Gender Issues in Lung Cancer

Silvia NovelloUniversity of Turin-Italysilvia.novello@unito.it

www.womenagainstlungcancer.eu

NO specific (“gender driven”) therapeutic approach is nowadays available

NO specific (“gender driven”) diagnostic approach is nowadays available

Deep-Sequencing Study of LungAdenocarcinoma in Female Never-Smokers

Kim SC et al, PlosONE Feb 2013

“…..none of the mutations or fusion genes was found inmore than one patient”

Lung cancer mortality in European women: Trends and predictions

Bosetti C, Malvezzi M et al Lung Cancer 2012

Thompson CA The Central European Journal of Medicine, 2012

Current Trends in Austria

Cancer Mortality in Italy

MEN WOMEN2008 Cancer Deaths registered 97,773

144.1/100,000 75010

84.3/100,000 Lung Cancer (all ages) 25,366 *

37.7/100,000 7,743°

9.5/100,000

Projection to 2012 Cancer Deaths 100.000

132,5/100,000 78,000

80.5/100,000 Lung Cancer (all ages) -

33.3 /100,0008,500§

9.8/100,000

Malvezzi M et al, Tumori May 2012

*leading cause for all ages accounting for over 25% of all male cancer deaths , °after breast and intestines §becoming second cause

US: Increasing Lung Cancer Death Rates Among Young Women in Southern and Midwestern

States

Jemal A et al, JCO Aug 2012

A: CaliforniaB: New YorkC: Alabama

Female Gender as indipendent Prognostic Factor in NSCLC: a Meta-analysis

Nakamura H et al, Ann Thorac Cardiovasc Surg 2011

N trials: 39N pts: 86800% ♀: 37.7%

Lung Cancer Prognosis in Spain

Salmeron D et al, Respiratory Medicine (2012) 106, 1301e1308

Cases diagnosed with lung cancer during the period 1995-1999 were followed up until December 31, 2004 in 7 region (15% Spain population).

28.7%16.8%

Salmeron D et al, Respiratory Medicine (2012) 106, 1301e1308

Cases diagnosed with lung cancer during the period 1995-1999 were followed up until December 31, 2004 in 7 region (15% Spain population).

Lung Cancer Prognosis in Spain

Impact of Cigarette Smoking on Cancer Risk in Europe

Agudo A et al, JCO Dec 2012

N= 441,211TRC=14,563Follow-up=11yrs

(TRC

)

[AFp= population attributable fraction using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country]

Funatogawa I et al, BMJ Open Sept 2012

Women’s attitudes regarding tobacco control policies

N=5000 (2935 never smoker) Czech Republic, France, Ireland, Italy, and Sweden June-July 2008 The largest proportions of women were >55 year age

Dresler C et al, Scandinavian Journal of Public Health Sept 2012

“New tobacco control laws would prompt smokers to quit”

AGREEMENT: 46.8% Ireland43.6% Sweden30.5% France20.9% Italy15.1% Czech Republic

Implementation of comprehensive smokefree laws

= % people quitting smoke

Gender differences in life expectancy in Korea (’70-2005)

Yang S et al; Social Science & Medicine, May 2012

Not only Smoking

J Sisti, P Boffetta, Int J Cancer 2012

NOT evaluated

- Diet- Outdoor air pollution- Occupational Exposures- High-temperature frying- Pneumonia in Europe/China

A. Ruano-Ravina et al., Arch Bronconeumol. 2012

Radon in Never Smokers (Spain)variable N (%)Sex Female Male

58 (84.1%)11 (15.9%)

Adenocarcinoma 56 (81%)Age at diagnosis Mean (95% CI) 68.6 (65.8–71.4)

[25% diagnosed ≤60yrs]Concentration of residential radon (Bq/m3) in the cases included Mean (95% CI) 266 (227–304)

The median concentration of radon in the males’ homes was 199 Bq/m3, vs 238 Bq/m3 in thefemales’ homes (Mann–Whitney U, P=.412), although there are only 11 males out of the 69 participants.

Weight for Height in Relation to Risk of Cancer in Canadian Women (N=90.000)

Kabat GC et al, American Journal of EpidemiologyFeb 2012

• W/Hx was positively associated with the risk of 4 cancers (postmenopausal breast cancer, endometrial cancer, kidney cancer, and lung cancer in never smokers)

Risk of lung cancer associated with domestic use of coal in China (N=37.272)

Barone-Adesi F et al, BMJ Aug 2012

Compared with

smokeless coal, an

increased risk of lung cancer death (HR 36

in M and 99 in W)

Association between mean time spent indoors at home each day (excluding sleeping) and risk of death from lung cancer among users of smoky coal

RT mortality from heart disease and lung cancer after radiotherapy for breast cancer

N=558 871 (45.8%b right, 46.2% left)

Henson KE et al, BJC Dec 2012

Risk of a second primary lung cancer after a first invasive breast cancer according to ER status

ER negative ER positiveWomen 50,781 171,367RT for breast 27,367 99,382Lung Cancer 418

(SIR 1.20)1444

(SIR 0.96)Time since breast cancer diagnosis1-<55-9≥10

24412252

672550222

Age at breast cancer diagnosis<5050-5960-69≥70

6612915766

134341661308

12 SEER registries, 1992–2008Schonfeld SJ et al, Cancer Causes Control Aug 2012

“the absolute rate of lung cancer increased with age at breast cancer diagnosis.”

“Ormonal Factors” and and Lung Cancer Risk: A Meta-analysis

Zhang Y et al, Chin J Lung Cancer, December 2012

older age at menarche in North America women RR=0.83; 95%CI: 0.73-0.94

Cases % (N=407)§

Controls % (N=499)§

*Model 1OR (95% CI)

p **Model 2OR (95% CI)

p

Age at first livebirth 22 22-25 26-30 ≥31

20.431.335.312.5

12.729.740.217

10.92 (0.54–1.56)0.77 (0.46–1.29)0.57 (0.31–1.06) 0.05

10.95(0.31–1.06)0.73 (0.42–1.27)0.52 (0.26–1.01) 0.03

Age at menopause<4646-51 ≥51

25.833.624.4

18.033.238.7

10.65 (0.41–1.02)0.49 (0.31–0.79) 0.003

10.70 (0.43–1.14)0.51 (0.31–0.84) 0.01

Reproductive duration<3333–3637-40≥41

26.324.124.110.1

20.431.216.713.8

10.77 (0.48–1.24)0.67 (0.43–1.06)0.44 (0.25–0.79) 0.01

10.84 (0.51–1.40)0.76 (0.47–1.25)0.46 (0.25–0.85) 0.02

Pesatori AC et al, Int J Cancer 2012

§ some missing data; *adjusted for area, age at study, smoking (ever/never, pack-years, time since quitting); **: adjusted for area, age at study,smoking (ever/never, pack-years, time since quitting), ETS, education, BMI.

Never Smokers: Geographic and Gender variations

Sun S et al, Nat Rev Cancer 2007

Genome-wide association lung cancer susceptibility loci in never-smoking women in Asia

Lan Q et al, Nature Genetics Nov 2012

- 5,510 lung cancer cases - 4,544 controls

known

new

We fight against the stigma……

BUT we MUST eradicate the problem at its root