1. Kristi McIntyre M.D. Resident’s lecture
Breast Cancer
Kristi McIntyre M.D.
Resident’s lecture

2. Breast cancer Risk factors Hereditary breast cancer Detection Staging
Surgical intervention
Prognostic factors
Management of early stage breast cancer

3. Breast cancer risk factors
Age/race
Reproductive issues/Estrogen-related factors
Breast histology
Life style factors
Family history/Genetic factors

4. Breast Cancer Risk Factors

5. Breast Cancer Incidence

6. Race/Ethnicity and Breast Cancer Risk
Annual incidence
Caucasian
African Americans
Hispanic
Asian
American Indian
SEER results: age adjusted only
Jemal CA:Cancer J.Clin ;2003,53:5

7. Race/Ethnicity and Breast Cancer Risk
“Adjusted Hazard Ratios”
0.4
0.6
0.8
1.0
1.2
African American
.72
Hispanics
American Indian
Asian
Only African Americans had lower breast cancer risk (p=o.oo6) than Caucasians
Cheblowski JNCI ;March 2005

8. Race/Ethnicity and Breast Cancer Risk
Combined Grade III and ER negative by race
Cheblowski JNCI ;March 2005

9. Race/Ethnicity and Breast Cancer Risk
Differences in breast cancer incidence rates between most ethnic groups can largely be explained by control of risk factors
African American women are at significantly reduced risk
African American women have a higher proportion of unfavorable features suggesting cause for higher mortality rates
Cheblowski JNCI ;March 2005

10. Reproductive Factors and Breast Cancer
Menarche < 16
Menopause >50
Menarche < OR 1.2
Menopause > OR 1.5
Null parity OR 2.0
Breastfeeding 4.3% decrease risk/yr
First live birth< OR 0.5
First live birth > OR 1.5

11. WHI Trial of Estrogen plus Progestin
E+P placebo p-value
Invasive Breast cancers
SEER high stage % %
Abnormal Mammograms
More breast cancers diagnosed at more advanced stage and increased abnormal mammograms
More breast cancers diagnosed at more advanced stage and increased abnormal mammograms
Chlebowski JAMA 2003;

12. Breast histology and breast cancer risk
Benign breast disease RR
Fibrocystic disease
Atypical ductal hyperplasia
Atypical ductal hyperplasia and
family history

13. Risk Factors for Breast Cancer
Family History Risk
First Degree relative
Premenopausal diagnosis
Bilateral disease
Premenopausal diagnosis and bilateral disease
Postmenopausal diagnosis
Second Degree relative
Premenopausal diagnosis
Postmenopausal diagnosis

14. Hereditary

15. Family history and breast cancer risk
Most hereditary breast cancers arise from mutations in BRCA1 and BRCA2
Autosomal dominant , tumor suppressor gene

19. BRCA mutations and lifetime cancer risk
50-85% breast cancer
50% Second breast cancers
15-45% ovarian cancer risk
Other malignancies:
prostrate
pancreatic
male breast cancer

20. Founder mutations and Breast cancer
Ethnic background should be considered in risk assessment for breast cancer
“ Founder” gene mutations discovered in individuals of Ashkenazi Jewish descent
50-90 % have gene susceptibility with positive family history
Founder mutations have been found in populations of Iceland,Finland, France, Holland , Russia,and Sweden

21. Models for risk assessment
Gail model
Claus model
Age
Age first live birth
Age first menses
FH-maternal only; no age
# prior breast biopsies/ADH
race
Family history
Age at diagnosis
Both models inadequate : not useful for mutation carriers or individual risk
www3.utsouthwestern.edu/cancergene/

22. Lifestyle factors and breast cancer risk
Body mass index: postmenopausal women >30% excess BMI increased risk
Dietary fat intake: increased risk
NSAID use: decreases risk
Physical activity: 1.25 to 2.5/hrs week brisk walking had 18 % decrease risk
Smoking : increased risk
Alcohol use: increased (dose dependent)

23. Risk Reduction Strategies
Average Risk
Moderate Risk
Early childbirth
Exercise
Maintain normal weight
Avoid smoking/alcohol
Avoid prolonged HRT
Chemoprevention

28. Most breast cancers are non palpable masses discovered only on screening mammograms
Malignant breast densities
have irregular borders, are stellate and
distort surrounding architecture

29. Breast Cancer Detection
United States Preventive Services Task Force
Mammogram every 1-2 years for female age 40-49(average risk)
Age > 50 annual mammography and clinical exam
Age > 70 debatable
Mammography detects only 85% of biopsy proven breast cancer hence not a substitute for tissue sampling of palpable mass

30. Breast Cancer Screening
There is almost universal agreement that randomized controlled trials of screening have demonstrated death rate from breast cancer can be reduced by periodic screening with mammography

32. MRI Breast Implant evaluation Axillary adenopathy ?occult primary
Breast cancer patients (extent of disease, response to neoadjuvant therapy)
Screening evaluation for high risk patient
Further evaluation of mammographic abnormality

33. Staging of breast cancer
Estimate extent of disease
Determine prognosis
Guide therapy

34. Staging of breast cancer
Stage 0 (DCIS)
Stage I node negative
Stage II node positive
Stage III advanced node
Stage IV distant metastasis
2003 AJCC staging change
Distinction between micrometastasis and isolated tumor cells
Identifiers for sentinel nodes
#number of positive LN

37. Management of Early stage breast cancer
1950 Halsted “radical mastectomy”
“breast cancer spreads in an orderly fashion”
12%
10 year survival
20-30% node negative breast cancer patients will develop metastatic disease
Micrometastatic disease paradigm

38. Management of Early stage breast cancer
Radical Mastectomy
Whole breast radiation
Axillary dissection
Lumpectomy
Partial breast radiation
Sentinel node biopsy
MORE LESS

39. Surgical intervention for Breast Cancer
NSABP B-04
Total Mastectomy +
Axillary dissection
Lumpectomy +
Breast radiation
Lumpectomy
alone
No difference in Overall Survival or Disease Free Survival
(20 year follow-up)
Fisher et al.NEJM2002;347:

40. Surgical Intervention of Breast Cancer
NSABP B-04
Cumulative incidence of ipsilateral breast cancer
Standard of care: lumpectomy+ Xrt
39%
14%

41. Surgical intervention for Breast Cancer
NSABP B-04
Fisher,et al.NEJM(2002):347;

42. Surgical Staging of Axilla
Axillary dissection= removal of level I and Level II lymph nodes
Morbidity : wound infection
motion restriction
arm stiffness
pain
lymphedema

44. Sentinel node mapping

45. Chemotherapy for early stage breast cancer

49. Prognostic factors in Breast cancer
Recognized Factors Potential factors
Proliferative index
Tumor grade
Vascular invasion
Her- 2
Gene microarray
Nodal status
Tumor size
Histologic type
ER/PR

50. Prognostic factors in Breast cancer
The most significant prognostic indicator for patients with early stage breast cancer is the presence or absence of axillary lymph node involvement.

52. Prognostic factors in Breast cancer
Recognized Factors Potential factors
Proliferative index
Tumor grade
Vascular invasion
Her- 2
Gene microarray
Nodal status
Tumor size
Histologic type
ER/PR

53. Prognostic factors in breast cancer
Multigene assay:
Paik et al.NEJM 2004;351:

54. Gene Microarray

55. Multigene assay to predict recurrence in node negative breast cancer

56. HER- 2/neu
Her-2/neu oncogene encodes for transmembrane receptor belonging to EGFR family
Amplified in 25-30% breast cancer
Overexpression associated with tumor aggressiveness and increased rates of recurrence

57. Her-2/neu
Basis for molecular targeted therapy with Herceptin

58. NCI clinical alert –April 25,2005
NSABP B-31
Operable breast cancer
Her 2 +, node +
Randomization
52% decrease in disease recurrence
AC x4cycles
Taxol x4 cycles +
Herceptin
AC x4cycles
Taxol x4 cycles

59. Thank you !