M. Catherine Lee

The Effect of Oncotype DX Recurrence Score on Treatment Recommendations for Patients with Estrogen Receptor–Positive Early Stage Breast Cancer and Correlation with Estimation of Recurrence Risk by Breast Cancer Specialists

PURPOSE The Oncotype DX assay predicts likelihood of distant recurrence and improves patient selection for adjuvant chemotherapy in estrogen receptor-positive (ER-positive) early stage breast cancer. This study has two primary endpoints: to evaluate the impact of Oncotype DX recurrence scores (RS) on chemotherapy recommendations and to compare the estimated recurrence risk predicted by breast oncology specialists to RS. METHODS One hundred fifty-four patients with ER-positive early stage breast cancer and available RS results were selected. Clinicopathologic data were provided to four surgeons, four medical oncologists, and four pathologists. Participants were asked to estimate recurrence risk category and offer their chemotherapy recommendations initially without and later with knowledge of RS results. The three most important clinicopathologic features guiding their recommendations were requested. RESULTS Ninety-five (61.7%), 45 (29.2%), and 14 (9.1%) tumors were low, intermediate, and high risk by RS, respectively. RS significantly correlated with tumor grade, mitotic activity, lymphovascular invasion, hormone receptor, and HER2/neu status. Estimated recurrence risk by participants agreed with RS in 54.2% ± 2.3% of cases. Without and with knowledge of RS, 82.3% ± 1.3% and 69.0% ± 6.9% of patients may be overtreated, respectively (p = 0.0322). Inclusion of RS data resulted in a 24.9% change in treatment recommendations. There was no significant difference in recommendations between groups of participants. CONCLUSIONS Breast oncology specialists tended to overestimate the risk of tumor recurrence compared with RS. RS provides useful information that improves patient selection for chemotherapy and changes treatment recommendations in approximately 25% of cases.

Role of Axillary Staging in Women Diagnosed With Ductal Carcinoma In Situ With Microinvasion

BACKGROUND Axillary staging via sentinel node biopsy (SLNB) in patients with ductal carcinoma in situ with microinvasion (DCISM) is routinely performed but remains controversial with regard to the risk-benefit ratio. METHODS Retrospective single-institution review of patients with diagnosis of DCISM (invasive tumor ≤ 0.1 cm). Age, clinicopathologic data, and follow-up were recorded. RESULTS Of 90 patients, 33% were diagnosed by core needle biopsy (CNB), 37% by excisional biopsy, and 29% were upstaged from DCIS on CNB to DCISM at final operation. Three (10%) of 30 patients with DCISM on CNB were upstaged to invasive cancer on final pathology. Median age at diagnosis was 58.9 years (range: 30-89). Lumpectomy was performed in 45% of patients and mastectomy in 55%. Mean number of sentinel nodes was 2.59 (SE 0.17). Six (6.9%) of 87 patients with DCISM as final diagnosis had a positive SLNB (four lumpectomies, two mastectomies). There was no correlation with any clinicopathologic features, including palpable DCIS, DCIS grade/necrosis, or age at diagnosis. All six SLNB-positive patients had a complete axillary dissection; two had additional disease. Median follow-up time was 74.2 months (range: 2-169). In-breast recurrence was seen in three patients (5%), regardless of SLN status, DCIS grade, or necrosis. Two patients developed distant metastasis. Overall survival was 94.19% at 5 years for DCISM and 100% for DCISM with nodal disease. CONCLUSION DCISM comprises 0.6% of breast cancer diagnoses at our institution. There is a low likelihood of nodal spread; however, a lack of identifiable clinicopathologic features associated with a positive SLNB limits selective SLNB use.

Surgical excision of pure flat epithelial atypia identified on core needle breast biopsy.

The biology of flat epithelial atypia (FEA) is still being investigated as its presence becomes more frequent on biopsy specimens. FEA is more commonly associated with malignancy when found in association with ADH, ALH or LCIS. Pure FEA is only upgraded to cancer in 3.2% of patients. Surgical excision of pure FEA found on core needle biopsy results in overtreatment in the vast majority of breast patients and may not be necessary.

Phyllodes tumors: race-related differences.

BACKGROUND Phyllodes tumors (PT) are rare breast malignancies accounting for 0.5% to 1% of all breast tumors. PT have unpredictable behavior, with recurrence rates as high as 40%. A dearth of information exists about racial differences; elucidation of these differences is the objective of this study. STUDY DESIGN A retrospective review of patients treated for PT at either Moffitt Cancer Center or University of Texas Health Science Center San Antonio from 1999 to 2010. RESULTS Of the 124 patients, 71 (57%) were treated at Moffitt Cancer Center and 53 (42%) at University of Texas Health Science Center San Antonio. Mean age at diagnosis was 44 years (15 to 70 years). Thirty-three patients required mastectomy. Combining both cohorts, 42% of the patients were Caucasian, 43% were Hispanic, and 12% were black. Tumors were benign in 49% patients, borderline in 35%, and malignant in 16%, with a higher percentage of borderline and malignant tumors in Hispanic patients (p < 0.01). Hispanic patients tended to have larger tumors and higher mitotic rates (p = 0.01; p = 0.03). At a median follow-up time of 13 months, the local recurrence rate (6.4%) was associated with tumor size, tumor grade, mitotic rate, and close margin status (<2 mm) (p <0.01; p = 0.01; p = 0.01; p = 0.04). However, these findings did not translate into a survival difference by race. CONCLUSIONS In this multi-institutional review of PT we found substantial pathologic differences by race with higher-grade tumors present more often in Hispanic patients. These differences did not substantially affect outcomes at short-term follow-up. Further investigation into additional molecular, biologic factors, geographic impact, and socioeconomic factors is needed to more clearly delineate this finding.

Indications for axillary ultrasound use in breast cancer patients.

BACKGROUND Axillary ultrasound has been adopted for preoperative planning in breast cancer. Our objective was to determine features predictive of abnormal AUS and/or positive axillary node needle biopsy (NBx). MATERIALS AND METHODS Single-institution database of breast cancer patients identified patients with preoperative AUS. Patient characteristics and outcomes were correlated with AUS and NBx. Significant features were identified using univariable and multivariable analysis and correlative statistics. RESULTS Three hundred thirteen breast cancers were evaluated. Abnormal AUS was demonstrated in 250 cases (80%). Node needle biopsy was performed in 247 cases (79%). Sensitivity and specificity was 93% and 48% for AUS and 86% and 100% for NBx, respectively. Palpable axillary adenopathy was significant in logistic regression model (P < .05). There were positive correlations between tumor grade, clinical T and tumor-node-metastasis stage, invasive ductal carcinoma histology, and inflammatory breast carcinoma with AUS and NBx (P < .05). CONCLUSION Clinicopathologic features (grade, histology, tumor size) might help guide judicious use of AUS.

Contralateral axillary nodal involvement from invasive breast cancer.

Metastatic breast cancer to the contralateral axilla (CAM) is defined as stage IV disease. We postulate that CAM represents an extension of local-regional disease rather than distant metastasis and may have a better outcome. A single-institution, retrospective review of breast cancer cases from January 2005 and May 2011 was performed to identify cases with CAM. Eligibility for the study included unilateral primary breast cancer at presentation with synchronous/metachronous documented CAM without a documented primary invasive breast cancer within the contralateral breast by surgery or MRI. Clinicopathologic data was recorded for these patients (pts). Thirteen pts were identified. 12/13 (92%) pts presented with a locally advanced breast tumor or an ipsilateral in-breast recurrence. 10/13 (77%) pts had documented dermal involvement of tumor either at initial presentation or local recurrence. CAM occurred synchronously with the initial primary tumor (5 pts, 38%), concomitant with a local recurrence (5 pts, 38%), metachronously with the initial tumor (1 pt, 8%), and metachronously with a local recurrence (2 pts, 15%). Three patients had other distant disease at presentation. Of the other 10 pts, seven developed distant disease with a mean follow up of 3.6 years (range 0.3-7.6 years). Three pts have no evidence of disease at a mean follow up of 5.8 years (range 1.5-8.2). CAM may have different prognostic implications than other distant metastases and may occur through dermal lymphatic spread. Further study is warranted on the prognosis and management of these challenging and rare cases.

Pathologic Tumor Response of Invasive Lobular Carcinoma to Neo‐adjuvant Chemotherapy

Abstract:  Neo‐adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo‐adjuvant chemotherapy on invasive lobular carcinoma. A review of a single‐institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo‐adjuvant chemotherapy. Patient demographics and clinicopathologic data were reviewed. Cases were reviewed by a single pathologist (NNE). Residual cancer burden class was determined for each case. Median patient age was 50 years (range 25–79). All tumors were hormone receptor positive and clinical stage II or III carcinomas. Most patients (53.3%) had combination anthracycline‐ and taxane‐based chemotherapy. Therapy‐related changes were noted within the tumor bed in 25 (83.3%) patients. Six (30%) of 20 patients with residual axillary disease had therapy‐related nodal changes. There were 11 patients with moderate residual disease (class II) and 18 (60%) with extensive (class III); there were no complete pathologic responses (class 0). Only one patient (3.3%) converted from mastectomy to breast‐conserving surgery. Four (13.3%) patients developed distant metastases; all had pleomorphic‐type, clinical stage III tumors with residual cancer burden III classification and developed distant disease in the 2 years after surgery (range 0–26 months). Median follow‐up time was 29.5 months (range 7–132). Patients with locally advanced pleomorphic‐type lobular carcinoma appear to develop early post‐treatment metastatic disease. Neo‐adjuvant chemotherapy did not appear to have significant impact on the surgical treatment of patients with invasive lobular carcinoma.

Early experience with ultrasound features after intrabeam intraoperative radiation for early stage breast cancer

Intraoperative radiation therapy (IORT) is an emerging option for partial breast radiotherapy in select women with early stage breast cancer. We assessed short‐term clinical and sonographic findings after breast conservation (BCT) and IORT.

Outcomes with and without axillary node dissection for node-positive lumpectomy and mastectomy patients.

BACKGROUND American College of Surgeons Oncology Group Z0011 trial of select node-positive breast cancer patients demonstrated no survival or recurrence differences between SLN/axillary lymph node dissection (ALND) vs SLN. Our comparable node-positive lumpectomy and mastectomy populations should have similar outcomes. METHODS An Institutional Review Board approved, retrospective review of pathologic SLN (N1) cases was performed. Treatment, recurrence, and survival were collected. Statistics was analyzed via exact chi-square test with Monte Carlo estimation, Kaplan-Meier curves, and log-rank tests. RESULTS Of 528 node-positive patients, 318 patients met criteria: 28 (21.7%) lumpectomy, 32 (16.9%) mastectomy had SLN; 101 (78.2%) lumpectomy, 157 (83.0%) mastectomy had SLN + ALND. Median age was 57.5 years for SLN and 53 years for SLN + ALND (P = .003). Mean positive nodes were 1.1 for SLN and 1.47 for SLN + ALND (P = .0018). Chemotherapy use differed (SLN = 73.5%, SLN + ALND = 89.7%, P = .0032). Stage and recurrence were higher for SLN + ALND (P = .0001, P = .007). No difference in comorbidities, nodes retrieved, extracapsular extension, radiation, hormone therapy, or overall survival was observed. CONCLUSION In clinically node-negative breast cancer patients, ALND for N1 disease has no impact on short-term recurrence or survival.

Magnetic Resonance Imaging for Axillary Breast Cancer Metastasis in the Neoadjuvant Setting: A Prospective Study

Background: Breast magnetic resonance imaging (MRI) for assessment of regional breast cancer metastasis is controversial owing to the variable specificity. We evaluated breast MRI for axillary metastasis in neoadjuvant chemotherapy patients. Materials and Methods: A single‐institution, institutional review board–approved prospective trial enrolled female breast cancer patients receiving neoadjuvant chemotherapy from 2008 to 2012 and collected the pre‐ and post‐treatment MRI, pretreatment axillary ultrasound, axillary biopsy, and surgical pathologic findings. The kappa coefficient was used to evaluate the strength of the agreement between the 2 modalities and Fishers exact test was used to evaluate the association. Results: A total of 43 patients were included. Of these 45 patients, 35 had stage N1‐N2 before treatment. Comparing the abnormal results on the pretreatment MRI scans and axillary biopsy examinations, a consistent diagnosis was found for 92%, with a moderate strength of agreement (kappa coefficient, 0.54). The pretreatment MRI findings were significantly associated with the axillary biopsy results (P = .014). The false‐positive rate, false‐negative rate, sensitivity, and specificity were 50%, 3%, 97%, 50%, respectively. Comparing the post‐treatment MRI and surgical pathologic findings revealed a consistent diagnosis rate of, with a slight strength of agreement (kappa, 0.16). The false‐positive rate, false‐negative rate, sensitivity, and specificity were 38%, 46%, 55%, and 63%, respectively. The post‐treatment MRI findings were not associated with the pathologic lymph node results (P = .342). Conclusion: Pretreatment breast MRI was more specific for axillary metastasis than was axillary ultrasonography. However, post‐treatment breast MRI was not predictive of residual axillary disease and should be used cautiously when altering treatment plans. Micro‐Abstract: Evaluation of the axilla on breast magnetic resonance imaging (MRI) for breast cancer is a growing practice. We reviewed a prospective breast cancer cohort undergoing neoadjuvant chemotherapy to compare the pretreatment breast MRI findings with the axillary ultrasound/fine needle aspiration findings and the post‐treatment breast MRI findings with the surgical pathologic findings. The prechemotherapy MRI findings were more specific for axillary metastasis than were the focused ultrasound findings. However, the postchemotherapy MRI findings were not predictive of residual axillary disease.