Breast Cancer

Steven Jones, MD

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Epidemiology of Breast Cancer

• 182,460 American women diagnosed each year.

• 40,480 die each year from the disease• Lifetime risk through age 85 is 1 in 8, or

12.5%• 2nd leading cause of cancer deaths among

US women, after lung cancer• Leading cause of death among women age

40-55

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Mammary GlandAnterior view

Lobar/Lactiferous duct

Lobule

Fat

Ampulla Nipple

Areola gland

Areola

Lobular duct

Bre

ast

An

ato

my

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Lobar/Lactiferous Duct Cross Section

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The entire duct may be filled with abnormal, atypical cells.

This condition is actually an early breast cancer.

Ductal Carcinoma In Situ (DCIS)

Lobar/Lactiferous Duct Cross Section

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Cancer cells that break out of the duct and invade the breast tissue.

Invasive Ductal Carcinoma (IDC)

Lobar/Lactiferous Duct Cross Section

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Breast Cancer Risks

• Gender – 1% male• Age - < 30 – rare ; risk rises sharply

after 40• Personal Hx – 0.5-1% per yr in contra

breast• Family Hx- 20-30% of Br Ca have +

fm hx; only 5-10% have an inherited mutation

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Consider BRCA 1 / 2 testing:

• < 35• <50 with another positive relative <

50• Any age with 2 other positive

relatives• Male relative with breast cancer• Jewish ancestry with young age or 1

relative

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Breast Cancer Risks

• Benign Breast disease – Atypical ductal hyperplasia – 4.5-5.0 RR

• Lobular Carcinoma in Situ – 5.4-12.0 RR, 1% per year.

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Excess growth within the duct includes abnormal or atypical cells.

The presence of this condition increases the risk of developing breast cancer.

Atypical Ductal Hyperplasia (ADH)

Lobar/Lactiferous Duct Cross Section

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Lobular Hyperplasia

Atypical Lobular Hyperplasia

Excess growth in the lobules

Lobular Hyperplasia

Atypical lobular hyperplasia may also develop. If atypical lobular hyperplasia progresses in severity a condition referred to as Lobular Carcinoma In Situ (LCIS) may develop.

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Breast Cancer Risks

• Hormonal factors – early menarche, late menopause, age of 1st pregnancy, HRT with progesterone

• Environment, lifestyle, and diet – ionizing radiation increase risk

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High Risk Patients

• Gail model• Chemo prevention• Increased surveillance

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Magnification Views– Improves resolution

– Better determination of the shape, distribution,

and number of microcalcifications

– Questionable density from summation shadows will dissipate

Mam

mog

rap

hy

Additional Views

Current status of the Digital Database for Screening Mammography," M. Heath, K.W. Bowyer, D. Kopans et al, pages 457-460 in Digital Mammography, Kluwer Academic Publishers, 1998.

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0

1

2

3

4

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Incomplete assessment

Negative

Benign finding

Probably benign

Suspicious

Highly suggestive of malignancy

Additional imaging evaluation

Short interval follow-up

Biopsy should be considered

Appropriate action to be taken

CategoryAssessment Recommendations

BI-

RA

DS

™

Report Organization

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Characteristics of imaged lesions • Size• Shape• Border definition• Internal echogenicity• Posterior enhancement• Architectural changes• Gray scale comparison to adjacent breast tissue

Breast Ultrasound

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Benign vs. Malignant

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Open Surgical BiopsyB

iop

sy O

pti

on

s

Performed in the Operating Room

An incision is made in the breast and a large tissue sample is cut and removed

In some cases, a wire is inserted into the breast to

aid in localizing the abnormality

Possible scarring and disfiguration that can

interfere with future mammograms

More costly than other biopsy methods

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Bio

psy O

pti

on

s

Can be performed in an outpatient setting or doctor’s office

No anesthesia

No sutures

Several needle insertions to collect fluid and/or cellular material

Cyst aspiration for fluids

Unable to mark biopsy site

Fine Needle Aspiration (FNA)

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Bio

psy O

pti

on

sCore Needle Biopsy

Can be performed in an outpatient setting or

doctor’s office

Local anesthesia

No sutures

4 – 6 needle insertions to collect a sufficient amount of breast tissue for an accurate diagnosis

Unable to mark biopsy site

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Cancer Cure?

cut it out or

burn it out

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National Surgical Adjuvant Breast Project

• Radical mastectomy vs

• Simple mastectomy with axillary irradiationvs

• Simple mastectomy with delayed axillary dissection

Started in 1971, 1665 patients enrolled, 25 year follow up

No difference in disease free or overall survival

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Breast Cancer Multifocality

Holland et al.

• Only 37% of cancers are confined to the primary tumor.

• 20% have additional cancer within 2 cms.

• 43% have additional cancer beyond 2 cms.

Holland R, Veling S, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving treatment. Cancer 1985; 56: 979

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NSABP B-06

• Total mastectomy vs lumpectomy vs lumpectomy plus irradiation

• No significant difference in survival• 14.3% recurrence in lumpectomy

plus radiation group at 25 years• 39.2% recurrence in lumpectomy

without radiation group at 25 years

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Conclusion NSABP B-06

• Lumpectomy followed by breast irradiation is the appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.

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Axillary Biopsy and Control

• 1. Staging– In the absence of distant mets number

of positive lymph nodes is the most important prognostic factor.

2. Regional ControlIn clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3%

3. Small survival advantage (3-5%)

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Parasternal (internal thoracic) nodes

Subclavian (apical axillary) nodes

Interpectoral(Rotter’s) nodes

Central axillarynodes

Brachial (lateral axillary)

nodes

Subscapular (posterior axillary)

nodes

Pectoral (anterior axillary)

nodes

Mammary GlandAnterior view

Bre

ast

An

ato

my

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Sentinel Lymph Node

• Technetium labeled sulfur colloid• Isosulfan blue (lymphazurin 1%)• Combined – 97% ID’ed; 6% false

negative• 1% anaphylactic reaction to blue dye

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Systemic Therapy

• Cytotoxic chemotherapy • Hormonal therapy – 50% reduction of

recurrence, 26% reduction in mortality

• Targeted therapy - Herceptin – 50% reduction of recurrence.

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NSABP B-18

• Started 1988; 1523 pts, 4 cycles AC• 80% overall response• 13% pathologic complete response• No difference in overall survival• Only 3% had progression of disease• 25% downstaging at axilla• 30% of women will downstage to allow

conversion from mastectomy to BCS

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Indications

• To downstage women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downstage.

• Early initiation of systemic treatment• In vivo assessment of response, good

biological model• Less radical surgery needed

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By age 30 1 out of 2,212By age 40 1 out of 235By age 50 1 out of 54By age 60 1 out of 23By age 70 1 out of 14By age 80 1 out of 10Ever 1 out of 8

By age 30 1 out of 2,212By age 40 1 out of 235By age 50 1 out of 54By age 60 1 out of 23By age 70 1 out of 14By age 80 1 out of 10Ever 1 out of 8

Risk of breast cancer increases with age

Feuer EJ, Wun LM. DEVACN: Probability of Developing or Dying of Cancer.

Version 4.0

Bethesda, MD: National Cancer Institute 1999

Facts

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