Tobacco is commonly described as the largest preventable cause of cancer. Over 50 years ago, tobacco was increasingly recognized as the primary cause of lung cancer, with definitive recognition for tobacco use as a causative factor in the seminal 1964 U.S. Surgeon General’s Report (SGR) on Smoking and Health.¹ Recent editions of the SGR have described the widespread adverse health effects of tobacco on a spectrum of diseases, including as a causative agent for a spectrum of cancers.^2,3 Tobacco use is an addiction usually initiated in youth prior to the age of 18 and is driven by the highly addictive drug, nicotine.⁴ As related to the cancer patient, considerable work has been conducted to associate tobacco use with the risk of developing cancer and how tobacco cessation can substantially reduce cancer risks. However, there is a relative paucity of effort that has been put forth to identify the effects of smoking on outcomes for cancer patients or to establish methods to help cancer patients quit smoking. Fortunately, in recent years, the importance of tobacco use by the cancer patient has been increasingly recognized as an important health behavior, including a National Cancer Institute (NCI)-sponsored conference on tobacco use in 2010, a joint sponsored NCI-American Association of Cancer Research (AACR)-sponsored workshop at the Institute of Medicine in 2012, and recent recommendations by the AACR and the American Society of Clinical Oncology (ASCO) to address tobacco use in cancer patients.^5,6 The recently released 2014 SGR now provides substantial evidence behind the effects of smoking by cancer patients with the following conclusions⁷:

The overall objective of this chapter is to discuss tobacco use by cancer patients, the clinical effects of smoking in cancer patients, methods to address tobacco use by cancer patients, and areas of needed research.

Nicotine is the primary addictive component of tobacco that increases extracellular concentrations of dopamine in the nucleus accumbens and stimulates the mesolimbic dopaminergic system,^8,9 resulting in nicotine’s rewarding effect experienced by tobacco users.^10,11,12 Dopaminergic neurotransmission may also be involved in the assignment of incentive salience, or stimulus for a pleasure based reward, to tobacco use-related environmental cues^13,14 that may become conditioned reinforcers of tobacco use behaviors. For example, an individual who smokes while drinking their morning coffee may associate coffee, or even holding a coffee cup in their hand, with the reward from smoking. Thus, cigarette smoking is directly linked to external nontobacco-based behavioral stimuli. Activation of the nucleus accumbens has further been implicated in drug reinstatement or relapse.^15,16 Individuals who have quit tobacco use for years have restarted a tobacco habit simply by sitting next to a smoker and being exposed to secondhand smoke. Substantial work has been conducted on the addictive nature of tobacco and nicotine, and readers are referred to several comprehensive reviews on this topic.^9,12,17

Much of the discussion on tobacco use epidemiology and carcinogenesis is presented in Chapter 4. In brief, the prevalence of cigarette smoking among adults in the United States decreased to 19.0% as compared with 22.8% in 2001, but it did not meet the Healthy People 2010 objective to reduce smoking prevalence to 12%.^18,19 There have been substantial changes in the landscape of tobacco use over time as a direct consequence of cigarette-centered policies and regulations aiming to reduce the harmful effects and number of deaths caused by smoking.^20,21,22 Under this new landscape, novel and reemergent noncigarette tobacco products such as cigars, cigarillos, snuff, chewing tobacco, water pipes (hookahs), and other forms of tobacco consumption have been growing in demand as a consequence of aggressive and sophisticated marketing by the tobacco industry.²³ Consumption patterns have also changed due to efforts by the tobacco industry to make cigarettes appear safer, such as low tar or filtered cigarettes, and the inclusion of flavoring (menthol, vanilla, fruits, etc.).²⁴ Although these efforts may have changed consumption patterns, they have not reduced cancer risk. Large patient cohorts demonstrate that the introduction of low tar and filtered cigarettes actually increased risk by promoting deeper inhalation and higher rates of addiction with no reductions in cancer risk,^24,25 resulting in subsequent changes in lung cancer from centrally located squamous cell cancers to peripherally located nonsquamous cell cancers.

The relatively recent introduction of electronic cigarettes (i.e., e-cigarettes, e-cigs, nicotine vaporizers, or electronic nicotine delivery systems [ENDS]) is noteworthy. These electronic or batterypowered devices activate a heating element that vaporizes a liquid solution contained in a cartridge, and then the user inhales this vapor. Levels of nicotine as well as other chemical additives and flavors in the cartridge are uncertain and vary according to the brand.²⁶ Although there are no research studies that have evaluated the potential harmful effects of the use of e-cigarettes for
cancer patients,²⁷ organizations such as the World Health Organization have already expressed concerns about the safety of these increasingly popular products.^28,29 To date, e-cigarettes have not been approved by the U.S. Food and Drug Administration (FDA) as therapeutic devices to aid in quitting smoking.²⁶ Readers are referred to a recent editorial on the use of e-cigarettes by cancer patients²⁷; however, it will likely be several years before evidencebased health information is available.

The prevalence of current smoking among long-term adult cancer survivors appears to have declined in the past decade,³⁰ but data suggest higher rates of smoking among cancer survivors than in the general population.^30,31,32 These data are often biased by the fact that assessments in cancer patients may not include cancer patients who were current smokers at the time of death. As a result, estimates of smoking rates in cancer survivors may be misleading and may underestimate true tobacco use patterns for cancer patients. Furthermore, alternative tobacco products are often not assessed in cancer patients. Data from the Childhood Cancer Survivor Study and the 2009 Behavioral Risk Factor Surveillance System indicate that approximately 3% to 8% of cancer survivors use smokeless tobacco products.^33,34 Patients may be attracted to these alternative products due to less social stigma and the nonevidencebased perception that these products are healthier alternatives compared to cigarette smoking.

Continued tobacco use by cancer patients often represents a combined failure by the patient to recognize the need to stop smoking even after a cancer diagnosis and the effort by health-care providers to address tobacco use with evidence-based assessments and tobacco cessation support. Approximately 30% of all cancer patients use tobacco at the time of cancer diagnosis with higher rates in traditionally tobacco-related disease sites, such as head and neck or lung cancers, and lower rates in traditionally nontobaccorelated disease sites, such as breast or prostate cancers.^{35,36,37,38,39,40,41,42,43,44} However, findings from several studies indicate that cancer patients are receptive to smoking cessation interventions even as they continue to smoke.^{35,38,45,46,47,48,49,50}

A cancer diagnosis can be used as a window of opportunity, or teachable moment, to intervene and provide assistance in the quitting process.⁵¹ A recent study in 12,000 cancer patients, including 2,700 patients who smoked, capitalized on the teachable moment and demonstrated that less than 3% of patients who were contacted by the cessation program rejected tobacco cessation assistance.⁴⁵ However, only 1.2% of patients who received a mailed invitation participated in the program. This highlights the idea that patients may be interested in quitting, but methods such as mailed tobacco cessation information may not yield effective participation by cancer patients. Once enrolled, patients and clinicians must realize that although relapses in the general population usually occur within 1 week of cessation, relapses in cancer patients may be delayed due to cancer treatment-related variables such as surgical or other posttreatment healing.⁵² Consequently, it is important to continue offering tobacco assessments and cessation support for cancer survivorship efforts.

Cancer treatment is generally defined according to disease site, stage, treatment type (e.g., surgery, chemotherapy [CT], radiotherapy [RT], or biologic therapy), and primary treatment objective, such as cure or palliation. A comprehensive discussion of the effects of smoking on cancer patients is beyond the scope of a single chapter, but the 2014 SGR provides an excellent evidence base, concluding that “the evidence is sufficient to infer a causal relationship between cigarette smoking and adverse health outcomes.”⁷ Overall, approximately 75% to 80% of studies in the SGR demonstrated a negative association between smoking and outcome, with approximately 65% to 70% of studies demonstrating statistically significant negative associations. This chapter will provide an illustrative review of studies that demonstrate the adverse effects of tobacco across disease sites and treatment modalities (e.g., surgery, CT, RT), and effects will be discussed across the categories of mortality, recurrence and cancer-related mortality, toxicity, and risk of a second primary cancer. Evidence for the benefits of smoking cessation will also be presented within each section.