BIOLOGICAL PRINCIPLES OF BIOLOGICAL PRINCIPLES OF BREAST CANCER TREAMENTBREAST CANCER TREAMENT

Benjamin O. Anderson, M.D.Director, Breast Health Clinic

Professor of Surgery and Global Health, University of WashingtonJoint Member, Fred Hutchinson Cancer Research Center

Seattle, Washington

U .W .S .O .M . F.H.C.R.C.

BIOLOGICAL BASIS OF TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

BIOLOGICAL BASIS OF TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

RADICAL MASTECTOMYRADICAL MASTECTOMY MODIFIED RADICAL MASTECTOMYMODIFIED RADICAL MASTECTOMY

EVOLUTION IN CANCER TREATMENTEVOLUTION IN CANCER TREATMENT

BREAST CONSERVATION:BREAST CONSERVATION:Long-term validationLong-term validation

NSABP B-06:NSABP B-06:Effect of Lumpectomy v. Mastectomy on RecurrenceEffect of Lumpectomy v. Mastectomy on Recurrence

CU

MU

LA

TIV

E I

NC

IDE

NC

E

All Patients Node Negative Node Positive

Lumpectomy LumpectomyLumpectomy

Lumpectomy + radiation Lumpectomy + radiationLumpectomy + radiation

Lumpectomy: 570/210 361/121 209/89

Lumpectomy + XRT: 567/62 375/50 192/12

No. of patients / No. of recurrences

YEAR

NSABP B-06:NSABP B-06:Effect of Lumpectomy v. Mastectomy on SurvivalEffect of Lumpectomy v. Mastectomy on Survival

DIS

TA

NT

DIS

EA

SE

-FR

EE

SU

RV

IVA

L (

%) Cohort A Cohort B Cohort C

Total Mastectomy: 692/265 569/233 494/192

Lumpectomy: 699/302 634/282 520/236

No. of patients / No. of recurrences

YEAR

Lumpectomy + XRT: 714/278 628/253 515/204

SURGICAL MARGINS:SURGICAL MARGINS:Surgical PrinciplesSurgical 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 TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

BIOLOGICAL BASIS OF TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

BREAST CONSERVING SURGERYBREAST CONSERVING SURGERY

BREAST CONSERVING RADIATION THERAPYBREAST CONSERVING RADIATION THERAPY

BREAST CONSERVATION:BREAST CONSERVATION:Radiation Therapy ConceptsRadiation 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 TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

BIOLOGICAL BASIS OF TREATMENTBIOLOGICAL BASIS OF TREATMENTOutlineOutline

Breast cancer surgery

Breast radiation therapy

Systemic (drug) therapy

AXILLARY NODE DISSECTION:AXILLARY NODE DISSECTION:Complication RatesComplication Rates

Lymphedema– Acute: 40%

– Chronic: 15-20%

Paraesthesia: 40%

Need for a drain: 100%

Seroma formation: 10%

SENTINEL NODE CONCEPTSENTINEL NODE CONCEPT

BREAST CANCER TREATMENT:BREAST CANCER TREATMENT:Adjuvant Systemic TherapyAdjuvant Systemic Therapy

Chemotherapy or hormonal therapy used after operation

Improves survival rates beyond operation alone

Used for node-positive and some node-negative invasive cancers

NEOADJUVANT CHEMOTHERAPY: NEOADJUVANT CHEMOTHERAPY: DefinitionDefinition

Preoperative systemic chemotherapy intentionally administered prior to

definitive surgical resection

NEOADJUVANT CHEMOTHERAPY: NEOADJUVANT CHEMOTHERAPY: NSABP B-18 - OperableNSABP 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, 1998Fisher, J Clin Oncol 16:2672, 1998

NEOADJUVANT THERAPYNEOADJUVANT THERAPYCategories 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 THERAPYNEOADJUVANT THERAPYRationale

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 RESPONSEPRIMARY NEOADJUVANT RESPONSEUtility of Breast MRI for Following Drug Response

Partridge AJR 2005;184:1774

Pre-treatment – 22 cm3 One Cycle 30% Decrease

Four Cycles88% decrease

CONCLUSIONSCONCLUSIONS 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.

F.H.C.R.C.

UNIVERSITY OF WASHINGTONUNIVERSITY OF WASHINGTON

FRED HUTCHINSON CANCER CENTERFRED HUTCHINSON CANCER CENTER

CHILDREN’S HOSPITALCHILDREN’S HOSPITAL

SEATTLE CANCER CARE ALLIANCESEATTLE CANCER CARE ALLIANCE

UNIVERSITY OF WASHINGTONUNIVERSITY OF WASHINGTON

FRED HUTCHINSON CANCER CENTERFRED HUTCHINSON CANCER CENTER