10 years were at an increased risk of developing lungcancer.8 In 2011, a study showed that women who take estrogen-blocking medication like tamoxifen to prevent a recurrence of breast cancer also reduce their risk of dying from lung cancer.9 For both the 2010 and 2011 studies, the link between hormones and lung cancer were maintained regardless of the person’s smoking status. For more information about hormone therapy and lung cancer, read Lung Cancer and Hormone Therapy: Bad News for Former and Current Smokers.
Women are nearly as likely as men to be diagnosed with lung cancer, but on a more positive note, they tend to survive longer than men with the disease. Women generally live longer than men at every stage of lung cancer, regardless of when they were diagnosed, the type of lung cancer they had, or how they were treated.1011 Studies have shown that women with non-small cell lung cancer (NSCLC) have a greater 5-year survival following partial removal of the lung (resection) than men.121314 Women with NSCLC who are treated with chemotherapy prior to removal of the tumor also have better survival rates than men.15 Furthermore, women with advanced lung cancer of any type who undergo chemotherapy survive longer than their male counterparts.16
Why do women with lung cancer live longer than men? No one is really certain. One reason may be that women tend to notice symptoms and go to the doctor earlier than men, allowing the disease to be caught at an earlier stage when the cancer is local (still in the lung) and can be completely removed.17 However, even when researchers control for this and other differences between men and women, women still live longer following surgery.13 For both women and men with lung cancer, complete removal of an entire lobe of the lung (lobectomy) results in higher survival rates than only partial removal of the lung. Younger patients and patients with smaller tumors are more likely to survive lung cancer than those who are older or have larger tumors, regardless of sex.14
The incidence of lung cancer among African American women is about the same as white women yet smoking rates among African American women are lower.18 In 2007, about 16% of African American women smoked, while the rate for white women was about 20%.19 Similarly, African-American men smoke less than white men yet have higher rates of lung cancer. Is there a genetic difference that places African Americans at higher risk? Or are African-Americans exposed to other lung cancer causing bacteria and chemicals that increase their risk?
No one knows the answer yet but there are several explanations for why African Americans—men and women—are more likely to die from lung cancer than white men and women. Even African American women who have never smoked have higher death rates from lung cancer than white women who have never smoked.20 Most experts believe African Americans with lung cancer don’t live as long because they don’t have the same access to health care. For instance, they are less likely to have insurance coverage which could impact diagnosis and treatment options.21 They are less likely to receive timely care and may not receive the most effective treatment for their type of lung cancer.22 One study found that African American patients underwent partial surgical removal of the lung less frequently than white patients. 23 Other factors that may contribute to the lower survival rates of African American lung cancer patients include differences in lung function,20 provider biases,24 inadequate physician-patient communication,25 distrust of physicians and the health care system,26 and a greater likelihood of refusing surgery.27 For more on African Americans and lung cancer, read here.
After African American and white women, native Hawaiian women have the highest incidence of lung cancer, while Hispanic and Japanese women have the lowest rates.20 Unlike other racial and ethnic groups where the incidence of lung cancer in women has increased over time, rates have actually declined among Hispanic women (who are more likely to be non-smokers than African Americans, whites or native Hawaiians): they decreased by 1.5% every year from 1994 to 2003.28 Despite the decline of lung cancer in both men and women, lung cancer remains the leading cause of cancer death among Hispanic men and the second leading cause of cancer death among Hispanic women.
The most commonly recognized symptoms of lung cancer include:
- persistent cough, coughing that wakes you up at night, and/or coughing up blood
- wheezing and/or shortness of breath
- chest pain
- swelling of the face and neck
- loss of appetite and/or unexplained weight loss
- unusual tiredness
- recurring pneumonia or bronchitis
While survival rates for many cancers have improved substantially over the last 30 years, little progress has been made in the survival rate for lung cancer. For example, between 1974 and 2007, the 5-year survival rate for breast cancer increased from 75% to 89% and the 5-year survival rate for prostate cancer increased from 67% to 99%. In contrast, the 5-year survival rate for lung cancer increased from 13% to just under 16% during the same time period.
What would be needed in order for the survival rates for lung cancer patients to parallel that of breast, prostate or cervical cancers? The main problem is that by the time most women are diagnosed with lung cancer, it has already spread to other organs, making a cure extremely unlikely. Pap smears and colonoscopies, for instance, make it possible to diagnose and remove pre-cancerous cells on the cervix or polyps in the colon before they can develop into cervical cancer or colon cancer or spread elsewhere in the body. And while better survival rates for women with breast cancer are mostly attributed to improvements in treatment, mammogram screenings have helped some women by detecting their breast cancer at earlier stages than before, when surgery, radiation, or chemotherapy have an even better chance of eliminating the disease. Earlier diagnosis and more effective treatments, therefore, will be necessary to improve the survival rate of lung cancer.
The National Lung Screening Trial, which started in 2002, evaluated the use of chest x-rays and low-dose computed tomography (low-dose CT scans) for early detection of lung cancer in men and women who were heavy smokers. Each randomized group was screened annually for 3 years. Researchers found that using low-dose CT scans reduced lung cancer deaths by 20% in the high-risk population. Compared to standard x-rays, CT scans may be more effective in detecting nodules and tumors. Based on a 2011 report of the trial, low-dose CT screening could potentially increase the 5-year lung cancer survival rate to 70% if it allowed lung cancer to be detected in its earliest stage (stage 1A), when the tumor is still relatively small, still in the lung, and can be removed easily through surgery.29303132
Although no U.S. public health agency has recommended screening for lung cancer, in January 2013 the American Cancer Society (ACS) did so for the first time, saying that annual screening with low dose CT scans “could save many lives.”33 ACS has recommended that people at highest risk for lung cancer, as defined by the National Lung Cancer Trial, have a discussion with their doctor about the benefits and risks of annual screening. They advised doctors to have this conversation only with patients who match the profile of the people who were enrolled in the National Lung Cancer Screening Trial: current and former smokers who are 55 to 74 years old and have a 30-pack-year history of smoking (20 cigarettes a day for 30 years, 40 cigarettes a day for 15 years, and so on. To calculate your pack years, visit http://smokingpackyears.com/). If the patients are former smokers, they should have quit within the last 15 years. Doctors should discuss screening with patients only if low dose CT scans and high quality treatment are available in their area, and only if the patient seems healthy and able to undergo treatment in the event that cancer is found. For all other patients, “there is too much uncertainty regarding the balance of benefits and harms …”
Three other organizations have issued their own slightly different guidelines. The National Comprehensive Cancer Network has two definitions of high risk: the one used by the American Cancer Society and one that includes people as young as 50 and as old as 79 with only a 20-pack-year history—provided they have one other risk factor for lung cancer such as a family history, Chronic Obstructive Pulmonary Disease (COPD), or exposure to radon. Given the close link between COPD and lung cancer, the Network’s screening criteria could potentially find more cases of lung cancer than the 30-pack criteria. (For more info on COPD, see Chronic Obstructive Pulmonary Disease and Lung Cancer.) The American College of Chest Physicians and the American Society of Clinical Oncology also have guidelines. Only time will tell which guidelines work best, but any of these guidelines make it more likely that insurance companies will pay for screening. As a result of the National Lung Cancer Screening Trial, the U.S. Department of Veterans Affairs is starting to implement a screening program using CT scans for veterans at high risk. However, most government health programs, such as Medicare and Medicaid, do not usually reimburse for lung cancer screening and might not do so until a public health agency has issued guidelines.
Unfortunately, CT scans are not a great solution for finding and diagnosing lung cancer in people who don’t have symptoms and aren’t at high risk. Low-dose CT scans have been shown to produce a high percentage of false positive results (people who the scan says have an abnormality when they don’t have cancer), which can lead to unnecessary lung biopsies. Since lung biopsies can be harmful, low-dose CT as a screening method isn’t useful for the general population. This is unfortunate because women who didn’t smoke are at higher risk than men who didn’t smoke, as are men and women exposed to years of second-hand smoke, but no screening has been found to be appropriate for them. For more information about screening, read Lung Cancer: Who Is at Risk and Can They be Screened?
Historically, lung cancer treatments have not been very effective. For instance, erlotinib (trade name Tarceva), which is taken as a pill, extends survival in patients with non-small cell lung cancer by only about 2 months on average and costs anywhere from $2,000 to $5,000 a month.343536 Patients usually take Tarceva after having already undergone chemotherapy, and many use it as a maintenance therapy to prevent further cancer progression and to shrink tumors that are already present. Patients stay on Tarceva for as long as it appears to be having an effect (developing a rash is considered a good sign) and scans show that the cancer is stable. Not only is Tarceva expensive but it doesn’t benefit everyone with lung cancer: it works best in patients who have never smoked or who have a specific gene mutation (EGFR mutation).36[37 Tarceva acts by inactivating the signal in the mutated EGFR gene that makes lung cancer grow.
New targeted treatments that interfere with specific molecules involved in tumor growth and progression and which promote cancer cell death are showing promise in the fight against lung cancer. In August of 2011, the Food and Drug Administration fast-tracked approval for crizotinib (trade name Xalkori) for use in a small subset of lung cancer patients with late-stage, non-small cell lung cancer (NSCLC) who express a rearrangement of the anaplastic lymphoma kinase (ALK) gene. Rearrangement of this gene leads to cancer growth and occurs in 1-7% of NSCLC patients. Xalkori was approved with an accompanying diagnostic test to determine if a patient has the abnormal ALKgene rearrangement.38 Based on an October 2011 study published in Lancet Oncology, the overall survival rate for Xalkori after 1 and 2 years was 74% and 54%, respectively. The recommended dose for Xalkori is 250mg twice daily and the drug costs about $9,600 per month or about $115,000 a year.39 Targeted treatments tend to be very expensive because they are usually taken by a very small number of patients who have limited treatment choices.
Far too many women and men are dying of lung cancer every year. Could an increase in research funding result in better screening, earlier diagnosis, more effective treatments, longer survival, and overall lower mortality for patients diagnosed with lung cancer? We believe the answer is “yes.”
The National Cancer Institute is the major source of cancer research funding in the U.S. Comparisons of NCI funding for various types of cancer in 2010 are shown below and clearly show that lung cancer research is under-funded in proportion to how deadly it is for so many people.140 Between 2003 and 2007, NCI funding for lung cancer actually decreased while funding for breast cancer increased.41 The same inequities are seen in funding for prevention. In the Centers for Disease Control and Prevention (CDC) 2008 budget, about $201M was allocated for breast cancer while $104M was allocated for smoking cessation programs (and not lung cancer specifically).42
Total NCI Funding (in millions)
New Cases Diagnosed
Funding per New Case
Funding per Patient Death
Many researchers and advocates point to the stigma associated with lung cancer as a reason for why the disease is under-funded.43 Since smoking is associated with the majority of lung cancer cases, many people believe lung cancer patients are responsible for their health problems and therefore not deserving of the same sympathy and research investments that patients of other deadly diseases receive. This attitude may also extend to clinicians who care for lung cancer patients. One study found that physicians were less likely to send their lung cancer patients with advanced stages of the disease to an oncologist than their breast cancer patients.44 Breast cancer patients were also more likely to be referred for further therapy where lung cancer patients were referred for only symptom control. We know now that more complex factors other than cigarette smoking contribute to lung cancer and the lack of funding over the years has hindered researchers from fully understanding why and how this disease progresses in different populations.
So how can we persuade the federal government to fund more lung cancer research? Some think legislation is needed.
In 2008, Congress approved the Peer Reviewed Lung Cancer Research Program which was the first time in history that federal funding was allocated specifically for the study of lung cancer. However, the program is funded by the Department of Defense to study early detection and disease management specifically in military men and women at high risk for lung cancer.
The Lung Cancer Mortality Reduction Act of 2011 is a bipartisan bill currently in Congress which aims to reduce lung cancer mortality by 50% by 2020.45 The bill, first introduced in 2008, calls on the cooperation of the Department of Health and Human Services, Department of Defense, and Veterans Affairs to meet that goal and develop a coordinated plan that addresses the prevention, early detection, and treatment of lung cancer. It would require the National Cancer Institute to review and prioritize research grants related to lung cancer, the Food and Drug Administration to establish quality standards and guidelines for facilities that conduct computed tomography screening for lung cancer, and the Centers for Disease Control and Prevention to establish a Lung Cancer Early Detection Program which would provide low-income, uninsured, and underserved populations at high risk for lung cancer with access to early detection services. For more information and to support this important legislation in the fight against lung cancer, visit http://www.opencongress.org/bill/112-h1394/show.
- U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999-2014 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2017. Available at: www.cdc.gov/uscs. ▲
- Egleston BL, Meireles SI, Flieder DB, Clapper ML. Population-based trends in lung cancer incidence in women. Semin Oncol. 2009;36(6):506-515. ▲
- Kohler BA, et al. Report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. JNCI. 2011. ▲
- Baldini EH, Strauss GM. Women and lung cancer: waiting to exhale. Chest. 1997;112(4):229S-234S. ▲
- Lung Cancer Risk Factors. Centers for Disease Control and Prevention Website. Available at: http://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm. Accessed March 1, 2012. ▲
- Smoking. The National Cancer Institute Website. Available at: http://www.cancer.gov/cancertopics/tobacco/smoking. Accessed February 23, 2012. ▲
- Chlebowski RT, et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374(9697):1243-1251. ▲
- Slatore CG, et al. Lung cancer and hormone replacement therapy: association in the vitamins and lifestyle study. J Clin Oncol. 2010;28(9):1540-1546. ▲
- Bouchardy C, et al. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. 2011;117(6):1288-1295. ▲
- Moore R, Doherty D, Chamberlain R, Khuri F. Sex differences in survival in non-small cell lung cancer patients 1974-1998. Acta Oncol. 2004;43(1):57-64. ▲
- Visbal AL, Williams BA, Nichols FC, et al. Gender differences in non-small-cell lung cancer survival: an analysis of 4,618 patients diagnosed between 1997 and 2002. Ann Thorac Surg. 2004 Jul;78(1):209-15. ▲
- Chang M, Mentzer S, Colson Y, et al. Factors predicting poor survival after resection of stage IA non–small cell lung cancer. J Thorac Cardiovacs Surg. 2007 Oct;134(4):850-6 ▲
- Alexiou C, Onyeaka CV, Beggs D, et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg. 2002 Feb;21(2):319-25. ▲
- Agarwal M, Brahmanday G, Chmielewski GW, Welsh RJ, Ravikrishnan KP. Age, tumor size, type of surgery, and gender predict survival in early stage (stage I and II) non-small cell lung cancer after surgical resection. Lung Cancer. 2009 Sept 15. ▲
- Goldberg S, Mulshine J, Hagstrom D, et al. An actuarial approach to comparing early stage and late stage lung cancer mortality and survival. Popul Health Manag. 2010 Feb:13(1)133-46. ▲
- Berardi R, Verdecchia L, Paolo M, et al. Women and lung cancer: clinical and molecular profiling as a determinate for treatment decisions: a literature review. Crit Rev Oncol Hematol. 2009 Mar;69(3):223-26. ▲
- Cerfoli RJ, Bryant AS, Scott E, et al. Women with pathologic state I, II, and III non-small cell lung cancer have better survival than men. Chest. 2006 Dec;130:1796-802. ▲
- Surveillance, epidemiology, and end results (SEER) program, 17 SEER Registries 2000-2005. National Cancer Institute Website. Revised 2008. ▲
- Women and lung cancer. Lung Cancer Alliance Web Site. Available at: www.lungcanceralliance.org/pdf…/LCA_Women_Fact_Sheet.pdf. ▲
- Haiman CA, Stram DO, Wilkens LR, et al. Ethnic and Racial Differences in the Smoking-Related Risk of Lung Cancer. N Engl J Med. 2006 Jan 26;354(4):333-42. ▲
- Jazieh AR, Kyasa MJ, Sethuraman G, Howington J. Disparities in surgical resection of early-stage non-small cell lung cancer. J Thorac Cardiovasc Surg. 2002 Jun;123(6):1173-6. ▲
- Bach PB, Cramer LD, Warren JL, Begg CB. Racial differences in the treatment of early-stage lung cancer. N Engl J Med.Oct 14 1999;341(16):1198-1205. ▲
- Farjah F, Wood DE, Yanez III ND, et al. Racial disparities among patients with lung cancer who were recommended operative therapy. Arch Surg. 2009 Jan;144(1):14-8. ▲
- Smedley BD, ed, Stith AY, ed, Nelson AR, ed. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care.National Academies Press. 2003. ▲
- Gordon HS, Street RL Jr, Sharf BF, Souchek J. Racial differences in doctors’ information-giving and patients’ participation. Cancer. 2006 Sept 15;107(6):1313-20. ▲
- Gordon HS, Street RL Jr, Sharf BF, Kelly PA, Souchek J. Racial differences in trust and lung cancer patients’ perceptions of physician communication. J Clin Oncol. 2006 Feb 20;24(6):904-9. ▲
- McCann J, Artinian V, Duhaime L, Lewis JW Jr, Kvale PA, DiGiovine B. Evaluation of the causes for racial disparity in surgical treatment of early stage lung cancer. Chest. 2005 Nov;128(5):3440-6. ▲
- Cancer facts & statistics for Hispanics/Latinos 2009-2011. American Cancer Society Web Site. www.cancer.org/…/STT_1x_Cancer_Facts__Figures_for_HispanicsLatinos_2009-2011.asp. Revised 2009. ▲
- Smith JJ, Berg CD. Lung cancer screening: promise and pitfalls. Semin Oncol Nurs. 2008;24(1):9-15. ▲
- Aberle DR, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409. ▲
- Nesbitt JC, et al. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg. 1995;60(2):466-472. ▲
- The National Lung Screening Trial Research Team. The National Lung Screening Trial: overview and study design. Radiology. 2011;258:243-253. ▲
- Wender R, et al “American Cancer Society lung cancer screening style=”text-decoration: underline;”> CA Cancer J style=”text-decoration: underline;”> 2013; DOI: 10.3322/caac.21171. ▲
- Shepherd FA, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123-132. ▲
- Ramsey SD, Clarke L, Kamath TV, Lubeck D. Evaluation of Erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan. J Manag Care Pharm. 2006;12(6):472-78. ▲
- Bradbury PA, et al. Economic analysis: randomized placebo-controlled clinical trial of Erlotinib in advanced non-small cell lung cancer. J Natl Cancer Inst. 2010;102:298–306. ▲
- Brugger W, et al. Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of Erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2011;29:4113-4120. ▲
- FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer. U.S. Food and Drug Administration Website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm. Accessed February 23, 2012. ▲
- Shaw AT, et al. Effect of crizotinib on overall survival in patients with advanced non-small cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011;12(11):1004-1012. ▲
- The National Cancer Institute Funded Research Portfolio. Available at: http://fundedresearch.cancer.gov/. Accessed February 23, 2012. ▲
- Disease-focused snapshots. National Cancer Institute Web Site. http://planning.cancer.gov/disease /snapshots.shtml. Revised 2009. ▲
- FY 2008 president’s budget. Centers for Disease Control Web Site. http://www.cdc.gov/FMO/FMOFYBUDGET.HTM. Revised 2008. ▲
- Roth M. Does lung cancer get short shrift? Post-Gazette Web Site. http://www.post-gazette.com/pg/09172/978938-114.stm. Revised June 21, 2009. ▲
- Wassenaar TR, Eickhoff JC, Jarzemsky DR, Smith SS, Larson ML, Schiller JH. Differences in primary care clinicians’ approach to non-small cell lung cancer (NSCLC) patients compared to breast cancer (BrCa). Oncology, 2006;24(18s):7041.ASCO Annual Meeting Proceedings (Post-Meeting Edition). ▲
- H.R. 1394 Lung Cancer Mortality Reduction Act of 2011. Open Congress. Available at http://www.opencongress.org/bill/112-h1394/show. Accessed on March 6, 2012. ▲