MANAGEMENT OF PRE-
MALIGNANT CONDITIONS IN
BREAST
DR. KARTIK KADIA
MMIMSR, AMBALA

INTRODUCTION
• NONINVASIVE CARCINOMA OF THE BREAST (STAGE TIS) INCLUDES –
 PAGET DISEASE OF THE NIPPLE AND
• TWO HISTOPATHOLOGIC ENTITIES THAT ARE DISTINCT IN BOTH THEIR CLINICAL
PRESENTATION AND BIOLOGIC POTENTIAL :
 LOBULAR CARCINOMA IN SITU (LCIS) AND
 DUCTAL CARCINOMA IN SITU (DCIS).

INTRODUCTION
• AS A RESULT OF THE INCREASE IN THE USE OF MAMMOGRAPHY, THESE THREE HISTOPATHOLOGIC
ENTITIES COMPRISE A LARGER PERCENTAGE OF ALL BREAST CANCER CASES SEEN TODAY.
• THERE REMAINS CONSIDERABLE CONTROVERSY REGARDING THE OPTIMAL TREATMENT APPROACH
AND, AS A CONSEQUENCE, TREATMENT RECOMMENDATIONS RANGE FROM OBSERVATION
BREAST-CONSERVATION THERAPY MASTECTOMY

LOBULAR CARCINOMA IN SITU
• LCIS IS CHARACTERIZED BY MULTICENTRIC BREAST
INVOLVEMENT AND CONSISTS OF –
• LOOSE AND DISCOHESIVE EPITHELIAL CELLS THAT
ARE LARGE IN SIZE
• VARIABLE IN SHAPE
• CONTAIN A NORMAL CYTOPLASM TO NUCLEUS
RATIO.

• THE EXTENT OF INVOLVEMENT OF THE LOBULAR LUMEN RANGES
FROM - SIMPLE FILLING
MODERATE
SEVERE DISTENTION
WITH EXTENSION INTO THE ADJACENT EXTRALOBULAR DUCTS.
LOBULAR CARCINOMA IN SITU

LOBULAR CARCINOMA IN SITU
• AS SUCH, THE LINES OF HISTOLOGIC DELINEATION CAN
BECOME BLURRED BETWEEN –
 ATYPICAL DUCTAL HYPERPLASIA
 LCIS
 DCIS
• THIS OVERLAP OF HISTOLOGIC MORPHOLOGY MAY
COMPLICATE THE INTERPRETATION OF STUDIES FROM
DIFFERENT INSTITUTIONS

• LCIS HAS BEEN REPORTED TO PRESENT WITH A –
 MULTICENTRIC DISTRIBUTION IN UP TO 90% OF
MASTECTOMY SPECIMENS
 WITH BILATERAL BREAST INVOLVEMENT IN 35%
TO 59%.
LOBULAR CARCINOMA IN SITU

LCIS – MOLECULAR BIOLGY
• LCIS CELLS ARE COMMONLY ESTROGEN RECEPTOR POSITIVE, ALTHOUGH
OVEREXPRESSION OF CERB-B2 AND P53 ARE UNCOMMON.
• THE LOSS OF E-CADHERIN IS OFTEN OBSERVED.
• THE ABSENCE OF E-CADHERIN MAY EXPLAIN THE GROWTH PATTERN SEEN WITH
LCIS

• LCIS REPRESENTS < 15 % OF ALL NONINVASIVE BREAST CANCER.
• THE MAJORITY OF WOMEN ARE PREMENOPAUSAL AT DIAGNOSIS, WITH AN
AVERAGE AGE OF 45 YEARS
• RISK FACTORS FOR THE DEVELOPMENT OF LCIS CORRESPOND TO THOSE
IDENTIFIED FOR INVASIVE CARCINOMA.
LOBULAR CARCINOMA IN SITU

• BECAUSE THE MALE BREAST LACKS LOBULAR ELEMENTS, THIS ENTITY HAS NOT
BEEN DESCRIBED IN MEN.
LOBULAR CARCINOMA IN SITU

• AS THERE ARE NO CLINICAL OR
MAMMOGRAPHIC INDICATORS THAT ARE
CHARACTERISTIC OF LCIS, IT IS OFTEN
DETECTED AS AN INCIDENTAL BIOPSY FINDING
LOBULAR CARCINOMA IN SITU

• LCIS IS CONSIDERED A MARKER OF INCREASED RISK FOR THE SUBSEQUENT
DEVELOPMENT OF INVASIVE (USUALLY DUCTAL) CARCINOMA - THAT MAY BE
GREATEST FOR HIGHGRADE OR MORE EXTENSIVE LESIONS.
• THIS RISK APPEARS TO BE NEARLY EQUAL FOR BOTH BREASTS

• THE QUESTION AS TO WHETHER LCIS CAN SERVE AS A DIRECT PRECURSOR
LESION TO THE SUBSEQUENT DEVELOPMENT OF INVASIVE LOBULAR CARCINOMA IS
UNRESOLVED.
LOBULAR CARCINOMA IN SITU

• SOME STUDIES HAVE SUGGESTED A CLONAL LINK OF SYNCHRONOUSLY DETECTED LCIS AND INVASIVE
LOBULAR CARCINOMA*
• WHEREAS OTHERS HAVE NOT**
*HWANG ES, NYANTE SJ, CHEN YY, ET AL. CLONALITY OF LOBULAR CARCINOMA IN SITU AND SYNCHRONOUS INVASIVE LOBULAR CARCINOMA. CANCER 2004;100:2562– 2572
**BEN-DAVID MA, KLEER CG, PARAMAGUL C, ET AL. IS LOBULAR CARCINOMA IN SITU AS A COMPONENT OF BREAST CARCINOMA A RISK FACTOR FOR LOCAL FAILURE AFTER
BREAST-CONSERVING THERAPY? CANCER 2006;106:28–34.

• THE EVIDENCE ASSOCIATING LCIS WITH THE SUBSEQUENT DEVELOPMENT OF INVASIVE
DISEASE RAISES THE QUESTION AS TO WHETHER MAGNETIC RESONANCE IMAGING (MRI)
WOULD BE A USEFUL SCREENING TOOL.
• LIMITED DATA EXIST TO FORMULATE A FIRM RECOMMENDATION.
• IN 2007, THE AMERICAN CANCER SOCIETY STATED THERE WERE INSUFFICIENT DATA;
• HOWEVER, IN 2009, THE NATIONAL COMPREHENSIVE CANCER NETWORK PUBLISHED
GUIDELINES REFLECTING A PANEL CONSENSUS OPINION THAT ANNUAL BREAST MRI
SHOULD BE CONSIDERED IN PATIENTS WITH LCIS.
ROLE OF IMAGING

• SEVERAL STUDIES HAVE BEEN PUBLISHED EVALUATING THE ROLE OF MRI IN PATIENTS
WITH LCIS*
• EACH DOCUMENT REVEALED A SMALL BUT DEFINED 3.3% TO 4.5% BREAST CANCER
DETECTION RATE AND A POSITIVE PREDICTIVE VALUE OF 31% BASED ON BIOPSIES
PERFORMED SUPPORTING CONSIDERATION FOR AN ANNUAL MRI IN THIS SUBSET OF
PATIENTS.
Friedlander LC, Roth SO, Gavenonis SC. Results of MR imaging screening for breast cancer in high-risk patients with lobular carcinoma in situ. Radiology
2011;261(2):421–427.
Port ER, Park A, Borgen PI, et al. Results of MRI screening for breast cancer in high risk patients with LCIS and atypical hyperplasia. Ann Surg Oncol 2007;14:1051–
1057.
Sung JS, Malak SF, Bajaj P, et al. Screening breast MR imaging in women with a history of lobular carcinoma in situ. Radiology 2011;261(2):414– 420.
Ehsani S, Strigel RM, Pettke E, et al. Screening magnetic resonance imaging recommendations and outcomes in patients at high risk for breast cancer. Breast J
2015;3:246–253.
ROLE OF IMAGING

• MANAGEMENT FOR LCIS DEPENDS ON WHETHER IT IS ASSOCIATED WITH
ANOTHER MALIGNANCY (DCIS OR INVASIVE CARCINOMA) OR IF LCIS IS THE
SOLE HISTOLOGIC DIAGNOSIS.
• APPROXIMATELY 10% OF EARLY-STAGE BREAST CANCERS HAVE AN ASSOCIATED
COMPONENT OF LCIS.
MANAGEMENT

• IF LCIS IS THE SOLE HISTOLOGIC DIAGNOSIS, TREATMENT RECOMMENDATIONS RANGE FROM CONSERVATIVE
TO RADICAL
• WHEN FIRST DESCRIBED AS AN ENTITY, THE SIGNIFICANCE OF LCIS WAS UNKNOWN AND MASTECTOMY
WAS OFTEN PERFORMED*
• THE HIGH FREQUENCY OF CONTRALATERAL BREAST INVOLVEMENT WAS SUBSEQUENTLY USED TO JUSTIFY
CONTRALATERAL BIOPSY AND EVEN BILATERAL MASTECTOMY
MANAGEMENT
*Foote FW, Stewart FW. Lobular carcinoma in situ—a rare form of
mammary cancer. Am J Pathol 1941;17:491–495.

• OBSERVATIONAL STUDIES AFTER WIDE LOCAL EXCISION ALONE HAVE LED TO A
BETTER UNDERSTANDING OF THE NATURAL HISTORY OF THIS CONDITION, AND A
MORE CONSERVATIVE APPROACH IS NOW COMMONLY PRACTICED*
*Haagensen CD, Bodian C, Haagensen DE. Lobular neoplasia (lobular
carcinoma in situ). Breast carcinoma: risk and detection. Philadelphia: WB
Saunders, 1981:238–292

• IN AN ANALYSIS OF 182 PATIENTS WITH LCIS WHO WERE INADVERTENTLY ENROLLED ON
THE NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT (NSABP) B-17
TRIAL FOR DCIS AND TREATED WITH –
• LUMPECTOMY ONLY
• THERE WAS A 14.4% IN-BREAST TUMOR RECURRENCE (IBTR) RATE AND A 7.8%
CONTRALATERAL BREAST TUMOR RECURRENCE RATE AFTER A MEDIAN FOLLOWUP OF 12
YEARS.

• IN PATIENTS WITH LCIS AS THE SOLE HISTOLOGIC DIAGNOSIS, THE MOST WIDELY
ACCEPTED CLINICAL PRACTICE IS CLOSE OBSERVATION WITH REGULAR PHYSICAL
EXAMINATION AND MAMMOGRAPHIC SURVEILLANCE
• THERE IS NO ROLE FOR RADIOTHERAPY IN THE MANAGEMENT OF LCIS.

• THE FACT THAT LCIS COMMONLY INVOLVES BOTH BREASTS MAKES TREATMENT
WITH UNILATERAL MASTECTOMY BOTH INADEQUATE AND ILLOGIC.
• BILATERAL PROPHYLACTIC MASTECTOMY IS LIKELY EXCESSIVE IN ALL BUT THOSE
PATIENTS BELIEVED TO BE AT HIGHEST RISK: YOUNG AGE, DIFFUSE HIGH-GRADE
LESION, AND SIGNIFICANT FAMILY HISTORY.

• A LESS RADICAL PROPHYLACTIC APPROACH IN HIGH-RISK PATIENTS IS TO
CONSIDER THE USE OF TAMOXIFEN
• TAMOXIFEN HAS DEMONSTRATED HIGH EFFICACY IN THE PREVENTION OF
INVASIVE CARCINOMA AND, IN THE CONTEXT OF LCIS, HAS BEEN SHOWN TO
REDUCE RISK BY 56% *
*Fisher B, Costantino J, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the
National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–1388

PAGET DISEASE
• THE CLINICAL PRESENTATION OF
CRUSTING AND ECZEMATOUS
CHANGES OF THE NIPPLE–
AREOLA COMPLEX WERE FIRST
DESCRIBED IN 1856
• HOWEVER, IT WAS NOT UNTIL
1874 THAT THE ASSOCIATION
WITH AN UNDERLYING BREAST
CANCER WAS REPORTED BY SIR
JAMES PAGET

• PAGET DISEASE OF THE NIPPLE IS
CHARACTERIZED BY THE PRESENCE OF
PAGET CELLS THAT ARE LOCATED
THROUGHOUT THE EPIDERMIS
• PAGET CELLS ARE LARGE AND HAVE
HYPERCHROMATIC, ROUND TO OVAL
NUCLEI
• THE CELLS CAN BE FOUND IN CLUSTERS
OR INDIVIDUALLY IN THE BASAL LAYERS
Paget cells

• PAGET DISEASE IS A RARE ENTITY REPRESENTING <5% OF ALL BREAST CANCER CASES*
• IT IS TYPICALLY DIAGNOSED IN THE FIFTH OR SIXTH DECADE OF LIFE.
• SYNCHRONOUS BILATERAL PAGET DISEASE AND MALE PAGET DISEASE HAVE BEEN
REPORTED
*Sakorafas GH, Blanchard K, Sarr MG, et al.
Paget’s disease of the breast. Cancer Treat Rev
2001;27:9–18

• PATIENTS WITH PAGET DISEASE DESCRIBE
ITCHING AND BURNING OF THE NIPPLE AND
AREOLA
• THERE IS A SLOW PROGRESSION TOWARD A
CRUSTING ECZEMATOID APPEARANCE THAT
CAN EXTEND TO THE PERIAREOLAR SKIN
PAGET DISEASE

• IF NEGLECTED - BLEEDING, PAIN, AND ULCERATION CAN OCCUR
• THE DIFFERENTIAL DIAGNOSIS INCLUDES –
 SUPERFICIAL SPREADING MELANOMA,
 PAGETOID SQUAMOUS CELL CARCINOMA IN SITU, AND
 CLEAR CELLS OF TOKER

• A PALPABLE MASS IS DETECTED IN APPROXIMATELY 50% OF PATIENTS AT
DIAGNOSIS; IN >90% OF CASES, THAT WILL BE AN INVASIVE CARCINOMA
• IN CONTRAST, IF NO PALPABLE MASS IS DETECTED, 66% TO 86% WILL HAVE
AN UNDERLYING DCIS
• THESE ASSOCIATED MALIGNANCIES ARE USUALLY LOCATED CENTRALY,
ALTHOUGH THEY CAN OCCUR ELSEWHERE IN THE BREAST
PAGET DISEASE

• AT PRESENTATION, CLINICAL EVALUATION INCLUDES –
 BILATERAL BREAST EXAMINATION
 MAMMOGRAPHY
 BIOPSY
• TO CONFIRM THE DIAGNOSIS OF PAGET DISEASE AND TO FULLY EVALUATE THE EXTENT
OF THE ASSOCIATED MALIGNANCY.
PAGET DISEASE

• THE PROGNOSIS DOES NOT DEPEND ON THE DIAGNOSIS OF PAGET DISEASE
BUT RATHER ON THE ASSOCIATED MALIGNANCY

• THEREFORE THE –
 LOCAL TREATMENT, AS WELL AS
 SYSTEMIC AND REGIONAL NODAL DISEASE RISK MANAGEMENT,
SHOULD BE BASED ON THE ASSOCIATED DISEASE

• MANAGEMENT OF PAGET DISEASE CONTINUES TO EVOLVE
• MASTECTOMY WAS EMPLOYED IN THE PAST, ALTHOUGH THIS HAS BEEN INCREASINGLY
SUPPLANTED BY BREAST CONSERVING TREATMENT
MANAGEMENT

• THE INFREQUENT OCCURRENCE OF THIS DISEASE ENTITY –
THE RANGE OF DISEASE PRESENTATIONS –
 NIPPLE INVOLVEMENT WITH OR WITHOUT AN UNDERLYING MASS
 ASSOCIATION WITH INVASIVE VS. NONINVASIVE DISEASE
 THE VARIABLE EXTENT OF SURGICAL RESECTION
HAS MADE THE EVALUATION OF TREATMENT OPTIONS DIFFICULT.

• SERIES HAVE DESCRIBED RESULTS WITH VARIOUS FORMS OF BREAST CONSERVING
TREATMENT, INCLUDING –
 WIDE LOCAL SURGICAL RESECTION ALONE,
 RADIOTHERAPY ALONE, AND
 WIDE EXCISION FOLLOWED BY WHOLE-BREAST RADIOTHERAPY

• CONSERVATIVE SURGERY ALONE FOR PAGET DISEASE APPEARS TO BE
INADEQUATE, WITH REPORTED LOCAL RECURRENCE RATES OF 25% TO 40%

• THE USE OF RADIOTHERAPY ALONE HAS BEEN REPORTED AS ACHIEVING AN 85%
LOCAL CONTROL RATE IN A SMALL SERIES OF PATIENTS WITH PAGET DISEASE OF
THE NIPPLE WHO PRESENTED WITHOUT AN ASSOCIATED PALPABLE MASS*
• HOWEVER, THIS APPROACH HAS NOT BEEN WIDELY ADOPTED BECAUSE OF THE
UNDEFINED HISTOLOGIC TYPE AND EXTENT OF THE UNDERLYING DISEASE LEADING
TO UNCERTAINTY IN FIELD DESIGN AND TOTAL RADIATION DOSE
Stockdale AD, Brierly JD, White WF, et al. Radiotherapy for Paget’s
disease of the nipple: a conservative alternative. Lancet 1989;2:664–
666

• THE COMBINATION OF LIMITED SURGICAL RESECTION AND POSTOPERATIVE
RADIOTHERAPY APPEARS TO BE THE MOST PRACTICAL BREAST-CONSERVING APPROACH
• TWO STUDIES HAVE EVALUATED THE COMBINED USE OF SURGERY AND RADIOTHERAPY
IN PAGET DISEASE OF THE NIPPLE.

• THE EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER (EORTC)
STUDY 10873 WAS A MULTIINSTITUTIONAL REGISTRY TRIAL THAT REPORTED A 5- YEAR
LOCAL RECURRENCE RATE OF 5.2%
• IN THIS STUDY, A COMPLETE EXCISION WITH TUMOR-FREE MARGINS OF THE NIPPLE–
AREOLAR COMPLEX AND UNDERLYING BREAST TISSUE WAS FOLLOWED BY WHOLE-BREAST
RADIOTHERAPY
• THE MEDIAN FOLLOW-UP WAS 6.4 YEARS, AND THE MAJORITY OF THESE PATIENTS WERE
FOUND TO HAVE AN UNDERLYING DCIS WITHOUT A PALPABLE MASS.

• A SEPARATE STUDY CONSISTED OF A SEVEN-INSTITUTION COLLABORATIVE REVIEW OF 36
PATIENTS WITH PAGET DISEASE WITHOUT A PALPABLE MASS OR MAMMOGRAPHIC DENSITY*
• PATIENT FOLLOW-UP WAS A MEDIAN OF 9.4 YEARS
• THE EXTENT OF SURGICAL RESECTION VARIED AS PATIENTS UNDERWENT COMPLETE (69%)
OR PARTIAL (25%) EXCISION OF THE NIPPLE–AREOLAR COMPLEX AND UNDERLYING
BREAST TISSUE
*Marshall JK, Griffith KA, Haffty BG, et al. Conservative management of Paget disease of the breast with
radiotherapy. Cancer 2003;97:2142–2149

• ALL RECEIVED WHOLE BREAST IRRADIATION, AND MOST RECEIVED AN
ADDITIONAL BOOST DOSE TO THE TUMOR BED.
• THE RATE OF LOCAL FAILURE AS THE ONLY SITE OF FIRST RECURRENCE WAS –
 9% AT 5 YEARS AND
 13% AT BOTH 10 AND 15 YEARS.
*Marshall JK, Griffith KA, Haffty BG, et al. Conservative management of Paget disease of the breast with
radiotherapy. Cancer 2003;97:2142–2149

MANAGEMENT OVERVIEW – PAGET’S DISEASE
• CURRENT DATA SUGGEST THAT A COMBINED MODALITY APPROACH THAT CONSERVES
THE BREAST IS AN APPROPRIATE ALTERNATIVE TO MASTECTOMY IN PROPERLY
SELECTED PATIENTS WITH UNDERLYING NONINVASIVE OR INVASIVE CARCINOMA OF
LIMITED EXTENT.
• SURGICAL RESECTION SHOULD INCLUDE THE NIPPLE–AREOLAR COMPLEX WITH
MICROSCOPICALLY CLEAR MARGINS SURROUNDING BOTH THE PAGET DISEASE AND
THE ASSOCIATED MALIGNANCY.
• WHOLE-BREAST RADIOTHERAPY SHOULD BE DELIVERED.

DUCTAL CARCINOMA IN SITU

CLINICAL PRESENTATION AND
EPIDEMIOLOGY
• DCIS IS A NEOPLASTIC PROCESS THAT IS CONFINED TO THE
DUCTAL SYSTEM OF THE BREAST AND LACKS HISTOLOGIC
EVIDENCE OF INVASION.
• THESE CELLS NEITHER DISRUPT THE BASEMENT MEMBRANE
NOR INVOLVE THE SURROUNDING BREAST STROMA.
• THIS ENTITY LACKS THE ABILITY TO METASTASIZE AND IS
CONFINED TO THE BREAST.
• AXILLARY NODE INVOLVEMENT IS RARE (0% TO 5%)

• RISK FACTORS FOR THE DEVELOPMENT OF DCIS ARE THE SAME AS THOSE
IDENTIFIED FOR INVASIVE CARCINOMA –
 FAMILY HISTORY,
 REPRODUCTIVE EVENTS SUCH AS DELAYED AGE OF FIRST LIVE BIRTH AND
NULLIPARITY,
 HISTORY OF BENIGN BREAST BIOPSY, AND
 DIETARY FACTORS SUCH AS ALCOHOL CONSUMPTION.

• DCIS TYPICALLY PRESENTS AS A –
 PALPABLE MASS OR
 NIPPLE DISCHARGE.
• THE WIDESPREAD USE OF MAMMOGRAPHY
ROUTINELY DETECTS –
DCIS < 1 CM IN DIAMETER

IMAGING
• NINETY-FIVE PERCENT OF NEW CASES OF DCIS
PRESENT WITH MAMMOGRAPHIC ABNORMALITIES, OF
WHICH MICROCALCIFICATIONS ARE MOST TYPICAL.
• NONCALCIFIED MAMMOGRAPHIC ABNORMALITIES
MAKE UP THE REMAINING FINDINGS, WITH –
 ASYMMETRIC DENSITIES IDENTIFIED IN 10%,
 DOMINANT MASSES IN 8%, AND

Asymmetric densities Dominant masses

• AMORPHOUS, COARSE, FINE PLEOMORPHIC, AND FINE LINEAR ARE ALL FORMS OF
CALCIFICATIONS THAT CAN BE RELATED TO DCIS.
Amorphous clusters Coarse Fine linear

• LINEAR AND BRANCHING CALCIFICATIONS FREQUENTLY ARE ASSOCIATED WITH
HIGH-GRADE DCIS AND NECROSIS
• WHEREAS FINE AND GRANULAR CALCIFICATIONS ARE ASSOCIATED MORE
COMMONLY WITH LOW-GRADE DCIS

• INITIAL EVALUATION SHOULD INCLUDE MAGNIFICATION VIEWS THAT ALLOW FOR –
 COMPLETE CHARACTERIZATION OF MAMMOGRAPHIC FINDINGS AND
 DETERMINATION OF THE NEED FOR BIOPSY

ROLE OF MRI
• PRIOR TO 2000, MRI WAS NOT
CONSIDERED A USEFUL IMAGING
MODALITY FOR DCIS.
• HOWEVER, CHANGE IN MRI IMAGING
ACQUISITION HAS LED MRI TO BE
CONSIDERED AS A VALUABLE IMAGING
TOOL FOR DCIS.
• THE SENSITIVITY OF MRI IS 92%
FOR DCIS AS COMPARED WITH ONLY
56% BY MAMMOGRAPHY

• IN CASES THAT PRESENT WITH NIPPLE
DISCHARGE AND A NEGATIVE
MAMMOGRAM, GALACTOGRAPHY MAY
BE HELPFUL IN DETERMINING THE
LIKELIHOOD OF UNDERLYING DCIS
VERSUS PAPILLOMA
Galactography or ductography
(or galactogram, ductogram) is a
medical diagnostic procedure for
viewing the milk ducts

PATHOLOGY AND BIOLOGY
• THE HISTOLOGIC DIVERSITY OF DCIS CAN LEAD TO DIFFICULTY IN DISTINGUISHING IT FROM OTHER PATHOLOGIC ENTITIES
• THE FIVE SUBTYPES OF DCIS ARE –
 COMEDO
 SOLID
 CRIBRIFORM
 MICROPAPILLARY
 PAPILLARY
• IT IS COMMON TO ENCOUNTER A MIXTURE OF SUBTYPES WITHIN THE SAME SPECIMEN

COMEDO DUCTAL CARCINOMA IN SITU (DCIS) CHARACTERIZED BY CENTRAL
NECROSIS, LARGE CELLS, AND POORLY DIFFERENTIATED NUCLEI

SOLID DCIS CHARACTERIZED BY DUCTAL SPACES FILLED WITH NEOPLASTIC CELLS
WITH LIMITED NECROSIS

CRIBRIFORM DCIS CHARACTERIZED BY MICROLUMENS AND FENESTRATIONS.

MICROPAPILLARY DCIS CHARACTERIZED BY INTRALUMINAL PROJECTIONS WITH NO
FIBROVASCULAR CORE

PAPILLARY DCIS CHARACTERIZED BY INTRALUMINAL PROJECTIONS WITH A
FIBROVASCULAR CORE.

• LESS COMMON SUBTYPES HAVE BEEN DESCRIBED AND INCLUDE –
 APOCRINE,
 NEUROENDOCRINE,
 SIGNET-CELL CYSTIC HYPERSECRETORY CARCINOMA, AND
 CLINGING DCIS

• IN 1997, A CONSENSUS CONFERENCE COMMITTEE WAS CONVENED TO REACH AN AGREEMENT ON
THE PATHOLOGIC CLASSIFICATION OF DCIS AND THE IDENTIFICATION OF SPECIFIC FEATURES THAT
MAY CONVEY PROGNOSTIC SIGNIFICANCE
• THESE FEATURES INCLUDED –
 NUCLEAR GRADE,
 PRESENCE OF NECROSIS,
 POLARIZATION, AND
 ARCHITECTURAL PATTERN

• THE CONSENSUS CONFERENCE COMMITTEE EXTENDED ITS RECOMMENDATIONS TO
INCLUDE –
 MARGIN STATUS,
 LESION SIZE,
 EXTENT OF MICROCALCIFICATIONS, AND
 CORRELATION BETWEEN SPECIMEN X-RAY AND MAMMOGRAPHIC FINDINGS.

• THREE-DIMENSIONAL RECONSTRUCTION TECHNIQUES
HAVE RESULTED IN A BETTER UNDERSTANDING OF THE –
 ENORMOUSLY COMPLEX STRUCTURE OF THE MAMMARY
DUCT–LOBULAR SYSTEM AND
 THE PATTERNS BY WHICH DCIS CAN SPREAD WITHIN THE
BREAST

• OHTAKE ET AL STUDIED THE DUCT–
LOBULAR SYSTEM WITH COMPUTER
GRAPHIC RECONSTRUCTION AND
FOUND THAT THE BREAST CONSISTS OF
16 TO 24 DUCT–LOBULAR SYSTEMS
• THEY ALSO IDENTIFIED DUCTAL
ANASTOMOSES THAT ESTABLISHED A
CONNECTION BETWEEN THE VARIOUS
DUCTAL–LOBULAR UNITS AND
PROVIDED A POTENTIAL PATHWAY FOR
TUMOR EXTENSION AND SUBSEQUENT
DIFFUSE INVOLVEMENT

MOLECULAR BIOLOGY - DCIS
• AT THE BIOLOGIC AND MOLECULAR LEVEL, MANY STUDIES HAVE DEMONSTRATED THAT DCIS AND INVASIVE
BREAST CANCER ARE HIGHLY SIMILAR AT THE CELLULAR AND MOLECULAR LEVELS
ALLRED DC, MOHSIN SK, FUQUA SAW. HISTOLOGICAL AND BIOLOGICAL EVOLUTION OF HUMAN PREMALIGNANT BREAST DISEASE. ENDOCR RELAT CANCER 2001;8:47–61.
ALLRED DC. DUCTAL CARCINOMA IN SITU: TERMINOLOGY, CLASSIFICATION AND NATURAL HISTORY. J NATL CANCER INST MONOGR 2010;2010(41):134–138.
HANNEMANN J, VELDS A, HALFWERK JB, ET AL. CLASSIFICATION OF DUCTAL CARCINOMA IN SITU BY GENE EXPRESSION PROFILING. BREAST CANCER RES 2006;8(5):R61.
KUERER HM, ALBARRACIN CT, YANG WT, ET AL. DUCTAL CARCINOMA IN SITU: STATE OF THE SCIENCE AND ROADMAP TO ADVANCE THE FIELD. J CLIN ONCOL 2009;27:279– 288

• THESE SIMILARITIES HAVE NOW BEEN SHOWN TO EXTEND TO GLOBAL GENE EXPRESSION PROFILES AS
DCIS HAS BEEN CLASSIFIED UNDER –
 LUMINAL
 BASAL, AND
 ERBB2 INTRINSIC MOLECULAR SUBTYPES

• GENETIC AND MOLECULAR DIFFERENCES HAVE BEEN DOCUMENTED THAT DIFFERENTIATE DCIS FROM
NORMAL BREAST TISSUE.
• GENETIC ALTERATIONS HAVE BEEN EVALUATED WITH AN ANALYSIS OF LOSS OF HETEROZYGOSITY THAT
HAS DEMONSTRATED GAIN OR LOSS OF MULTIPLE LOCI.
• LOSS OF HETEROZYGOSITY IS NOT SEEN IN NORMAL BREAST TISSUE.
• AMONG SPECIMENS HARVESTED FROM CANCEROUS BREASTS –
 77% OF NONCOMEDO AND
 80% OF COMEDO DCIS LESIONS
SHARE LOSS OF HETEROZYGOSITY

• MOLECULAR MARKERS HAVE BEEN STUDIED IN DCIS AND ARE FOUND TO HAVE A
HETEROGENEOUS DISTRIBUTION OF EXPRESSION
• THE ESTROGEN RECEPTOR IS PRESENT IN 70% OF DCIS; HOWEVER, THE RATE OF EXPRESSION-
 HIGHER IN LOW-GRADE LESIONS (90%)
 LOWER IN HIGH-GRADE LESIONS (25%).

• THIS ASSOCIATION WITH HISTOLOGIC GRADE IS REVERSED FOR THE RATE OF OVEREXPRESSION OF-
 HER2/NEU PROTOONCOGENE AND
 P53 TUMOR SUPPRESSION GENE.
• APPROXIMATELY 50% OF ALL DCIS LESIONS HAVE OVEREXPRESSION OF HER2/NEU
• IN 25%, THE P53 TUMOR SUPPRESSOR GENE IS ALSO DETECTED.

• ALTERATIONS IN THE SURROUNDING BREAST PARENCHYMA MAY ALSO BE SEEN WITH DCIS.
• HIGH-GRADE DCIS, IN PARTICULAR, HAS BEEN ASSOCIATED WITH THE BREAKDOWN OF THE
MYOEPITHELIAL CELL LAYER AND BASEMENT MEMBRANE SURROUNDING THE DUCTAL LUMEN

NATURAL HISTORY OF DUCTAL
CARCINOMA IN SITU
• A PRIMARY CONSIDERATION IN THE NATURAL HISTORY OF DCIS IS THE RISK OF PROGRESSION TO
INVASIVE CARCINOMA.
• WOMEN WITH DCIS IN ONE BREAST ARE AT RISK FOR A SECOND TUMOR (EITHER INVASIVE OR
IN SITU) IN THE CONTRALATERAL BREAST
• MOST OF THE SUBSEQUENT MALIGNANCIES OCCUR WITHIN 10 YEARS, ALTHOUGH AS MANY AS
ONE-THIRD MAY DEVELOP AFTER 15 YEARS

• DCIS IS A PART OF THE BREAST/OVARIAN CANCER SYNDROMES DEFINED BY BRCA1 AND BRCA2,
WITH MUTATION RATES SIMILAR TO THOSE FOUND FOR INVASIVE BREAST CANCER
• THESE FINDINGS SUGGEST THAT PATIENTS WITH DCIS WITH AN APPROPRIATE PERSONAL OR FAMILY
HISTORY OF BREAST AND/OR OVARIAN CANCER SHOULD BE SCREENED AND FOLLOWED ACCORDING
TO THE SAME HIGH-RISK PROTOCOLS AS DEVELOPED FOR INVASIVE BREAST CANCER

TREATMENT OPTIONS FOR
DUCTAL CARCINOMA IN SITU

PROGNOSTIC FACTORS AND
THEIR INTERPRETATION
• THE GOAL OF TREATMENT WITH DCIS IS PREVENTION OF LOCAL RECURRENCE, WITH
PARTICULAR EMPHASIS ON THE PREVENTION OF INVASIVE BREAST CANCER
• TREATMENT DECISIONS ARE LARGELY BASED ON INFORMATION PROVIDED BY
 MAMMOGRAPHY AND, MOST ESPECIALLY
 PATHOLOGIC EVALUATION OF THE BIOPSY SPECIMEN

• AS SUCH, IN THE CONSIDERATION OF TREATMENT OPTIONS, IT IS IMPORTANT TO BE AWARE OF SOME OF
THE TECHNICAL LIMITATIONS ASSOCIATED WITH THE CLINICAL AND HISTOPATHOLOGIC ASSESSMENT OF
DCIS.
• STUDIES PERFORMED DURING THE PAST TWO DECADES CLEARLY HAVE SUGGESTED THAT DCIS IS NOT A
SINGLE DISEASE.
• RATHER, DCIS ENCOMPASSES A DIVERSE GROUP OF LESIONS THAT DIFFER WITH REGARD TO THEIR –
 CLINICAL PRESENTATION,
 MAMMOGRAPHIC FEATURES,
 EXTENT AND DISTRIBUTION WITHIN THE BREAST,
 HISTOLOGIC CHARACTERISTICS, AND
 BIOLOGIC MARKERS.

• A SIGNIFICANT PROPORTION OF PATIENTS DIAGNOSED WITH DCIS CAN BE TREATED ADEQUATELY
WITH BREAST-CONSERVING THERAPY (I.E., EXCISION WITH OR WITHOUT RADIATION THERAPY).
• WHICH PATIENTS WITH DCIS CAN BE TREATED SAFELY WITH EXCISION ALONE AND WHICH PATIENTS
REQUIRE RADIATION THERAPY AFTER EXCISION ARE PRESSING CLINICAL QUESTIONS
• ATTEMPTS TO RESOLVE THIS ISSUE HAVE FOCUSED ON THE IDENTIFICATION OF RISK FACTORS FOR
LOCAL RECURRENCE AFTER BREAST CONSERVATION THERAPY FOR DCIS.

MASTECTOMY FOR DUCTAL
CARCINOMA IN SITU
• MASTECTOMY WAS THE STANDARD TREATMENT OF DCIS THROUGH THE FIRST FOUR DECADES OF ITS
RECOGNITION AS A DISTINCT HISTOPATHOLOGIC ENTITY.
• MASTECTOMY IS A HIGHLY EFFECTIVE TREATMENT FOR DCIS, WITH A LOCOREGIONAL CONTROL RATE
OF 96% TO 100% AND CANCER-SPECIFIC MORTALITY RATES OF ≤4%*
• NO RANDOMIZED STUDY HAS COMPARED MASTECTOMY WITH BREAST-CONSERVATION TREATMENT
FOR DCIS.
*Silverstein MJ. Van Nuys experience by treatment. In: Silverstein MJ, Lagios MD, Poller DN, et al, eds. Ductal
carcinoma in situ of the breast. Philadelphia: Williams & Wilkins, 1997:443–447.

• LOCAL TREATMENT FAILURE AFTER
MASTECTOMY MAY OCCUR BECAUSE OF-
 UNRECOGNIZED INVASIVE CARCINOMA THAT
RESULTS IN LOCAL RECURRENCE OR DISTANT
METASTASIS
 IT MAY BE THE RESULT OF INCOMPLETE
REMOVAL OF BREAST TISSUE WITH THE
SUBSEQUENT FORMATION OF A NEW PRIMARY
TUMOR.

• THE ROLE OF POSTMASTECTOMY CHEST WALL RADIATION FOLLOWING
MASTECTOMY OR SKIN-SPARING MASTECTOMY AND CLOSE PATHOLOGIC MARGINS
HAS BEEN DEBATED IN THE LITERATURE BUT IS NOT PRESENTLY CONSIDERED THE
STANDARD OF CARE.

• STUDIES HAVE SHOWN AN INCREASED RISK OF CHEST WALL FAILURE IN SELECTED
CASES OF HIGH-GRADE DCIS UNDERGOING MASTECTOMY WITH PATHOLOGIC
MARGINS < 1 MM LEADING TO A ROUTINE RECOMMENDATION OF
POSTMASTECTOMY RADIATION IN THESE CASES*
*Carlson G, Page A, Johnson E, et al. Local recurrence of ductal carcinoma in situ after skin-sparing mastectomy.
J Am Coll Surg 2007;204:1074–1078.

BREAST CONSERVATION FOR
DUCTAL CARCINOMA IN SITU
• FOUR PROSPECTIVE RANDOMIZED STUDIES OF –
 EXCISION ONLY
 VERSUS EXCISION PLUS BREAST IRRADIATION FOR DCIS
HAVE BEEN PERFORMED WITH REPORTED RESULTS, AND ALL HAVE SHOWN THAT
THE RATE OF LOCAL RECURRENCE WAS REDUCED WITH THE ADDITION OF
RADIATION

• THE NSABP B-17 TRIAL CONSISTED OF 813 PATIENTS WHO WERE STRATIFIED BY –
 AGE (≤49 VS. >49 YEARS),
 DCIS VERSUS DCIS PLUS LCIS,
 METHOD OF DETECTION, AND
 WHETHER AN AXILLARY DISSECTION WAS PERFORMED.
Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapyfor the treatment of intraductal
breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol
1998;16:441–452.

• TUMOR SIZE WAS DETERMINED BY MAMMOGRAM, GROSS PATHOLOGIC MEASUREMENT, OR
CLINICAL EXAMINATION.
• OF THE PATIENTS ENROLLED, 83% HAD NONPALPABLE TUMORS.
• THE 17.5- YEAR RATE OF LOCAL RECURRENCE WAS 19.8% WITH RADIATION AND 35.9%
WITHOUT RADIATION.
Fisher B, Dignam J, Wolmark N, et al. Lumpectomy and radiation therapyfor the treatment of intraductal
breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol
1998;16:441–452.

• THE EORTC 10853 TRIAL RANDOMLY ALLOCATED 1,010 PATIENTS WITH ≤5 CM DCIS
AND NEGATIVE MARGINS TO EXCISION VERSUS EXCISION PLUS BREAST IRRADIATION.
• LESIONS WERE NONPALPABLE IN 79% OF PATIENTS, AND THE MEAN MAXIMAL TUMOR
DIAMETER WAS APPROXIMATELY 2 CM
• THE 15-YEAR RATE OF LOCAL RECURRENCE WAS 18% FOR PATIENTS TREATED WITH
RADIATION, AS COMPARED WITH 31% FOR PATIENTS TREATED WITHOUT RADIATION
Donker M, Litiere GW, Julien J-P, et al. Breast-conserving treatment with or without
radiotherapy in ductal carcinoma in situ: 15-year recurrence rates and outcomes after a
recurrence, from the EORTC 10853 randomized phase III trial. J Clin Oncol 2013;31:4054–4059

(UK/ANZ) DCIS TRIAL
• THE UNITED KINGDOM, AUSTRALIA, AND NEW ZEALAND (UK/ANZ) DCIS TRIAL WAS A
RANDOMIZED TRIAL INVESTIGATING THE ROLE OF ADJUVANT RADIOTHERAPY
• THE AIM OF THIS STUDY WAS TO COMPARE –
 EXCISION ALONE VERSUS
 EXCISION PLUS TAMOXIFEN VERSUS
 EXCISION PLUS RADIOTHERAPY VERSUS
 EXCISION PLUS RADIOTHERAPY AND TAMOXIFEN
Cusck J, Sestak I, Pinder SE, et al. Effect of tamoxifen and radiotherapy in women with locally excised
ductal carcinoma in situ: long-term resulrs from the UK/ANZ DCIS trial. Lancet Oncol 2011;12:21–29

• TAMOXIFEN WAS PRESCRIBED AT 20 MG PER DAY
• RADIOTHERAPY WAS DELIVERED THROUGH WHOLE-BREAST TANGENTIAL FIELDS TO
A TOTAL DOSE OF 50 GY
(UK/ANZ) DCIS TRIAL

• DATA HAVE BEEN REPORTED WITH A MEDIAN FOLLOW-UP OF 12.7 YEARS
• THE ADDITION OF RADIOTHERAPY WAS DEMONSTRATED TO REDUCE THE RISK OF
IBTR.
• OF THE 1,030 PATIENTS RANDOMIZED BETWEEN –
NO RADIOTHERAPY VERSUS RADIOTHERAPY
IBTR WAS 19.4% VERSUS 7.1%
(UK/ANZ) DCIS TRIAL

• THE ADDITION OF TAMOXIFEN OFFERED NO BENEFIT TOWARD OVERALL
IPSILATERAL LOCAL CONTROL WHEN ADMINISTERED IN ADDITION TO
RADIOTHERAPY;
• HOWEVER, TAMOXIFEN REDUCED THE IPSILATERAL RECURRENCE RATE OF DISEASE
(UK/ANZ) DCIS TRIAL

SWEDISH BREAST CANCER GROUP
(SWE-DCIS) TRIAL
• THE SWEDISH BREAST CANCER GROUP (SWE-DCIS) STUDY WAS A RANDOMIZED TRIAL THAT ENROLLED 1,067
PATIENTS FROM 1987 TO 1999, WITH 1,046 OF THESE PATIENTS FOLLOWED FOR A MEDIAN OF 17 YEARS.
• PATIENTS WERE RANDOMIZED BETWEEN –
 LUMPECTOMY FOLLOWED BY RADIOTHERAPY AND
 LUMPECTOMY ONLY FOR TREATMENT OF DCIS.
• FOLLOWING SECTOR RESECTION, MICROSCOPICALLY CLEAR RESECTION MARGINS WERE NOT REQUIRED, AND 50 GY IN
25 FRACTIONS TO THE WHOLE BREAST WAS DELIVERED IN THE MAJORITY OF PATIENTS.
Warnberg F, Garmo H, Emdin S, et al. Effect of radiotherapy after breasconserving surgery for ductal
carcinoma in situ: 20 years follow-up in the randomized SweDCIS trial. J Clin Oncol 2014;32:3613–3618.

• DETAILED ANALYSIS DID NOT IDENTIFY ANY PATIENT OR TUMOR CHARACTERISTIC
SUBGROUPS, WHICH DID NOT BENEFIT FROM THE ADDITION OF POSTOPERATIVE
RADIOTHERAPY.
SWEDISH BREAST CANCER GROUP
(SWE-DCIS) TRIAL

• A META-ANALYSIS WAS COMPLETED UTILIZING THE INDIVIDUAL PATIENT DATA FROM EACH OF THE FOUR
RANDOMIZED TRIALS DISCUSSED, AND AN OVERVIEW OF RESULTS WAS REPORTED BY THE EARLY BREAST
CANCER TRIALISTS’ COLLABORATIVE GROUP (EBCTCG)*
• WITH A TOTAL OF 3,729 WOMEN ELIGIBLE FOR ANALYSIS, IT WAS DEMONSTRATED THAT RADIOTHERAPY
REDUCED THE ABSOLUTE 10-YEAR RISK OF ANY IPSILATERAL BREAST EVENT (RECURRENT DCIS OR INVASIVE
DISEASE) BY 15.2%
• THIS ANALYSIS FURTHER ESTABLISHED STRONG AND CONSISTENT EVIDENCE THAT THE ADDITION OF
RADIOTHERAPY FOLLOWING BREAST-CONSERVING SURGERY FOR DCIS APPROXIMATELY REDUCES THE RISK
OF IBTR BY 50%
*Early Breast Cancer Trialists’ Collaborative Group, Correa C, McGale P, Taylor C, et al. Overview of the
randomized trials of radiotherapy in dictal carcinoma in situ of the breast. J Natl Cancer Inst Monogr
2010;(41):162– 167.

• PATIENT AGE IS AN IMPORTANT PROGNOSTIC VARIABLE FOR LOCAL RECURRENCE
AFTER BREAST CONSERVATION FOR DCIS
• IN YOUNGER PATIENTS, DCIS MORE FREQUENTLY CONTAINS ADVERSE
PATHOLOGIC FEATURES AND EXTENDS OVER A GREATER DISTANCE IN THE BREAST
THAN IN OLDER PATIENTS

• IN SERIES WITH ADEQUATE FOLLOW-UP, YOUNGER PATIENTS TREATED WITH
LUMPECTOMY AND RADIATION THERAPY HAD A SIGNIFICANTLY HIGHER RATE OF
LOCAL RECURRENCE THAN OLDER PATIENTS, ESPECIALLY INVASIVE LOCAL
RECURRENCES*
• HOWEVER THERE IS NO AVAILABLE DATA WHICH SHOWS THAT YOUNGER
PATIENTS HAVE BETTER LONG-TERM CANCER-FREE SURVIVAL RATES IF TREATED BY
MASTECTOMY RATHER THAN LUMPECTOMY AND RADIATION THERAPY
*Vicini FA, Recht A. Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast:
a critical review of the literature. J Clin Oncol 2002;20:2736–2744

FOLLOW-UP AND MANAGEMENT
OF RECURRENCE
• IPSILATERAL TUMOR RECURRENCES IN PATIENTS WITH DCIS ARE USUALLY
DETECTED ON SURVEILLANCE MAMMOGRAPHY, ALTHOUGH ONE-QUARTER MAY BE
DETECTED ON THE BASIS OF CHANGES ON PHYSICAL EXAMINATION OF THE
BREAST OR CHEST WALL.
• FOR THIS REASON, PATIENTS SHOULD BE SCHEDULED FOR A BASELINE
MAMMOGRAM 6 TO 12 MONTHS AFTER INITIAL THERAPY AND AT LEAST
ANNUALLY THEREAFTER.

MANAGEMENT OF RECURRENCE
• LOCAL RECURRENCES AFTER BREAST-CONSERVING SURGERY AND RADIOTHERAPY
ARE GENERALLY TREATED WITH MASTECTOMY
• PATIENTS WITH RECURRENT DCIS HAVE AN EXCELLENT PROGNOSIS, WITH <1%
RISK OF FURTHER RECURRENCE AFTER SALVAGE MASTECTOMY.

• SELECTED PATIENTS WITH LOCAL RECURRENCES WHO HAVE NOT PREVIOUSLY
RECEIVED RADIOTHERAPY MAY BE CANDIDATES FOR LOCAL EXCISION AND
RADIOTHERAPY

THE ROLE OF TAMOXIFEN AND AROMATASE
INHIBITORS FOR DUCTAL CARCINOMA IN SITU
• THE USE OF TAMOXIFEN IN THE TREATMENT OF DCIS HAS BEEN STUDIED; HOWEVER, RESULTS
HAVE BEEN CONFLICTING
• THEREFORE, ITS ROLE IS NOT CLEARLY DEFINED

• THE ROLE OF HER2NEU TARGETED TREATMENT IS PRESENTLY BEING INVESTIGATED
IN THE NSABP B-43 TRIAL.
• IN THIS PROSPECTIVE RANDOMIZED TRIAL, PATIENTS WITH HER 2 NEU - POSITIVE
DCIS ARE TREATED WITH POST LUMPECTOMY RADIOTHERAPY AND RANDOMIZED
BETWEEN –
 HERCEPTIN OR
 OBSERVATION

• IN CONTRAST TO THE FINDINGS OF THE NSABP B-24 TRIAL, THE UK/ANZ DCIS TRIAL
FOUND THAT TAMOXIFEN HAD NO EFFECT IN REDUCING LOCAL RECURRENCE RATE WHEN
COMBINED WITH WHOLE-BREAST RADIATION THERAPY
• WHEN USED AS SINGLE AGENT WITHOUT RADIATION THERAPY AFTER LUMPECTOMY,
TAMOXIFEN HAD NO EFFECT ON THE INCIDENCE OF INVASIVE RECURRENCE BUT DID SHOW
A STATISTICALLY SIGNIFICANT REDUCTION IN THE RISK OF DCIS RECURRENCE*
• AS SUCH, THE ROLE OF TAMOXIFEN FOR DCIS IN THE ABSENCE OF WHOLE-BREAST
RADIOTHERAPY REMAINS TO BE DEFINED
Cusck J, Sestak I, Pinder SE, et al. Effect of tamoxifen and radiotherapy in women with locally excised
ductal carcinoma in situ: long-term resulrs from the UK/ANZ DCIS trial. Lancet Oncol 2011;12:21–29.

• THE ROLE OF TAMOXIFEN VERSUS ANASTRAZOLE (AN AROMATASE INHIBITOR) IN THE
MANAGEMENT OF DCIS HAS BEEN EVALUATED IN THE NSABP B-35 TRIAL.
• ELIGIBILITY INCLUDED POSTMENOPAUSAL WOMEN WITH DCIS, WITH OR WITHOUT
ASSOCIATED LCIS WITH ESTROGEN OR PROGESTERONE POSITIVE RECEPTORS WHO
UNDERWENT LUMPECTOMY WITH CLEAR MARGINS AND ADJUVANT WHOLE BREAST
RADIATION THERAPY.
• A TOTAL OF 3,104 WOMEN WERE ENROLLED WITH 3,084 WOMEN HAVING A MEDIAN
FOLLOW UP OF 9 YEARS

• BREAST CANCER-FREE INTERVAL IMPROVED WITH THE USE OF ANASTRAZOLE,
WITH NO SIGNIFICANT DIFFERENCE IN REGARD TO THE RATES OF IN-BREAST
RECURRENCE, CONTRALATERAL BREAST CANCER, OR DISTANT DISEASE.
• IMPROVEMENT IN DISEASE-FREE SURVIVAL WAS REPORTED IN WOMEN UNDER THE
AGE OF 60 YEARS WITH THE USE OF ANASTRAZOLE COMPARED TO THE
TAMOXIFEN ARM, 89.8% VERSUS 85.7%.

A DECISION TREE FOR DUCTAL
CARCINOMA IN SITU
• THE MANAGEMENT OF DCIS REQUIRES THE COORDINATED, MULTIDISCIPLINARY INTERACTION OF-
 RADIOLOGISTS
 SURGEONS
 PATHOLOGISTS
 ONCOLOGISTS
• PATIENTS ARE FIRST ASSESSED TO DETERMINE IF THEY ARE CANDIDATES FOR BREAST-CONSERVING
SURGERY.

• WOMEN WITH MULTICENTRIC DCIS, AS DEFINED BY THE PRESENCE OF –
 TWO OR MORE TUMORS IN SEPARATE QUADRANTS OF THE BREAST, AND THOSE
 WITH EXTENSIVE OR DIFFUSE DCIS OR SUSPICIOUS APPEARING
MICROCALCIFICATIONS THROUGHOUT THE BREAST ARE CANDIDATES FOR –
MASTECTOMY

• SOME WOMEN MAY PREFER MASTECTOMY TO BREAST CONSERVATION TO
MINIMIZE THE CHANCE OF IPSILATERAL RECURRENCE
• PATIENTS DEEMED TO BE APPROPRIATE CANDIDATES FOR BREAST CONSERVATION
REQUIRE COMPLETE SURGICAL EXCISION OF THE AFFECTED AREA

• NEITHER DISSECTION OF AXILLARY LYMPH NODES NOR MAPPING OF SENTINEL
LYMPH NODES IS ROUTINELY WARRANTED IN PATIENTS WITH DCIS BECAUSE OF-
VERY LOW INCIDENCE OF AXILLARY METASTASES

• AFTER BREAST-CONSERVING SURGERY, RADIOTHERAPY IS ADMINISTERED USING
TANGENTIAL FIELDS TO THE WHOLE BREAST WITH A STANDARD DOSE OF 45 TO
50 GY DELIVERED IN DAILY FRACTIONS OF 180 TO 200 CGY

THE BASIS OF EXTRAPOLATION FROM DATA ON THE TREATMENT OF INVASIVE BREAST
CANCER, A RADIATION BOOST TO THE TUMOR BED MAY BE ADDED TO WHOLE-
BREAST TREATMENT, PARTICULARLY FOR WOMEN WITH CLOSE SURGICAL MARGINS,
ALTHOUGH THE BENEFIT OF A BOOST IN THE MANAGEMENT OF DCIS IS NOT
ESTABLISHED.
Bartelink H, Horiot J-C, Poortmans P, et al. Recurrence rates after treatment of breast cancer with standard
radiotherapy with or without additional radiation. N Engl J Med 2001;345:1378–1387.

• IN SUMMARY, DESPITE CONSIDERABLE ADVANCES IN OUR CLINICAL KNOWLEDGE BASE, THE ANSWER
TO THE QUESTION “WHEN SHOULD RADIOTHERAPY BE USED FOR DCIS?” REMAINS COMPLEX AND
SURROUNDED BY CONSIDERABLE CONTROVERSY.
• TWO FUNDAMENTAL CONSIDERATIONS MUST BE EMPHASIZED:

1. A PRIMARY GOAL OF BREAST-CONSERVING THERAPY FOR DCIS IS TO ACHIEVE
THE BEST POSSIBLE COSMETIC OUTCOME.
ATTEMPTS TO OBTAIN WIDE SURGICAL MARGINS THROUGH DEFORMING,
LARGE-VOLUME BREAST EXCISIONS REPRESENT COSMETIC FAILURES AND DEFEAT
THE PURPOSE OF BREAST CONSERVATION.

2. BREAST IRRADIATION REDUCES THE RISK OF SUBSEQUENT INVASIVE OR
NONINVASIVE CARCINOMA IN THE TREATED BREAST AND THUS REDUCES THE
RISK OF THE ULTIMATE COSMETIC FAILURE—MASTECTOMY

• ACCORDING TO PROSPECTIVELY RANDOMIZED TRIALS OF BREAST-CONSERVING
THERAPY FOR DCIS, RADIOTHERAPY REDUCES SUBSEQUENT BREAST RECURRENCE
IN ALL PATIENT GROUPS IRRESPECTIVE OF PROGNOSTIC RISK FACTORS.

• THAT IS NOT TO SAY, HOWEVER, THAT RADIOTHERAPY MUST BE USED FOR ALL
PATIENTS WITH DCIS.
• IN ALL CASES, A REALISTIC AND BALANCED DISCUSSION OF THE RELATIVE RISKS
AND BENEFITS OF TREATMENT OPTIONS SHOULD BE LOOKED FORWARD FOR.

THANK YOU