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Sex-Specific Differences in Lung Cancer

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Gender, Sex Hormones and Respiratory Disease

Part of the book series: Respiratory Medicine ((RM))

Abstract

Lung cancer is the leading cause of cancer deaths for both men and women in the United States. Lung cancer exceeded breast cancer as the primary cause of female cancer deaths in 1987 and now kills more women than the next two most common cancers in females (breast and colorectal) combined. The rate of lung cancer diagnoses for men has declined in the last 30 years; however, lung cancer incidence has risen for women. Whether or not women have an increased risk of lung cancer remains controversial. There is, however, no debate to the fact that the biology of lung cancer differs between the sexes. Here we review the explanations for the observed sex differences in lung cancer presentation, including disparities in clinical characteristics, genetic factors and hormonal influences, as well as variations in incidence rates, outcomes, and therapeutic response. Finally, the current status and future implications for pharmacological blockade of the estrogen pathway for lung cancer treatment are discussed.

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Abbreviations

AC:

Adenocarcinoma

AI:

Aromatase inhibitor

AI:

Aromatase inhibitor, ER, estrogen receptor

ALK:

Anaplastic lymphoma kinase

CBR:

Clinical benefit rate

CYP1A1:

Cytochrome P450 1A1

DRC:

DNA repair capacity

EGFR:

Epidermal growth factor receptor

ER:

Estrogen Receptor

GRPR:

Gastrin-releasing peptide receptor

GSTM1:

Glutathione S-transferase M1

HPV:

Human papillomavirus

IGFR-1:

Insulin-like growth factor-1 receptor

NSCLC:

Non-small cell lung cancer

PFS:

Progression-free survival

PR:

Partial response

RR:

Response rate

SCC:

Squamous cell carcinoma

SCLC:

Small cell lung cancer

SERM:

Selective estrogen receptor modulator

TKI:

Tyrosine kinase inhibitor

VEGFR:

Vascular endothelial growth factor receptor

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. Epub 2014/01/09.

    Google Scholar 

  2. Jemal A, Thun MJ, Ries LAG, Howe HL, Weir HK, Center MM, et al. Annual Report to the Nation on the Status of Cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100(23):1672–94.

    PubMed Central  Google Scholar 

  3. Kosmidis P, Mylonakis N, Skarlos D, Samantas E, Dimopoulos M, Papadimitriou C, et al. Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): a multicenter randomized trial. Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2000;11(7):799–805. Epub 2000/09/21.

    CAS  Google Scholar 

  4. Giovino GA. Epidemiology of tobacco use in the United States. Oncogene. 2002;21(48):7326–40. Epub 2002/10/16.

    CAS  Google Scholar 

  5. Thun MJ, Carter BD, Feskanich D, Freedman ND, Prentice R, Lopez AD, et al. 50-year trends in smoking-related mortality in the United States. N Engl J Med. 2013;368(4):351–64.

    CAS  PubMed Central  Google Scholar 

  6. Brownson RC, Chang JC, Davis JR. Gender and histologic type variations in smoking-related risk of lung cancer. Epidemiology. 1992;3(1):61–4. Epub 1992/01/01.

    CAS  Google Scholar 

  7. Harris RE, Zang EA, Anderson JI, Wynder EL. Race and sex differences in lung cancer risk associated with cigarette smoking. Int J Epidemiol. 1993;22(4):592–9. Epub 1993/08/01.

    CAS  Google Scholar 

  8. McDuffie HH, Klaassen DJ, Dosman JA. Female–male differences in patients with primary lung cancer. Cancer. 1987;59(10):1825–30. Epub 1987/05/15.

    CAS  Google Scholar 

  9. Osann KE, Anton-Culver H, Kurosaki T, Taylor T. Sex differences in lung-cancer risk associated with cigarette smoking. Int J Cancer (Journal international du cancer). 1993;54(1):44–8. Epub 1993/04/22.

    CAS  Google Scholar 

  10. Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Are female smokers at higher risk for lung cancer than male smokers? A case–control analysis by histologic type. Am J Epidemiol. 1993;138(5):281–93. Epub 1993/09/01.

    CAS  Google Scholar 

  11. Schoenberg JB, Wilcox HB, Mason TJ, Bill J, Stemhagen A. Variation in smoking-related lung cancer risk among New Jersey women. Am J Epidemiol. 1989;130(4):688–95. Epub 1989/10/01.

    CAS  Google Scholar 

  12. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst. 1996;88(3–4):183–92. Epub 1996/02/21.

    CAS  Google Scholar 

  13. Kure EH, Ryberg D, Hewer A, Phillips DH, Skaug V, Bæera R, et al. p53mutations in lung tumours: relationship to gender and lung DNA adduct levels. Carcinogenesis. 1996;17(10):2201–5.

    CAS  Google Scholar 

  14. Guinee DG, Travis WD, Trivers GE, Benedetti VMGD, Cawley H, Welsh JA, et al. Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression. Carcinogenesis. 1995;16(5):993–1002.

    CAS  Google Scholar 

  15. Toyooka S, Tsuda T, Gazdar AF. The TP53 gene, tobacco exposure, and lung cancer. Hum Mutat. 2003;21(3):229–39.

    CAS  Google Scholar 

  16. Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, et al. Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003;95(6):470–8. Epub 2003/03/20.

    Google Scholar 

  17. Bain C, Feskanich D, Speizer FE, Thun M, Hertzmark E, Rosner BA, et al. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst. 2004;96(11):826–34. Epub 2004/06/03.

    Google Scholar 

  18. De Matteis S, Consonni D, Pesatori AC, Bergen AW, Bertazzi PA, Caporaso NE, et al. Are women who smoke at higher risk for lung cancer than men who smoke? Am J Epidemiol. 2013;177(7):601–12. Epub 2013/02/22.

    PubMed Central  Google Scholar 

  19. Halpern MT, Gillespie BW, Warner KE. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst. 1993;85(6):457–64. Epub 1993/03/17.

    CAS  Google Scholar 

  20. Kreuzer M, Boffetta P, Whitley E, Ahrens W, Gaborieau V, Heinrich J, et al. Gender differences in lung cancer risk by smoking: a multicentre case–control study in Germany and Italy. Br J Cancer. 2000;82(1):227–33. Epub 2000/01/19.

    CAS  Google Scholar 

  21. Prescott E, Osler M, Hein HO, Borch-Johnsen K, Lange P, Schnohr P, et al. Gender and smoking-related risk of lung cancer. The Copenhagen Center for Prospective Population Studies. Epidemiology. 1998;9(1):79–83. Epub 1998/01/16.

    CAS  Google Scholar 

  22. Radzikowska E, Głaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases. Ann Oncol. 2002;13(7):1087–93.

    CAS  Google Scholar 

  23. Egleston BL, Meireles SI, Flieder DB, Clapper ML. Population-based trends in lung cancer incidence in women. Semin Oncol. 2009;36(6):506–15. Epub 2009/12/10.

    PubMed Central  Google Scholar 

  24. Kligerman S, White C. Epidemiology of lung cancer in women: risk factors, survival, and screening. AJR Am J Roentgenol. 2011;196(2):287–95. Epub 2011/01/25.

    Google Scholar 

  25. Lewis DR, Check DP, Caporaso NE, Travis WD, Devesa SS. US lung cancer trends by histologic type. Cancer. 2014;120(18):2883–92.

    PubMed Central  Google Scholar 

  26. Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath Jr CW. Cigarette smoking and changes in the histopathology of lung cancer. J Natl Cancer Inst. 1997;89(21):1580–6. Epub 1997/11/15.

    CAS  Google Scholar 

  27. Stellman SD, Muscat JE, Thompson S, Hoffmann D, Wynder EL. Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to lifetime filter cigarette smoking. Cancer. 1997;80(3):382–8. Epub 1997/08/01.

    CAS  Google Scholar 

  28. Samet JM, Avila-Tang E, Boffetta P, Hannan LM, Olivo-Marston S, Thun MJ, et al. Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res. 2009;15(18):5626–45. Epub 2009/09/17.

    PubMed Central  Google Scholar 

  29. Gorlova OY, Zhang Y, Schabath MB, Lei L, Zhang Q, Amos CI, et al. Never smokers and lung cancer risk: a case–control study of epidemiological factors. Int J Cancer (Journal international du cancer). 2006;118(7):1798–804. Epub 2005/10/12.

    CAS  Google Scholar 

  30. Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease. Nat Rev Cancer. 2007;7(10):778–90. Epub 2007/09/21.

    CAS  Google Scholar 

  31. Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, et al. Lung cancer incidence in never smokers. J Clin Oncol. 2007;25(5):472–8. Epub 2007/02/10.

    PubMed Central  Google Scholar 

  32. Thun MJ, Henley SJ, Burns D, Jemal A, Shanks TG, Calle EE. Lung cancer death rates in lifelong nonsmokers. J Natl Cancer Inst. 2006;98(10):691–9.

    Google Scholar 

  33. Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998–2006.

    PubMed Central  Google Scholar 

  34. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004;101(36):13306–11. Epub 2004/08/27.

    CAS  PubMed Central  Google Scholar 

  35. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–500.

    CAS  Google Scholar 

  36. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–39.

    CAS  Google Scholar 

  37. Yang SH, Mechanic LE, Yang P, Landi MT, Bowman ED, Wampfler J, et al. Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-small cell lung cancer. Clin Cancer Res. 2005;11(6):2106–10. Epub 2005/03/25.

    CAS  Google Scholar 

  38. Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, et al. Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: Higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res. 2012;18(22):6169–77.

    CAS  PubMed Central  Google Scholar 

  39. Camidge DR, Bang Y-J, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13(10):1011–9.

    CAS  PubMed Central  Google Scholar 

  40. Kwak EL, Bang Y-J, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703.

    CAS  PubMed Central  Google Scholar 

  41. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27(26):4247–53. Epub 2009/08/12.

    CAS  PubMed Central  Google Scholar 

  42. Wang Y, Wang S, Xu S, Qu J, Liu B. Clinicopathologic features of patients with non-small cell lung cancer harboring the EML4-ALK fusion gene: a meta-analysis. PLoS One. 2014;9(10), e110617. Epub 2014/11/02.

    PubMed Central  Google Scholar 

  43. Fan L, Feng Y, Wan H, Shi G, Niu W. Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis. PLoS One. 2014;9(6), e100866. Epub 2014/06/25.

    PubMed Central  Google Scholar 

  44. Riely GJ, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc. 2009;6(2):201–5.

    CAS  Google Scholar 

  45. Lung ML, Wong M, Lam WK, Lau KS, Kwan S, Fu KH, et al. Incidence of ras oncogene activation in lung carcinomas in Hong Kong. Cancer. 1992;70(4):760–3. Epub 1992/08/15.

    CAS  Google Scholar 

  46. Spitz MR, Wei Q, Li G, Wu X. Genetic susceptibility to tobacco carcinogenesis. Cancer Invest. 1999;17(8):645–59. Epub 1999/12/11.

    CAS  Google Scholar 

  47. Cheng YW, Chiou HL, Sheu GT, Hsieh LL, Chen JT, Chen CY, et al. The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Cancer Res. 2001;61(7):2799–803. Epub 2001/04/18.

    CAS  Google Scholar 

  48. Syrjänen KJ. HPV infections and lung cancer. J Clin Pathol. 2002;55(12):885–91.

    PubMed Central  Google Scholar 

  49. Li YJ, Tsai YC, Chen YC, Christiani DC. Human papilloma virus and female lung adenocarcinoma. Semin Oncol. 2009;36(6):542–52. Epub 2009/12/10.

    Google Scholar 

  50. Zhai K, Ding J, Shi H-Z. HPV and lung cancer risk: a meta-analysis. J Clin Virol. 2015;63:84–90.

    Google Scholar 

  51. Frisch M, Melbye M. Risk of lung cancer in pre- and post-menopausal women with ano-genital malignancies. Int J Cancer. 1995;62(5):508–11.

    CAS  Google Scholar 

  52. Smith EM, Ritchie JM, Summersgill KF, Klussmann JP, Lee JH, Wang D, et al. Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer. 2004;108(5):766–72.

    CAS  Google Scholar 

  53. Fu JB, Kau TY, Severson RK, Kalemkerian GP. Lung cancer in women: analysis of the national Surveillance, Epidemiology, and End Results database. Chest. 2005;127(3):768–77. Epub 2005/03/15.

    Google Scholar 

  54. Thomas L, Doyle LA, Edelman MJ. Lung cancer in women: emerging differences in epidemiology, biology, and therapy. Chest. 2005;128(1):370–81. Epub 2005/07/09.

    Google Scholar 

  55. Ramalingam S, Pawlish K, Gadgeel S, Demers R, Kalemkerian GP. Lung cancer in young patients: analysis of a Surveillance, Epidemiology, and End Results database. J Clin Oncol. 1998;16(2):651–7. Epub 1998/02/20.

    CAS  Google Scholar 

  56. de Perrot M, Licker M, Bouchardy C, Usel M, Robert J, Spiliopoulos A. Sex differences in presentation, management, and prognosis of patients with non-small cell lung carcinoma. J Thorac Cardiovasc Surg. 2000;119(1):21–6. Epub 1999/12/29.

    Google Scholar 

  57. Baldini EH, Strauss GM. Women and lung cancer: waiting to exhale. Chest. 1997;112(4 Suppl):229s–34s. Epub 1997/10/23.

    CAS  Google Scholar 

  58. Minami H, Yoshimura M, Miyamoto Y, Matsuoka H, Tsubota N. Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer. Chest. 2000;118(6):1603–9. Epub 2000/12/15.

    CAS  Google Scholar 

  59. Alexiou C, Onyeaka CV, Beggs D, Akar R, Beggs L, Salama FD, et al. Do women live longer following lung resection for carcinoma? Eur J Cardiothorac Surg. 2002;21(2):319–25. Epub 2002/02/05.

    Google Scholar 

  60. Ferguson MK, Wang J, Hoffman PC, Haraf DJ, Olak J, Masters GA, et al. Sex-associated differences in survival of patients undergoing resection for lung cancer. Ann Thorac Surg. 2000;69(1):245–9. discussion 9–50. Epub 2000/02/02.

    CAS  Google Scholar 

  61. Yoshino I, Baba H, Fukuyama S, Kameyama T, Shikada Y, Tomiyasu M, et al. A time trend of profile and surgical results in 1123 patients with non-small cell lung cancer. Surgery. 2002;131(1 Suppl):S242–8. Epub 2002/02/01.

    Google Scholar 

  62. Ouellette D, Desbiens G, Emond C, Beauchamp G. Lung cancer in women compared with men: stage, treatment, and survival. Ann Thorac Surg. 1998;66(4):1140–3. discussion 3–4. Epub 1998/11/04.

    CAS  Google Scholar 

  63. Rena O, Massera F, Boldorini R, Papalia E, Turello D, Davoli F, et al. Non-small cell lung cancer in surgically treated women. Tumori. 2013;99(6):661–6. Epub 2014/02/08.

    Google Scholar 

  64. Spiegelman D, Maurer LH, Ware JH, Perry MC, Chahinian AP, Comis R, et al. Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients. J Clin Oncol. 1989;7(3):344–54. Epub 1989/03/01.

    CAS  Google Scholar 

  65. Osterlind K, Andersen PK. Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation. Cancer Res. 1986;46(8):4189–94. Epub 1986/08/01.

    CAS  Google Scholar 

  66. Nakamura H, Ando K, Shinmyo T, Morita K, Mochizuki A, Kurimoto N, et al. Female gender is an independent prognostic factor in non-small-cell lung cancer: a meta-analysis. Ann Thorac Cardiovasc Surg. 2011;17(5):469–80. Epub 2011/09/02.

    Google Scholar 

  67. Singh S, Parulekar W, Murray N, Feld R, Evans WK, Tu D, et al. Influence of sex on toxicity and treatment outcome in small-cell lung cancer. J Clin Oncol. 2005;23(4):850–6. Epub 2005/02/01.

    Google Scholar 

  68. Paesmans M, Sculier JP, Lecomte J, Thiriaux J, Libert P, Sergysels R, et al. Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years. Cancer. 2000;89(3):523–33. Epub 2000/08/10.

    CAS  Google Scholar 

  69. Wakelee HA, Wang W, Schiller JH, Langer CJ, Sandler AB, Belani CP, et al. Survival differences by sex for patients with advanced non-small cell lung cancer on Eastern Cooperative Oncology Group trial 1594. J Thorac oncol. 2006;1(5):441–6. Epub 2007/04/06.

    Google Scholar 

  70. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–51. Epub 2008/05/29.

    CAS  Google Scholar 

  71. Kris MG, Natale RB, Herbst RS, Lynch Jr TJ, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003;290(16):2149–58. Epub 2003/10/23.

    CAS  Google Scholar 

  72. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003;21(12):2237–46. Epub 2003/05/16.

    CAS  Google Scholar 

  73. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–32. Epub 2005/07/15.

    CAS  Google Scholar 

  74. Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16:141–51. Epub 2015/01/16.

    CAS  Google Scholar 

  75. Solomon BJ, Mok T, Kim D-W, Wu Y-L, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–77.

    Google Scholar 

  76. Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol. 2007;25(27):4270–7. Epub 2007/09/20.

    CAS  Google Scholar 

  77. Heymach JV, Paz-Ares L, De Braud F, Sebastian M, Stewart DJ, Eberhardt WE, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2008;26(33):5407–15. Epub 2008/10/22.

    CAS  Google Scholar 

  78. Siddiqui F, Bae K, Langer CJ, Coyne JC, Gamerman V, Komaki R, et al. The influence of gender, race, and marital status on survival in lung cancer patients: analysis of Radiation Therapy Oncology Group trials. J Thorac Oncol. 2010;5(5):631–9. Epub 2010/05/01.

    Google Scholar 

  79. Russell K, Healy B, Pantarotto J, Laurie SA, MacRae R, Sabri E, et al. Prognostic factors in the radical nonsurgical treatment of stage IIIB non-small-cell lung cancer. Clin Lung Cancer. 2014;15(3):237–43. Epub 2014/01/28.

    Google Scholar 

  80. Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst. 1999;91(14):1194–210. Epub 1999/07/21.

    CAS  Google Scholar 

  81. Dresler CM, Fratelli C, Babb J, Everley L, Evans AA, Clapper ML. Gender differences in genetic susceptibility for lung cancer. Lung Cancer. 2000;30(3):153–60. Epub 2001/01/04.

    CAS  Google Scholar 

  82. Tang DL, Rundle A, Warburton D, Santella RM, Tsai WY, Chiamprasert S, et al. Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers. Carcinogenesis. 1998;19(11):1949–53. Epub 1998/12/17.

    CAS  Google Scholar 

  83. Spivack SD, Hurteau GJ, Fasco MJ, Kaminsky LS. Phase I and II carcinogen metabolism gene expression in human lung tissue and tumors. Clin Cancer Res. 2003;9(16 Pt 1):6002–11. Epub 2003/12/17.

    CAS  Google Scholar 

  84. Cote ML, Yoo W, Wenzlaff AS, Prysak GM, Santer SK, Claeys GB, et al. Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women. Carcinogenesis. 2009;30(4):626–35. Epub 2009/01/29.

    CAS  PubMed Central  Google Scholar 

  85. Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, et al. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst. 2000;92(21):1764–72. Epub 2000/11/04.

    CAS  Google Scholar 

  86. Spitz MR, Wei Q, Dong Q, Amos CI, Wu X. Genetic susceptibility to lung cancer: the role of DNA damage and repair. Cancer Epidemiol Biomarkers Prev. 2003;12(8):689–98. Epub 2003/08/15.

    CAS  Google Scholar 

  87. Wang LE, Gorlova OY, Ying J, Qiao Y, Weng SF, Lee AT, et al. Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer. Cancer Res. 2013;73(1):256–64. Epub 2012/10/31.

    CAS  Google Scholar 

  88. Yang SY, Yang TY, Li YJ, Chen KC, Liao KM, Hsu KH, et al. EGFR exon 19 in-frame deletion and polymorphisms of DNA repair genes in never-smoking female lung adenocarcinoma patients. Int J Cancer (Journal international du cancer). 2013;132(2):449–58. Epub 2012/05/11.

    CAS  Google Scholar 

  89. Ishikawa-Brush Y, Powell JF, Bolton P, Miller AP, Francis F, Willard HF, et al. Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3′ to the SDC2 gene. Hum Mol Genet. 1997;6(8):1241–50.

    CAS  Google Scholar 

  90. Shriver SP, Bourdeau HA, Gubish CT, Tirpak DL, Davis AL, Luketich JD, et al. Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer. J Natl Cancer Inst. 2000;92(1):24–33. Epub 2000/01/06.

    CAS  Google Scholar 

  91. Egloff AM, Gaither Davis A, Shuai Y, Land S, Pilewski JM, Luketich JD, et al. Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case–control study. Respir Res. 2012;13:9. Epub 2012/02/03.

    CAS  PubMed Central  Google Scholar 

  92. Wu AH, Yu MC, Thomas DC, Pike MC, Henderson BE. Personal and family history of lung disease as risk factors for adenocarcinoma of the lung. Cancer Res. 1988;48(24 Pt 1):7279–84. Epub 1988/12/15.

    CAS  Google Scholar 

  93. Adami HO, Persson I, Hoover R, Schairer C, Bergkvist L. Risk of cancer in women receiving hormone replacement therapy. Int J Cancer (Journal international du cancer). 1989;44(5):833–9. Epub 1989/11/15.

    CAS  Google Scholar 

  94. Taioli E, Wynder EL. Re: Endocrine factors and adenocarcinoma of the lung in women. J Natl Cancer Inst. 1994;86(11):869–70. Epub 1994/06/01.

    CAS  Google Scholar 

  95. Ganti AK, Sahmoun AE, Panwalkar AW, Tendulkar KK, Potti A. Hormone replacement therapy is associated with decreased survival in women with lung cancer. J Clin Oncol. 2006;24(1):59–63. Epub 2005/11/30.

    CAS  Google Scholar 

  96. Rodriguez C, Spencer Feigelson H, Deka A, Patel AV, Jacobs EJ, Thun MJ, et al. Postmenopausal hormone therapy and lung cancer risk in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomarkers Prev. 2008;17(3):655–60. Epub 2008/03/20.

    CAS  Google Scholar 

  97. Mahabir S, Spitz MR, Barrera SL, Dong YQ, Eastham C, Forman MR. Dietary boron and hormone replacement therapy as risk factors for lung cancer in women. Am J Epidemiol. 2008;167(9):1070–80. Epub 2008/03/18.

    CAS  PubMed Central  Google Scholar 

  98. Schwartz AG, Wenzlaff AS, Prysak GM, Murphy V, Cote ML, Brooks SC, et al. Reproductive factors, hormone use, estrogen receptor expression and risk of non small-cell lung cancer in women. J Clin Oncol. 2007;25(36):5785–92. Epub 2007/12/20.

    Google Scholar 

  99. Schabath MB, Wu X, Vassilopoulou-Sellin R, Vaporciyan AA, Spitz MR. Hormone replacement therapy and lung cancer risk: a case–control analysis. Clin Cancer Res. 2004;10(1 Pt 1):113–23. Epub 2004/01/22.

    CAS  Google Scholar 

  100. Ramnath N, Menezes RJ, Loewen G, Dua P, Eid F, Alkhaddo J, et al. Hormone replacement therapy as a risk factor for non-small cell lung cancer: results of a case–control study. Oncology. 2007;73(5–6):305–10. Epub 2008/05/22.

    CAS  Google Scholar 

  101. Kreuzer M, Gerken M, Heinrich J, Kreienbrock L, Wichmann HE. Hormonal factors and risk of lung cancer among women? Int J Epidemiol. 2003;32(2):263–71. Epub 2003/04/26.

    Google Scholar 

  102. Pesatori AC, Carugno M, Consonni D, Hung RJ, Papadoupolos A, Landi MT, et al. Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO). Br J Cancer. 2013;109(7):1954–64. Epub 2013/09/05.

    CAS  PubMed Central  Google Scholar 

  103. Chlebowski RT, Schwartz AG, Wakelee H, Anderson GL, Stefanick ML, Manson JE, 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):1243–51. Epub 2009/09/22.

    CAS  PubMed Central  Google Scholar 

  104. Chlebowski RT, Anderson GL, Manson JE, Schwartz AG, Wakelee H, Gass M, et al. Lung cancer among postmenopausal women treated with estrogen alone in the women’s health initiative randomized trial. J Natl Cancer Inst. 2010;102(18):1413–21. Epub 2010/08/17.

    PubMed Central  Google Scholar 

  105. Slatore CG, Chien JW, Au DH, Satia JA, White E. Lung cancer and hormone replacement therapy: association in the vitamins and lifestyle study. J Clin Oncol. 2010;28(9):1540–6. Epub 2010/02/18.

    PubMed Central  Google Scholar 

  106. Bouchardy C, Benhamou S, Schaffar R, Verkooijen HM, Fioretta G, Schubert H, et al. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens. Cancer. 2011;117(6):1288–95. Epub 2011/01/26.

    Google Scholar 

  107. Lother SA, Harding GA, Musto G, Navaratnam S, Pitz MW. Antiestrogen use and survival of women with non-small cell lung cancer in Manitoba, Canada. Horm Cancer. 2013;4(5):270–6. Epub 2013/05/30.

    CAS  Google Scholar 

  108. Planey SL, Kumar R, Arnott JA. Estrogen receptors (ERalpha versus ERbeta): friends or foes in human biology? J Recept Signal Transduct Res. 2014;34(1):1–5. Epub 2013/11/06.

    CAS  Google Scholar 

  109. Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, et al. Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002;62(7):2141–50. Epub 2002/04/04.

    CAS  Google Scholar 

  110. Stabile LP, Dacic S, Land SR, Lenzner DE, Dhir R, Acquafondata M, et al. Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome. Clin Cancer Res. 2011;17(1):154–64. Epub 2010/11/11.

    CAS  Google Scholar 

  111. Skov BG, Fischer BM, Pappot H. Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival. Lung Cancer. 2008;59(1):88–94. Epub 2007/10/02.

    Google Scholar 

  112. Wu CT, Chang YL, Shih JY, Lee YC. The significance of estrogen receptor beta in 301 surgically treated non-small cell lung cancers. J Thorac Cardiovasc Surg. 2005;130(4):979–86. Epub 2005/10/11.

    CAS  Google Scholar 

  113. Kawai H, Ishii A, Washiya K, Konno T, Kon H, Yamaya C, et al. Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer. Clin Cancer Res. 2005;11(14):5084–9. Epub 2005/07/22.

    CAS  Google Scholar 

  114. Raso MG, Behrens C, Herynk MH, Liu S, Prudkin L, Ozburn NC, et al. Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation. Clin Cancer Res. 2009;15(17):5359–68. Epub 2009/08/27.

    CAS  PubMed Central  Google Scholar 

  115. Schwartz AG, Prysak GM, Murphy V, Lonardo F, Pass H, Schwartz J, et al. Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex. Clin Cancer Res. 2005;11(20):7280–7. Epub 2005/10/26.

    CAS  Google Scholar 

  116. Ishibashi H, Suzuki T, Suzuki S, Niikawa H, Lu L, Miki Y, et al. Progesterone receptor in non-small cell lung cancer—a potent prognostic factor and possible target for endocrine therapy. Cancer Res. 2005;65(14):6450–8. Epub 2005/07/19.

    CAS  Google Scholar 

  117. Hershberger PA, Stabile LP, Kanterewicz B, Rothstein ME, Gubish CT, Land S, et al. Estrogen receptor beta (ERbeta) subtype-specific ligands increase transcription, p44/p42 mitogen activated protein kinase (MAPK) activation and growth in human non-small cell lung cancer cells. J Steroid Biochem Mol Biol. 2009;116(1–2):102–9. Epub 2009/05/23.

    CAS  PubMed Central  Google Scholar 

  118. Burns TF, Stabile LP. Targeting the estrogen pathway for the treatment and prevention of lung cancer. Lung Cancer Manag. 2014;3(1):43–52. Epub 2014/11/15.

    CAS  PubMed Central  Google Scholar 

  119. Nose N, Sugio K, Oyama T, Nozoe T, Uramoto H, Iwata T, et al. Association between estrogen receptor-beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung. J Clin Oncol. 2009;27(3):411–7. Epub 2008/12/10.

    CAS  Google Scholar 

  120. Sethi S, Coti M, Lonardo F. Expression of estrogen receptor beta 1 but not estrogen receptor beta 2 or alpha is linked to worse prognosis in stage I adenocarcinoma in women, in a large epidemiological cohort but not in a smaller, single hospital based series. US Canadian Acad Pathol. 2010; Abstract 1843.

    Google Scholar 

  121. Navaratnam S, Skliris G, Qing G, Banerji S, Badiani K, Tu D, et al. Differential role of estrogen receptor beta in early versus metastatic non-small cell lung cancer. Horm Cancer. 2012;3(3):93–100. Epub 2012/02/04.

    CAS  Google Scholar 

  122. Liu Z, Liao Y, Tang H, Chen G. The expression of estrogen receptors beta2, 5 identifies and is associated with prognosis in non-small cell lung cancer. Endocrine. 2013;44(2):517–24. Epub 2013/03/12.

    CAS  Google Scholar 

  123. Lim VW, Lim WY, Zhang Z, Li J, Gong Y, Seow A, et al. Serum estrogen receptor beta mediated bioactivity correlates with poor outcome in lung cancer patients. Lung Cancer. 2014;85(2):293–8. Epub 2014/06/22.

    Google Scholar 

  124. Zhang G, Yanamala N, Lathrop KL, Zhang L, Klein-Seetharaman J, Srinivas H. Ligand-independent antiapoptotic function of estrogen receptor-beta in lung cancer cells. Mol Endocrinol. 2010;24(9):1737–47. Epub 2010/07/28.

    CAS  PubMed Central  Google Scholar 

  125. Niikawa H, Suzuki T, Miki Y, Suzuki S, Nagasaki S, Akahira J, et al. Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma. Clin Cancer Res. 2008;14(14):4417–26. Epub 2008/06/27.

    CAS  Google Scholar 

  126. Weinberg OK, Marquez-Garban DC, Fishbein MC, Goodglick L, Garban HJ, Dubinett SM, et al. Aromatase inhibitors in human lung cancer therapy. Cancer Res. 2005;65(24):11287–91. Epub 2005/12/17.

    CAS  Google Scholar 

  127. Marquez-Garban DC, Chen HW, Goodglick L, Fishbein MC, Pietras RJ. Targeting aromatase and estrogen signaling in human non-small cell lung cancer. Ann N Y Acad Sci. 2009;1155:194–205. Epub 2009/03/03.

    CAS  PubMed Central  Google Scholar 

  128. Mah V, Seligson DB, Li A, Marquez DC, Wistuba II, Elshimali Y, et al. Aromatase expression predicts survival in women with early-stage non small cell lung cancer. Cancer Res. 2007;67(21):10484–90. Epub 2007/11/03.

    CAS  PubMed Central  Google Scholar 

  129. Abe K, Miki Y, Ono K, Mori M, Kakinuma H, Kou Y, et al. Highly concordant coexpression of aromatase and estrogen receptor beta in non-small cell lung cancer. Hum Pathol. 2010;41(2):190–8. Epub 2009/10/06.

    CAS  Google Scholar 

  130. Mah V, Marquez D, Alavi M, Maresh EL, Zhang L, Yoon N, et al. Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer. Lung Cancer. 2011;74(2):318–25. Epub 2011/04/23.

    PubMed Central  Google Scholar 

  131. Stabile LP, Rothstein ME, Cunningham DE, Land SR, Dacic S, Keohavong P, et al. Prevention of tobacco carcinogen-induced lung cancer in female mice using antiestrogens. Carcinogenesis. 2012;33(11):2181–9. Epub 2012/08/04.

    CAS  PubMed Central  Google Scholar 

  132. Verma MK, Miki Y, Abe K, Suzuki T, Niikawa H, Suzuki S, et al. Intratumoral localization and activity of 17beta-hydroxysteroid dehydrogenase type 1 in non-small cell lung cancer: a potent prognostic factor. J Transl Med. 2013;11:167. Epub 2013/07/11.

    CAS  PubMed Central  Google Scholar 

  133. Marquez-Garban DC, Chen HW, Fishbein MC, Goodglick L, Pietras RJ. Estrogen receptor signaling pathways in human non-small cell lung cancer. Steroids. 2007;72(2):135–43. Epub 2007/02/06.

    CAS  Google Scholar 

  134. Hammoud Z, Tan B, Badve S, Bigsby RM. Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma. Endocr Relat Cancer. 2008;15(2):475–83. Epub 2008/05/30.

    CAS  Google Scholar 

  135. Garon EB, Pietras RJ, Finn RS, Kamranpour N, Pitts S, Marquez-Garban DC, et al. Antiestrogen fulvestrant enhances the antiproliferative effects of epidermal growth factor receptor inhibitors in human non-small-cell lung cancer. J Thorac Oncol. 2013;8(3):270–8. Epub 2013/02/13.

    CAS  PubMed Central  Google Scholar 

  136. Shen L, Li Z, Shen S, Niu X, Yu Y, Li Z, et al. The synergistic effect of EGFR tyrosine kinase inhibitor gefitinib in combination with aromatase inhibitor anastrozole in non-small cell lung cancer cell lines. Lung Cancer. 2012;78(3):193–200. Epub 2012/09/19.

    Google Scholar 

  137. Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM. Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res. 2005;65(4):1459–70. Epub 2005/03/01.

    CAS  Google Scholar 

  138. Xu R, Shen H, Guo R, Sun J, Gao W, Shu Y. Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib. Biomed Pharmacother. 2012;66(5):384–9. Epub 2012/05/09.

    CAS  Google Scholar 

  139. Tang H, Liao Y, Xu L, Zhang C, Liu Z, Deng Y, et al. Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice. Int J Cancer. 2013;133:2473–82. Epub 2013/05/08.

    CAS  Google Scholar 

  140. Siegfried JM, Gubish CT, Rothstein ME, Henry C, Stabile LP. Combining the multitargeted tyrosine kinase inhibitor vandetanib with the antiestrogen fulvestrant enhances its antitumor effect in non-small cell lung cancer. J Thorac Oncol. 2012;7(3):485–95. Epub 2012/01/20.

    CAS  PubMed Central  Google Scholar 

  141. Sainsbury R. The development of endocrine therapy for women with breast cancer. Cancer Treat Rev. 2013;39(5):507–17.

    CAS  Google Scholar 

  142. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. Epub 2013/01/22.

    Google Scholar 

  143. Miller WR, Bartlett J, Brodie AM, Brueggemeier RW, di Salle E, Lonning PE, et al. Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist. 2008;13(8):829–37. Epub 2008/08/13.

    CAS  Google Scholar 

  144. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010;28(30):4594–600. Epub 2010/09/22.

    Google Scholar 

  145. Garon EB, Siegfried JM, Dubinett SM, Elashoff RM, Park DJ, Parikh RJ, et al. Result of TORI L-03, a randomized, multicenter phase II clinical trial of erlotinib (E) or E + fulvestrant (F) in previously treated advanced non-small cell lung cancer (NSCLC) AACR Annual Meeting 2013. 2013:abstract #4664

    Google Scholar 

  146. Traynor AM, Schiller JH, Stabile LP, Kolesar JM, Eickhoff JC, Dacic S, et al. Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer. Lung cancer. 2009;64(1):51–9. Epub 2008/08/15.

    Google Scholar 

  147. http://clinicaltrials.gov/.

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Authors and Affiliations

  1. Department of Pharmacology & Chemical Biology, University of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, 2.32b, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA

    Laura P. Stabile PhD

  2. Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, 2.18e, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA

    Timothy F. Burns MD, PhD

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Correspondence to Laura P. Stabile PhD .

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  1. Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Anna R. Hemnes

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Stabile, L.P., Burns, T.F. (2016). Sex-Specific Differences in Lung Cancer. In: Hemnes, A. (eds) Gender, Sex Hormones and Respiratory Disease. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-23998-9_7

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