Beatriz E. Adrada

Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection

PURPOSE Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. METHODS A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). RESULTS Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). CONCLUSION Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

Invasive micropapillary carcinoma of the breast: mammographic, sonographic, and MRI features.

OBJECTIVE The purpose of this study was to describe the clinical, imaging, and histopathologic findings of invasive micropapillary carcinoma of the breast. CONCLUSION The imaging characteristics of invasive micropapillary carcinoma are highly suggestive of malignancy. The lesion is a high-density irregular mass with indistinct margins associated with microcalcifications on mammograms; a solid irregular hypoechoic mass with indistinct margins and frequent axillary nodal involvement on sonograms; and a multifocal mass on MR images. This tumor may necessitate aggressive management.

Influence of Biospecimen Variables on Proteomic Biomarkers in Breast Cancer

Background: PI3K/Akt/mTOR signaling is being actively pursued as a therapeutic target for breast cancer. We sought to determine if tumor heterogeneity and biospecimen variables affect the evaluation of PI3K/Akt/mTOR pathway markers. Methods: Intraoperative image-guided core-needle biopsies (CNB), and central and peripheral surgical tumor specimens were prospectively collected in 53 patients with invasive breast cancer. Specimens were assessed with reverse-phase protein arrays (RPPA) and immunohistochemistry (IHC). Results: There was a moderate or strong correlation between the expression of 149 (97%) of the 154 different RPPA markers in the center and periphery. Correlation was higher for smaller tumors, in patients who did not undergo neoadjuvant therapy, and with shorter cold ischemia time. Of 154 markers, 132 (86%) were not statistically different between the center and periphery, and 97 (63%) were not different between the CNB and the surgical specimen (average of the central and peripheral specimen). pAkt S473 and PTEN had a significant correlation between central and peripheral specimens, and between CNB and surgical specimen. However, pAkt S473, pS6 S235/236, and pS6 240/244 levels were significantly higher in CNB than the central specimens both by RPPA and by IHC. Conclusions: Most individual proteomic biomarkers studied do not have significant intratumoral heterogeneity. However, protein and phosphoprotein levels are affected by biospecimen type and other preanalytic variables. PI3K pathway activation is greater in CNB compared with postexcision surgical samples suggesting a potential loss of phosphorylation during surgical manipulation, or with cold ischemia of surgical specimens. Clin Cancer Res; 20(14); 3870–83. ©2014 AACR.

Identification of Patients With Documented Pathologic Complete Response in the Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery

Importance A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. Design, Setting, and Participants This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Main Outcomes and Measures Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. Results The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (P < .01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared with those with a breast pCR. Conclusions and Relevance Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.

Stereotactic breast biopsy: Pitfalls and pearls

Stereotactic breast biopsies have become indispensable and the standard of care for patients in whom screening mammography or tomosynthesis reveals breast lesions suggestive of malignancy. A variety of stereotactic biopsy systems and needle types are now available, which allow more accurate sampling of lesions as well as successful biopsy of lesions in difficult locations in patients of all body habitus. We discuss how to plan, perform, and follow up stereotactic biopsies. Most importantly, we offer suggestions on how to avoid problems and complications and detail how to achieve technical success even in the most challenging cases. Stereotactic biopsy has proven over time to be an accurate and acceptable alternative to surgical biopsy for histopathologic diagnosis of breast abnormalities. Successful performance of this minimally invasive procedure spares women from undergoing potentially deforming and expensive procedures to diagnose breast disease.

Hyperechoic Lesions of the Breast: Radiologic-Histopathologic Correlation

OBJECTIVE Breast ultrasound is helpful in the characterization of masses to differentiate benign from malignant disease. The internal echotexture of a mass is an important ultra-sound feature in breast diagnostic workup. This article reviews the imaging and histopathology findings of benign and malignant hyperechoic masses to better recognize these conditions. CONCLUSION Hyperechoic masses are frequently benign, including hematoma, fat necrosis, abscess, and benign neoplasm. Malignant hyperechoic lesions include invasive ductal and invasive lobular carcinoma, lymphoma, and sarcoma. Understanding lesion echotexture in the context of clinical and mammographic findings will help establish appropriate diagnoses for hyperechoic masses.

Investigating the limit of detectability of a positron emission mammography device: a phantom study.

PURPOSE A new positron emission mammography (PEM) device (PEM Flex Solo II, Naviscan Inc., San Diego, CA) has recently been introduced and its performance characteristics have been documented. However, no systematic assessment of its limit of detectability has been evaluated. The aim of this work is to investigate the limit of detectability of this new PEM system using a novel, customized breast phantom. METHODS Two sets of F-18 infused gelatin breast phantoms of varying thicknesses (2, 4, 6, and 8 cm) were constructed with and without (blank) small, shell-less contrast objects (2 mm thick disks) of varying diameters (3-14.5 mm) [volumes: 0.15-3.3 cc] and activity concentration to background ratio (ACR) (2.7-58). For the phantom set with contrast objects, the disks were placed centrally inside the phantoms and both phantom sets were imaged for a period of 10 min on the PEM device. In addition, scans for the 2 and 6 cm phantoms were repeated at different times (0, 90, and 150 min) post phantom construction to evaluate the impact of total activity concentration (count density) on lesion detectability. Each object from each phantom scan was then segmented and placed randomly in a corresponding blank phantom image. The resulting individual images were presented blindly to seven physician observers (two nuclear medicine and five breast imaging radiologists) and scored in a binary fashion (1-correctly identified object, 0-incorrect). The sensitivity, specificity, and accuracy of lesion detectability were calculated and plots of sensitivity versus ACR and lesion diameters for different phantom thicknesses and count density were generated. RESULTS The overall (mean) detection sensitivity across all variables was 0.68 (95% CI: [0.64, 0.72]) with a corresponding specificity of 0.93 [0.87, 0.98], and diagnostic accuracy of 0.72 [0.70, 0.75]. The smallest detectable object varied strongly as a function of ACR, as sensitivity ranged from 0.36 [0.29, 0.44] for the smallest lesion size (3 mm) to 0.80 [0.75, 0.84] for the largest (14.5 mm). CONCLUSIONS The detectability performance of this PEM system demonstrated its ability to resolve small objects with low activity concentration ratios which may assist in the identification of early stage breast cancer. The results of this investigation can be used to correlate lesion detectability with tumor size, ACR, count rate, and breast thickness.

A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy

Objective: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST). Summary Background Data: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma. Methods: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST. Results: Median initial clinical tumor size was 3.3 cm (range, 1.2–7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0–4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%–100%), false-negative rate of 5% (95% CI, 0%–24%), and negative predictive value of 95% (95% CI, 75%–100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011). Conclusions: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Screening for breast cancer with sonography.

C a c It has been well established that early detection of breast cancer through screening and the resulting treatment improve outcomes in breast cancer, which is the most common malignancy worldwide among women.1 Mammography is till the modality of choice for screening women for the early etection of breast cancer, because it is relatively fast, reasonbly accurate, widely available, reproducible, and cost-effecive in quality-adjusted years of life saved.2 Currently, the nly screening test that has been shown to reduce deaths aused by breast cancer is mammography.3 The decrease in mortality rates is almost entirely attributable to a decrease in the size of the cancers detected on screening mammography.4 The sensitivity of mammography in the diagnosis of breast cancer is variable and inversely proportional to the breast density.5,6 Mammographic sensitivity may be as low as 30%48% in patients with dense breasts, with much higher interval cancer rates noted in dense breasts.6 Furthermore, mammographically dense breast tissue is now considered a significant risk factor for the development of breast cancer.6-11 Kerlikowske et al12 reported results of 27,281 screening ammograms and found the sensitivity to be 98.4% in omen age 50 years or older with fatty breasts and 83.7% in omen with dense breasts (P 0.01). In women 50 years f age with a family history of breast cancer, mammographic ensitivity decreased to 68.8%. In women with dense breasts, nd particularly in women with a high lifetime risk for breast ancer, methods to supplement mammographic screening re needed. Digital mammography has been shown to be more sensiive than screen-film mammography in women with dense arenchyma and the overlapping groups of premenopausal omen and those under the age of 50 years.13 However, igital mammography does not eliminate the fact that small,

How to Establish a Cost-Effective Mobile Mammography Program

OBJECTIVE The purpose of this article is to describe how to establish a cost-effective mobile mammography program on the basis of examples from a 20-year experience with film-screen and digital mammography units. CONCLUSION Mobile mammography programs can reduce many barriers to breast cancer screening faced by medically underserved women. Finding and maintaining resources, having appropriate equipment and infrastructure, and having a dedicated team with an efficient workflow are the key elements of establishing a cost-effective mobile mammography program.