Emilia Diego

The Importance of Detection of Subclinical Lymphedema for the Prevention of Breast Cancer-Related Clinical Lymphedema after Axillary Lymph Node Dissection; A Prospective Observational Study

PURPOSE Early detection and timely intervention have potential to reduce late-stage lymphedema (LE) in patients with breast cancer undergoing axillary lymph node dissection (ALND). This study aims to determine if detection and early treatment of subclinical LE by using prospective monitoring with bioimpedance spectroscopy (BIS) can lead to reduced development of clinical LE. METHODS AND RESULTS Subclinical LE was prospectively detected using an L-Dex(®) U400 analyzer to measure BIS in 186 patients who underwent ALND between 2010 and 2013 through our LE monitoring program. Baseline measurements were obtained and at 3-6 month intervals for 5 years. Patients diagnosed with subclinical LE received short-term physical therapy, compression garments, and education about exercise, elevation, infection precautions, BMI, and hand usage. The control group had a preoperative baseline L-Dex(®) measurement, but had only clinical follow-ups with circumferential arm measurements. Mean age and BMI were 56 years and 28.3 kg/m(2), respectively. The majority of the women underwent mastectomy (61%) and received chemotherapy (89%) and radiotherapy (77%). Thirty-three percent patients who had repeated L-Dex measurements were diagnosed with subclinical LE and received early intervention. Progression to clinical lymphedema occurred in 4.4% over an average of 20 months follow-up. In the control group, the incidence of clinical LE was 36.4%. CONCLUSION Periodic monitoring of women at high risk for LE with BIS allows early detection and timely intervention for LE, which reduces the incidence of clinical LE from 36.4% to 4.4%. This may have implications for quality of life and health care costs.

Magee Equation 3 predicts pathologic response to neoadjuvant systemic chemotherapy in estrogen receptor positive, HER2 negative|[sol]|equivocal breast tumors

Magee Equations were derived as an inexpensive, rapid alternative to Oncotype DX. The Magee Equation 3 utilizes immunohistochemical and FISH data for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 for its calculation (24.30812+ERIHC × (−0.02177)+PRIHC × (−0.02884)+(0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive)+Ki-67 × 0.18649). We hypothesize that Magee Equation 3 scores from pre-therapy core biopsy can predict response to neoadjuvant systemic chemotherapy. A prospectively-maintained database of patients who received neoadjuvant systemic therapy from 2010 to 2014 at a single institution was retrospectively reviewed. Pathologic complete response was defined as absence of invasive tumor in the breast and regional lymph nodes. Of the 614 cases, tumors with missing immunohistochemical results and those that were ER negative or HER2 positive were excluded. This resulted in 237 ER positive, HER2 negative/equivocal tumors that formed the basis of this study. Magee Equation 3 scores were divided into 3 categories similar to Oncotype DX, ie, 0 to <18 (low), 18 to <31 (intermediate), and 31 or higher (high) scores. The pathologic complete response rate for low, intermediate and high Magee Equation 3 scores was 0%, 4%, and 36%, respectively. Patients with high Magee Equation 3 scores were 13 times more likely to achieve pathologic complete response compared to those with Magee Equation 3 scores less than 31 (95% CI 5.09–32.87, P<0.0001). For patients that did not achieve pathologic complete response, high Magee Equation 3 correlated with higher recurrence rate, with the majority occurring in patients with positive lymph nodes in the resection specimen. Magee Equation 3 score ≥31 predicts pathologic complete response in the neoadjuvant setting and for tumor recurrence, when pathologic complete response is not achieved. These results show the utility of Magee Equation 3 in predicting patients who will benefit from chemotherapy but warrant prospective multi-institutional validation.

Case report of a large lactating adenoma with rapid antepartum enlargement.

Highlights • We report a giant 10 cm lactating adenoma with rapid antepartum enlargement.• The lactating adenoma doubled in size within six weeks during the third trimester.• The giant lactating adenoma was excised at 31-week gestation without complications.• Excision of giant, enlarging lactating adenoma in the third trimester is feasible.

Abstract P3-05-14: A neoadjuvant window trial of endocrine response in women with invasive lobular carcinoma

Background: Patients with invasive lobular carcinoma (ILC) would be expected to have favorable outcomes compared to patients with invasive ductal carcinoma (IDC) given that ILC is more often hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, of lower grade, and displays decreased proliferation markers. Based on our preclinical studies showing differential hormone response in HR+ ILC vs. IDC and on recent studies suggesting differences in endocrine treatment response between patients with ILC vs. IDC, we designed a biomarker-driven, neoadjuvant window trial for newly diagnosed women with HR+, HER2-negative ILC. We hypothesize that Ki67 will be reduced by 85% in the fulvestrant arm compared with 60% and 75% reduction in the tamoxifen and anastrozole arms, respectively, and that Ki67 reduction will correlate with alterations in expression of ER and ER-regulated genes. Differential Ki67 effect will serve as a surrogate for outcome of patients with ILC on endocrine therapy. Trial Design: This multicenter study (NCT02206984) will enroll 150 women with HR+ and HER2-negative ILC. A mandatory research breast tumor biopsy will be performed at baseline. Fifty patients will be randomized to each of three open-label treatment arms for 21 days: fulvestrant (two 250 mg IM injections on both day 1 and day 14), anastrozole (1mg orally daily), or tamoxifen (20 mg orally daily). Biomarkers of response will be assessed on baseline and post-treatment tumor tissue. Patients will proceed to definitive surgery on day 21 after study drug exposure, or they will undergo a second research breast core biopsy if further neoadjuvant treatment is planned. Eligibility Criteria: Eligible patients include postmenopausal women with newly diagnosed, HR+, HER2-negative ILC (excluding pleomorphic subtype) measuring ≥ 1cm, with adequate organ function, ECOG PS ≥ 2, and agreeable to baseline research breast tumor biopsy. Specific Aims: The primary endpoint is percent change from baseline to post-treatment Ki67 values in ILC tissue after 21 days of endocrine treatment. Comparisons across study arms will be made using a general linear model adjusting for institutional effect, with 80% power estimated for pairwise comparisons of log 2 (% staining) between treatment arms, allowing for 10% attrition. Secondary endpoints include post-therapy Ki67, and change in ER and PR protein expression by IHC. Finally, planned correlative studies include evaluation of gene expression, epigenetic markers, and DNA sequence variants in ILC tissues in an effort to identify biomarkers of endocrine response and putative drivers of endocrine resistance in ILC. Target Accrual: This study will be open to enrollment by August 2015 at the University of Pittsburgh. Additional sites will be opened through the Translational Breast Cancer Research Consortium (TBCRC). We anticipate an accrual rate of 8 patients per month. (Funding from Susan G. Komen® and AstraZeneca). Citation Format: Jankowitz RC, McAuliffe PF, Sikora MJ, Butler L, Ahrendt G, Johnson R, Diego E, Bonaventura M, Puhalla S, Lembersky B, Clark B, Brufsky A, Kurland BF, Davidson NE, Dabbs DJ, Oesterreich S. A neoadjuvant window trial of endocrine response in women with invasive lobular carcinoma. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-05-14.

A rare case of tumor-to-tumor metastasis: breast cancer metastatic to a benign renal mass

Tumor-to-tumor metastasis is a clinical entity that has been documented in medical literature as early as the 1900s. It is rare and published primarily as case reports, although its incidence seems to be on the rise as a result of improving medical care in developed countries. We report an unusual case of metatstatic breast tumor to a benign renal tumor, in a patient with a remote history of breast cancer. This case reinforces in our minds the enigmatic nature of breast cancer and its wide spectrum of clinical behavior.

Standardization of nodal radiation therapy through changes to a breast cancer clinical pathway throughout a large, integrated cancer center network

BACKGROUND Studies demonstrate safety of omitting axillary nodal dissection for early-stage breast cancer with positive sentinel lymph node (+SLN) biopsy, although trial designs differed in radiation therapy (RT) fields. Regional nodal irradiation was separately shown to improve outcomes in high-risk patients. This led to lack of consensus in RT volumes. Clinical pathways (CPs) standardize care where practice varies unnecessarily. We evaluated the impact of changes to a CP guiding postoperative RT in women with +SLNs on practice patterns throughout a network. METHODS AND MATERIALS We implemented a CP for management of breast cancer with postoperative RT designed to promote uniform nodal treatment. The CP recommended modified tangents (MTs) including level I/II nodes for women with micrometastases (pN1mi). For women with macrometastases (pN1a), CPs recommended including level I/II LN in MT and a third supraclavicular node (SCN) LN ± internal mammary nodes for women with adverse factors present. RESULTS RT fields of 233 women undergoing breast-conserving surgery with +SLN but not axillary nodal dissection were retrospectively reviewed: 25% had pN1mi disease and 75% pN1a. Of 127 women treated before CP changes, 35% with pN1mi and 22% with pN1a were treated with whole-breast irradiation alone. Following CP changes, 106 women were treated: 5% with whole-breast irradiation alone, 58% with MT, and 38% with MT + SCN field. Utilization of MT was associated with CP changes. Utilization of a third SCN field was associated with CP changes, pN stage, extracapsular extension, and total number of adverse factors. CONCLUSIONS CPs translate published data and institutional experience into management plans that promote evidence-based care and eliminate unnecessary practice variations. Recognizing that postoperative RT treatment volumes were heterogeneous, we modified the CP based upon the latest evidence for regional nodal irradiation, after which we found increased compliance and consistency with quality guidelines, which will also aid in tracking outcomes in future investigations.

Prognostic Significance of Modified Residual Disease in Breast and Nodes (mRDBN) Algorithm After Neoadjuvant Chemotherapy for Breast Cancer

Objectives We hypothesized that prognostic accuracy of the residual disease in breast and lymph nodes (RDBN) method, which is calculated using residual tumor size, nodal involvement, and tumor grade, may be improved by incorporating residual tumor cellularity. Methods Cases included 614 patients who underwent neoadjuvant therapy for breast cancer. Tumor size was adjusted for residual cellularity of invasive carcinoma and used to calculate modified RDBN (mRDBN) and compared with unmodified gross tumor size (gRDBN). Results RDBN could be calculated in 428 cases. Relative risks of recurrence and death were significantly higher for RDBN-3 and RDBN-4 compared with RDBN-1. Kaplan-Meier analysis showed significant differences in disease-free survival and overall survival for estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative and ER-positive/HER2-negative subgroups (P < .0001). Conclusions Both mRDBN and gRDBN provide prognostic information, particularly in HER2-negative carcinoma; however, mRDBN showed better stratification of RDBN-3 and RDBN-4 patients.

Low Estrogen Receptor (ER)–Positive Breast Cancer and Neoadjuvant Systemic ChemotherapyIs Response Similar to Typical ER-Positive or ER-Negative Disease?

Objectives Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Methods Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. Results The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Conclusions Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

Is completion axillary lymph node dissection necessary in patients who are underrepresented in the ACOSOG Z0011 trial

Purpose The American College of Surgeons Oncology Group trial Z0011 demonstrated that axillary node dissection (ALND) can be omitted in patients managed with breast conserving surgery and 1 to 2 positive sentinel lymph nodes (SLNs) without adverse effects on locoregional recurrence or disease-free survival (DFS). We investigated patients with breast cancer for whom clinicopathologic features were underrepresented in the Z0011 trial and analyzed radiation therapy treatment patterns and clinical outcomes. Methods and materials We retrospectively reviewed records of patients who underwent a lumpectomy and SLN biopsy with positive SLNs but not an ALND and completed adjuvant radiation therapy. Eligible patients had T3 tumors, >2 positive SLNs, invasive lobular carcinoma, estrogen receptor negative status, extranodal extension, Nottingham Grade 3, or were age <50 years. Results We identified 105 women treated between July 2011 and July 2016 with a median follow-up time of 48.5 months (Range, 11-83 months). There were 40 women with an extranodal extension (38.9%) and 42 women with grade 3 disease (40.0%). Nineteen patients received whole breast irradiation alone (18.1%) and 86 patients were treated with modified tangent fields including the superior axilla level I/II (81.9%). Thirty-three patients (31.4%) also received a 3rd supraclavicular, nodal-directed field. Among the 86 patients who received axillary nodal irradiation, nodal volume contouring was performed in 77 patients (89.5%). Fifty-one patients (48.6%) also received adjuvant chemotherapy. The overall rates of 4-year DFS and locoregional control (LRC) were 94.3% and 98.1%, respectively. Off all patients, 1 patient experienced an internal mammary nodal recurrence, another patient a contralateral breast tumor, and two patients distant metastases. There were no axillary or ipsilateral breast tumor recurrences. Conclusions This retrospective analysis of women who were underrepresented or excluded from the Z11 trial and underwent a lumpectomy and SLN biopsy with positive SLNs demonstrated comparable rates of LRC and DFS. The high rates of LRC and DFS suggest that completion ALND may be safely omitted in this patient population but larger data sets and longer follow-up times are needed to confirm this finding.

The importance of tattoo pigment in sentinel lymph nodes

BACKGROUND The presence of pigment in axillary lymph nodes (LN) secondary to migration of tattoo ink can imitate the appearance of a blue sentinel lymph node (SLN) on visual inspection, causing the operator to either miss the true SLN or excise more than is needed. OBJECTIVE We present patients with tattoos ipsilateral to an early stage breast cancer who underwent a SLN biopsy. METHODS Patients were retrospectively reviewed from medical records and clinicopathologic data was collected. A total of 52 LNs were retrieved from 15 patients for sentinel mapping and 29 of them had tattoo pigmentation on pathologic evaluation. RESULTS Of those 29 SLNs, 2 of them (6.9%) were pigmented, but did not contain either blue dye or Tc-99m (pseudopigmented SLN). Two (3.8%) SLNs were positive for metastasis; both of these had either blue dye or Tc99m uptake, and 1 demonstrated tattoo pigment in the node. CONCLUSIONS In this cohort of patients with ipsilateral tattoos, removed more LNs lead to unnecessary excision which may important for increasing the risk of arm morbidity from SLN biopsy. However, the presence of tattoo pigment did not interfere with understaging for axillary mapping and it did not effect of pathological identification of SLNs positivity.