12 Assessment of Extent of Disease Using Magnetic Resonance Imaging

(1)

Accurate assessment of extent of disease is essential for planning appropriate treatment for women with breast cancer. The presence of cancer in more than one quadrant (multicentric disease) usually indicates the need for mas- tectomy rather than breast conservation. The presence of multiple sites of cancer in one quadrant (multifocal disease) indicates the need for wider excision and may pre- clude breast conservation. Involvement of the pectoral muscle, chest wall, and/or skin may indicate the need for surgical excision to include the involved areas. Finally, identiﬁcation of cancer in the contralateral breast indicates the need for contralateral surgery. This chapter discusses the use of magnetic resonance imaging (MRI) in women with breast cancer to determine tumor size; detect additional sites of disease in the ipsilateral breast; assess for involvement of the pectoral muscle, chest wall, and skin;

and evaluate the contralateral breast.

1. Ipsilateral Breast

1.1. Tumor Size

Breast MRI may provide more accurate assessment of tumor size than mammography or sonography. Gribbestad and colleagues¹found excellent correlation between MRI measurement and size determined at histology for 29 patients with known breast tumors. Boetes and coworkers² correlated mammography, ultrasound, and MRI in 61 breast cancers. The index cancer was identified by ultrasound in 85%, by mammography in 90%, and by MRI in 98% of women. On mammogram and ultrasound images, tumor size was underestimated significantly (P< 0.005) by 14% and 18%, respectively, while MRI showed no significant difference in size compared with pathologic examination. In another study correlating MRI, ultrasound, and mammographic measurements with histologic measurements in 14 breast cancers, Davis and colleagues³ found that MRI measurements had the highest correlation coef-

ﬁcient (r= 0.98), compared with lower correlation coefﬁ- cients for ultrasound (r = 0.45) and mammography (r = 0.46). Magnetic resonance imaging measurements also had the smallest standard error (0.34), compared with higher standard errors for ultrasound (0.78) and mammography (1.04).

Although in many cases the size assessment by MRI is more accurate than that of other imaging modalities, MRI size does not always correlate with histologic size of the cancer. Merchant and colleagues⁴performed preoperative MRI in 40 patients, including 32 with malignant tumors.

Magnetic resonance imaging estimated the tumor size to be larger than mammography in 71% of cases and larger than histologic measurement in 84%. Magnetic resonance imaging would have upstaged 22% of evaluated cases from T1 to T2 and 10% of cases from T2 to T3. In spite of the high accuracy of MRI in assessing tumor size, it is impor- tant to remember that not all enhancement in the region of the tumor represents malignancy; enhancement could represent ﬁbrosis, atypia, or other benign ﬁndings.

1.2. Additional Sites of Cancer:

Pathologic Considerations

Women with one area of proven breast cancer may harbor additional sites of cancer in the ipsilateral breast.⁵Patho- logic analyses of mastectomy specimens have shown sites of cancer other than the index lesion in 20% to 63%^6–13 (Table 12.1). Of these additional sites of cancer, 19% to 67% were invasive. In 20% to 47% of mastectomy specimens, additional sites of cancer were present in quadrants other than that of the index tumor. Among women who had mastectomy for ductal carcinoma in situ (DCIS), a multifocal distribution with gaps larger than 1 cm was present in 8%¹⁴and DCIS involved more than one quadrant in 23% to 47%^14,15; the likelihood of cancer outside the index quadrant was higher in women with DCIS measuring 2.5cm or larger.⁸

12

Assessment of Extent of Disease Using Magnetic Resonance Imaging

Laura Liberman

200

(2)

1.3. Local Recurrences

In previous studies of women with invasive breast cancer who had breast conservation, local recurrence rates at 15- year follow up were 36% for women who did not receive radiation and 12% for women who received radiation.¹⁶In previous studies of women with DCIS who had breast conservation, local recurrence rates at 8-year follow up were 31% for women who did not receive radiation and 13%

for women who received radiation.¹⁷The greater than 30%

local recurrence rates in women who did not receive radiation are within the 20% to 63% range expected on the basis of the frequency of cancer at additional sites in the breast in the pathology studies.⁵That the local recurrence rates are lower in women who receive radiation therapy indicates that radiation destroys or retards growth of some of these sites of disease.

One could hypothesize that preoperative identiﬁcation of additional sites of cancer may allow their removal and could lower the frequency of local recurrence. It is also possible that MRI-guided resection of these additional sites could reduce the need for postoperative radiation therapy. Further work is needed to validate these hypotheses.

1.4. Additional Sites of Cancer at Magnetic Resonance Imaging

In published studies, MRI identiﬁed additional sites of ipsilateral cancer that were not identiﬁed on mammography or physical examination in 6% to 34% of women with breast cancer^5,18–25(Table 12.2). Additional sites of cancer in the same quadrant as the index cancer were found in 1% to 20% of women, and additional sites of cancer in different quadrants from the index cancer were found in 2%

to 24% of women^5,18–25(Table 12.2).

1.5. Magnetic Resonance Imaging of the Ipsilateral Breast at Memorial Sloan-Kettering Cancer Center

In a study of 70 women with percutaneously diagnosed breast cancer who were considering breast conservation at our hospital, MRI identiﬁed additional sites of cancer in the ipsilateral breast in 19 (27%)⁵(Figures 12.1 and 12.2).

Additional sites of cancer in 19 women were inﬁltrating in 11 (16%) and ductal carcinoma in situ in 8 (11%) women.

These additional sites of cancer were in the same quadrant

12. Assessment of Extent of Disease Using Magnetic Resonance Imaging 201

Table 12.1. Pathologic Analysis of the Ipsilateral Breast in Mastectomy Studies No. with Additional

No. of Mastectomy Sites of Ipsilateral No. Same No. Different

Investigator Specimens Cancer (%)^a Quadrant (%)^b Quadrant (%)^b

Qualheim^6c 157 85 (54) 27 (17) 58 (37)

Rosen^7d 203 65 (32) NA 65 (32)

Lagios^8e 84 17 (20) NA 17 (20)

Schwartz^9f 43 16 (37) NA 16 (37)

Egan^10g 116 71 (61) NS NS

Holland^11h 282 177 (63) 56 (20) 121 (43)

Anastassiades¹²ⁱ 365 169 (46) NA 169 (46)

Vaidya^13j 30 19 (63) 5 (17) 14 (47)

Source: Adapted from Liberman et al.⁵with permission.

Abbreviations: NA, not applicable: study focused on quadrants other than index cancer; NS, not stated.

Note: Many of these pathology studies included cases of lobular carcinoma in situ (LCIS) among index lesions, additional sites of cancer, or both.

Currently, LCIS is not considered cancer, but rather a risk factor for subsequent development of cancer. Therefore, in calculating proportion of mastectomies in which additional sites of cancer were found for this table, an attempt was made to remove cases in which index cancer was LCIS from denominator and cases in which additional sites were LCIS from numerator.

a Number of mastectomies in which cancer was found in areas other than index cancer, expressed as percent of all mastectomies.

b Number of mastectomies with additional sites of cancer in quadrant indicated, expressed as percent of all mastectomies.

c Number of cases of LCIS not stated but authors state that “The few examples of lobular carcinoma in situ appearing in this series were obviously manifestations of independency of origin.”

d All index cancers were invasive. Number of additional sites that were LCIS was not stated. Additional sites of cancer were found in 26% (26 of 100) mastectomies with index cancers <2cm and in 38% (39/103) mastectomies with index cancers ⭐2cm.

e Excludes one case in which index cancer was LCIS and one case in which additional site was LCIS.

f Excludes one case in which index cancer was LCIS and three cases in which additional sites were LCIS.

g Excludes one case in which index cancer was unicentric LCIS and one case in which index lesion and additional sites were LCIS.

h All index cancers were invasive. Number of additional sites that were LCIS was not stated. Analysis was with respect to distance from index cancer rather than quadrant: of 177 additional sites of cancer, distance from index cancer was ⭐2cm in 56 and >2cm in 121.

i Excludes one case in which index cancer and additional sites were LCIS and 17 cases in which additional sites were LCIS.

j All index cancers were invasive. Includes one case in which index cancer was inﬁltrating lobular and additional site was LCIS.

(3)

Table 12.2. MRI of the Ipsilateral Breast in Women with Breast Cancer No. of Women

with Additional No. of

No. of Ipsilateral MRI- No. of Same Different

Investigator Women Detected Cancer (%)^a Quadrant (%)^b Quadrant (%)^b

Harms¹⁸ 29^c 10 (34) 3 (10) 7 (24)

Orel¹⁹ 64 13 (20) NS^d NS^d

Boetes²⁰ 61^c 9 (15) 8 (13) 1 (2)

Mumtaz²¹ 92^c 10 (11) 1 (1) 9 (10)

Fischer²² 336 54 (16) 30 (9) 24 (7)

Drew²³ 178 41 (23) 15 (8) 26 (15)

Esserman²⁴ 58^c 6 (10) NS NS

Bedrosian²⁵ 231 14 (6) 6 (3) 8 (3)

Liberman⁵ 70 19 (27) 14 (20) 5 (7)^e

Source: Adapted from Liberman et al.⁵with permission. Abbreviation: NS, not stated.

a Number of women with MRI-detected sites of cancer other than index lesion, as percent of all women in study.

b Number of women with MRI-detected sites of cancer in quadrant indicated, as percentage of all women in study.

c Expressed as number of breasts rather than number of women.

d Quadrant of additional sites of MRI-detected cancer, given for 11 of 13 women, was same as index cancer in 7 and different in 4. Among 13 women with additional sites of cancer detected at MRI, 9 were considered to have multifocal disease (defined in study as distinct at gross examination or demonstrating separate, dispersed, microscopic foci) and 4 were considered to have diffuse disease (defined in study as several lesions that were ill- defined at gross examination with large areas of dispersed intraductal and infiltrating carcinoma).

e Includes two women with additional MRI-detected sites of cancer in both same quadrant and different quadrant.

Figure 12.1. A 39-year-old woman 1 month status post excision of a palpable, uncalciﬁed, spiculated mass in the right breast retroareolar region, lower inner quadrant. Surgical pathology yielded invasive ductal carcinoma, measuring 0.1–0.4 cm, and DCIS, with positive margins. (A) Sagittal, T1-weighted, contrast- enhanced MRI of right breast shows 3-cm seroma right lower inner quadrant with extensive surrounding clumped enhancement, suspicious for residual disease. (B) Sagittal, T1-weighted, contrast-enhanced MRI of right breast shows separate spicu-

lated, heterogeneously enhancing, 1.8-cm mass right lower outer quadrant, not seen on mammography or ultrasound. Magnetic resonance imaging guided needle localization of this mass yielded invasive ductal carcinoma, 1.7 cm, and DCIS (i.e., multicentric disease). Mastectomy, performed during the same procedure, revealed residual invasive ductal carcinoma and DCIS at and extending away from the lumpectomy site. Sentinel nodes were free of tumor.

A B

(4)

Figure 12.2. A 47-year-old woman who had stereotactic biopsy of a subcentimeter cluster of calciﬁcations in the left breast 1 month previously, yielding DCIS. (A) Sagittal, contrast-enhanced, T1-weighted MRI of left breast shows stereotactic clip in the left lower inner quadrant evident as 3 mm focus of low signal inten- sity (arrow), with subtle surrounding clumped enhancement. (B) Sagittal, contrast-enhanced, T1-weighted MRI of left breast shows additional irregular, heterogeneously enhancing mass left breast 6:00 axis (arrow). (C) Sagittal, contrast-enhanced, T1- weighted MRI of left breast shows ductal, heterogeneous

enhancement left lower outer quadrant (arrow).All three of these areas underwent MRI-guided needle localization, yielding DCIS.

(D) Sagittal, contrast-enhanced, T1-weighted MRI of right (contralateral) breast shows irregularly shaped, irregularly marginated, heterogeneously enhancing mass posteriorly (straight arrow) and clumped enhancement anteriorly (curved arrow).

Magnetic resonance imaging guided needle localization with bracketing wires yielded ductal carcinoma in situ, with a small focus of microinvasion at the site of the posterior lesion. The patient had bilateral mastectomies. Sentinel nodes were negative.

A B

C D

(5)

as the index cancer in 14 (20%) women, in a different quadrant in 3 (4%) women, and in the same and different quadrants in 2 (3%) women. In 17 (24%) women, MRI detected ipsilateral lesions that were benign. Changes caused by prior percutaneous biopsy were infrequent on MRI examination and included a clip in 12 (17%) women and small hematoma in two (3%) women. No skin thickening or skin enhancement were observed, and no needle tract could be identiﬁed. Postbiopsy change did not inter- fere with MRI interpretation.

The 27% frequency of ﬁnding additional sites of cancer by MRI is within the 20% to 63% range of frequencies of additional sites of cancer reported in previous pathologic analyses of mastectomy specimens (Table 12.1), as well as within the 6% to 34% range of ipsilateral MRI-detected cancers in previously published literature⁵ (Table 12.2).

The proportion of women in whom MRI depicted additional sites of ipsilateral cancer was higher in women with a family history of breast cancer than in women without this history (14/33 = 42% vs. 5/37 = 14%, P < 0.02), and in women in whom the index tumor was inﬁltrating lobular carcinoma rather than other histologies (6/11 = 55% vs.

13/70= 19%, P < 0.06).

Among women with additional ipsilateral sites of cancer detected by MRI in the study from our hospital, approximately three fourths (74%) had additional sites only in the quadrant of the index cancer and one fourth (26%) had additional sites of cancer in other quadrants.⁵This distribution mirrors the distribution of local recurrences at 15- year follow up of women with invasive breast cancer who had breast conservation, in which 75% were found within the same quadrant as the index lesion and 25% in different quadrants.¹⁶In other studies of MRI, the distribution of MRI-detected additional sites of cancer has been variable, with 10% to 89% in the same quadrant as the index tumor.⁵

In our study of women with percutaneously proven cancer, biopsy was recommended for MRI-detected ipsilateral lesions in 51% of women; the positive predictive value of biopsy for these lesions was high (52%).⁵This 52%

positive predictive value is within the 18% to 88% range of positive predictive values for biopsy based on MRI ﬁnd- ings in high-risk women^26–32and higher than the 20% to 40% range of PPVs for mammographically guided needle localization and surgical excision in the general population.³³The positive predictive value was higher in lesions in the same quadrant as the index cancer as compared with lesions in different quadrants (18/28 = 64% vs. 5/16 = 31%, P= 0.07.)

1.6. Detection of Ductal Carcinoma In Situ in the Ipsilateral Breast

In published studies, the sensitivity of MRI in DCIS detection has ranged from 40% to 100%.³⁴ Recent data,

however, suggest that MRI may be more sensitive than mammography in detection of DCIS. In a retrospective study of 37 breasts in 35 women with pure DCIS who had preoperative breast MRI, Menell and colleagues³⁵ found that the sensitivity for DCIS detection was higher for MRI than for mammography (89% vs. 30%, P< 0.001). Mag- netic resonance imaging was the only study to ﬁnd DCIS in 24 (65%) breasts; in 2 (5%) breasts, DCIS was found only with mammography. Magnetic resonance imaging detection of additional sites of DCIS, if conﬁrmed by biopsy, may assist in treatment planning (Figure 12.2).

1.7. Ultrasound Versus Magnetic Resonance Imaging to Detect Additional Disease in the Ipsilateral Breast

Breast ultrasound can detect additional ipsilateral disease in women with breast cancer,^2,36–39but breast MRI may be more sensitive in this regard. Boetes and colleagues²compared accuracy of MRI, mammography, and ultrasound in 61 cancers in 60 women undergoing mastectomy for cancer. They found that mammography depicted 31% of additional invasive cancers, while ultrasound showed showed 38% and MRI showed 100%.

Berg and colleagues³⁸ compared mammography, ultrasound, and MRI in 77 women with recently diagnosed breast cancer. Pathologic examination yielded 110 foci of cancer, of which 89 were invasive and 21 were DCIS. Of 89 foci of invasive cancer, mammography depicted 56 (63%), ultrasound 85 (96%), and MRI 84 (94%). Of 21 foci of DCIS, mammography depicted 14 (67%), ultrasound 13 (62%), and MRI 15 (71%). Either MRI or ultrasound depicted additional mammographically occult malignant foci in approximately one third of women with breast cancer. Size and extent of tumor was more accurately depicted with MRI than ultrasound, with 12% of patients undergoing more extensive surgery on the basis of MRI even after combined ultrasound, mammography, and clinical breast examination.

Hlawatsch and colleagues³⁹ compared whole breast ultrasound and MRI as adjuncts to mammography in 101 women with breast cancer. Twenty-seven tumors showed multifocal or multicentric invasive cancer at pathology. Of these 27, 48% were correctly diagnosed by mammography alone, 63% by a combination of mammography and ultrasound, and 81% by MRI. Nine of the index cancers were not seen at mammography but were visible at ultrasound.

Use of ultrasound beneﬁted 13 women and yielded false- positive studies in 2. Use of MRI beneﬁted seven women and produced false-positive studies in eight.

Data regarding extent of disease assessment in the ipsilateral breast should be interpreted in conjunction with other published data comparing breast ultrasound and MRI. Studies of high-risk women who were screened with

(6)

mammography, ultrasound, and MRI reported sensitivities of 86% to 100% for MRI versus 33% to 43% for ultrasound.^26,29 Magnetic resonance imaging is more sensitive than ultrasound in the detection of DCIS.³⁶The 18% to 88% positive predictive value (PPV) of biopsy in studies of MRI screening^26–32 is signiﬁcantly higher than the 7%

to 14% PPV of biopsy in studies of screening breast ultrasound.^26,40–42

Both ultrasound and MRI may detect additional sites of ipsilateral cancer, potentially impacting on treatment.

Magnetic resonance imaging has the advantage of higher sensitivity, particularly for detecting DCIS. Breast ultrasound has the advantages of speed, lower cost, wider avail- ability, and ready access for biopsy procedures. Both examinations have the disadvantage of false-positive results, with the proportion of false-positives depending on operator experience and technique. Further study comparing MRI and ultrasound in assessment of extent of disease would be helpful. At our institution if the decision is made to supplement mammography with another imaging test to assess extent of disease, we generally start with MRI; if suspicious lesions are identiﬁed on MRI, we often perform directed ultrasound examination to determine if there is an ultrasound correlate that would be amenable to ultrasound-guided biopsy.

1.8. Involvement of Pectoral Muscle, Chest Wall, and Skin

Masses that are posterior in location can be difficult to evaluate with mammograms and physical examination.⁴³ Involvement of the pectoral muscle may require specific surgical treatment, such as excision of a portion of the muscle if the tumor superficially invades it, radical mastectomy if the tumor involves the full thickness of the muscle, or chest wall resection for a tumor that extends to involve chest wall (ribs, intercostal muscles, serratus anterior muscle).⁴⁴Preoperative knowledge of involvement of pectoral muscle and/or chest wall therefore impacts on treatment planning.

Breast MRI may be useful in assessing involvement of the pectoral muscle and chest wall. Morris and colleagues⁴³ reported 19 patients with posterior breast masses who had preoperative breast MRI. Enhancing masses were identified at breast MRI in all 19 patients. Five (26%) had masses that abutted the muscles, with obliteration of the fat plane and muscle enhancement. All five had muscle involvement at surgery. In the remaining 14 (74%) patients, no enhancement of muscle was seen; none of these had invasion of the muscle at surgery. The authors concluded that extension of tumor into underlying muscle or chest wall was indicated by abnormal enhancement within these deep structures (Figure 12.3); violation of the fat plane without other findings did not indicate muscle or chest wall involvement.⁴³

Skin involvement can also be assessed with breast MRI (Figure 12.4). The identification of skin enhancement may help to identify a site for biopsy, may guide the surgeon toward excision to include the suspect area, and may serve as a baseline for follow up after treatment for locally advanced breast cancer.⁴⁴Inflammatory carcinoma is char- acterized by tumor involvement of the dermal lymphatics and produces skin induration. In inflammatory carcinoma, MRI may show focal or diffuse enhancement of the thick- ened skin, a pattern similar to that of mastitis⁴⁴ (Figure 12.5). Rieber and colleagues⁴⁵ reported skin thickening that was bright on T2-weighted images and medium inten- sity on T1-weighted images in 90% of patients with inflammatory carcinoma versus 55% of patients with mastitis.

Further study is needed to deﬁne the sensitivity and speciﬁcity of breast MRI in the assessment of skin involvement.

Figure 12.3. A 39-year-old woman with palpable, mammographically evident mass left lower inner quadrant, for which core biopsy yielded invasive ductal carcinoma and ductal carcinoma in situ. Sagittal, contrast-enhanced, T1-weighted MRI of the left breast shows an irregularly shaped, irregularly marginated, heterogeneously enhancing mass in the left lower inner quadrant corresponding to the palpable cancer. Enhancement extends into the chest wall, consistent with chest wall invasion.

(7)

Figure 12.4. A 65-year-old woman with palpable lump breast mass lower inner quadrant, for which core biopsy yielded invasive ductal carcinoma. Sagittal, contrast-enhanced, T1-weighted MRI of the left breast shows minimally spiculated, irregular, heterogeneously enhancing mass left lower inner quadrant, corresponding to biopsy proven cancer. Contiguous with the lesion is thickening and irregular, heterogeneous, mass enhancement involving the overlying skin. The mass abuts the pectoral muscle, but there is no enhancement in the muscle;

therefore, no evidence of pectoral invasion. Mastectomy, performed after chemotherapy, revealed invasive ductal carcinoma and DCIS.

Invasive cancer involved the skin dermis by direct extension. No pectoral muscle involvement was found at surgery.

Figure 12.5. A 59-year-old woman who presented with inﬂam- matory right breast cancer. (A) Sagittal, post-contrast, T1- weighted MRI of the medial right breast shows multiple conglomerate heterogeneously enhancing masses, as well as nodular enhancement in the skin. (B) Sagittal, post-contrast, T1- weighted MRI of the right breast at the plane of the nipple shows

extensive heterogeneous mass enhancement within the breast, with heterogeneous nodular enhancement involving the nipple.

Mastectomy, performed after chemotherapy, yielded invasive ductal carcinoma, histologic and nuclear grade III, measuring 0.1 to 3.5 cm, and DCIS. Skin and dermal lymphatics were involved with invasive cancer. No tumor was found in the axillary nodes.

A B

(8)

2. Contralateral Breast

2.1. Synchronous Bilateral Breast Cancer

For women with breast cancer, the contralateral breast is at high risk. A synchronous contralateral cancer, variably deﬁned as occurring within 3 months, 6 months, or 1 year after diagnosis of the index cancer, is found by mammography, physical examination, or both in approximately 2%

of women with breast cancer. Women with synchronous bilateral breast cancer are more likely to have a genetic predisposition to breast cancer, multicentric disease in the index cancer, and a trend toward decreased local control and overall survival.⁴⁶

2.2. Metachronous Contralateral Cancer

For women with unilateral breast cancer, a subsequent (metachronous) contralateral cancer develops in 0.5% to 1.0% per year, with a cumulative risk of 15%. Sixteen percent of metachronous contralateral cancers metastasize and 7% are fatal. Management options for the asymptomatic contralateral breast have included close observation, blind contralateral biopsy, chemoprevention, and prophylactic mastectomy.⁴⁶

2.3. Magnetic Resonance Imaging Detection of Contralateral Cancer

In published reports of women with breast cancer, MRI detected an otherwise occult cancer in the contralateral breast in 3% to 24%^22,46–50 (Table 12.3; Figures 12.6 and 12.7). These results should be interpreted in the context of high-risk screening MRI investigations, in which MRI identiﬁed a cancer occult to mammography and physical examination in 2% to 7%.^26–32

2.4. Magnetic Resonance Imaging of the Contralateral Breast at Memorial Sloan-Kettering Cancer Center

Among 223 women with breast cancer who had contralateral breast MRI at our institution, contralateral breast biopsy was recommended in 72 (32%) women and performed in 61 women.⁴⁶ Cancer occult to mammography and physical examination was detected by MRI in 12 women, constituting 20% (12 of 61) women who had contralateral biopsy and 5% (12 of 223) women who had contralateral breast MRI. Among these 12 cancers, 6 (50%) were DCIS and 6 (50%) were invasive cancer (median size, 0.5cm; range, 0.1–1.0 cm). Contralateral biopsy revealed

Table 12.3. MRI of the Contralateral Breast in Women with Breast Cancer

No. of PPV of No. MRI-

No. of Biopsies Biopsy only Cancer

Investigator Women (%)^a (%)^b (%)^c

Rieber⁴⁷ 34 NS NS 3/34 (9)

Fischer²² 336 NS NS 15/363 (4)

Kuhl⁴⁸ 710^d 91 (13) 45/91 (49) 45/710 (6)

Slanetz⁴⁹ 17 5 (29)^e 4/5 (80)^e 4/17 (24)

Liberman⁴⁶ 223 72 (32) 12/61 (20) 12/223 (5)

Lee⁵⁰ 182 15 (8) 7/15 (47) 6/182 (3)^f

Source: Adapted from Liberman et al.⁴⁶with permission. Abbreviations:

PPV, positive predictive value; NS, not stated.

a Refers to number of women in whom contralateral biopsy was recommended.

b Refers to number of women in whom contralateral biopsy showed cancer divided by number of women who had contralateral biopsy.

c Refers to number of women with mammographically occult, nonpalpa- ble cancers detected by MRI divided by number of women in study.

d Includes women with synchronous and prior cancer in contralateral breast.

e Ten contralateral lesions were identiﬁed in ﬁve women; nine lesions in four women were malignant.

f One additional cancer (invasive ductal carcinoma and DCIS) was iden- tiﬁed on mammography performed after MRI.

benign (n = 31) or high-risk (n = 18) lesions in 49 women, constituting 80% (49 of 61) women who had contralateral biopsy and in 22% (49 of 223) women who had contralateral MRI.

Magnetic resonance imaging depicted an otherwise unsuspected contralateral cancer in 5% of women with breast cancer in our study. A contralateral cancer was more often found in women with rather than without a family history of breast cancer in a ﬁrst-degree relative (13% vs.

3%, P= 0.02) and in women whose index tumor was invasive lobular cancer rather than other histologies (13% vs.

4%, P< 0.07). The frequency of identifying a contralateral cancer was higher in postmenopausal as compared with premenopausal women, but this difference did not achieve statistical significance (9% vs. 3%, P= 0.13). No significant difference was observed in the frequency of finding contralateral cancer as a function of mammographic parenchymal density, but most (87%) women had either heterogeneously dense or dense breasts.

The 5% frequency of detecting contralateral breast cancer by MRI in our study does not differ signiﬁcantly (P= 0.12) from the 3% (26 of 871) prevalence of cancer at blind contralateral upper outer quadrant surgical biopsy reported by Cody.⁵¹However, all of the patients in Cody’s study had contralateral breast biopsy⁵¹; in our study, MRI enabled diagnosis of these contralateral cancers while only requiring biopsy in one third (32%) of women.

(9)

Figure 12.6. A 74-year-old woman with mammographic and sonographically evident right breast mass, for which ultrasound- guided core biopsy yielded invasive lobular carcinoma. (A) Sagittal, T1-weighted, contrast-enhanced MRI of the right breast shows irregular, spiculated, heterogeneously enhancing 1-cm mass in the right lower outer quadrant, corresponding to

the biopsy-proven cancer. (B) Sagittal, T1-weighted, contrast- enhanced MRI of the left breast shows lobulated, minimally irregular, mildly heterogeneously enhancing mass left upper outer quadrant, without mammographic or sonographic correlate. Magnetic resonance imaging guided needle localization yielded invasive ductal carcinoma, 0.6 cm.

Figure 12.7. A 61-year-old woman 5 years status post excision of DCIS from the right breast, with abnormal right mammogram showing dilated duct. Ultrasound-guided core biopsy yielded invasive ductal carcinoma and DCIS. (A) Collimated photograph of sagittal, contrast-enhanced, T1-weighted MRI of the right breast shows heterogeneous ductal enhancement spanning 4.6 cm

in right upper outer quadrant (arrows), corresponding to biopsy- proven cancer. (B) Collimated photograph of sagittal, contrast- enhanced, T1-weighted MRI of the left (contralateral) breast shows clumped ductal enhancement spanning 2.8 cm (arrows).

Magnetic resonance imaging guided needle localization yielded invasive ductal carcinoma measuring 0.3 cm and DCIS.

In our study, cancer was found in 20% of women who had contralateral breast biopsy based on MRI ﬁndings.⁴⁶ This positive predictive value is lower than the 47% to 80% range of positive predictive values previously reported for biopsy based on MRI ﬁndings in the con-

tralateral breast in women with known breast cancer^48–50 and on the low end of the 18% to 64% range of positive predictive values reported for biopsy based on MRI ﬁnd- ings in women at high risk for developing breast cancer.^26–30 The 20% positive predictive value is also at the low end of

A B

(10)

the 20% to 40% range of positive predictive values for mammographically guided needle localization and surgical excision in the general population.³³

Our data suggest a potentially disturbing consequence of MRI of the contralateral breast. Prophylactic contralateral mastectomy was performed in 5% of our women. The frequency of prophylactic mastectomy was higher in women in whom a biopsy was recommended based on MRI findings than among women who were not referred for biopsy, although this difference did not achieve statis- tical significance (9% vs. 3%, P= 0.11). Identification of an abnormality on MRI may have contributed to the decision to perform prophylactic contralateral mastectomy. Pro- phylactic mastectomy can be a rational choice, but women and their physicians should be aware of the limited speci- ficity of MRI to make an informed decision⁵²: In our practice, 80% of breast biopsies for MRI-detected contralateral lesions were benign.

3. Invasive Lobular Cancer

Invasive lobular cancer accounts for approximately 10%

to 14% of invasive breast carcinomas.⁵³The mammogram is more often falsely negative in invasive lobular than in invasive ductal cancer, due to the tendency of the cells to grow in a single ﬁle arrangement, usually without calciﬁ- cation.⁵⁴ Invasive lobular cancer also may have a higher frequency of multicentricity and bilaterality than invasive ductal cancer.⁵³Breast MRI may be particularly helpful in assessing extent of disease in women with invasive lobular cancer (Figure 12.8).

Rodenko and colleagues⁵⁵ correlated MRI and mammography with pathology in the ipsilateral breast in 20 women with invasive lobular cancer. Correlation between imaging and pathologic extent of disease was 85% for breast MRI versus 32% for mammography (P < 0.0001).

Interobserver agreement regarding lesion morphology and extent of disease was higher for MRI (91% and 100%, respectively) than for mammography (64% and 91%, respectively). Magnetic resonance imaging correctly clas- siﬁed all nine pathologically conﬁrmed multicentric cases (100%) and overestimated 2 of 11 unicentric cases (18%).

In comparison, mammography incorrectly classified all seven pathologically confirmed multicentric cases as unicentric disease; one woman classified as having multicentric disease by mammography had unicentric disease at pathology.⁵⁵

Weinstein and colleagues⁵⁶ reviewed MRI and pathology ﬁndings in the ipsilateral breast in 32 women with invasive lobular cancer. Overall, MRI showed more extensive tumor than conventional imaging and impacted on clinical management in half (16 of 32) of the women. Among 18 women who did not have excisional biopsy before MRI, MRI was equal to mammography and sonography in pre-

dicting extent of disease in 10 (56%) and superior to mammography and sonography in 8 (44%). Patterns of invasive lobular cancer on MRI in these 18 women were spiculated or irregular mass (n = 10), regional or multifocal contrast enhancement (n = 7), or regional enhancement and archi- tectural distortion (n = 1).

Qayyum and colleagues⁵⁷reviewed MRI ﬁndings in 13 women with invasive lobular cancer. They reported three patterns: a solitary mass with irregular margins (n = 4), correlating with the same pattern at pathologic analysis; multiple lesions, either connected by enhancing strands (n = 6) or separated by nonenhancing intervening tissue (n = 2), that correlated with the pathologic appearance of non- contiguous tumor foci, with malignant cells in single-ﬁle arrangement; and enhancing septa (n = 1), correlated at pathology with tumor cells streaming in breast stroma.

Comparison of MRI ﬁndings with mammography and sonography was not provided in this study.

Yeh and colleagues⁵⁸ reviewed the preoperative MRI findings of 19 women with invasive lobular cancer and found focal heterogeneously enhancing mass in 8 (42%) cases, regional enhancement in 5 (26%), and other patterns in 6 (32%), including segmental enhancement (n = 1), segmental enhancement with multiple small nodules (n = 1), a mixture of focal mass and regional enhancement (n = 1), diffuse enhancement (n = 1), multiple small nodules (n = 1), and bilateral disease (n = 1). Among eight focal masses, shape was irregular in seven and round in one; margins were ill-defined in six and spiculated in two. The extraction flow (EF) product, a quantitative measure of gadolinium uptake over time, was assessed in 15 cases. In these 15 invasive lobular cancers, peak EFs ranged from 25 to 120 (with normal tissue threshold EF level 25 or less); most tumors had EFs in the 30s. Four cases had multifocal disease and one had unsuspected contralateral disease detected by MRI.

Quan and colleagues⁵⁹ evaluated the impact of breast MRI on surgical management in 62 women with invasive lobular carcinoma at our institution. Among 51 women who had ipsilateral breast MRI, biopsy was recommended in 19 (37%) and yielded a cancer separate from the index lesion in 11 women, constituting 58% (11 of 19) women who had ipsilateral biopsy and 22% (11 of 51) women who had ipsilateral breast MRI. Histology of these 11 ipsilateral cancers was invasive lobular in 10 and DCIS in 1.

Among 53 women who had contralateral breast MRI, biopsy was recommended in 20 (38%) and led to detection of cancer in 5 women, constituting 25% (5 of 20) women who had contralateral biopsy and 9% (5 of 53) women who had contralateral breast MRI. Of the ﬁve contralateral cancers, three were invasive (ductal in two and lobular in one) and two were DCIS.

These studies show the variable MRI patterns of invasive lobular cancer and indicate that breast MRI has a high likelihood of detecting more than one site of cancer in

(11)

Figure 12.8. A 60-year-old woman with palpable right breast mass, for which core biopsy yielded invasive lobular carcinoma.

(A) Sagittal, contrast-enhanced, T1-weighted MRI of right breast shows irregular, spiculated, heterogeneously enhancing 2.4-cm mass in the 12:00 axis corresponding to biopsy-proven invasive lobular cancer. (B) Sagittal, contrast-enhanced,T1-weighted MRI of the right (ipsilateral) breast more laterally shows lobulated, minimally irregular, heterogeneously enhancing 0.8-cm mass right breast upper outer quadrant, just anterior to a vessel. Mag- netic resonance imaging guided needle localization of this mass

showed inﬁltrating lobular carcinoma, metastatic to an intra- mammary lymph node. (C) Sagittal, contrast-enhanced, T1- weighted MRI of the left (contralateral) breast shows irregularly shaped, irregularly marginated, heterogeneously enhancing mass in the 12:00 axis abutting the pectoral muscle, not seen on mammography or ultrasound. Magnetic resonance imaging guided needle localization yielded multifocal invasive mammary carcinoma with mixed ductal and lobular features, 1.0 cm at maximal diameter, and lobular carcinoma in situ.

A B

C

(12)

women with invasive lobular cancer. The frequency of rec- ommending biopsy and the likelihood of detecting cancer are higher in the ipsilateral breast than in the contralateral breast. Even in women with invasive lobular cancer, a sub- stantial proportion of biopsies based on MRI ﬁndings prove to be benign. Therefore, we do not recommend mastectomy based on MRI ﬁndings; if a woman with cancer desires breast conservation, and MRI depicts additional suspicious areas, biopsy is necessary.

4. Conclusion

Accurate assessment of extent of disease is necessary to plan optimal surgical treatment for women with breast cancer. Magnetic resonance imaging can detect breast cancer that is not palpable and not evident at mammography or ultrasound and may provide more accurate assessment of tumor size than these other modalities. In studies of women with breast cancer who had breast MRI for assessment of extent of disease, MRI detected an otherwise unsuspected cancer in the ipsilateral breast in 6% to 34% of women and in the contralateral breast in 3% to 24%. Magnetic resonance imaging can also assess for involvement of the pectoral muscle, chest wall, and skin, information that affects surgical planning. The American College of Radiology states that indications for breast MRI include (but are not limited to) assessment for extent of disease in women with inﬁltrating cancer, evaluation of the contralateral breast in women with breast cancer, and deﬁning the relationship of a breast cancer to the pectoral muscle or chest wall.⁶⁰ Magnetic resonance imaging for extent of disease assessment may be most valuable for women with a strong family history of breast cancer and invasive lobular histology in the index cancer.

Although MRI can detect additional sites of cancer in women with proven breast cancer, a few caveats should be remembered. No data address the impact of MRI detection of additional sites of breast cancer on survival. Fur- thermore, the beneﬁt of detecting these additional sites of cancer must be weighed against the added time, expense, and consequences of MRI and downstream examinations.

Breast MRI may beneﬁt from new sequences that allow rapid, high-resolution, simultaneous imaging of both breasts. Further work, including reﬁnement of criteria and methods for performing of biopsy for MRI-detected lesions, analysis of cost effectiveness, and long-term follow up, is necessary to optimize the use of MRI for assessment of extent of disease in women with breast cancer.

References

1. Gribbestad IS, Nilsen G, Fiosene H, et al. Contrast-enhanced magnetic resonance imaging of the breast. Oncologica 1992;

31:833–842.

2. Boetes C, Mus RDM, Holland R, et al. Breast tumors:

comparative accuracy of MR imaging relative to mammog- raphy and US for demonstrating extent. Radiology 1995;197:

743–737.

3. Davis PL, Staiger MJ, Harris KB, et al. Breast cancer measurements with magnetic resonance imaging, ultrasonogra- phy, and mammography. Breast Cancer Res Treat. 1996;37:

1–9.

4. Merchant TE, Obertop H, de Graaf PW. Advantages of magnetic resonance imaging in breast surgery treatment plan- ning. Breast Cancer Res Treat. 1993;25:257–264.

5. Liberman L, Morris EA, Dershaw DD, et al. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol. 2003;180:901–910.

6. Qualheim RE, Gall EA. Breast carcinoma with multiple sites of origin. Cancer 1957;10:460–408.

7. Rosen PP, Fracchia AA, Urban JA, et al. “Residual” mammary carcinoma following simulated partial mastectomy.

Cancer 1975;35:739–747.

8. Lagios MD. Multicentricity of breast carcinoma demon- strated by routine correlated serial subgross and radiographic examination. Cancer 1977;40:1726–1734.

9. Schwartz GF, Patchefsky AS, Feig SA, et al. Multicentricity of non-palpable breast cancer. Cancer 1980;45:2916.

10. Egan RL. Multicentric breast carcinomas: clinical- radiolographic-pathologic whole organ studies and 10-year survival. Cancer 1982;49:1123–1130.

11. Holland R, Veling SH, Mravunac M, Hendriks JH. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving surgery. Cancer 1985;56:

979–990.

12. Anastassiades O, Iakovou E, Stavridou N, et al. Multicen- tricity in breast cancer.A study of 366 cases. Am J Clin Pathol.

1993;99:238–243.

13. Vaidya J, Vyas J, Chinoy R, et al. Multicentricity of breast cancer: whole-organ analysis and clinical implications. Br J Cancer 1996;74:820–824.

14. Faverly DRG, Burgers L, Bult P, Holland R. Three-dimen- sional imaging of mammary ductal carcinoma in situ: clinical implications. Semin Diagn Pathol. 1994;11:193–198.

15. Holland R, Hendriks JH, Verbeek AL, et al. Extent, distribution, and mammographic/histological correlations of breast ductal carcinoma in situ. Lancet 1990;335:519–522.

16. Fisher ER, Anderson S, Tan-Chiu E, et al. Fifteen-year prog- nostic discriminants for invasive breast carcinoma: National Surgical Adjuvant Breast and Bowel Project Protocol-06.

Cancer 2001;91:1679–1687.

17. Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic ﬁndings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer 1999;86:429–438.

18. Harms SE, Flamig DP, Hesley KL, et al. MR imaging of the breast with rotating delivery of excitation off resonance:

clinical experience with pathologic correlation. Radiology 1993;187:493–501.

19. Orel SG, Schnall MD, Powell CM, et al. Staging of suspected breast cancer: effect of MR imaging and MR-guided biopsy.

Radiology 1995;196:115–122.

20. Boetes C, Mus RDM, Holland R, et al. Breast tumors: comparative accuracy of MR imaging relative to mammography

(13)

and US for demonstrating extent. Radiology 1995;197:

743–747.

21. Mumtaz H, Hall-Craggs MA, Davidson T, et al. Staging of symptomatic primary breast cancer with MR imaging. AJR Am J Roentgenol. 1997;169:417–424.

22. Fischer U, Kopka L, Grabbe E. Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the thera- peutic approach. Radiology 1999;213:881–888.

23. Drew P, Chatterjee S, Turnbull L, et al. Dynamic contrast-enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detec- tion of multifocal breast cancer. Ann Surg Oncol. 1999;5:

599–603.

24. Esserman L, Hylton NM, Yassa L, et al. Utility of magnetic resonance imaging in the management of breast cancer:

evidence for improved preoperative staging. J Clin Oncol.

1999;17:110–119.

25. Bedrosian I, Schlencker J, Spitz FR, et al. Magnetic resonance imaging-guided biopsy of mammographically and clinically occult breast lesions. Ann Surg Oncol. 2002;9:457–461.

26. Kuhl CK, Schmutzler RK, Leutner CC, et al. Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 2000;215:267–279.

27. Tilanus-Linthorst MMA, Obdeijn IMM, Bartels KCM, et al.

First experiences in screening women at high risk for breast cancer with MR imaging. Breast Cancer Res Treat. 2000;63:

53–60.

28. Lo LD, Rosen MA, Schnall MD, et al. Pilot study of breast MR screening of a high-risk cohort. Radiology 2001;

221:432.

29. Warner E, Plewes DB, Shumak RS, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol. 2001;19:3524–3531.

30. Stoutjesdijk MJ, Boetes C, Jager GJ, et al. Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer. J Natl Cancer Inst. 2001;93:1095–

1102.

31. Sardanelli F, Trecate G, Morassut S, et al. Gd-enhanced MR screening in women at genetic high risk of breast cancer:

preliminary results of a prospective non-randomized multi- center trial [abstract]. Radiology 2002;225:326.

32. Morris EA, Liberman L, Ballon DJ, et al. MRI of occult breast carcinoma in a high risk population. AJR Am J Roentgenol. 2003;181:619–626.

33. Jackman RJ, Marzoni FA. Needle-localized breast biopsy:

why do we fail? Radiology 1997;204:677–684.

34. Orel SG, Mendonca MH, Reynolds C, et al. MR imaging of ductal carcinoma in situ. Radiology 1997;202:413–420.

35. Menell JH, Morris EA, Dershaw DD, et al. Determination of presence and extent of pure ductal carcinoma in situ by mam- mography and MR imaging [abstract]. AJR Am J Roentgenol.

2003;180(Suppl):52–53.

36. Berg WA, Gilbreath PL. Multicentric and multifocal cancer:

whole-breast US in preoperative evaluation. Radiology 2000;

214:59–66.

37. Kolb TM, Lichy J, Newhouse JH. The impact of bilateral whole breast ultrasound in women with dense breasts and

recently diagnosed breast cancer [abstr]. Radiology 2000;217:

318.

38. Berg WA, Nguyen TK, Gutierrez L, Segers A. Local extent of disease: preoperative evaluation of the breast cancer patient with mammography, ultrasound, and MRI [abstr].

Radiology 2001;221:230.

39. Hlawatsch A, Teifke A, Schmidt M, Thelen M. Preoperative assessment of breast cancer: sonography versus MR imaging.

AJR Am J Roentgenol. 2002;179:1493–1501.

40. Kolb TM, Lichy J, Newhouse JH. Occult cancer in women with dense breasts: detection with screening US–

diagnostic yield and tumor characteristics. Radiology 1998;

207:191–199.

41. Buchberger W, DeKoekkoek-Doll P, Springer P, et al.

Incidental ﬁndings on sonography of the breast: clinical signiﬁcance and diagnostic workup. AJR Am J Roentgenol.

1999;173:921–927.

42. Kaplan SS. Clinical utility of bilateral whole-breast US in the evaluation of women with dense breast tissue. Radiology 2001;221:641–649.

43. Morris EA, Schwartz LH, Drotman MB, et al. Evaluation of pectoralis major muscle in patients with posterior breast tumors on breast MRI: early experience. Radiology 2000;214:

67–72.

44. Morris EA. Cancer staging with breast MR imaging. In:

Schnall MD, Orel SG, eds. Breast MR Imaging. Philadelphia:

Saunders; 2001:333–344.

45. Rieber A, Tomczak RJ, Mergo PJ, et al. MRI of the breast in the differential diagnosis of mastitis versus inﬂammatory carcinoma and follow-up. J Comput Assist Tomogr. 1997;21:

128–132.

46. Liberman L, Morris EA, Kim CM, et al. MR imaging ﬁndings in the contralateral breast in women with recently diagnosed breast cancer. AJR Am J Roentgenol. 2003;180:

333–341.

47. Rieber A, Tomczak R, Merkle E, et al. MRI of histologically conﬁrmed mammary carcinoma: clinical relevance of diagnostic procedures for detection of multifocal or contralateral secondary carcinoma [abstract]. AJR Am J Roentgenol. 1998;

170(Suppl):48–49.

48. Kuhl CK, Schmiedel A, Morakkabati N, et al. Breast MR imaging of the asymptomatic contralateral breast in the work-up or follow-up of patients with unilateral breast cancer [abstract]. Radiology 2000;217:268.

49. Slanetz PJ, Edmister WB, Yeh ED, et al. Occult contralateral breast carcinoma incidentally detected by breast magnetic resonance imaging. Breast J. 2002;8:145–148.

50. Lee SG, Orel SG, Woo IJ, et al. MR imaging screening of the contralateral breast in patients with newly diagnosed breast cancer: preliminary results. Radiology 2003;226:

773–778.

51. Cody HS. Routine contralateral breast biopsy: helpful or irrelevant? Ann Surg. 1997;225:370–376.

52. Montgomery LL, Tran KN, Heelan MC, et al. Issues of regret in women with contralateral prophylactic mastectomies. Ann Surg Oncol. 1999;6:546–552.

53. Rosen PP. Invasive lobular carcinoma. In: Rosen PP, ed.

Rosen’s Breast Pathology. Philadelphia: Lippincott-Raven;

1997:545–565.

(14)

54. Dershaw DD. False negative mammograms. Contemp Diagn Radiol. 1995;18:1–5.

55. Rodenko GN, Harms SE, Pruneda JM, et al. MR imaging in the management before surgery of lobular carcinoma of the breast: correlation with pathology. AJR Am J Roentgenol.

1996;167:1415–1419.

56. Weinstein SP, Orel SG, Heller R, et al. MR imaging of the breast in patients with invasive lobular carcinoma. AJR Am J Roentgenol. 2001;176:399–406.

57. Qayyum A, Birdwell RL, Daniel BL, et al. MR imaging features of inﬁltrating lobular carcinoma of the breast:

histopathologic correlation. AJR Am J Roentgenol. 2002;178:

1227–1232.

58. Yeh ED, Slanetz PJ, Edmister WB, et al. Invasive lobular carcinoma: spectrum of enhancement and morphology on mag- netic resonance imaging. Breast J. 2003;9:13–8.

59. Quan ML, Sclafani L, Heerdt A, et al. Magnetic resonance imaging detects unsuspected disease in patients with invasive lobular cancer. Ann Surg Oncol. 2003;10:1048–1053.

60. American College of Radiology. ACR practice guideline for the performance of magnetic imaging (MRI) of the breast.

In: Practice Guidelines and Technical Standards 2004.

Reston, VA: American College of Radiology, 2004:269–274.