Breast cancer:

why do people get it and

can we prevent it?
T. Kuan Yu, M.D., Ph.D.
Houston Precision Cancer Center

What is Cancer?
Our own cells that grows without
control
Grow (faster or slower than normal cells)
Die (slower than normal cells)
Proteins and structures that are very similar to
normal cell

Why do we get cancer?

???

Basics of Cells

DNA RNA Protein

DNA is Blueprint for Cells

DNA is blue print
of cells.
Its radius is 1 nm.
If you stretch DNA
into single strand, it
would be 1600 km
long.
Only 1.5% of DNA
are genes (~20,000)
that encode proteins

Why do we get cancer?

Different events can change (i.e. mutate)
the DNA and change the protein function
With the right sets of mutations, the cells
stop listening to the control of the body
Events

cancer

that mutate DNA leads to

Breast Cancer Statistics

200,000 new cases in 2003

40,200 breast cancer deaths in 2003
Most common female malignancy
Second leading cause of female ca mortality
SEER data:
Lifetime risk of developing breast ca
13.1% in white American female
9.6% in African-American female

Breast Cancer Risk Factors

Age
Female sex

Non Modifiable

Inherited Factors
Family history
Benign breast disease
Hormones

Modifiable

Dietary Factors
Environmental factors

Largest Risk Factors

Age
DNA less stable
Accumulation of previous changes
Woman
Hormone
Breast tissue

( Courtesy of Dr. Arun Banu)

( Courtesy of Dr. Arun Banu)

10 Relative with Breast Cancer

RR* of breast cancer
Premenopausal

3.2

Postmenopausal

1.5

Premenopausal, b/l

8.8

Postmenopausal, b/l

4.0

( * RR = Relative Risk )

Family history of breast cancer

Personal history: 0.5-1%/yr
Family history:

Lifetime risk: 20-30%

Mother
Sister

BRCA 1& BRCA 2: Lifetime risk: 50-80%

( Courtesy of Dr. Arun Banu)

( Courtesy of Dr. Arun Banu)

( Courtesy of Dr. Arun Banu)

( Courtesy of Dr. Arun Banu)

( Courtesy of Dr. Arun Banu)

Estrogen Exposure Can Drive

Breast Cancer Development

Estrogen Exposure
Early menarche (< 12 yo)
Late menopause (> 55 yo)
Having no pregnancy
Childbirth after 30 yo (RR: 4-5x)
Exogenous estrogen use
Obesity (post-menopausal)

Combined Oral Contraceptive May

Increase Risk of Breast Cancer
53 297 women with breast cancer and 100 239 women
without breast cancer from 54 studies
Combined oral contraceptives:
current users RR 1.24 [1.15-1.33]
1-4 years after stopping RR 1.16 [1.08-1.23],
5-9 years after stopping RR 1.07 [1.02-1.13]
10+ years after stopping use RR 1.01 [NS]
(Lancet. (1996)22;347(9017):1713)

Combined Oral Contraceptive May

Not Increase Risk of Breast Cancer
4575 women with breast cancer and 4682 controls
Combined oral contraceptives:
current users RR 1.0 [NS]
Former users RR 0.9 [NS]
No association with family history or use at
young age
(Lancet. (1996)22;347(9017):1713)

Risk from Hormone

Replacement after Menopause

What Can We Do to Prevent

Breast Cancer?
Estrogen Exposure Risk:
Pregnancy
Early Childbirth
Breast Feed
Limit Exogenous Estrogen

Western Lifestyle/Food Increase Breast

Cancer Risk in Asian-American
>1500 Asian-American immigrants (1983)
born in the West 60% higher risk than born in the East.
Among those born in the West: women with three or four
grandparents born in the West 50% higher risk than those
with all grandparents born in the East.
Among those born in the East: lived in the West for > 10
years 80% higher than more recent migrants.
Risk was unrelated to age at migration for women migrating
at ages less than 36 years.
(JNCI (1993) 85 (22): 1819)

Obesity Increases Breast Cancer Risk in

Postmenopausal Woman
Obesity leads to 11,000 to 18,000 deaths per year
from breast cancer in U.S. for women over age 50
Obesity increase the risk of breast cancer by 1.5
fold among postmenopausal women who do not
use menopausal hormones
Due to increased levels of estrogen in obese postmenopausal women, whose ovary is not
functioning

What Can We Do to Prevent

Breast Cancer?
Food Risk:
Western diet/lifestyle
Weight control (post-menopausal)
Soy isoflavones may be protective
for prememopausal breast cancer
(RR 0.41)

Chemicals May Increase Breast

Cancer risk
Many chemicals led to cancer developments
in lab animal
No association seen with DDT, DDE,
polychlorinated biphenyls and High power
line in population studies

Radiation Increases Breast

Cancer risk
Woman of the atomic bombings in Japan during
World War II;
Women with Hodgkins disease treated with
radiation therapy
Girls treated with RT for non-malignant conditions
Young women with large numbers of diagnostic xray to monitor treatment for TB or severe scoliosis.

Prior RT to breast
Mantle RT
Relative risk of breast ca depends on the age at
which she received RT
56% for women 19 yrs of age at RT
7% for women b/ 20-29 yrs of age at RT
1% for women 30 yrs of age at RT

Cancer develops 10-15 yrs later

Usually medial portion of the breast

What Can We Do to Prevent

Breast Cancer?
Chemical Risk:
Not clear
Radiation Risk:
Avoid unnecessary exposure of RT
such as diagnostic X-ray that are not
needed

What Can We Do to Prevent

Breast Cancer?
Early Detection:
Self Breast Awareness
Annual Mammogram ( 40)
Clinical breast exam about every 3
years for women in their 20s and 30s
and every year for women 40

Screening Mammography
HIP (Health Insurance plan of NY) Study
61,000 women, age 0-64 yrs
Randomization:
Screening mammo vs. routine medical care

Results:
Mortality rate was reduced by 33% in screened
women 50-59 yrs of age
Survival difference was higher by 7 to 10 yrs after
diagnosis in women who had screening mammography

The Gail Model

Calculates a womans 5-year and lifetime risk of
developing breast cancer

Includes:
Current age

Number of breast biopsies

Number of 1st-degree
female relatives with a
history of breast cancer

History of atypical
hyperplasia

Age at first live birth,

or nulliparity

Race

Age at menarche

For Woman with BRCA1/2 Mutations

( Courtesy of Dr. Arun Banu)

NSABP-P1(BCPT): Schema

Eligible Women at High Risk

(5-yr risk 1.66% or age over 60)

Randomization
n = 13,388
Tamoxifen
5 Years
n = 6681
Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.

Placebo
5 Years
n = 6707

Invasive Breast Cancer Cases by ER Status

150
130

Number of Events

Placebo
Tamoxifen

100

50
31

38

41
14

Negative

Positive
ER Status

Adapted from Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.

10

Unknown

Rate of Invasive Breast Cancer

Events

Rate/1000

40

Placebo
Tamoxifen

30

175
89

Rate per 1000

43.4
22.0

Placebo

P < 0.00001

49%
reduction

20
10
0

Tamoxifen

Years
Adapted from Fisher B, Constantion JP, Wickerham DL, et al. J Natl Cancer Inst. 1998;90:1371-1388.

Why Not Just Treat All High-Risk

Women With Tamoxifen?
Less than 5% of high-risk women elect to take tamoxifen when
offered.
Tamoxifen has some serious side effects (particularly for
women age 50).
Type of event

Risk Ratio
(all ages)

Risk Ratio
(ages 50)

Endometrial
cancer

2.53

4.01

Stroke

1.59

1.75

Pulmonary
embolism

3.01

3.19

Deep vein
thrombosis

1.60

1.71

Breast Cancer Prevention

Raloxifene (MORE Trial)*
Post menopausal female with osteoporosis
Breast cancer reduction by 62%
Invasive breast cancer by 72%
Invasive ER+ive breast cancer
No associated with uterine cancer
Side Effects:
Increased risk of thromboembolic event
28% hot flashes with raloxifene vs. 21% in placebo
40% reduction in cardiovascular events
*Breast Cancer Res Treat 65:125-134, 2001

Prophylactic Mastectomy for High risk Woman

Removes most but not all breast tissue

Total (simple) mastectomy appears more
effective than subcutaneous mastectomy
Shown to reduce risk of breast cancer by
90% in women with BRCA mutations
Hartmann LC, Sellars TA, Schaid DJ, et al. J Natl Cancer
Inst. 2001;93:1633-37.

NewEnglJMed 2001;345:159-64

Oophorectomy for Woman with High Risk for

Breast cancer
Oophorectomy
Prevents breast ca in BRCA 1 and 2
RR reduction is 50% in premenopausal pts
RR reductions may be higher if done before the
age of 40 yrs and that the duration of protection
is approx. 15yrs
JCO 23(8):1656-1663; 2005

Conclusions
Many Non-Modifiable risk factors for breast
cancer
Early dectection

Many Modifiable risk factors for breast cancer

Reduce estrogen exposure
Adjust diet and weight
Prevent exposure from unnecessary chemical and
radiation

Thank You
Acknowledgement for materials in slides:
Dr. Arun Banu
Dr. Hemangini Shah