Breast Cancer

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Breast Cancer

• Kristi McIntyre M.D.
• Residents lecture

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Breast cancer

• Risk factors
• Hereditary breast cancer
• Detection
• Staging
• Surgical intervention
• Prognostic factors
• Management of early stage breast cancer

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Breast cancer risk factors

• Age/race
• Reproductive issues/Estrogen-related factors
• Breast histology
• Life style factors
• Family history/Genetic factors

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Breast Cancer Risk Factors
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Breast Cancer Incidence
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Race/Ethnicity and Breast Cancer Risk

• Annual incidence

Caucasian
137 African Americans
120 Hispanic
82 Asian
93 American Indian
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SEER results age adjusted only
Jemal CACancer J.Clin 2003,535
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Race/Ethnicity and Breast Cancer Risk

• Adjusted Hazard Ratios

1.0
0.8
0.6
0.4
1.2
.72
African American
Hispanics
American Indian
Asian
Only African Americans had lower breast cancer
risk (po.oo6) than Caucasians
Cheblowski JNCI March 2005
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Race/Ethnicity and Breast Cancer Risk

• Combined Grade III and ER negative by race

Cheblowski JNCI March 2005
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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
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Reproductive Factors and Breast Cancer

• Menarche lt 16

Menopause gt50
Menarche lt16 OR
1.2 Menopause gt50 OR
1.5 Null parity
OR 2.0 Breastfeeding 4.3 decrease
risk/yr First live birthlt20
OR 0.5 First live birth gt35
OR 1.5
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WHI Trial of Estrogen plus Progestin

• EP
  placebo p-value

Invasive Breast cancers 199
150 0.003
SEER high stage 25
16 0.041
Abnormal Mammograms 716 395
0.0001
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 2003289. 3243
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Breast histology and breast cancer risk

• Benign breast disease RR

Fibrocystic disease
0 Atypical ductal hyperplasia
4.3 Atypical ductal
hyperplasia and 11.0
family history
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Risk Factors for Breast Cancer

• Family History
  Risk

• First Degree relative
• Premenopausal diagnosis 3.0
• Bilateral disease 5.0
• Premenopausal diagnosis and bilateral disease
  9.0
• Postmenopausal diagnosis 1.5
• Second Degree relative
• Premenopausal diagnosis 1.2
• Postmenopausal diagnosis 0

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Hereditary
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Family history and breast cancer risk

• Most hereditary breast cancers arise from
  mutations in BRCA1 and BRCA2

Autosomal dominant , tumor suppressor gene
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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
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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

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Models for risk assessment

• Gail model

Claus model
http//bcra.nci.nih.gov/brc
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/
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Lifestyle factors and breast cancer risk

• Body mass index postmenopausal women gt30 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)

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Risk Reduction Strategies
Average Risk
Moderate Risk

• Early childbirth
• Exercise
• Maintain normal weight
• Avoid smoking/alcohol
• Avoid prolonged HRT

• Chemoprevention

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

• United States Preventive Services Task Force

• Mammogram every 1-2 years for female age
  40-49(average risk)
• Age gt 50 annual mammography and clinical exam
• Age gt 70 debatable

Mammography detects only 85 of biopsy proven
breast cancer hence not a substitute for tissue
sampling of palpable mass
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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

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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

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Staging of breast cancer

• Estimate extent of disease

Determine prognosis
Guide therapy
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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

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

• MORE
  LESS

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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
Fisher et al.NEJM20023471456-61
(20 year follow-up)
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Surgical Intervention of Breast Cancer

• NSABP B-04
• Cumulative incidence of ipsilateral breast cancer
• Standard of care lumpectomy Xrt

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Surgical intervention for Breast Cancer

• NSABP B-04

Fisher,et al.NEJM(2002)3471454-61
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Surgical Staging of Axilla

• Axillary dissection removal of level I and Level
  II lymph nodes

Morbidity wound infection motion
restriction arm stiffness pain
lymphedema
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Sentinel node mapping
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Chemotherapy for early stage breast cancer
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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
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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.

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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
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Prognostic factors in breast cancer

• Multigene assay

Paik et al.NEJM 20043512817-26
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Gene Microarray
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Multigene assay to predict recurrence in node
negative breast cancer
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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

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Her-2/neu
Basis for molecular targeted therapy with
Herceptin
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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
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Thank you !