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The Lung Cancer Epidemic: is there anything we can do?. Diana C. Márquez-Garbán. University of California, Los Angeles Division of Hematology-Oncology. Acknowledgements. National Program Excellent University EU/Slovakia Dr. Martina Nebohácová. National Program Excellent University

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slide1

The Lung Cancer Epidemic:is there anything we can do?

Diana C. Márquez-Garbán

University of California, Los Angeles

Division of Hematology-Oncology

slide2

Acknowledgements

National Program Excellent University

EU/Slovakia

Dr. Martina Nebohácová

National Program Excellent University

EU/Slovakia

UCLA

Richard J. Pietras

Hermes J. Garbán

Hsiao-Wang Chen

Olga Weinberg

Edward Garon

Eugene Tsai

Jeison Recinos

UCLA Lung Cancer SPORE Program

Dr. Steven Dubinett

slide3

Global Incidence

  • 1.3 million deaths/year worldwide.
  • Lung cancer kills more people than any other cancer
  • Number one killer in men and second in women
  • 5 year survival still at 14%
  • Risk factors: radon, asbestos, air pollution

Tobacco smoke responsible for 87% of cases of Lung Cancer

slide4

Smoking and Lung Cancer: History

“Phenomenal increase in the number of deaths attributed to cancer of the lung” (1922-1947)

Cigarette smoking is related to Lung Cancer

slide5

Death rate from lung cancer and consumption of tobacco (1900-1950)

Lung Cancer

Tobacco

Cigarettes

Doll et al. British Medical Journal (1950)

slide7

Smoking prevalence for men in Slovakia

The Tobacco Atlas, WHO, 2002

slide8

Smoking prevalence for women in Slovakia

The Tobacco Atlas, WHO, 2002

slide9

Toxic chemicals in tobacco smoke

* Nicotine – the addictive agent in tobacco smoke

* Formaldehyde – used in preservation of laboratory specimens

* Ammonia – used in toilet cleaner

* Hydrogen Cyanide – used in rat poison

* Acetone – used in nail polish remover

* Carbon monoxide - found in car exhaust

* Tar - particulate matter in cigarette smoke

* Toluene - found in paint thinners

* Phenol – used in fertilisers.1,2

slide11

Second-Hand Smoke

Second-hand smoke also does

slide12

Smoker’s lung

Lung Cancer

Normal and Smoker’s lung

Normal

slide14

Lung Cancer Facts

Myth: Lung cancer is a man’s disease.

Fact: The incidence of lung cancer in men has been leveling off in recent years. In women, however, the incidence is rising rapidly.

slide15

Lung cancer among women at epidemic proportions

Age-adjusted death rates for lung cancer and breast cancer among women,

US, 1930-1997.

600% increase in death rate in 50 years

slide16

1960: First brand specifically manufactured for women

Virginia Slims:

“You've come a long way, baby"

"It's a woman thing”

"Find Your Voice”

slide20

Classification

  • Non-Small Cell (~85%):
  • Adenocarcinoma: 40% of all cases
    • Most common among women
  • Squamous
  • Large Cell
  • Small Cell
  • Related to Smoking
  • More Aggressive than NSCLC
slide22

Lung Cancer

Symptoms

Persistent cough

Hoarseness

Change in color (blood) or amount of sputum

Recurrent pneumonia, bronchitis

Diagnosis

Radiology: Chest X-ray, CT scan, MRI scan, PET scan

Biopsy: Needle, bronchoscope-directed, open surgical

slide23

CT Scan

Lung Cancer

X-ray

slide24

Staging and Treatment of Lung Cancer

Stage IEarlySurgery

Stage II +/- Radiation

Stage III +/- Chemotherapy

Stage IV AdvancedChemotherapy

slide25

Non-small Cell Lung Cancer

  • Staging:

Estimate prognosis

Guide treatment decisions

  • 70% present with advanced locoregional or metastatic involvement

Stage IIIA, IIIB, or IV

5 year survival 1-25%

Ginsberg RJ, et al. Cancer: Principles and Practices of Oncology. 5th ed. 1997;858-911.

slide26

Lung Cancer: One Name, Many Diseases

  • Heterogenous disease:
    • Smokers vs. non-smokers
    • Women vs men
  • Epidemiologic findings suggest women more susceptible than men to the effects of tobacco smoke (Henschke C, JAMA 2006)
  • Women develop the disease at an earlier age and with less reported tobacco exposure than men
  • Among non-smokers, women are particularly vulnerable to lung cancer (80% of cases) ?
  • Women: increasing incidence
slide27

Do Hormones Influence Lung Cancer Progression?

  • Estrogen contributes to normal lung development
  • Association of estrogen levels and lung cancer survival
    • Serum estrogen elevated in women with lung cancer compared to similar age without lung cancer(Tiuriunova et al, 1986)
    • Hormone replacement therapy and lung cancer survival
  • Lung epithelium express ER- and ER-
    • Receptors are active
  • Lung epithelium produce estrogen (via aromatase)
  • Estrogen stimulates proliferation in vitro and in vivo
slide28

Cell functions and alterations

In vitro: cell models

In vivo: tumor xenografts in mice

slide29

Estrogen Receptor : Membrane and Nuclear Actions in Tumor Growth Regulation

Gruber et al. New Engl J Med (2002)

slide30

Antibodies to ERa and ERb React with Nuclei and Membrane-Cytoplasmic Sites in NSCLC Cells in vitro

ERa ERb

Non-Permeabilized

FITC-conjugated secondary antibody to primary

C-terminal or N-terminal ER antibodies

Permeabilized

slide31

Estrogens stimulate growth of non-small cell lung cancer

Estrogen enhances NSCLC proliferation several-fold

(Stabile et al. 2002, 2004; Pietras et al. 2005)

slide32

Estrogen Receptor a and Estrogen Receptor b: Expression in NSCLC from the Clinic

Extra-nuclear localization

Nuclear localization

ER-alpha

ER-beta

estrogen signaling interacts with egfr her pathways

Src

Estrogen signaling interacts with EGFR/HER pathways

EGFR/HER

estrogen

shc

Faslodex (ICI 182,780)

ER

TKI (Erlotinib/Gefitinib)

MNAR

ER

ARO

cytoplasm

MAPK/AKT

ER

ER

Ligand-independent

Ligand-dependent

P

ER

SRC-3

Growth Survival Angiogenesis

TF

ER

ER

nucleus

slide35

Activated Estrogen Receptor Alpha is present in NSCLC tumor specimens

S118

S167

A/B

C

D

E

F

N

C

Estrogen receptor alpha serine phosphorylation

ER-phospho S118

ER-phospho S167

80% (16/20 adeno)

88% (15/17 adeno)

slide37

NSCLC Tissue Microarray

Standard Histologic Block

Tissue

Cores

slide38

Lung tumor microarray: tumor aromatase and survival

Low Aromatase

Low Aromatase

(blue curve)

High Aromatase

High Aromatase

(red curve)

Survival probability in postmenopausal women with Stage I/II NSCLC and tumor aromatase expression (P<0.038)

slide39

What can we do?

Tobacco is the world’s single most avoidable cause of death

slide40

Most Countries Have Not Implemented Effective Tobacco Control Policies

WHO Report on the Global Tobacco Epidemic, 2008

slide41

In the 20th century the tobacco epidemic killed 100 million people worldwide

During the 21st century, it could kill 1,000 million

WHO Report on the Global Tobacco Epidemic, 2008

slide43

Lung Cancer Facts

90% of new smokers begin as teenagers; one third of these new smokers will eventually die of tobacco related diseases.

slide44

1970-today: advertising with so-called “light” and “low-tart”

Tobacco companies use lies:

cigarettes with “reduced risk”

slide45

Risks men are not exposed to:

Birth Control Pill- Increased risk of heart attack and stroke

Mother to be- baby likely to be under weight

Smoking reduces fertility

Reach menopause earlier than non smokers

Higher risk of osteoporosis

Increased risk of cervical cancer

Stopping:

- Improves weight of baby

- After 2y risk of HA and stroke decrease

slide46

Myths about smoking

It won't happen to me.

It’s not like I am hurting anyone but myself.

I'm not hooked. I can stop anytime I want.

4 Sure I smoke, but at least I don't do drugs, have unsafe sex, or get drunk.

5 It’s better to smoke because if I quit, I’m going to get fat.

6 I smoke "light" cigarettes, so I won't get hurt as much.

7 I've tried to quit, but I can't.

slide47

Second Hand Smoke

It causes heart disease and lung cancer

Exposed at home or work- Increased risk of lung cancer and heart disease

People with heart disease at increased risk of HA

Even brief exposure can be dangerous

In children:

  • Respiratory symptoms in children and slows the growth of their lungs
  • Sudent infant death syndrome, acute respiratory infections, ear problems and worsens asthma
slide48

Advertisement from Australian campaign to prevent smoking in teenagers

Every cigarette is doing you damage