03 - Radiol Clin N Am 2007 - Imaging Breast Cancer.pdf - książki - Bio Med 21 - bibiariel

RADIOLOGIC

CLINICS

OF NORTH AMERICA

Radiol Clin N Am 45 (2007) 45–67

Imaging Breast Cancer

Lia Bartella, MD, FRCR a,b, *, Clare S. Smith, MB,BCh,BAO,FRCR a ,

D. David Dershaw, MD a,b , Laura Liberman, MD a,b

- Breast cancer screening

- Percutaneous image-guided biopsy

- Guidance

Stereotaxis

Ultrasound

MR imaging

- Percutaneous biopsy: future directions

- Staging breast cancer

Preoperative staging

Sentinel lymph node biopsy

- Breast MR imaging

Indications for the use of breast MR

imaging

Neoadjuvant chemotherapy response

Assessment of residual disease

Tumor recurrence at the lumpectomy site

Occult primary breast cancer

- Proton MR spectroscopy of the breast

The use of proton MR spectroscopy in the

breast

Differentiating benign from malignant

breast lesions

Characterization of histopathologic

subtypes

Evaluation of normal and lactating breast

parenchyma

Predicting response to neoadjuvant

chemotherapy

MR spectroscopy of axillary lymph nodes

in breast cancer patients

High-resolution magic angle spinning MR

spectroscopy of breast tissue

- Positron emission tomography and breast

cancer

- Other new techniques

- Summary

- References

Breast cancer is now the most common nonskin

cancer in women in the United States. Women have

an average risk of one in eight of being diagnosed

with breast cancer at some time in their lives. Al-

though the breast cancer diagnosis rate has in-

creased, there has been a steady drop in the

overall breast cancer death rate since the early

1990s [1] , most likely due to a combination of

screening, improved treatments, and better

awareness.

Invasive ductal carcinoma is the most common

breast cancer histologic type, accounting for 70%

to 80% of all cases. Invasive lobular carcinoma is

the second most common histologic type (5% to

10% of all breast cancers). It is associated with

a high rate of multifocality and bilaterality and can

be difﬁcult to diagnose clinically and mammo-

graphically because of its tendency to spread dif-

fusely through breast tissue instead of forming

a mass and causing architectural distortion. Other

less common cancers include tubular, medullary,

mucinous, and papillary cancers. Cystosarcoma,

phyllodes, angiosarcoma, and lymphoma also occur

in the breast but are not considered typical breast

a Department of Radiology, Breast Imaging Section H-118, Memorial Sloan-Kettering Cancer Center, 1275

York Avenue, New York, NY 10021, USA

b Weill Medical College of Comell University, New York, NY, USA

* Corresponding author. Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

E-mail address: bartelll@mskcc.org (L. Bartella).

doi:10.1016/j.rcl.2006.10.007

radiologic.theclinics.com

Bartella et al

cancers. Inﬂammatory cancer is diagnosed clinically

based on the associationwith edema, erythema, and

skin dimpling. Paget’s disease is a relatively rare dis-

ease, affecting the nipple–areolar complex. It ac-

counts for 1% of all breast cancer cases.

In situ carcinoma is contained within the duct,

and the basement membrane surrounding the

duct is not breached. Ductal carcinoma in situ

(DCIS) originates from the major lactiferous ducts.

Approximately 30% to 50% of patients who have

DCIS will develop invasive ductal carcinoma over

a 10-year period [2] . Lobular carcinoma in situ

(LCIS) arises from the terminal duct lobule and

can be distributed diffusely throughout the breast.

In contrast to DCIS, women who have LCIS have

up to 30% risk of developing invasive carcinoma,

mostly of the ductal type and with equal frequency

in both breasts [3] . Therefore, LCIS is considered

a marker of increased risk rather than a precursor

of breast cancer.

Controversy exists around the diagnosis and

treatment of DCIS, particularly in relation to

screening and the phenomenon of overdiagnosis

(ﬁnding early neoplasms, of which many would

not become clinically evident if screening had not

occurred). It has been estimated that 1 in 3 in situ

tumors are overdiagnosed at the ﬁrst screen and 1

in 25 are overdiagnosed at subsequent screens [4] .

It is not yet possible to say which patients who

have DCIS will go on to develop invasive cancers

and whether survival rates would be the same if sur-

gery were undertaken only after early invasive can-

cer had been diagnosed ( Tables 1–3 ). The

diagnosis and management of breast cancer has un-

dergone tremendous changes over the years. The

mammogram has taken over from clinical examina-

tion in the diagnosis of breast cancer. Ultrasound

and stereotactic biopsy have replaced many surgical

biopsies, and early detection of breast cancer has re-

sulted in breast conservation and sentinel lymph

node biopsy, replacing the radical mastectomy

and axillary lymph node dissection. Mammography

remains the traditional ﬁrst-line radiologic test of

choice in the detection and diagnosis of breast can-

cer; however, mammography is not perfect. About

10% of cancers are mammographically occult

even after they are palpable and, in women who

have dense breasts, the sensitivity of mammogra-

phy can be as low as 68% [5] . This low sensitivity

has led to the expansion of breast imaging to in-

clude sonography and MR imaging and the devel-

opment of newer imaging techniques such as

positron emission tomography (PET), lymphoscin-

tigraphy, scintimammography, breast tomosynthe-

sis, and contrast-enhanced mammography to aid

in the detection and staging of breast cancer and

to monitor response to therapy.

Mammography is used for diagnostic and screen-

ing purposes. Diagnostic mammography is com-

monly used to identify possible breast cancers in

women who present with signs or symptoms and

it has higher sensitivities (85%–93%) compared

with screening mammography [6,7] . Tumors de-

tected by diagnostic mammography are larger and

more likely to be node positive than those detected

by screening mammography [8] . The last decade

has seen the development of full-ﬁeld digital mam-

mography. Digital mammography devices are simi-

lar to ﬁlm-screen units except that the ﬁlm-screen

cassette used to record the image is replaced by

a digital detector. Digital mammography has a num-

ber of advantages over traditional ﬁlm-screen mam-

mography. It has a higher contrast resolution yet

maintains a good dynamic range. It allows for dig-

ital transmission and storage of images, eliminating

the need for the ﬁlm library. The images can be ma-

nipulated to enhance visualization of subtle struc-

tures and calciﬁcations, and the procedure is

quicker for the patient because there are no wait

times for the ﬁlms to be processed. It also elimi-

nates ﬁlm artifacts such as dust and uses a lower

dose of radiation [9] . The major disadvantage of

digital mammography is cost, with digital systems

currently costing approximately one to four times

as much as ﬁlm-screen systems. The results of the

largest trial to date comparing digital versus ﬁlm

mammography for breast cancer screening, the Dig-

ital Mammographic Imaging Screening Trial [10] ,

were recently published. In this multicenter trial,

the investigators found that digital mammography

was better than conventional ﬁlm mammography

at detecting breast cancer in young, premenopausal,

and perimenopausal women and in women who

have dense breasts; however, there was no signiﬁ-

cant difference in diagnostic accuracy between dig-

ital and ﬁlm mammography in the population as

a whole or in the other predeﬁned subgroups.

Breast sonography is well established as a valu-

able imaging technique. The current indications

for performing breast ultrasound, as listed in the

‘‘ACR Practice Guideline for the Performance of

Breast Ultrasound Examination,’’ include identiﬁ-

cation and characterization of palpable and non-

palpable abnormalities, evaluation of clinical

and mammographic ﬁndings, guidance of inter-

ventional procedures, evaluation of breast im-

plants, and treatment planning for radiation

therapy [11] . It is also the imaging technique of

choice to evaluate palpable masses in women

younger than age 30 years and in lactating and

pregnant women. Its advantage lies in the fact

that it is easily accessible, relatively low in cost,

and does not involve the use of ionizing radia-

tion. Its main disadvantage is that its performance

Breast Cancer Imaging 47

Table 1: TNM staging system

Primary tumor – T

Primary tumor cannot be assessed

No evidence of primary tumor

Tis (DCIS)

Ductal carcinoma in situ

Tis (LCIS)

Lobular carcinoma in situ

Tis (Paget’s)

Paget’s disease of the nipple with no tumor (note: Paget’s disease associated

with a tumor is classiﬁed according to the size of the tumor)

Tumor % 2.0 cm in greatest dimension

T1mic

Microinvasion % 0.1 cm in greatest dimension

T1a

Tumor >0.1 cm but % 0.5 cm in greatest dimension

T1b

Tumor >0.5 cm but % 1.0 cm in greatest dimension

T1c

Tumor >1.0 cm but % 2.0 cm in greatest dimension

Tumor >2.0 cm but % 5.0 cm in greatest dimension

Tumor >5.0 cm in greatest dimension

Tumor of any size with direct extension to (a) chest wall or (b) skin, only as

described below

T4a

Extension to chest wall, not including pectoralis muscle

T4b

Edema (including peau d’orange) or ulceration of the skin of the breast, or

satellite skin nodules conﬁned to the same breast

T4c

Both T4a and T4b

T4d

Inﬂammatory carcinoma

Regional lymph nodes – N

Regional lymph nodes cannot be assessed (eg, previously removed)

No regional lymph node metastasis

Metastasis to movable ipsilateral axillary lymph node(s)

Metastasis to ipsilateral axillary lymph node(s) ﬁxed or matted, or in clinically

apparent ipsilateral internal mammary nodes in the absence of clinically

evident axillary lymph node metastasis

N2a

Metastasis in ipsilateral axillary lymph nodes ﬁxed to one another (matted)

or to other structures

N2b

Metastasis only in clinically apparent* ipsilateral internal mammary nodes

and in the absence of clinically evident axillary lymph node metastasis

Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary

lymph node involvement, or in clinically apparent* ipsilateral internal

mammary lymph node(s) and in the presence of clinically evident axillary

lymph node metastasis; or, metastasis in ipsilateral supraclavicular lymph

node(s) with or without axillary or internal mammary lymph node

involvement

N3a

Metastasis in ipsilateral infraclavicular lymph node(s)

N3b

Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph

node(s)

N3c

Metastasis in ipsilateral supraclavicular lymph node(s)

Distant metastasis – M

Distant metastasis cannot be assessed

No distant metastasis

Distant metastasis

Histologic grade – G

Grade cannot be assessed

Low combined histologic grade (favorable)

Intermediate combined histologic grade (moderately favorable)

High combined histologic grade (unfavorable)

is operator dependent and it can be time-

consuming.

Several studies have shown that breast sonogra-

phy can help distinguish benign from malignant

solid nodules [12] and that the use of ultrasound

as an adjunct to mammography has led to an

overall increase in diagnostic accuracy [13] . Studies

on the impact of ultrasound have also shown that

its use can affect management in 64% of patients

and prevent unnecessary biopsies in 22% [14] . Ul-

trasound is also useful in the assessment of the ax-

illa in a patient who has newly diagnosed breast

Tis

Carcinoma in situ

Bartella et al

Table 2: Stage grouping

Stage

Tumor Node Metastasis

Because of these differences, the conclusions of

these studies have varied from trial to trial. Based

on these trials, however, there is little doubt that

mammographic screening has efﬁcacy. A recent

meta-analysis of data from these seven trials shows

a 24% mortality reduction in women invited to

screening.

The estimation of mortality reduction with mam-

mographic screening is generally considered to be

underestimated by these trials because of noncom-

pliance of those invited to screening and contami-

nation of the control groups (the women

included in these studies who were not invited to

be screened). The percentage of women invited to

screening who actually underwent screening was

as low as 67%. Although they underwent some

screening, many women did not undergo all the

screening mammography to which they were in-

vited. This lack of compliance degrades the impact

of screening on breast cancer mortality in all stud-

ies. In addition, of the women not invited to screen-

ing, some underwent mammographic screening

outside of the study situation, further decreasing

the study’s estimate of the impact of

mammography.

Results of prospective randomized trials have

now been augmented by experience with popula-

tion-based screening. In the Uppsala region of Swe-

den, a comparison of breast cancer mortality before

and after the introduction of mammographic

screening has estimated a 39% mortality reduction

due to screening [17] . In Italy, the rate of fatal breast

cancer cases has been reduced by 50% with the in-

troduction of mammographic screening [18] . These

data suggest that the impact of screening may be

greater than that estimated by prospective random-

ized trials.

Although the beneﬁt of mammographic screen-

ing is widely accepted, limitations and adverse

effects from screening are also generally acknowl-

edged and include biopsies to diagnose benign

lesions, anxiety about mammography and biopsy

results, scarring from biopsies, and time lost from

work to undergo screening and follow-up. Of biop-

sies done on the basis of mammographic abnor-

malities, only 25% to 45% result in a diagnosis of

carcinoma.

The failure of mammography to detect all breast

cancers is also widely acknowledged, with the false-

negative rate of screening mammography usually in

the 20% to 30% range. Tumors without associated

calciﬁcations and subtle masses are particularly dif-

ﬁcult to diagnose. Invasive lobular carcinoma and

uncalciﬁed DCIS are especially difﬁcult to detect

with mammography.

Despite these limitations, mammography has

been incorporated in the routine medical care of

Tis

IIA

IIB

IIIA

IIIB

IIIC

Any T

Any N

cancer. If lymph nodes are seen to have cortical con-

tour bulges or masses, then ultrasound-guided per-

cutaneous needle biopsy can conﬁrm metastatic

involvement, obviating the need for sentinel lymph

node biopsy [15] .

An American College of Radiology Imaging Net-

work trial (Protocol 6666) is now underway to as-

sess the efﬁcacy of screening breast sonography.

The primary aim of this multicenter protocol is to

determine whether screening whole-breast sonog-

raphy can identify mammographically occult can-

cers and whether such results can be generalized

across multiple centers.

Breast cancer screening

Abundant evidence has accumulated over the past 4

decades to support the ability of mammographic

screening to decrease breast cancer mortality. Seven

prospective randomized trials have been con-

ducted. Study designs of these trials have differed,

with variable intervals between mammographic

screenings, variable ages at invitation to screening

and cessation of screening, and even with varying

mammographic techniques. ( Table 4 ) [16] .

Table 3: Stage and 5-year survival rate

Stage

Rate (%)

100

IIA

IIB

IIIA

IIIB

Breast Cancer Imaging 49

Table 4: Results of prospective randomized trials of mortality reduction by mammographic screening

Study

Year

begun

Age of

women (y)

Mammography

interval (mo)

% Participation

of invited women

% Mortality

reduction (95% CI)

HIP

1963

40–64

24 (7–38)

Two county,

Sweden

1977

40–74

32 (20–41)

Malmo

1976

45–69

18–24

19 ( 8–39)

Stockholm

1981

40–64

26 ( 10–50)

Gothenburg

1982

39–59

16 ( 39–49)

Canada NBSS1 1980

40–49

100

3( 26–27)

Canada NBSS2 1980

50–59

100

2( 33–22)

All trials

combined

24 (18–30)

Abbreviations: CI, conﬁdence interval; HIP, health insurance plan of greater NY; NBSS, National Breast Cancer Screening

study.

Data from Smith RA, Saslow D, Sawyer KA, et al. American Cancer Society guidelines for breast cancer screening: update

2003. CA Cancer J Clin 2003;53:141–69; and Heywang-Koebrunner SH, Dershaw DD, Schreer I. Diagnostic breast imaging.

2nd edition. New York: Thieme; 2001.

women. The usual recommendation for mammo-

graphic screening in the United States is currently

annual mammography starting at age 40 years

[19] . No upper age limit has been applied to the

screening recommendation in the United States.

In women at higher risk than the general popula-

tion, screening for the development of breast cancer

may be more aggressive. Women at highest risk are

those who are gene positive on testing for BRCA

genes or who have a very strong family history.

These histories include multiple ﬁrst- and second-

degree relatives who have had breast or ovarian car-

cinoma, a ﬁrst-degree relative who has had breast

cancer before age 50 years, male relatives who

have had breast cancer, and Ashkenazi Jewish

women who have a family history of breast or ovar-

ian cancer. In some families, gene-positive women

have been calculated to have up to an 85% lifetime

risk of developing breast cancer. In families in

which premenopausal breast cancer develops, it

has been recommended that women should start

screening 10 years earlier than the youngest age at

which breast cancer was diagnosed, starting as early

as age 25 years. Because breast cancers in younger

women may grow more quickly and because famil-

ial breast cancers may grow more quickly than spo-

radic cancers, it has been suggested that screening

may be useful more frequently than every 12

months in this population. Although 6-month

mammographic screening has been suggested for

these women, there are no data to indicate whether

it is of any advantage over annual examinations.

Other women at signiﬁcantly higher risk include

those who have a personal history of breast cancer

or prior biopsy diagnosis of atypical ductal hyper-

plasia (ADH) or LCIS. Screening for these women

should commence at the time of diagnosis. Women

treated for Hodgkin’s disease with mantle radiation

are at risk for developing radiation-induced breast

cancer and should commence screening as early

as 8 years after their cure [20] .

The addition of other imaging modalities to

mammography in the screening algorithm for

high-risk women has undergone some study, but

screening with nonmammographic imaging re-

mains controversial. It should be remembered

that mammography is the cornerstone of breast

cancer screening, and there are no recommenda-

tions that it be abandoned for other screening mo-

dalities. The ability of mammography to detect

subcentimeter carcinomas based on easily identi-

ﬁed microcalciﬁcations has not been replaced by

any other screening tool [21] .

When used in a high-risk population, there are

data to suggest that sonography and MR imaging

can detect early, curable cancers not found by mam-

mography. In a study of Dutch women who had

a genetic predisposition to develop breast cancer,

MR imaging was able to ﬁnd more cancers than

mammography at initial and follow-up screenings.

Cancers found by both modalities had a similar

prognosis, and the positive predictive values of

mammography and MR imaging were comparable

[22] . Other studies from the United States and Eu-

rope support these results. Data for sonographic

screening are less compelling, suggesting a sensitiv-

ity that is inferior to MR imaging and an inability to

detect most in situ disease. There may also be

a lower positive predictive value for sonographi-

cally recommended biopsies than those based on

mammographic or MR imaging ﬁndings. The wider

availability and lesser cost of sonography compared

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