Andrea V. Barrio

Clinicopathologic Features and Long-Term Outcomes of 293 Phyllodes Tumors of the Breast

BackgroundPhyllodes tumors (PT) are rare fibroepithelial neoplasms of the breast with unpredictable behavior. We reviewed our single institution experience with PT over 51 years to identify factors predictive of local recurrence (LR) and metastasis.MethodsFrom 1954 to 2005, a total of 352 cases of PT were identified; 293 had follow-up. All available pathology slides (90%) were rereviewed for margins, borders, fibroproliferation in the surrounding breast tissue, stromal pattern, stromal cellularity, frequency of mitoses, and necrosis.ResultsAll cases occurred in women, with a median age of 42, with 203 originally categorized as benign and 90 as malignant. Median follow-up was 7.9 years. A total of 35 patients developed LR at a median of 2 years. In univariate analyses, a higher actuarial LR rate was associated with positive margins (P = .04), fibroproliferation (P = .001), and necrosis (P = .006). PT classified as malignant did not have a higher risk of LR (P = .79). Five patients developed distant disease at a median of 1.2 years. These patients constituted 71% of the seven patients who had uniformly aggressive pathologic features, including large tumor size (≥7.0 cm), infiltrative borders, marked stromal overgrowth, marked stromal cellularity, high mitotic count, and necrosis.ConclusionsPositive margins, fibroproliferation in the surrounding breast tissue, and necrosis are associated with a marked increase in LR rates. Efforts should be made to achieve negative surgical margins to reduce risk of LR. Death from PT is rare (2%), and only PT that demonstrate uniformly aggressive pathologic features seem to be associated with mortality.

A Randomized Prospective Comparison of Patient-Assessed Satisfaction and Clinical Outcomes with Radioactive Seed Localization versus Wire Localization

Radioactive seed localization (RSL) has emerged as an alternative to wire localization (WL) in patients with nonpalpable breast cancer. Few studies have prospectively evaluated patient satisfaction and outcomes with RSL. We report the results of a randomized trial comparing RSL to WL in our community hospital. We prospectively enrolled 135 patients with nonpalpable breast cancer between 2011 and 2014. Patients were randomized to RSL or WL. Patients rated the pain and the convenience of the localization on a 5‐point Likert scale. Characteristics and outcomes were compared between groups. Of 135 patients enrolled, 10 were excluded (benign pathology, palpable cancer, mastectomy, and previous ipsilateral cancer) resulting in 125 patients. Seventy patients (56%) were randomized to RSL and 55 (44%) to WL. Fewer patients in the RSL group reported moderate to severe pain during the localization procedure compared to the WL group (12% versus 26%, respectively, p = 0.058). The overall convenience of the procedure was rated as very good to excellent in 85% of RSL patients compared to 44% of WL patients (p < 0.0001). There was no difference between the volume of the main specimen (p = 0.67), volume of the first surgery (p = 0.67), or rate of positive margins (p = 0.53) between groups. RSL resulted in less severe pain and higher convenience compared to WL, with comparable excision volume and positive margin rates. High patient satisfaction with RSL provides another incentive for surgeons to strongly consider RSL as an alternative to WL.

Axillary Dissection and Nodal Irradiation Can Be Avoided for Most Node-positive Z0011-eligible Breast Cancers: A Prospective Validation Study of 793 Patients.

Objective: To determine rates of axillary dissection (ALND) and nodal recurrence in patients eligible for ACOSOG Z0011. Background: Z0011 demonstrated that patients with cT1-2N0 breast cancers and 1 to 2 involved sentinel lymph nodes (SLNs) having breast-conserving therapy had no difference in locoregional recurrence or survival after SLN biopsy alone or ALND. The generalizability of the results and importance of nodal radiotherapy (RT) is unclear. Methods: Patients eligible for Z0011 had SLN biopsy alone. Prospectively defined indications for ALND were metastases in ≥3 SLNs or gross extracapsular extension. Axillary imaging was not routine. SLN and ALND groups and radiation fields were compared with chi-square and t tests. Cumulative incidence of recurrences was estimated with competing risk analysis. Results: From August 2010 to December 2016, 793 patients met Z0011 eligibility criteria and had SLN metastases. Among them, 130 (16%) had ALND; ALND did not vary based on age, estrogen receptor, progesterone receptor, or HER2 status. Five-year event-free survival after SLN alone was 93% with no isolated axillary recurrences. Cumulative 5-year rates of breast + nodal and nodal + distant recurrence were each 0.7%. In 484 SLN-only patients with known RT fields (103 prone, 280 supine tangent, 101 breast + nodes) and follow-up ≥12 months, the 5-year cumulative nodal recurrence rate was 1% and did not differ significantly by RT fields. Conclusions: We confirm that even without preoperative axillary imaging or routine use of nodal RT, ALND can be avoided in a large majority of Z0011-eligible patients with excellent regional control. This approach has the potential to spare substantial numbers of women the morbidity of ALND.

Are the American Society for Radiation Oncology Guidelines Accurate Predictors of Recurrence in Early Stage Breast Cancer Patients Treated with Balloon-Based Brachytherapy?

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) provides guidelines for patient selection for accelerated partial breast irradiation (APBI) following breast conserving surgery. The purpose of this study was to evaluate recurrence rates based on ASTRO CS groupings. A single institution review of 238 early stage breast cancer patients treated with balloon-based APBI via balloon based brachytherapy demonstrated a 4-year actuarial ipsilateral breast tumor recurrence (IBTR) rate of 5.1%. There were no significant differences in the 4-year actuarial IBTR rates between the “suitable,” “cautionary,” and “unsuitable” ASTRO categories (0%, 7.2%, and 4.3%, resp., P = 0.28). ER negative tumors had higher rates of IBTR than ER positive tumors. The ASTRO groupings are poor predictors of patient outcomes. Further studies evaluating individual clinicopathologic features are needed to determine the safety of APBI in higher risk patients.

Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2‐Positive Early Stage Breast Cancer: A Single Center Experience

OBJECTIVES Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported. METHODS An electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0). RESULTS Charts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients. CONCLUSION At a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:139-143Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast + lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

Infrared Imaging Does Not Predict the Presence of Malignancy in Patients with Suspicious Radiologic Breast Abnormalities

The NoTouch BreastScan (NTBS) is a non‐invasive infrared imaging device which measures thermal gradients in breasts using dual infrared cameras and computer analysis. We evaluated NTBS as a predictor of breast cancer in patients undergoing minimally invasive biopsy. In this IRB‐approved prospective trial, 121 female patients underwent NTBS prior to scheduled tissue biopsy. Twenty‐two patients were excluded due to uninterpretable scans (n = 18), diagnosis of a nonprimary breast malignancy (n = 1), or no biopsy performed (n = 3) for a total of 99 patients. Five patients had bilateral breast biopsies and one patient had two ipsilateral biopsies, resulting in 105 biopsies. Patients were prospectively scanned using a high specificity mode, termed NTBS1. All 99 patients were retrospectively re‐evaluated in a high sensitivity mode, NTBS2. Of 105 biopsies performed in 99 women, 33 (31.4%) were malignant and 72 (68.6%) were benign. NTBS1 demonstrated a sensitivity of 45.5% and a specificity of 88.9%. Of 94 normal contralateral breasts, 9.6% had a positive NTBS1. In the retrospective evaluation, NTBS2 demonstrated a sensitivity of 78.8% and a specificity of 48.6%. Half (50%) of the normal contralateral breasts had a positive NTBS2. NTBS does not accurately predict malignancy in women with suspicious imaging abnormalities. The higher sensitivity mode results in an unacceptable number of false positives, precluding its use. Infrared imaging did not improve the sensitivity or specificity of mammography in this clinical setting.

Guidelines for Guidelines: An Assessment of the American Society of Breast Surgeons Contralateral Prophylactic Mastectomy Consensus Statement.

The rates of contralateral prophylactic mastectomy (CPM) have markedly increased in the US over the past 2 decades. These trends have been observed in all patient age groups, cancer stages, races, and in all geographic regions of the US. In the most recently published analyses from the Surveillance Epidemiology and End Results database, the CPM rates were still increasing with no plateau. Most patients who undergo CPM do not have strong genetic or familial risk factors for developing contralateral breast cancer. Recent survey studies have demonstrated that breast cancer patients substantially overestimate the risk of contralateral breast cancer and have unrealistic outcomes from CPM. Moreover, in a survey study among active members of the American Society of Breast Surgeons (ASBrS), Yao et al. concluded that 39.2 % of respondents had a ‘low level of knowledge about CPM’. Given the gaps in knowledge among both patients and surgeons, the publication of the ASBrS consensus statement is timely. In 1993, the Society of Surgical Oncology (SSO) developed a position statement on the use of CPM, which was most recently edited and updated in March 2007. Since the last revision of this position statement, many important studies have been published evaluating the risks of contralateral breast cancer, outcomes after CPM, and patients’ perceptions and preferences. The ASBrS consensus statement appropriately incorporates most of this relevant recent research. In the strongest language to date, the consensus statement recommends that CPM should be ‘discouraged’ for patients with an average risk of contralateral breast cancer. This population of patients represents the vast majority of women who undergo CPM in the US. The statement further concludes that ‘CPM should be considered’ for selected groups at significant risk of contralateral breast cancer (including carriers of BRCA 1 or 2 deleterious mutations). Furthermore, ‘CPM can be considered’ for selected groups at lower risk of contralateral breast cancer (including other gene mutation carriers). Additionally, ‘CPM may be considered’ for non-oncologic reasons (including limiting contralateral breast surveillance). Finally, ‘CPM should be discouraged’ for patients with advanced primary-stage breast cancer and patients who are in overall poor health or at very high risk of associated complications. In recent years, there has been a rapid proliferation in the number and scope of published clinical practice guidelines and consensus statements. To address the substantial variation in the clinical guideline development processes, the Institute of Medicine (IOM) published eight standards in ‘Clinical Practice Guidelines We Can Trust’ in 2011. Although there are subtle differences between consensus statements and clinical practice guidelines, both should be transparent, multidisciplinary, evidence-based, and intended to provide guidance to clinicians and patients. The ASBrS CPM consensus statement adheres to some, but not all, of the IOM standards. For example, the IOM recommends that the clinical guideline development group be multidisciplinary, balanced, and include current/former Society of Surgical Oncology 2016

Effect of Preoperative MRI on Mastectomy and Contralateral Prophylactic Mastectomy rates at a Community Hospital by a Single Surgeon

Magnetic resonance imaging (MRI) use in the preoperative evaluation of newly diagnosed breast cancer (BC) patients is rising. We evaluated MRI as a function of surgical year with respect to mastectomy and contralateral prophylactic mastectomy (CPM) rates by a single surgeon. From January 2000 to December 2010, 1,279 patients with 1,296 breast cancers were identified. Our breast MRI was installed in April 2006. Mastectomy and CPM rates were evaluated by surgical year and stratified as “pre‐MRI” or “MRI” depending on whether surgery occurred before or after April 2006. There was a significant increase in the percentage of patients undergoing MRI in the “pre‐MRI” versus “MRI” era (17.2% versus 78.7%, p < 0.001). In contrast, mastectomy rates decreased with 29.9% undergoing mastectomy before 2006 versus 24.5% after 2006 (p = 0.038). Except for 2007, where CPM rates dropped to 7.1%, CPM rates increased from 16.7% in 2000 to 51.9% in 2010 (p = 0.033). The use of MRI, additional MRI findings and additional MRI biopsies were not associated with the decision for CPM. Age <50 was the only factor associated with CPM (RR = 2.12, p = 0.001). In our community hospital, mastectomy rates have decreased despite the increased use of preoperative MRI. MRI alone may not explain the increasing rates of mastectomy reported in other series. CPM rates have dramatically increased over time, seemingly independent of MRI use. Prospective studies are needed to assess the role of surgeon bias, along with other factors, in surgical decision making.

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

Background/ObjectiveIntraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND).MethodsPatients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined.ResultsFrom July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND.ConclusionLow-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.

MRI and Prediction of Pathologic Complete Response in the Breast and Axilla after Neoadjuvant Chemotherapy for Breast Cancer

BACKGROUND In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), we evaluate the reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes after NAC. STUDY DESIGN Patients who had MRI before and after NAC between June 2014 and August 2015 were identified in a prospective database after IRB approval. Post-NAC MRI of the breast and axillary nodes was correlated with residual disease on final pathology. Pathologic complete response was defined as absence of invasive and in situ disease. RESULTS We analyzed 129 breast cancers. Median patient age was 50.8 years (range 27.2 to 80.6 years). Tumors were human epidermal growth factor receptor 2 amplified in 52 of 129 (40%), estrogen receptor-positive/human epidermal growth factor receptor 2-negative in 45 of 129 (35%), and triple negative in 32 of 129 (25%), with respective pCR rates of 50%, 9%, and 31%. Median tumor size pre- and post-NAC MRI were 4.1 cm and 1.45 cm, respectively. Magnetic resonance imaging had a positive predictive value of 63.4% (26 of 41) and negative predictive value of 84.1% (74 of 88) for in-breast pCR. Axillary nodes were abnormal on pre-NAC MRI in 97 patients; 65 had biopsy-confirmed metastases. The nodes normalized on post-NAC MRI in 33 of 65 (51%); axillary pCR was present in 22 of 33 (67%). In 32 patients with proven nodal metastases and abnormal nodes on post-NAC MRI, 11 achieved axillary pCR. In 32 patients with normal nodes on pre- and post-NAC MRI, 6 (19%) had metastasis on final pathology. CONCLUSIONS Radiologic complete response by MRI does not predict pCR with adequate accuracy to replace pathologic evaluation of the breast tumor and axillary nodes.