In California, 87.1% of API women and 83.1% of Latina women have never smoked, compared with 56.3% of NH White and 65.9% of NH Black women (13
). It has previously been documented that risks of lung cancer by level of smoking is modified by race/ethnicity (14
). We found substantially poorer lung-cancer specific survival among APIs and Latinas, particularly among the US-born, compared with NH White women. These survival disparities were not explained by differences in selected sociodemographic or clinical factors, indicating that unmeasured factors associated with race/ethnicity and immigration status, such as cultural behaviors, access to or attitudes toward health care, genetic variation, and/or treatment response, may in part explain these striking differences.
Few studies have examined survival following a diagnosis of lung cancer among Latina women who have never smoked. The slight survival advantage among foreign-born compared to US-born Latina women is consistent with other studies of cancer mortality (15
) and may reflect the “Latino paradox” (17
), which refers to better health among immigrants despite their being of lower SES. The better survival in foreign-born Latinos could be a result of under-ascertainment of deaths or loss to follow-up, when foreign-born Latinos with cancer return to their native countries and die there. However, prior studies have shown that while the migratory effect may exist to some extent, its magnitude is too small to explain the mortality paradox (20
). In our data, loss to follow-up was not significantly different between US- and foreign-born Latinas, suggesting that emigration does not explain our results. Alternatively, this paradox could be due to a true health advantage among Latinos in general due to more favorable health behaviors, use of traditional medicines, and greater extended family support; or it could reflect selective migration of healthier individuals to the US. The relative importance of these factors would be worth evaluating further with regards to lung cancer survival among Latinas.
Our results for APIs are contrary to those from southern California cancer registry data showing that survival after NSCLC was better among Asian males and females than other racial/ethnic groups, regardless of smoking status (9
). The discrepant findings may be due to gender differences and/or population differences between southern and northern California, as it is known that Asian settlement patterns differ across regions within California (24
). For instance, while Chinese comprised 45% of our population, they comprised only 15% of the female never-smoker population in the southern California analysis (25
). The differences in findings may also be due to methodologic differences. In the prior analyses, smoking status was inferred based on a text-mining program that abstracted patients’ medical record information (9
), and nearly 30% of patients were excluded because smoking status could not be determined (9
). By contrast, smoking status in our study was based on self-report, which corresponds well with cotinine levels in most populations (26
), whereas medical records can be inaccurate or lacking in any smoking information at all (32
). In the southern California study, the proportions of women with NSCLC who had never smoked were approximately 15% among all races/ethnicities and 55% among Asians. The former proportion is slightly lower than the 20% that we recently documented (7
), and the latter proportion is considerably lower than the 70% of API never smokers in the SFBALCS. These discrepancies suggest that never smokers may have been disproportionately excluded from the southern California analyses due to missing smoking data in the medical record. Although the survival benefit among Asians relative to non-Hispanic Whites found in the southern California study was independent of smoking status (25
), there was likely differential exclusion of Asian never-smokers. It is perhaps more likely that the differences between the two studies are due to the population differences noted above, as well as to effect modification by gender, as our effects were noted only among women, who were not evaluated separately in the southern California study. It is worth noting that the method for follow-up was the same in both studies.
Our study revealed other interesting associations with survival after NSCLC among female never smokers. Consistent with prior findings in lung (9
) and other cancers (35
), higher mortality was evident for patients who were widowed, divorced, or separated, compared with those who were married, even with adjustment for age, indicating that greater spousal social support improves survival. We also observed that first course radiation therapy was associated with slightly higher mortality, whereas surgery was associated with lower mortality; however, given the known limitations with cancer registry data on treatment, these patterns are likely reflective of residual confounding due to extent of disease.
Regardless of therapy, NSCLC patients who are never-smokers seem to have a small survival benefit compared to those with a smoking history (6
), although this pattern is not confirmed in all studies (37
). The studies that show better survival among never-smokers may be reflective of a greater number of comorbidities among patients with a history of smoking. In addition, for advanced-stage NSCLC, some studies have shown a clear difference in chemotherapy response between smokers and non-smokers (38
), although others have not (39
). Clinically important differences in treatment response are seen with EGFR tyrosine kinase inhibitors (erlotinib, gefitinib). Higher treatment response rates and better survival have been reported in never-smokers with these drugs compared to ever smokers (40
). It is likely, however, that never-smoking status is a surrogate for EGFR activating mutations, as indicated by the results from the iPASS and First-Signal trials of first line gefitinib versus chemotherapy for never-smoking Asian patients with advanced stage NSCLC (43
). In both studies, only patients with EGFR activating mutations had a progression-free survival benefit. However, as these are relatively new drug regimens, it is unlikely that they would impact the results seen in our study, based on cases diagnosed from 1998 through 2008. Asian race/ethnicity has also been shown to be associated with better survival following NSCLC (45
), even adjusted for smoking status and gender (46
). However, survival differences across racial/ethnic groups may be modified by smoking status and/or gender, as suggested by our results, which are discordant with those reported from the National Cancer Institute of Canada Clinical Trials Study Group BR.21 (46
This study has its strengths in being population-based and in its availability of patient-level variables, such as self-reported smoking status and second-hand smoke exposure. The major limitation in this study is the limited sample size, especially after stratification by race/ethnicity and immigrant status, and thus, the results should be interpreted with caution. As a result, we were not able to examine survival patterns for detailed API or Latina ethnic groups, which have documented differences in lung cancer survival (45
). Self-reported smoking status may be misclassified, possibly to a slightly higher extent among racial/ethnic minorities (47
), and among proxy reports (although, in the literature, minorities are not consistently more likely to be misclassified on smoking status than non-Hispanic Whites) (48
). Even though patients in this study were identified through rapid case ascertainment, patients sometimes were deceased or too ill to participate by the time they were contacted for this study; this is affirmed by the fact that participating patients were more likely to have early stage disease than the general patient population. The screening interview was conducted in English or Spanish only, therefore possibly restricting participation for subjects who speak a different language; however, participating APIs and Latinas were not significantly more likely to be US-born than the registry patient population. The findings for race/ethnicity may also be impacted by our inability to fully adjust for treatment (51
). Our study may also be limited by possible biases in loss to follow-up, such that certain patients, particularly foreign-born APIs and Latinas, may have been more likely to return to their countries of origin upon learning of their serious illness (19
). This effect would result in underestimation of the hazard ratios for foreign-born APIs and Latinas. We could not evaluate lung cancer-specific mortality due to how cause of death is coded in the cancer registries. However, given the rapid fatality of this disease and that of deaths of known causes of death, nearly 80% are due to lung cancer as the underlying cause, it is likely that the racial/ethnic and nativity results will be similar for lung cancer-specific mortality.
In summary, this study identified disparities in survival among API and Latina women never smokers who have been diagnosed with lung cancer, particularly those who were born in the US. These disparities present public health and clinical issues of concern, given the large and growing population of never smokers who present with lung cancer in these racial/ethnic groups. These results highlight the need for additional research to identify the underlying reasons for the disparities, as well as heightened clinical awareness.