Mark J. Dryden

Multimodality Imaging of Triple Receptor-Negative Tumors With Mammography, Ultrasound, and MRI

OBJECTIVE We retrospectively reviewed imaging findings for 44 patients with triple receptor-negative breast carcinomas on mammography, sonography, and MRI to determine the imaging characteristics of triple receptor-negative cancers that may improve diagnosis at the time of presentation. CONCLUSION Despite their large size at presentation, triple receptor-negative cancers may be occult on mammography or sonography and frequently have benign or indeterminate features. MRI identified all triple receptor-negative cancers and showed features that had a high positive predictive value for malignancy.

Locoregional Control of Clinically Diagnosed Multifocal or Multicentric Breast Cancer After Neoadjuvant Chemotherapy and Locoregional Therapy

PURPOSE The purpose was to assess whether patients with clinical multifocal or multicentric (MFMC) breast cancer determined by mammogram, ultrasound, or physical examination have inferior outcome compared with patients with clinical unicentric lesions. PATIENTS AND METHODS We retrospectively analyzed 706 consecutive patients with stages I-III breast cancer treated at the M.D. Anderson Cancer Center (Houston, TX) from 1976 to 2003 who received neoadjuvant anthracycline-based chemotherapy followed by breast conservation therapy (BCT), mastectomy alone, or mastectomy plus postmastectomy radiation therapy. RESULTS The mean follow-up was 66 months. At presentation, 97 of 706 patients had clinically MFMC disease (13.7%). The 5-year rate of locoregional failure was 10% for unicentric disease compared with 7% for MFMC disease (P = .78). Subset analyses of patients by treatment groups confirmed no statistical difference in locoregional control regardless of the type of locoregional treatment. Among patients with multifocal disease treated with BCT, there were no in-breast recurrences and one supraclavicular recurrence. Five-year disease-free survival and overall survival was equivalent between patients with MFMC and unicentric breast cancers. CONCLUSION Patients with clinical MFMC breast cancer at the time of diagnosis treated with neoadjuvant chemotherapy followed by locoregional therapy have similar 5-year rates of locoregional control, disease-free survival, and overall survival as those with unicentric disease. Clinically detected MFMC disease did not predict for inferior outcome.

Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer†.

BACKGROUND Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). PATIENTS AND METHODS Phase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m(2) i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m(2) i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity. RESULTS Sixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31-75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred. CONCLUSION The addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. CLINICAL TRIAL NUMBER NCT00499603.

Microcalcification detectability for four mammographic detectors: Flat‐panel, CCD, CR, and screen/film

Amorphous silicon/cesium iodide (a-Si:H/CsI:Tl) flat-panel (FP)-based full-field digital mammography systems have recently become commercially available for clinical use. Some investigations on physical properties and imaging characteristics of these types of detectors have been conducted and reported. In this perception study, a phantom containing simulated microcalcifications (microCs) of various sizes was imaged with four detector systems: a FP system, a small field-of-view charge coupled device (CCD) system, a high resolution computed radiography (CR) system, and a conventional mammography screen/film (SF) system. The images were reviewed by mammographers as well as nonradiologist participants. Scores reflecting confidence ratings were given and recorded for each detection task. The results were used to determine the average confidence-rating scores for the four imaging systems. Receiver operating characteristics (ROC) analysis was also performed to evaluate and compare the overall detection accuracy for the four detector systems. For calcifications of 125-140 microm in size, the FP system was found to have the best performance with the highest confidence-rating scores and the greatest detection accuracy (Az = 0.9) in the ROC analysis. The SF system was ranked second while the CCD system outperformed the CR system. The p values obtained by applying a Student t-test to the results of the ROC analysis indicate that the differences between any two systems are statistically significant (p<0.005). Differences in microC detectability for the large (150-160 microm) and small (112-125 microm) size microC groups showed a wider range of p values (not all p values are smaller than 0.005, ranging from 0.6 to <0.001) compared to the p values obtained for the medium (125-140 microm) size microC group. Using the p values to assess the statistical significance, the use of the average confidence-rating scores was not as significant as the use of the ROC analysis p value for p value.

Specimen Radiography in Confirmation of MRI-Guided Needle Localization and Surgical Excision of Breast Lesions

OBJECTIVE Confirmation of lesion retrieval after MRI-guided needle localization and surgical excision of breast lesions are difficult because the targeted lesion is not enhanced ex vivo. The aim of this study was to determine the feasibility of using specimen radiography to verify lesion removal after MRI-guided needle localization and surgical excision. CONCLUSION To our knowledge, our study was the first to examine the use of specimen radiography in the localization and excision of breast lesions. Specimen radiography is a reliable, cost-effective alternative to repeated dynamic contrast-enhanced MRI for confirming lesion removal after surgery. Specimen radiography has the additional advantage of facilitating immediate assessment of surgical margins.

Comparison of Full-Field Digital Mammography and Screen-Film Mammography for Detection and Characterization of Simulated Small Masses

OBJECTIVE The two objectives of this study were to create an ex vivo phantom model that closely mimics human breast cancer for detection tasks and to compare the performance of full-field digital mammography with screen-film mammography in detecting and characterizing small breast masses in a phantom with a spectrum of complex tissue backgrounds. MATERIALS AND METHODS Sixteen phantom breast masses of varying sizes (0.3-1.2 cm), shapes (round and irregular), and densities (high and low) were created from shaved tumor specimens and imaged using both full-field digital and screen-film mammography techniques. We created 408 detection tasks that were captured on 68 films. On each radiograph, six detection tasks were partially obscured by areas of varying breast-pattern complexity, including low (predominantly fatty), mixed (scattered fibroglandular densities and heterogeneously dense), and high (extremely dense) density patterns. Each detection task was scored using a five-point confidence scale by three mammographers. Receiver operating characteristic (ROC) curve analysis was performed to analyze differences in detection of masses between the two imaging systems, and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were computed. RESULTS Full-field digital mammography showed higher area under the ROC curve than screen-film mammography for detecting masses in each breast background and performed significantly better than screen-film mammography in mixed (p = 0.010), dense (p = 0.029), and all breast backgrounds combined (p = 0.004). Full-field digital mammography was superior to screen-film mammography for characterizing round and irregular masses and low- and high-density masses. CONCLUSION Full-field digital mammography was significantly superior to screen-film technique for detecting and characterizing small masses in mixed and dense breast backgrounds in a phantom model.

Imaging Factors That Influence Surgical Margins After Preoperative 125I Radioactive Seed Localization of Breast Lesions: Comparison With Wire Localization

OBJECTIVE The objective of this study was to compare the potential influence of imaging variables on surgical margins after preoperative radioactive seed localization (RSL) and wire localization (WL) techniques. MATERIALS AND METHODS A total of 565 women with 660 breast lesions underwent RSL or WL between May 16, 2012, and May 30, 2013. Patient age, lesion type (mass, calcifications, mass with associated calcifications, other), lesion size, number of seeds or wires used, surgical margin status (close positive or negative margins), and reexcision and mastectomy rates were recorded. RESULTS Of 660 lesions, 127 (19%) underwent RSL and 533 (81%) underwent WL preoperatively. Mean lesion size was 1.8 cm in the RSL group and 1.8 cm in the WL group (p = 0.35). No difference in lesion type was identified in the RSL and WL groups (p = 0.63). RSL with a single seed was used in 105 of 127 (83%) RSLs compared with WL with a single wire in 349 of 533 (65%) WLs (p = 0.0003). The number of cases with a close positive margin was similar for RSLs (26/127, 20%) and WLs (104/533, 20%) (p = 0.81). There was no difference between the RSL group and the WL group in close positive margin status (20% each, p = 0.81), reexcision rates (20% vs 16%, respectively; p = 0.36), or mastectomy rates (6% each, p = 0.96). Lesions containing calcifications were more likely to require more than one wire (odds ratio [OR], 4.44; 95% CI, 2.8-7.0) or more than one seed (OR, 7.03; 95% CI, 1.6-30.0) when compared with masses alone (p < 0.0001). Increasing lesion size and the presence of calcifications were significant predictors of positive margins, whereas the use of more than one wire or seed was not (OR, 0.9; 95% CI, 0.5-1.5) (p = 0.75). CONCLUSION Close positive margin, reexcision, and mastectomy rates remained similar in the WL group and RSL group. The presence of calcifications and increasing lesion size increased the odds of a close positive margin in both the WL and RSL groups, whereas the use of one versus more than one seed or wire did not.

Sonography and Sonographically Guided Needle Biopsy of Internal Mammary Nodes in Staging of Patients With Breast Cancer

OBJECTIVE The purpose of this study was to identify the prevalence of occult nodal metastases on routine ultrasound examination of internal mammary (IM) nodal basins in patients with breast cancer. MATERIALS AND METHODS Patients with primary breast cancer (n = 595) underwent breast ultrasound evaluation between September 1, 2011, and April 1, 2012. For all patients, ultrasound examination included a survey of the axillary, infraclavicular, IM, and supraclavicular nodal basins. Patient demographics, breast cancer histopathologic type, and grade, size, location, and presence of metastatic nodes in regional nodal basins were recorded. Fisher exact test and Wilcoxon rank test were used for statistical analysis. RESULTS Fifty-eight of 595 (10%) patients had positive IM ultrasound finding, with eight (1.3%) patients having isolated IM involvement. Patients with positive IM ultrasound findings were statistically significantly younger than those without such findings (median age, 42 vs 57 years; p < 0.0001). Of the 58 patients with positive IM ultrasound, 29 (50%) underwent ultrasound-guided needle biopsy, which confirmed malignancy in 26 of 29 (90%) patients. Nonlateral (p < 0.001) grade 3 (p < 0.001) tumors larger than 5 cm (p < 0.0006) with the estrogen receptor-negative HER2/neu-negative subtype (p < 0.001) associated with axillary, infraclavicular, or supraclavicular metastases (p < 0.001) were more likely to be associated with positive IM ultrasound findings. IM ultrasound resulted in an N status change for 46 of 595 (8%) patients and of the overall clinical stage for 38 (6.4%) patients. CONCLUSION IM ultrasound and ultrasound-guided fine-needle aspiration biopsy are feasible, sensitive, and specific. Application of IM ultrasound and ultrasound-guided needle biopsy in a selected subpopulation of young patients with medial or central estrogen receptor-negative HER2/neu-negative breast cancer may result in a change in clinical stage and modify the treatment plan.

External Qigong Therapy for Women With Breast Cancer Prior to Surgery

The majority of patients with cancer use some form of complementary or alternative medicine. External qigong treatment (EQT), classified as a bioenergy therapy, is one such approach that patients combine with conventional medicine or, in some cases, use in place of conventional medicine. This study aimed to determine whether EQT could shrink breast cancer tumors and improve quality of life (QOL) in women with pathologically confirmed breast cancer awaiting surgery. A total of 9 women with pathologically confirmed breast cancer were recruited from large cancer centers in the United States (n = 5) and China (n = 4). A single-arm pre/post design was used. Each patient underwent 5 consecutive days of EQT, with each treatment lasting from 2 to 5 minutes. All treatments were performed by the same qigong master. Tumor measurements were made before and after the EQT sessions. Tumor assessments were conducted prior to study initiation and following the last EQT. Patients underwent both an ultrasound and mammogram (United States) or an ultrasound and magnetic resonance imaging (China). All patients also underwent physical breast examinations (PBEs) and completed QOL questionnaires before and after the last EQT. No clinical changes in tumor measurements from pre- to post-EQT were noted. There was also no suggestion of change in tumor size by PBE or change in QOL. Using the current study design, EQT did not have any effect on tumor size. EQT also does not appear to have any effect on patient QOL. Because of the small sample size and working with only one qigong practitioner, to definitively determine the efficacy or lack of efficacy of EQT, a larger study with multiple qigong practitioners would need to be conducted.

Transection of Radioactive Seeds in Breast Specimens.

Radioactive seed localization is a new procedure for localizing breast lesions that has several advantages over the standard wire-localization procedure. It is reported to be safe for both patients and medical personnel. Although it is theoretically possible to transect the titanium-encapsulated seed while processing the breast specimen in the pathology laboratory, the likelihood of such an event is thought to be exceedingly low. In fact, there are no previous reports of such an event in the literature to date. We recently encountered 2 cases in which a radioactive seed was inadvertently transected while slicing a breast specimen at the grossing bench. In this report, we describe each case and offer recommendations for minimizing radioactive exposure to personnel and for preventing radioactive contamination of laboratory equipment.