breast cancer diagnosis and treament planning1

8/9/2019 Breast Cancer Diagnosis and Treament Planning1

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BREAST CANCER DIAGNOSIS AND TREAMENT PLANNING: THE

ROLE OF SCINTIMAMMOGRAPHY.

CHAPTER ONE

1.1 IntroductionThe breast isanaccessory sexualand reproductiveorgan found in both females

andmales. It islargely rudimentary inmales. Itdevelops fromthethickened

mammary ridge (milkline)ofectodermalong aline fromtheaxillatothe inguinal

regionasearly asthe fourth weekof intrauterinelife.1,2The female breast isa

dynamic structure which undergoes changes throughout a womans reproductive

lifeand, superimposed upon this, cyclical changes throughout themenstrual cycle.

These changesand some breast pathologies, affect itsshape, sizeand most

importantly its function(s). Breast problems can beeither benign ormalignant and

can lead to serious complications if not diagnosed early and adequately treated.1

Benign casesare themost common causes of breast problems up to 30 per cent

of women willsuffer froma benign breast disorder requiring treatment at some

time in theirlives. Examples of benign breast problems include Cysts, Abscesses,

Fibroadenomatosis, Cyclicalmodularity, Fibroadenoma, Duct ecfasia/periductal

mastitis, Nipple dischargeand inversion etc. Breast cancers, whichmay be

invasive or non-invasiveare themost important lesions of concern in the breast.


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Breast Cancer is found mostly inpostmenopausal women, but can also be found in

younger women especially those in their 40sand very rarely in males. It is one of

theleading cancers diagnosed in women. In America for instance, it is recognized

to be themost common malignancy in women afterskin cancerand theleading

cause of nonpreventable deaths in women.2,3

In England and Walesalso, John et

al, observed that there isahighmortality rate due to breast cancer, thehighest rate

in Europe. This they said standsat 27 deathsper 100,000 per year.4

Data from

centers in Nigeriashows that the incidence of breast cancer ishigh. It also reveals

that the detection of thisand itssubsequent treatment depends on theavailability of

screening toolslikemammography and specialists.20

The threat posed by breast cancerhaslead to a continuoussearch forasolution,

which basisand effectivenesslie in theaccurateand timely detection of thelesions

in order to instituteadequate therapeutic measures.2-5

Selfexamination, Clinical

examination and Mammographic screeningsare the basicprocedures used to detect

breast cancersearly. It has thus been correctly noted that themortality rate due to

breast cancers is dependent mostly on theearly accurate detection and subsequent

treatment.3-6, 8,9

Women up to 50 yearsare usually advised, and often required by law in some

countries to go forannualmammographic screening. Selfexamination isalso

taught and encouraged.2,3

Mammography screening can also be carried out on

younger women, especially thoseat ahigh riskof developing breast cancerlike


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those who haveahistory of the breast cancer in their families.2,3,5

It is not very

efficient in determining cancershaving alow sensitivity and Negativepredictive

values.2

Negativepredictive value isameasure of theability ofaprocedure to correctly

confirm theabsence ofa variable, and has been identified as the best indicator

measure of theprocedures for the diagnosis of breast cancer. Hence, though

mammography is themost readily breast cancerscreening method that has been

shown to savelives, it is notperfect.

Perfect or, in theleast nearperfect modalitiesare therefore required to improve

timely and accurate diagnosis to guidemanagement.2

Some of themodalities that

have been introduced include Ultrasonography, MRI breast imaging, and

functional imaging using Radionuclides, known as SCINTIMAMMOGRAPHY.

SCINTIMAMMOGRAPHY, from inception ismeant to serveasasupplementary

test to mammography to help in overcoming thelimitations of the former,

especially in distinguishing malignant from benign lesions thusavoiding many

avoidable biopsies. It can also be useful in primary breast examination and

confirmation of thestate of observed lesions in some cases wheremammography

islimited suchas in dense breasts. It hasalso been used to ascertain thepresence

and extent ofmetastasesand recurrenceand thus direct treatmentplans.

This work isa review of the Role of SCINTIMAMMOGRAPHY l) in the detection

of breast cancersand theirmanagement.


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CHAPTER TWO

BREAST CANCER FEATURES

2.1 Pathology

Malignant breast lesions (cancers)are defined asabnormally growing cells which

have the capacity for invasion of tissues within thelocal vicinity and disseminating

throughlymphatic channels or the blood stream. These include the following;

1. Those with ductal origin.- Pre-invasive (intraductal cancer)- Invasive (invasive ductal cancer)

2. Those from thelobule.- Pre-invasive (lobular carcinoma in situ.)- Invasive (lobular invasive carcinoma).c 14

2.2 Clinical features of breast cancer

Over 95% ofpatients with breast canceraresubjectively symptomatic at the

time of detection. Thesymptoms can be caused by localmetastatic or remote

effects of the disease. The common symptomsare thelocaleffects, which

include:

- Lump formation- Discharge from nipple(s)


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- Nipplealteration i.e. retraction and deviation- Skin alteration i.e. ulceration of theskin- Axillary nodesenlargements.

Theseare usually detected mostly on clinicalexamination.15

Metastatic or remoteeffectsare usually absent at the time of first diagnosis. They

include:

- Supraclavicular nodes involvement- L

ungsand liverlesions

- Central nervoussystem involvement- Weight loss- Fatigueand Malaise.15

2.3 DISTRIBUTIONS

Geographical - It occurs commonly in the Western world, accounting for 35

per cent of deaths, yet isa rare tumour in Japan. In developing countries it accounts

for 13 per cent of deaths.

Age - Carcinoma of the breast isextremely rare below theage of 20, but thereafter

the incidencesteadily risesso that by theage of 90 nearly 20per Cent of women

areaffected. Only 1 % ofpatients with breast canceraremale.

Genetic - It occursmore commonly in women witha family history of breast


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cancer than in the generalpopulation. Genetic linkageanalysisstudieshave

revealed that an abnormality frequently exists in theshort arm of chromosome 17

in these women witha family history ofearly-onset breast cancer theactual

gene is yet to be doned.

Diet - Because breast cancerso commonly affects women in the developed

world, dietary factorsmayplay apart in its causation. There is increasing evidence

that there isalinkbetween diets rich in saturated fatty acidsand vitamin C. A high

intake ofalcoholmay also beassociated withan increased riskof developing

breast cancer.

2.4 The Spread Of Mammary Carcinoma

Local spread -The tumour increases in sizeand invades otherportions of the

breast. It tends to involve theskin and to penetrate thepectoralmuscles, and even

the chest wall.

Lymphatic metastasis - Occursprimarily to theaxillaty nodesand to the internal

mammary chain oflymph nodes. Thesite of the tumour within the breast does not

dictate which nodes will be involved, e.g. medial tumoursspread just as readily to

theaxillary nodesas do lateral tumours. The involvement oflymph nodes is not

necessarily a chronologicalevent in theevolution of the carcinoma, but rathera

marker for themetastatic potential of that tumour. In advanced disease theremay

be involvement ofsupraclavicular nodesand ofany contralaterallymph nodes.


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Spread by the bloodstream - It is by this route that skeletalmetastases occur (in

order of frequency) in thelumbar vertebrae, femurs, thoracic vertebrae, ribsand

skull; they are generally osteolytic. Metastasesmay also occur in theliver, lung

and brain, and occasionally theadrenal glandsand ovaries.


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CHAPTER THREE

Breast Cancer Detection Options

Although clinical diagnosis from thepresenting symptomsand physical

examination are valuable diagnostic tools, they arelimited in the diagnosis of

breast cancer. For this, suchmodalitiesas the following are used to ensureearly

and moreaccurate diagnosis:

3.1 MAMMOGRAPHY

Presently, in most third world countries, Nigeria inclusive, themain diagnostic

option for the detection of breast cancerare Physicalexamination, which can be

done by a clinician or the woman herself, and Mammography. Thesehavea

potential to detect breast cancer or itsprecursorearly enough to lead to good

prognosiseventually.2-5

Yet, despite itsavailability and acceptability,

mammography isstill not efficient in breast lesion detection and in distinguishing

benign frommalignant lesions to informappropriatemanagement in all cases. This

modality exhibitsalow sensitivity and specificity. Estimates of the numbers of

cancersmissed by mammography are usually around 10%30%.2-6

The value of

mammography islimited in women with:

y Dense breast as is usually found in younger women.y Breast implantsand inpatients undergoing hormone therapy.y Presence ofmultiple tumoursand hormone influence.


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y cases where there isaseverearchitectural deformation of the breast suchasaftera radical breast surgery, radiation therapy, severe inflammatory

reactionsetc.2,7.8

3.2. ULTRASOND AND MRI

The conditions noted abovehavelead to the continued search for othermodalities

to improve on theachievements ofmammography. Thissearch, according to Iraj et

al is focused on intensiveefforts to achieveearly diagnosis.2,4,8

In line with this,

anatomical imaging proceduressuchas Ultrasonography have been introduced and

successfully used to confirm the true nature oflesions detected either by palpation

or withmammography likelumpsand breast cysts. Anatomicaland Functional

imaging toolslike contrast enhanced MRI havealso been introduced7.

3.3 RADIONUCLIDE BREAST IMAGING (SCINTIMAMMOGRAPHY) .

More than two decadesago, radionuclide imaging was introduced into breast

imaging field. This isa functional imaging tool that supplementsmammography in

diagnosing breast malignancy and adds to the information required in treatment

planning.

Scintimammography makes use of radiopharmaceuticalsand aspecial gamma

camera to image the breast and detect abnormalities. Single Positron Emission

Tomography (SPECT) technique is themostly used for thisprocedure. The

principle of Scintimammography is based on the fact that these


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radiopharmaceuticalsareaccumulated orabsorbed more by abnormal breast tissues

than normal tissues thusaiding in their identification. The rate ofabsorption helps

to determine theextent orseverity of thelesion.4,9,10

In all, detection options in breast cancer cases can be categorized into two as

follows:

a. Theprimary screening tools, which include Physicalexamination either bythepatient ora clinician and Mammography, and

b. Thesupplementary tools, whichmainly are used to confirm the findingsfrom theabove or to refute themand they include Ultrasonography, MRI

and Scintimammography.


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CHAPTER FOUR

SCINTIMAMMOGRAPHY PROCEDURE ASSESSMENT

4.1 Radiopharmaceuticals Used In Scintimammography.

A variety of radiopharmaceuticalsmay be used, including technetium-99m

Sestamibi (Miraluma), technetium-99m tetrofosmin, technetium-99m MDP,

thallium-201, indium-111 satumomab pendetide (Oncoscint CR/OV), indium -11

pentetreotide (OctreoScan), and technetium-99marcitumomab (CEA-Scan).7,10

TechnetiumTc 99m Sestamibi (TechnetiumTc 99m Methoxy Isobutyl Isonitril,(

MIBI), a radionuclide, hasearlier been utilized asamyocardial imaging agent as

has been TechnetiumTc 99m tetrofosmin. TechnetiumTc 99m MDP ismainly

employed in bonescintigraphy.4,8,12,

MIBI wasapproved by the United States Food

and Drug Administration in December 1990 for use in cardiac imaging and in May

1997 for use in breast imaging. Presently, it is themost widely used

radiopharmaceuticalemployed in breast imaging. A good review of the

contribution ofTechnetiumTc 99m MIBI in breast imaging will requirean

explanation of itsmechanism ofaction.

4.2 Mechanism Of Action Of Technetium Tc 99m Mibi

TechnetiumTc 99msestamibi concentrates in tissues inproportion to blood flow,

metabolic activity, and inflammatory activity . These tissuespecific parameters


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affect the concentration not in isolation but in interaction.12,14

Soon after injection,

MIBI localizes in most tumors in greater concentration than in thesurrounding

tissues because tumors generally havea greater blood supplyper gram of tissue

compared withsurrounding tissues; malignant tumors display greatermetabolic

activity than benign tumors orsurrounding breast tissues; most tumorsalso havea

higher intracellularmitochondrial concentration and MIBI accumulation is roughly

proportional to mitochondrial concentration. These factorsallow localization of the

radionuclide in most breast tumors.12

The concentration in tumours is detected

withappropriateequipment and the imageproduced used for diagnosis.

Fig.1 Lateralscintimammograms withapositive finding Fig.2

indicating focally increased activity in the breast (arrow). Thisanterior view

demonstrates increased activity in theleft

axilla (arrow).This finding indicates

metastasis to axillary lymph nodes.


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4.3 Equipment And Patient Selection

Conventional gamma cameras, also known aslarge field of view (LFOV) cameras,

havehistorically been used to image radiopharmaceuticals during

Scintimammography. These camerashavealarge inactiveareaat theedge of the

detector that prevents the camera from imaging breast tissueadjacent to the chest

wall. Therefore, breast Scintimammography using a conventional gamma camera

is typicallyperformed with thepatient supine, with the camerapositioned to takea

lateral view of the breast, or in theproneposition whichpermits the breast to hang

freely. Compression of the breast is notpossible with this, which in turn decreases

thesensitivity for detecting smallerlesions10

. Theplanar camerahasapoor

resolution, unable to identify lesionsless than 1cm withhighspecificity, haspoor

sensitivity and has been suggested to be used with caution.16

Recently, dedicated

Breast Specific Gamma Camera imaging systemshave been developed in an

attempt to overcome thelimitations of conventional Scintimammography

cameras10,17,18

. These new camerashaveasmaller field of vision (SFOV) that

provideshigher resolution and improved maneuverability compared to the

conventional gamma camera.10

Some BSGI camerasallow positioning similar to

that ofamammography examination with theability to apply compression to the

breast during imaging. Improvements in this technology has renewed interest in

Scintimammography asaprimary screening technique.10


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It ishowever imperative to note that there is no commercially availableequipment

to localizeand biopsy alesion identified solely on a nuclearmedicinestudy

because the Scintimammogramshave poorspatial resolution Thus, anypotential

use of the information from this test to promoteearlier detection ofmalignancy

would behampered by the technical inability to act on such information through

biopsy and treatment. This is unless the findings clearly correlated withalesion

already identified by some othermeans (mammography, ultrasound, or clinical

exam).10

4.4 Patient Selection

Patient selection is ofpivotal importance for the use of Scintimammography. In

general, aphysician should only referpatients withlesions found onphysical

examination ormammography for MIBI imaging. Physiciansmust beaware that

Scintimammography is not ascreening examination. If Scintimammography is

used to evaluatehighly suspicious clinical ormammographic findings, suchas

microcalcifications that are not associated withamass, a negative test result should

notpreclude biopsy.

Thismodality generally can appropriately be used inpatients with the following

conditions:

y Breast lesions that are not clearly malignant or benigny Breast abnormalities on mammogramafter breast irradiation orsurgeryy Dense breasts that are difficult to examine bypalpation and mammography


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y Breast implantsy Patients uncomfortable with theapproach of waiting and reevaluating at a 6-

month follow-up

y In patients where recurrence is feared among others6,10,12It should not be considered under the following conditions:

y Highly suspicious breast lesions (i.e, category 5 mammograms)y Breast microcalcifications that are not associated withamassy Breast lesions that areless than 1 cm in diameter12

In these cases, biopsy should be carried out to confirm diagnosis.

Scintimammography usefulness in confirming diagnosis, asascreening tooland a

tool for detection of Axillary metastaseshas been reviewed for the following

conditions:

y Suspicious Mammograms or Palpable Massesy Lesions withLow Probability of Malignancyy Probably Benign Mammogram but Recommended Close Follow-up in 3-6

Months

y Dense Breast Tissue Difficult to Evaluate on Mammographyy Detection of Axillary Metastases10

An extensiveliteraturesearch under theabove guidesstillleavesmuch to be

desired from thismodality, but worksarestill going on and conclusionsare yet not

generally accepted or rejected.10,12


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4.5 CONTRAINDICATIONS

No known contraindications ormajorsideeffectshave been reported with MIBI.

Approximately 20% ofpatientsexperiencea transient metallic taste or other

transient minorsensations including headache, flushing, nausea, andpruritus.

Thesesideeffectshave been reported in clinical trials but are rare.12The

examination lasts forabout an hour, and costsabout N10,000 (ten thousand naira)

only hence it is not too stressfuland not too expensive.


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CHAPTER FIVE

SUMMARY AND CONCLUSION

5.1. Assessment Of The Applications And Potentials Of Scintimammography

The usefulness of Scintimammography is determined by itssensitivity and

specificity as wellas itspositiveand negativepredictive values. Thishas been the

major issue ofseveral researches. Generally, thesensitivity of MIBI for the

detection of breast tumors is dependent on tissuespecific propertiessuchas

vascularity, metabolic activity and very importantly thelesion size.12,14

Recent

studieshaveshown that thesensitivity of MIBI for detection ofmalignancy in

smalllesions ispoor.2,10,12

Approximately 25% oflesionsless than 1 cm in

diameterand 78% oflesions 1 to 1.5 cmhave been reported to beeffectively

detected. Most importantly, 94% oflesions greater than 1.5 cm in diameter were

detected.12

Thesensitivity of thisprocedureaccording availableliterature ranges

from 75.4 to 93.7%2,5,6,10-12 However, thehighsensitivity has been suggested to be

occasioned by the bias in selection ofsubjects for thestudies, in whichpatients

withhigh chances ofhaving cancer wereselected for thestudies.10

Nonetheless,

multicenter trialsstillpresented highsensitivity, especially forlesions bigger than

1cmand in the categories ofpatientslisted above. These findings further

established the incremental use of Scintimammography in confirming canersand

in avoiding unnecessary biopsies2Thespecificity of Scintimammography isalso

high, being an average of 83%.2,5,6,10-12

Also, the combination of conventional


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mammography and Scintimammography, which ishighly recommended, hasa

highersensitivity and specificity.5

Scintimammography also hasahighpositivepredictive value, withan average of

about 82% and ahigh Negativepredictive value withan average ofabout

85%.2,5,6,10-12

. When Scintimammography is used asan adjunct to mammography

to improvepatient selection for biopsy, thekey diagnostic statistic is the negative

predictive value.10

Given the relativeeaseand diagnostic accuracy of the gold

standard of biopsy, coupled with theadverse consequences ofamissed breast

cancer diagnosis, the negativepredictive value of Scintimammography would have

to be very high to influence treatment decisions.10

Thisshould be near 100% to be

very effective, but isabout 5% lower on theaveragehence not highenough to

influence treatment decisionsmostly. Specifically, even at thelow end of the

intermediate range ofprevalence formalignancy, ifa negative Scintimammogram

were to be used to recommend against doing biopsy, the riskof undetected

malignancy would be 4.5% on theaverage. This is considered too high given the

relatively low morbidity of breast biopsy, the gold standard.10

This isalso the case

in the detection ofaxillary metastases. Yet, as noted above, a combination of

mammography and Scintimammography improves thesensitivity, and as the

negativepredictive value is improved by improved sensitivity, the use of

radionuclides in the functional imaging of the breast to contribute to management

plans is important still.


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5.2 CONCLUSION

Scintimammography isa functional imaging modality of the breast used mainly as

asupplementary modality to physicalexamination and conventional x-ray

mammography. It usessome radiopharmaceutical, themost widely used being

technicium-99 Sestamibi (methoxy isobutyl isonitril). It is useful in patients with

dense breast, breast implants, underhormone treatment; it can detect multifocal

ductal carcinoma in situ and lobular carcinomain situ;

is

useful in assessing

recurrent disease; can successfully monitorresponse to chemotherapy. The

practical goals of Scintimammography are two-fold: improving early detection of

breast carcinomaand/orpreventing unnecessary biopsies. Achievement of these

goals is dependent upon the referringphysiciansknowledge of theprocedureand

appropriateness ofpatient selection. It isprimarily employed in determining which

lesionsaremalignant or benign, thus reducing the number of biopsies, avoiding the

unnecessary one, and in detection ofaxillary metastases, which is usually the first

indication of breast cancermetastases.From introduction about two decadesago,

studieshave been going on to sufficiently prove the usefulness of thismodality.

Though it hasahighsensitivity and specificity, thepotential ofaccurately

identifying cancersand excluding benign lesionshave been shown not to behigh

enough to completely exclude the use of biopsies, which is the gold standard. It is

estimated that about 90 cancersaremissed out of 1000 cases when biopsy is

avoided due to result from Scintimammography. This isapproximately amissed

cancer in every ten cases, a not very favourable ratio.10


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Nevertheless, thisprocedurehas beenproven to beeffective frompractical

applications. And studiesarestill on to developaspects of thismodality suchas

equipment andpatient selection methodsand combination of this with other

modalities in order to improve itsefficiency. It ishoped that theseareas of interest

will bring more improvement in the use of Scintimammography, especially the

area of combining it with othermodalitieslikemammography, ultrasonography etc

in the timely and accurate diagnosis of breast cancerand in avoiding many

avoidable biopsies.


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breast cancer diagnosis and treament planning1

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