50th Anniversary Report: Even More Known About Smoking, Cancer Connections

It’s been 50 years since the announcement from US Surgeon General Luther L. Terry, MD, that smoking causes lung cancer in men and probably in women.¹ Terry’s action unleashed the public health crusade against cigarettes; since 1964, adult smoking rates have fallen from 43% to 18%.²

But a report issued on the milestone of Terry’s bold step, during a White House ceremony held on January 17, 2014,³ pores through the most recent data and makes several new findings about smoking and cancer, including:

• Female smokers face a greater risk of lung cancer than ever.⁴
• Cigarettes are linked to multiple other cancers; scientists can say with certainty that smoking causes colorectal cancer. While the report stops short of saying that smoking causes breast cancer, it states, “The evidence is sufficient to identify mechanisms by which cigarette smoking may cause breast cancer³ (Figure 1).
• Falling rates of squamous cell cancer of the lung, accompanied by the relative rise of adenocarcinoma of the lung among smokers, are most certainly due to changes in the design of cigarettes themselves.^3,5 The consequences have been deadly, and US cigarettes may be the deadliest of all.^3,6

An important lesson of the anniversary report, officially titled The Health Consequences of Smoking: 50 Years of Progress, is aimed at oncologists and payers, rather than smokers. According to Timothy McAfee, MD, director of the Office of Smoking and Health, the amazing advances in cancer therapy, which have created drugs with $100,000 price tags, are not as important to survival as getting a smoker with cancer to quit.

“Does it make sense to spend this kind of money, $100,000 for a drug to add a fe w months to someone’s life, and ignore somebody’s tobacco status during treatment?” McAfee asked in an interview. All the evidence, he said, suggests that quitting smoking would do as much good for the patient with cancer as “the best available chemotherapy,” and yet there are cases where a patient undergoes the rigors of treatment while his or her smoking habit goes unaddressed.

“In 2014, after this report, it isn’t fair to individuals for smoking status to be ignored,” McAfee said. “There are historical and cultural reasons why that was the case. But that doesn’t make sense anymore.”

Figure 1. The Health Consequences Causally Linked to Smoking

Source: US Department of Health and Human Services, 2004, 2006, 2010.

Conditions in red indicate new diseases that have been causally linked to smoking in The Health Consequences of Smoking: 50 Years of Progress.

The Rise of Adenocarcinoma of the Lung

McAfee’s call to arms has implications not only for healthcare providers, but also for the US taxpayers. Demographic data contained in the report³ and available from the Centers for Disease Control and Prevention (CDC)^2,7 show that while smoking has declined significantly since 1964, progress against tobacco is leveling off. Those who still smoke or who start smoking are more likely to be poor and have limited education^2,7; this means without a renewed commitment to end smoking, the expanding ranks of Medicaid clients under the Affordable Care Act (ACA) will include a larger share of smokers than the population as a whole.When Terry unveiled the first Surgeon General’s Report (SGR) in 1964, “lung cancer in men” typically meant squamous cell carcinoma of the lung. Men smoked more than women, and thus accounted for more cases of lung cancer.³ In the wake of the 1964 announcement, the tobacco industry’s attempts to create “safer” cigarettes, coupled with efforts to market directly to women in an era of change, led to shifts in both the type of lung cancer diagnosed and in the makeup of who suffered, changes that are only now fully understood.⁴

A study of smokers by the American Cancer Society (ACS) from 1959 to 1965 had been an important source for the advisory panel that created the 1964 report.³ Behaviors exhibited by those smokers informed scientists who created models to predict the number of future lung cancer deaths. They also informed tobacco company researchers, who created machines to measure supposedly lower levels of “tar” and “nicotine” on filtered and ventilated cigarettes that were put on the market in the decade after 1964.

This new SGR chronicles how scientists missed the mark for years in predicting lung cancer deaths, until they began to account for the changes in smoking behavior that were a direct result of modifications to cigarettes, supposedly to make them “safer.” Reengineered cigarettes did not provide the same “hit” of nicotine, so smokers responded by puffing longer or holding smoke in their mouths, actions that fundamentally altered the nature of the way their bodies reacted to the 69 different carcinogens identified in cigarette smoke.^3-5

Over time, the health consequences of a different cigarette became clear. The United States and other countries saw falling rates of squamous cell cancer of the lung, which may first affect the bronchial areas and cause a patient to cough up blood. Among smokers, the United States in particular saw rising rates of adenocarcinoma of the lung, which develops in the far reaches of the lung tissue and may not cause symptoms beyond a cough until the cancer is in later stages. While overall death rates for men from lung cancer peaked in 1990 and for women in 2003, likely due to reduced prevalence of smoking, the climb of adenocarcinoma of the lung continues among those who do smoke, and rising incidence has been steeper for women^3,8 (Figure 2). Differences in the composition and manufacturing practices of US cigarettes, compared with those from Canada and Australia, are believed to account for larger increases in adenocarcinoma incidence here than in those nations.^3,6

Key work in this area includes a 2011 study led by David M. Burns, MD,⁵ which first factored the change in cigarette design in modeling to account for changing rates of adenocarcinoma; and the 2013 study in The New England Journal of Medicine led by Michael J. Thun, MD,⁴ which tracked smoking-related mortality over a 50-year period. Thun and his coauthors concluded that the relative risk (RR) of lung cancer for women smokers, compared with women who have never smoked, is higher than ever: RR was 2.73 in the original ACS study, 12.65 in a follow-up study begun in 1982, and 25.66 in a cohort ending in 2010. Women smokers today face higher lung cancer risks than men relative to their nonsmoking counterparts; for men, RR of lung cancer in the 2010 cohort was 24.97.⁴

A panel of experts convened recently by The American Journal of Managed Care to discuss non-small cell lung cancer said the increased understanding of adenocarcinoma of the lung has changed treatment over the past decade, putting more onus on the pathologist to properly evaluate tumor types.¹⁰ It has also caused the US Preventive Services Task Force to recommend lung cancer screening among smokers and former smokers who meet certain criteria.

Figure 2. Standardized Incidence of Lung Cancer, by Gender and Histology (age-adjusted to 2000 US population),1973-2010

Source: Surveillance, Epidemiology, and End Results (SEER) Program, public use data.

Other non-small-cell lung carcinoma (NSCLC) includes code 8046 from the SEER Registry, as well as others. In the most recent years (2001—2010), most of the “Other NSCLC” were 8046. Before 2001, most “Other NSCLC” were coded as 8010 “Carcinoma, NOS.” Around 2004 there were changes in how lung cancers were coded in the SEER Registry data (Travis et al, 2004, 2011; Johnson et al, 2007). There were also advances in diagnosis and treatment around 2004 (erlotinib or gefitinib for patients with EGFR mutations, bevacizumab for patients with nonsquamous NSCLC) that make accurate histologic classification important (Langer et al, 2010; Kulesza et al, 2011; Conde et al, 2013).

Smoking’s Links to Other Cancers

McAfee said that while lung cancer screening is important and will save lives, the CDC is working hard to craft an education message that does not lead smokers to believe that screening is a substitute for quitting; in fact, the CDC hopes that being screened will provide an opening for a conversation with a smoker about how to stop. “We are working very closely with our cancer prevention control office on this specific issue,” McAfee said. “How do we turn this into a positive educational opportunity?”While smoking is most associated with lung cancer, successive SGRs have assembled evidence of its ties to other cancers. Reports are careful to never overstep what is known at the time; thus, when any report says for the first time that there is a “causal relationship,” it is an important step, as no SGR has ever had to reverse a previous finding, according to Terry F. Pechacek, PhD, associate director for science at the Office of Safety and Health (OSH) and a veteran of crafting multiple reports.

So, the finding for the first time that, “The evidence is sufficient to infer a causal relationship between smoking and colorectal adenomatous polyps and colorectal cancer”³ is a critical statement, especially since colorectal cancer is now the second-leading cause of cancer deaths in the United States, according to CDC statistics.⁹

The report also examined possible connections to liver, prostate, and breast cancers, and found:

• The evidence is sufficient to infer a causal relationship between smoking and hepatocellular carcinoma.
• The evidence is suggestive of no causal relationship between smoking and the risk of incident prostate cancer; however, there is evidence suggestive of a higher risk of death from prostate cancer among smokers than nonsmokers.
• In men who have prostate cancer, the evidence suggests a higher risk of advanced-stage disease and less well-differentiated cancer in smokers than nonsmokers.
• Besides evidence of the mechanism by which smoking may cause breast cancer, the report says there is “suggestive but not sufficient” evidence to infer a causal relationship between smoking and breast cancer. The same characterization was made of evidence linking second-hand tobacco smoke and breast cancer.

Smoking Hinders Cancer Care, Survivorship

The anniversary report bolsters the message long-term smokers most need to hear: Quitting improves health at any age, no matter how long a person has smoked, except perhaps in the very final stages of cancer.

But for the smoker who has received a cancer diagnosis, the need to quit immediately comes through as never before. Not only is there clear evidence that smoking harms a cancer patient’s overall health and chances of survival, but evidence is accumulating that smoking interferes directly with cancer treatment, making it less effective and rougher on the patient.³

For the first time, the SGR features a section on what happens when cancer patients continue to smoke, and the simple answer is: It certainly doesn’t help, and it probably causes greater harm.

Evidence is “suggestive but not sufficient” of a causal relationship between smoking and poor responses to cancer treatment, increased toxicity, and cancer recurrence, adding weight to McAfee’s call to put the highest priority on getting smokers to quit if they are about to undergo treatment.

The report evaluated 16 studies that examined whether cigarette smoking affects patients’ response to cancer therapy, and found that in 72% of the studies, smoking had a statistically significant association with a worse response. Of 82 studies examining the relationship between smoking and increased toxicity, 80% found that smoking made treatment more toxic. In 49 studies that included a category of “current smoking,” the association with increased toxicity was even higher, at 88%.³

While major groups, including ASCO, have called for increased efforts to help patients with cancer quit smoking, the SGR raises the bar with provocative questions: Do the optimal approaches to treat cancer differ in patients who are current smokers compared with nonsmokers? And, is it better to make smoking cessation an initial priority before implementing the patient’s cancer treatment regimen?³

“This needs to be a serious discussion,” said McAfee. The nation still loses more than 400,000 lives each year due to smoking, a statistic he said “would not be tolerated” if the offending substance were something other than cigarettes. Americans moved quickly to remove threats like asbestos and lead paint, yet tobacco remains part of the landscape.

“It didn’t take 50 years to remove lead paint,” he said. “This shouldn’t take another 50 years.”

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References

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2. CNN Money. Who smokes in the US? http://www.money.cnn.com/infographic/news/who-smokes-inthe-us/. Accessed February 23, 2014.
3. The health consequences of smoking—50 years of progress: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2014. http://www.surgeongeneral.gov/initiatives/tobacco.
4. Thun MJ, Carter BD, Feskanich D, et al. 50-year trends in smoking-related mortality in the United States. N Eng J Med. 2013;368:351-364.
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8. Surveillance, Epidemiology, and End Results (SEER) Program. Data reported in Chapter 6. The health consequences of smoking—50 years of progress: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2014. http://www.surgeongeneral.gov/library/reports/50-yearsof-progress/sgr50-chap-6.pdf.
9. US Cancer Statistics Working Group. United States Cancer Statistics: 1999—2010 Incidence and Mortality Web-based Report. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2013. http://www.cdc.gov/uscs. Accessed March 8, 2014.
10. Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(36):5311—5320.