Metastatic patterns of breast cancer subtypes: what radiologists should know in the era of personalized cancer medicine.

There is accumulating evidence that molecular phenotyping of breast cancer determines the timing, pattern, and outcome of metastatic disease. The most clinically relevant subtypes are hormonal-positive [oestrogen and progesterone receptor (ER/PR) positive], HER2 expressing, and triple-negative breast cancers (TNBCs). ER/PR-positive breast cancers demonstrate the best prognosis; however, metastases, in particular osseous disease, may develop much later. HER2-expressing breast cancers, although aggressive, have improved outcomes due to the advent of HER2-targeted therapies, with increased risk of central nervous system (CNS) relapses later. Finally, TNBCs present in younger women, BRCA1 mutations carriers, and carry the worst overall prognosis, with high incidence of CNS metastases, especially during the first 5 years of diagnosis. It is important for radiologists to understand the nuances of these breast cancer subtypes to predict metastatic behaviours and guide possible imaging surveillance.

Revisiting the relationship between tumour volume and diameter in advanced NSCLC patients: An exercise to maximize the utility of each measure to assess response to therapy.

AIM: To revisit the presumed relationship between tumour diameter and volume in advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the measured volume using volume-analysis software and its proportional changes during therapy matches with the calculated volume obtained from the presumed relationship and results in concordant response assessment. MATERIALS AND METHODS: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53 measurable lung lesions, treated in a phase II trial of erlotinib, were studied with institutional review board approval. Tumour volume and diameter were measured at baseline and at the first follow-up computed tomography (CT) examination using volume-analysis software. Using the measured diameter (2r) and the equation, calculated volume was obtained as (4/3)πr(3) at baseline and at the follow-up. Percent volume change was obtained by comparing to baseline for measured and calculated volumes, and response assessment was assigned. RESULTS: The measured volume was significantly smaller than the calculated volume at baseline (median 11,488.9 mm(3) versus 17,148.6 mm(3); p < 0.0001), with a concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured volume was once again significantly smaller than the calculated volume (median 6573.5 mm(3) versus 9198.1 mm(3); p = 0.0022), with a CCC of 0.7408. Response assessment by calculated versus measured volume changes had only moderate agreement (weighted κ = 0.545), with discordant assessment results in 20% (8/40) of lesions. CONCLUSION: Calculated volume based on the presumed relationship significantly differed from the measured volume in advanced NSCLC patients, with only moderate concordance in response assessment, indicating the limitations of presumed relationship.

A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer.

We aimed to evaluate the efficacy and feasibility of combining trastuzumab/vinorelbine with bevacizumab in patients with first-or second-line HER2-positive, metastatic breast cancer (MBC). Eligible patients had HER2-positive measureable MBC, with no more than one prior line of chemotherapy, and were treated with trastuzumab (4 mg/kg × 2 mg/kg weekly thereafter), vinorelbine (25 mg/m(2) weekly), and bevacizumab (10 mg/kg every 2 weeks). Co-primary endpoints were (a) the proportion of patients alive and progression-free at 1 year and (b) safety profile/feasibility. Feasibility was defined as a rate of grade 3/4 non-hematologic toxicity attributable to protocol-based therapy <20 %. Twenty-nine patients were enrolled (n = 22 first-line, n = 7 second-line). Median age was 48 years (range 37-68). The median number of cycles received was 8 (1-23) and median duration on treatment was 7.4 months (range 1-22). The study was closed early due to higher-than-expected rates of grade 3/4 non-hematologic toxicities, with 50 events in 20 patients. A total of six patients (21 %) were taken off study for treatment-related toxicity. Most common treatment-related toxicities included fatigue (n = 7), febrile neutropenia (n = 4), and headache (n = 3). At 1 year, 8/22 first-line (36 %) and 2/7 second-line (29 %) patients were alive and progression-free. Median PFS was 9.9 months and 7.8 months in the first- and second-line cohorts, respectively. Objective responses were observed in 16/22 (73 %) and 5/7 (71 %) patients in the first- and second-line settings. Although the combination of vinorelbine, trastuzumab, and bevacizumab showed notable activity in HER2-positive MBC, the proportion of first-line patients alive and progression-free at 1 year was deemed unlikely to reach the pre-defined threshold for declaring success. Additionally, unacceptable toxicity was observed, at rates greater than previously reported with vinorelbine/trastuzumab or vinorelbine/bevacizumab doublet combinations.

Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer.

BACKGROUND: Women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) can respond to multiple lines of anti-HER2 therapy. It is unknown whether these patients will derive further clinical benefit following treatment with trastuzumab-MCC-DM1 (T-DM1). PATIENTS AND METHODS: We retrospectively identified HER2-positive MBC patients treated with T-DM1 and characterized outcomes during subsequent lines of anti-HER2 therapy. Response was determined by a blinded radiology review. Time-dependent analyses were carried out using Kaplan-Meier estimates. RESULTS: We identified 23 patients treated with single-agent T-DM1 and report on the 20 patients who discontinued protocol therapy. All patients received trastuzumab-based metastatic therapy before initiation of T-DM1 [median 7 regimens (range 3-14)]. Of these 20 patients, 75% (15 of 20) received further therapy with or without anti-HER2 agents after discontinuing T-DM1. Partial response to either first- or second-subsequent line(s) of therapy was seen in 5 of 15 (33%) treated patients, including 33% (4 of 12) who received a regimen containing trastuzumab and/or lapatinib. Median durations of therapy to first- and second-subsequent regimens after T-DM1 were 5.5 and 6.4 months, respectively. CONCLUSIONS: In heavily pretreated HER2-positive MBC patients, prior exposure to T-DM1 does not exhaust the potential benefit of ongoing anti-HER2 therapy with trastuzumab- and/or lapatinib-based regimens.

Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision.

OBJECTIVE: This investigation compares the frequency of histologic underestimation of breast carcinoma that occurs when a large-core needle biopsy reveals atypical ductal hyperplasia or ductal carcinoma in situ with the automated 14-gauge needle, the 14-gauge directional vacuum-assisted biopsy device, and the 11-gauge directional vacuum-assisted biopsy device. SUBJECTS AND METHODS: Evaluation of 428 large-core needle biopsies yielding atypical ductal hyperplasia (139 lesions) or ductal carcinoma in situ (289 lesions) was performed. The results of subsequent surgical excision were retrospectively compared with the needle biopsy results. RESULTS: For lesions initially diagnosed as ductal carcinoma in situ, underestimation of invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device when compared with the automated 14-gauge needle (10% versus 21%, p < 0.05) but was not significantly less frequent when compared with the 14-gauge directional vacuum-assisted device (10% versus 17%, p > 0.1). For lesions diagnosed initially as atypical ductal hyperplasia, underestimation of ductal carcinoma in situ and invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device compared with the 14-gauge directional vacuum-assisted device (19% versus 39%, p = 0. 025) and with the automated 14-gauge needle (19% versus 44%, p = 0. 01). CONCLUSION: The frequency of histologic underestimation of breast carcinoma in lesions initially diagnosed as atypical ductal hyperplasia or ductal carcinoma in situ using large-core needle biopsy is substantially lower with the 11-gauge directional vacuum-assisted device than with the automated 14-gauge needle and with the 14-gauge directional vacuum-assisted device.

Mammographic and sonographic appearances of nodular adenosis.

OBJECTIVE: We determined whether nodular adenosis of the breast possesses any pathognomonic features on imaging studies. CONCLUSION: The imaging features of nodular adenosis are often benign-appearing and can be indistinguishable from other ellipsoid, circumscribed, or hypodense masses. Occasionally, nodular adenosis may appear suggestive of malignancy. Pathologic evaluation by excisional or large core needle biopsy is necessary for diagnosis.

Image-guided core breast biopsy of ductal carcinoma in situ presenting as a non-calcified abnormality.

OBJECTIVE: Ductal carcinoma in situ (DCIS) typically presents as calcifications which are detected mammographically. Our aim was to evaluate the less common presentations of ductal carcinoma in situ diagnosed by image-guided core biopsy and correlate with histopathologic diagnoses. METHODS AND MATERIAL: Imaging and histopathologic findings were retrospectively reviewed in 11 patients with ductal carcinoma in situ diagnosed at core biopsy that presented as noncalcified radiographic abnormalities. RESULTS: Mammography showed non-calcified, circumscribed nodules, ill-defined nodules and architectural distortion. In two patients, no mammographic abnormality was detected. Sonography showed circumscribed, round or oval, solid masses; irregular, heterogeneous masses; and a tubular structure. Histopathologic diagnoses included multiple architectural subtypes and ranged from low to high nuclear grade. CONCLUSION: Although image-guided core biopsy diagnosis of ductal carcinoma is typically made when sampling calcifications, DCIS can be diagnosed following biopsy of non-calcified masses or distortion. There is no correlation between histopathologic subtype and radiologic appearance.

Large-core needle biopsy of nonpalpable breast lesions.

CONTEXT: An increasing number of nonpalpable abnormalities requiring breast biopsy are being identified due to the widespread use of screening mammography. Large-core needle biopsy (LCNB) has become an alternative to surgical excision. OBJECTIVE: To determine whether LCNB is a safe and accurate technique to evaluate nonpalpable abnormalities found on breast imaging studies. DESIGN AND SETTING: Case series at an institutional referral center from August 1, 1991, to December 31, 1997. PATIENTS: A total of 1643 women with 1 or more suspicious breast abnormalities received LCNBs (n = 1836 lesions). INTERVENTION: The LCNB of the breast uses a 14- or 11-gauge needle with stereotactic localization or ultrasound guidance. MAIN OUTCOME MEASURE: Utility and potential limitations of LCNB compared with the criterion standard, surgical excision after wire localization. RESULTS: Of the 1836 breast lesions sampled, 444 (24%) were found to be malignant. A total of 412 (22%) were found to be malignant on the initial LCNB and 202 repeat biopsies yielded 32 additional malignancies. Complications were infrequent: 1 patient experienced a superficial infection and 1 developed a pneumothorax after LCNB. CONCLUSION: Image-guided LCNB is a reliable diagnostic alternative to surgical excision of suspicious nonpalpable breast abnormalities.

Fibrous nodules found at large-core needle biopsy of the breast: imaging features.

PURPOSE: To describe the imaging and histologic features of large-core needle biopsy (LCNB) specimens of fibrous nodules. MATERIALS AND METHODS: Of 853 breast masses in which LCNB was performed, 38 (4%) revealed histologic findings of fibrous nodules. Repeat biopsy was performed in 16 lesions (surgical excision, 13 lesions; repeat LCNB, three lesions). The mammographic and ultrasonographic findings in these 16 cases, the histologic LCNB findings, and the repeat biopsy findings were retrospectively reviewed. RESULTS: Repeat biopsy findings confirmed the diagnosis of fibrous nodules in 15 of the 16 masses. In one mass, repeat LCNB findings showed a fibroadenoma. The imaging features of the fibrous nodules varied. Five nodules (33%) manifested as masses with indistinct margins; six (40%), as circumscribed masses. In four cases (27%), imaging suggested malignancy. None were calcified masses. An additional 22 masses had circumscribed or indistinct borders and were diagnosed with LCNB as fibrous nodules. None of these masses had suspicious findings, and repeat biopsy was not performed. CONCLUSION: Fibrous nodules usually manifest as masses with circumscribed or indistinct margins but can have findings suggestive of malignancy. LCNB can reveal histologic findings consistent with this diagnosis. In all masses in which repeat biopsy was performed, the diagnosis of a fibrous nodule was confirmed or another benign stromal lesion was diagnosed.

Large-needle core biopsy: nonmalignant breast abnormalities evaluated with surgical excision or repeat core biopsy.

PURPOSE: To classify lesions initially considered nonmalignant at large-needle core biopsy that were subsequently surgically excised or sampled at repeat biopsy. MATERIALS AND METHODS: From August 1, 1991, to December 31, 1996, 1,032 breast abnormalities (214 malignant and 818 nonmalignant lesions) were sampled at large-needle core biopsy. Of the nonmalignant lesions, 112 (14%) abnormalities were studied. Twenty-four abnormalities were subsequently excised because of discordant imaging and pathologic findings; 41 may have been missed at biopsy (25 were surgically excised, and 16 were sampled at repeat biopsy); 40 were surgically excised as recommended by the pathologist; and seven were excised for other indications. RESULTS: None of 24 abnormalities excised because of discordant findings was malignant. Among the 41 possibly missed lesions, infiltrating ductal carcinoma was found in one lesion that was removed surgically and in one sampled at repeat biopsy. Among the 40 lesions recommended for excision by the pathologist, 16 malignancies were found (ductal carcinoma in situ, 11; infiltrating ductal carcinoma, three; phyllodes tumor, two). None of the remaining seven lesions was malignant. CONCLUSION: Correlation of the technical quality of the biopsy, imaging features, and pathologic findings resulted in 96 surgical excisions and 16 repeat biopsies of lesions initially considered nonmalignant. Eighteen additional malignancies were identified.

Epidermal inclusion cysts of the breast: three lesions with calcifications.

PURPOSE: To determine whether there are any mammographic and ultrasonographic (US) features of epidermal inclusion cysts of the breast, including heterogeneous microcalcifications, that may be used to preclude unnecessary biopsy. MATERIALS AND METHODS: Clinical history and imaging findings in 15 patients who had undergone surgical excision of an epidermal inclusion cyst were reviewed. RESULTS: In 11 patients, imaging findings of an epidermal inclusion cyst were noted, including 10 patients with mammographic findings, one with US findings only, and seven with mammographic and US findings. The most common mammographic finding (in nine of 10 patients) was an isodense to high-density mass with a circumscribed margin; three circumscribed masses had multiple associated heterogeneous microcalcifications. In the seven patients with corresponding US findings, a circumscribed hypoechoic mass with through transmission was depicted. An additional US feature in six patients was extension of the mass into the dermis. CONCLUSION: Biopsy may be deemed unnecessary if the characteristic US and physical examination findings are present, even in the case of a cyst with heterogeneous microcalcifications.

Stereotactic breast biopsy of clustered microcalcifications with a directional, vacuum-assisted device.

The success rate with the traditional 14-gauge, core-biopsy, multiple-pass technique was compared with that of a directional vacuum-assisted device in sampling calcification clusters in the breast. Of the 130 focal calcification clusters sampled with the multiple-pass technique, 12 clusters (9.2%) had no particles depicted on radiographs of the specimen. Specimens from all 106 (100%) clusters sampled with the directional, vacuum-assisted instrument contained calcifications at radiography. The directional, vacuum-assisted device improved the ability to percutaneously sample breast calcifications.

Evaluation of nonpalpable solid breast masses with stereotaxic large-needle core biopsy using a dedicated unit.

OBJECTIVE: In our institution for the past 4 years, stereotaxic core breast biopsy using a 14-gauge needle has been offered as an alternative to surgical excision. The purpose of this paper is to describe our protocol, results, and lessons learned from our experience. MATERIALS AND METHODS: From August 1991 to July 1995, 388 stereotaxic needle core biopsies of clinically occult, noncalcified, mammographically detected solid masses were performed. In this group, 103 patients underwent subsequent surgical excision. Another 169 have had follow-up examinations 1 year or more after their biopsies. RESULTS: Of the 61 patients diagnosed with a malignant process on core biopsy, all had confirmation on subsequent surgical excision. Forty-one of the 42 core biopsies that showed a benign process were subsequently confirmed on surgical excision. One patient with atypical ductal hyperplasia on core biopsy had ductal carcinoma in situ on surgical excision. Patients with 169 benign masses on core biopsy have been followed for at least 1 year by mammography. Of these women, 110 have been followed for at least 2 years, and no malignant lesions have been found. CONCLUSION: Stereotaxic large-needle core biopsy appears to be an accurate alternative to surgical excision for evaluating a solid breast mass. However, the mammographic appearance, technical quality of the biopsy, and pathologic findings in each patient must be correlated to ensure the highest possible accuracy when using this technique.

Usefulness of the routine magnification view after breast conservation therapy for carcinoma.

PURPOSE: To assess the usefulness of the routine supplementary magnification view in patients who have undergone breast conservation therapy. MATERIALS AND METHODS: Four hundred seventy-one mammograms in 392 patients were evaluated. Conventional craniocaudal and mediolateral oblique views were obtained in each patient. After a preliminary interpretation was made, a magnification view of the excision site was evaluated and any additional information was documented. RESULTS: In 115 examinations (24%), the magnification view was considered necessary to better evaluate equivocal or questionable calcifications seen on standard views. In 18 cases (4%), review of the magnification view influenced the decision to perform biopsy. None of the magnification views that were considered unnecessary caused the interpretation made from conventional views to be altered. CONCLUSION: Magnification mammographic views should be obtained in patients who have undergone breast conservation therapy only when considered necessary after review of findings on conventional views.

Seat belt injuries of the breast: findings on mammography and sonography.

OBJECTIVE: The purpose of this study was to determine the mammographic and sonographic findings of injuries of the breast caused by seat belts in automobile accidents. The imaging findings of such injuries must be differentiated from those of carcinoma, so that inappropriate treatment is avoided. MATERIALS AND METHODS: Five patients who had breast injuries caused by seat belts with shoulder restraints between 1988 and 1993 and who underwent mammography were included in this study. Four of these women had imaging studies done in our department, and one was examined elsewhere. The initial mammograms for four patients were obtained 1-2 months after trauma to the breast. For the fifth patient, the initial study was obtained 13 months after injury. For all women, follow-up examinations were performed from 3 months to 4 years after injury. Two patients also underwent sonography of the breast during the course of their evaluation. RESULTS: At 1-2 months after breast injury caused by a seat belt, mammograms showed thin-walled fat-density cysts in a linear distribution and, in less dense breasts, an associated 2-3-cm band of increased density. The band of increased density was not seen in more dense breasts. These findings correlated with the line of contusion across the breast and resultant fat necrosis, which ultimately led to the formation of lipid cysts. By 3-4 months after the injury, the lipid cysts and contusion were less apparent, and a line of fibrosis had developed. On sonography, the lipid cysts were smoothly marginated; such cysts may be either anechoic or hypoechoic. Parenchymal calcification may develop 3.5-4 years after such an injury. CONCLUSION: Mammograms in women with breast injuries caused by seat belts show areas of contusion, lipid cysts, and parenchymal calcifications occurring in a bandlike distribution corresponding to the path of the seat belt shoulder restraint across the chest. Lipid cysts are seen sonographically as smoothly marginated anechoic or hypoechoic nodules.