BIOLOGICAL PRINCIPLES OF
BREAST CANCER TREAMENT
Benjamin O. Anderson, M.D.
Director, Breast Health Clinic
Professor of Surgery and Global Health, University of Washington
Joint Member, Fred Hutchinson Cancer Research Center
Seattle, Washington
U.W.S.O.M.
F.H.C.R.C.
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
RADICAL MASTECTOMY
MODIFIED RADICAL MASTECTOMY
EVOLUTION IN CANCER TREATMENT
BREAST CONSERVATION:
Long-term validation
NSABP B-06:
Effect of Lumpectomy v. Mastectomy on Recurrence
CUMULATIVE INCIDENCE
All Patients
Node Negative
Lumpectomy
Lumpectomy
Lumpectomy + radiation
Lumpectomy + radiation
Node Positive
Lumpectomy
Lumpectomy + radiation
YEAR
No. of patients / No. of recurrences
Lumpectomy:
Lumpectomy + XRT:
570/210
361/121
209/89
567/62
375/50
192/12
NSABP B-06:
Effect of Lumpectomy v. Mastectomy on Survival
Cohort B
Cohort C
DISTANT DISEASE-FREE SURVIVAL (%)
Cohort A
YEAR
Total Mastectomy:
Lumpectomy:
Lumpectomy + XRT:
692/265
No. of patients / No. of recurrences
569/233
494/192
699/302
714/278
634/282
628/253
520/236
515/204
SURGICAL MARGINS:
Surgical Principles

Cancers must be removed with NEGATIVE
MARGINS for adequate local treatment

Some cancers can be removed with negative
margins with a partial mastectomy

Other cancers require mastectomy for complete
removal with negative margins
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
BREAST CONSERVING SURGERY
BREAST CONSERVING RADIATION THERAPY
BREAST CONSERVATION:
Radiation Therapy Concepts

Surgical lumpectomy: removes tumor bulk

Radiation therapy after surgery: eradicates residual
microscopic cancer

POSTOPERATIVE RADIATION TREATMENT
DECREASES LOCAL RECURRENCE RISK OF
BREAST CANCER FROM 30-40% to 10%
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
BIOLOGICAL BASIS OF TREATMENT
Outline
 Breast
cancer surgery
 Breast
radiation therapy
 Systemic
(drug) therapy
AXILLARY NODE DISSECTION:
Complication Rates

Lymphedema
– Acute: 40%
– Chronic: 15-20%

Paraesthesia: 40%

Need for a drain: 100%

Seroma formation: 10%
SENTINEL NODE CONCEPT
BREAST CANCER TREATMENT:
Adjuvant Systemic Therapy

Chemotherapy or hormonal therapy used
after operation

Improves survival rates beyond operation
alone

Used for node-positive and some nodenegative invasive cancers
NEOADJUVANT CHEMOTHERAPY:
Definition
Preoperative systemic chemotherapy
intentionally administered prior to
definitive surgical resection
NEOADJUVANT CHEMOTHERAPY:
NSABP B-18 - Operable
1,523 randomized: AC / preop vs. postop

No difference in DFS or OS at 5 years

cCR / m CR / pCR correlated with outcome

Increased Lumpectomy / XRT after NCT
(67.8% vs 59.8%, p < 0.05)

Similar local recurrence after lumpectomy
(7.9% vs 5.8%, p = .23)
Fisher, J Clin Oncol 16:2672, 1998
NEOADJUVANT THERAPY
Categories of Breast Cancer

Inflammatory breast cancer
– Stage III B

Locally advanced breast cancer
– Stage III non-inflammatory:
– T3 / clinN1-2

“Operable” breast cancer
– Stage II B: T3N0, T2 (borderline BCT)
NEOADJUVANT THERAPY
Rationale

Inflammatory breast cancer
– Convert inoperable to marginally operable

Locally advanced breast cancer
– Convert marginally operable to resectable

“Operable” breast cancer
– Improve breast conservation rates
PRIMARY NEOADJUVANT RESPONSE
Utility of Breast MRI for Following Drug Response
Pre-treatment – 22 cm3
One Cycle
30% Decrease
Four Cycles
88% decrease
Partridge AJR 2005;184:1774
CONCLUSIONS

Breast surgery removes the primary disease in the breast and
provides staging information to determine adjuvant treatment.

Radiation therapy allows for conservation of the breast (as
opposed to mastectomy) in properly selected patients.

Systemic (drug) treatment is critical for improving mortality
and is not replaced by more extensive local therapy.

Multidisciplinary collaboration is the heart and soul of breast
cancer treatment and is required to improve patient outcome.
SEATTLE CANCER CARE ALLIANCE
UNIVERSITY OF WASHINGTON
FRED HUTCHINSON CANCER CENTER
CHILDREN’S HOSPITAL
U.W.S.O.M.
F.H.C.R.C.