Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair.

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. AJI-100 significantly reduces the frequency of skin-homing CLA+ donor T cells, limiting allograft invasion and tissue destruction by T effectors. AJI-100 also suppresses pathogenic Th1 and Th17 cells in the spleen yet spares beneficial regulatory T cells. We show dual JAK2/Aurora kinase A blockade enhances human type 2 innate lymphoid cell (ILC2) responses, which are capable of tissue repair. ILC2 differentiation mediated by GATA3 requires STAT5 phosphorylation (pSTAT5) but is opposed by STAT3. Further, we demonstrate that Aurora kinase A activation correlates with low pSTAT5 in ILC2s. Importantly, AJI-100 maintains pSTAT5 levels in ILC2s by blocking Aurora kinase A and reduces interference by STAT3. Therefore, combined JAK2/Aurora kinase A inhibition is an innovative strategy to merge immune suppression with tissue repair after transplantation.

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

BACKGROUND: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. MATERIALS AND METHODS: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). RESULTS: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CONCLUSIONS: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

Characteristics of Microinvasive Ductal Carcinoma In Situ Versus Noninvasive and Invasive Breast Cancer.

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.

High-output chyle leak after breast-conserving surgery and sentinel lymph node biopsy.

Postoperative chyle leak is an exceedingly rare complication following breast and axillary surgery. We present the first described case of chyle leak following breast-conserving surgery and sentinel lymph node biopsy. Management should begin with appropriated conservative measures aimed at reduction of lymph production and flow. Intervention is warranted when conservative strategies fail and include sclerotherapy, lymphangiography, embolization, and surgery. Breast surgeons should be mindful of this potential complication when operating in the axilla and be familiar with its stepwise management.

Enhanced REVENUE After Surgery? A Cost-Standardized Enhanced Recovery Pathway for Mastectomy Decreases Length of Stay.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to improve surgical, anesthetic, and economic outcomes in intermediate-to-high-risk surgeries. Its influence on length of stay and cost of low-risk surgeries has yet to be robustly studied. As value-based patient care comes to the forefront of anesthesiology research, the focus shifts to strategies that maintain quality while effectively containing cost. METHODS: In July 2016, we implemented an ERAS for mastectomy protocol consisting of limiting fasting state, preoperative multimodal analgesia, and pectoralis I and II blocks. After 1 year, patient records were retrospectively reviewed for length of stay, opioid consumption, pain scores, and hospital charges. RESULTS: Implementation of an ERAS protocol for mastectomies led to a decrease in opioid consumption, and statistically significant decrease in length of stay (1.19 vs. 1.44, p = 0.01). No significant change in hospital charges was observed ($25,787 vs. $25,863, p = 0.97); however, the variance of charges was significantly decreased (6.8 × 107 vs. 1.5 × 108, p = 0.002). The decrease in length of stay translated to an extra 100 hospital bed days which can provide up to an additional $2,100,000 in gross patient service revenue from additional mastectomy volume. CONCLUSION: ERAS protocols for mastectomies may prove beneficial by allowing growing hospitals to increase bed capacity and consequently surgical volume. Despite no change in hospital charges, we predict a potential increase in gross patient service revenue of $2.1 million due to saved hospital bed days.

A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer.

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI-RADS criteria as "suspicious" or "not suspicious" for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false-negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS.

Early Postoperative Complications after Oncoplastic Reduction.

BACKGROUND: Breast-conserving surgery with adjuvant radiation therapy (BCT) has been established as safe oncologically. Oncoplastic breast surgery uses both oncologic and plastic surgery techniques for breast conservation to improve cosmetic outcomes. We evaluated the risk factors associated with complications after oncoplastic breast reduction. METHODS: A single-institution, institutional review board-approved, retrospective review of electronic medical records of female patients with breast cancer who underwent oncoplastic breast reduction from 2008 to 2014. A review of electronic medical records collected relevant medical history, clinical and pathological information, and data on postoperative complications within 6 months stratified into major or minor complications. Categorical variables analyzed with the χ2 exact method; continuous variables were analyzed with the Wilcoxon rank sum test exact method. RESULTS: We identified 59 patients; 4 required re-excision for positive margins, and 1 moved on to completion mastectomy. The overall complication rate was 33.9% (n = 20): 12 major (20.3%) and 8 minor (13.6%). Of the continuous variables (age, body mass index, and tissue removed), increased age was associated with minor complications (P = 0.02). Among the categorical variables (stratified body mass index, prior breast surgery, hypertension, diabetes mellitus, hyperlipidemia, vascular disease, pulmonary disease, and stratified weight of tissue removed), none were associated with overall or major complications. Pulmonary disease was associated with minor complications (P = 0.03). Bilateral versus unilateral oncoplastic breast reduction showed no statistically significant increase in complications. CONCLUSIONS: The overall complication rate after oncoplastic breast reduction was markedly higher than that in nationally published data for breast-conserving surgery. The complication rate resembled more closely the complication rate after bilateral mastectomy with immediate reconstruction. No risk factors were associated with major or overall complications. Age and pulmonary disease were associated with minor complications. Patients should be selected and counseled appropriately when considering oncoplastic breast reduction.

Clinical Considerations of Risk, Incidence, and Outcomes of Breast Cancer in Sexual Minorities.

BACKGROUND: Breast cancer is a leading cause of cancer-related mortality in women. Limited research exists on the impact of sexual orientation on overall risk of and mortality from breast cancer. We sought to summarize the medical literature on breast cancer in sexual minority women and identify possible disparities in this population. METHODS: A comprehensive literature search was conducted for English-language studies in peer-reviewed medical journals that referenced breast cancer and sexual minority, lesbian, bisexual, or transgender individuals. Articles published between January 2000 and November 2015 were included. They were reviewed for relevance to breast cancer risk stratification, breast cancer mortality, breast reconstruction, and transgender issues. RESULTS: Behavioral risks, reproductive risks, and risks associated with decreased access to health care may all affect outcomes for sexual minorities with breast cancer. Limited studies have mixed results regarding mortality associated with breast cancer in sexual minorities due to an inconsistent reporting of sexual orientation. CONCLUSIONS: Overall, the research examining breast cancer in sexual minority women remains limited. This finding is likely due to limitations in the reporting of sexual orientation within large databases, thus making broader-scale research difficult.

Prospective trial of breast MRI versus 2D and 3D ultrasound for evaluation of response to neoadjuvant chemotherapy.

BACKGROUND: Preoperative imaging to assess response to neoadjuvant chemotherapy in breast cancer is routine but no single imaging modality is standard of practice. Our hypothesis is that ultrasound (US) is comparable to magnetic resonance imaging (MRI) in the prediction of residual disease. METHODS: A single-institution, Institutional Review Board-approved prospective trial of primary invasive ductal breast cancer patients receiving neoadjuvant chemotherapy enrolled women from 2008 to 2012. Two-dimensional (2D) and three-dimensional (3D) US, as well as MRI images of pre- and post-neoadjuvant tumors were obtained. Skin involvement or inadequate images were excluded. Residual tumor on imaging was compared with surgical pathology. Differences of tumor volume on imaging and pathology were compared using the non-parametric Wilcoxon signed-rank test. US to MRI agreement was determined by the kappa coefficient. Tumor volumes in estrogen receptor (ER), progesterone receptor (PR), and Her2neu subgroups were compared using the Kruskal-Wallis test. ER/PR staining <5 % was considered negative; Her2neu status was determined by in situ hybridization. RESULTS: Forty-two patients were enrolled in the study; 39 had evaluable post-treatment data. Four patients were Her2neu positive, and 17 (46 %) patients had triple-negative tumors. Among 11 (28 %) patients with pathologic complete response (pCR), US correctly predicted pCR in six (54.5 %) patients compared with eight (72.7 %) patients when MRI was used. This is a substantial agreement between US and MRI in predicting pCR (kappa = 0.62). There was no difference between 2D and 3D US modalities. For the 39 patients, US and MRI had no significant difference in volume estimation of pathology, even stratified by receptor status. CONCLUSION: The estimation of residual breast tumor volume by US and MRI achieves similar results, including prediction of pCR.

Impact of axillary ultrasound (AUS) on axillary dissection in breast conserving surgery (BCS).

BACKGROUND AND OBJECTIVES: Preoperative axillary ultrasound (AUS) in clinically node-negative patients may increase axillary lymph node dissection (ALND) in ACoSOG Z0011-eligible patients. We hypothesize that AUS identifies operative axillary disease (>3 positive nodes) in women undergoing breast conserving surgery (BCS). METHODS: After IRB approval, a retrospective review of female breast cancer patients was performed; patients with clinical T1/T2 tumors undergoing BCS were included. Clinical, radiologic, and pathologic data were collected. RESULTS: Of 139 eligible subjects, 119/139 (86%) had nonpalpable axillary nodes. 47/119 patients (40%) had abnormal AUS and 15/47 (32%) had a positive FNA. Fourteen had ALND ;10/14 (71%) had >3 positive nodes. 6/32 (18%) with abnormal AUS but FNA negative were sentinel lymph node (SLN) positive. Of 72 normal AUS, 15 (22%) were SLN positive; 9/15 (60%) had ALND; 1 (11%) had >3 positive nodes. When evaluating for >3 positive nodes, AUS plus FNA had a sensitivity of 91%, specificity of 95%, NPV of 99%, and PPV of 71%. CONCLUSIONS: AUS/FNA has a high NPV for axillary metastasis and remarkable sensitivity for three or more positive axillary nodes, therefore AUS-identified metastasis should be treated as clinically node-positive disease, and is appropriate even in patients planning breast conserving surgery.

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

BACKGROUND: 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. METHODS: An IRB-approved, single institution retrospective chart review was conducted of patients (pts) treated with BCT/IORT from 1/2011 to 6/2012. Follow-up clinical breast exams and ultrasounds (US) obtained 6 and 12 months after BCT/IORT were retrospectively reviewed by a single breast radiologist (JD) for sonographic findings. P values were calculated using McNemar's test, Wilcoxon Rank Sum Test, and Chi-square. RESULTS: Seventy-one pts underwent BCT/IORT and 38 pts had an US. All 38 pts had a seroma, 10/38 (26%) pts were symptomatic. Eighteen pts had deep tissue closure (DTC) of the lumpectomy cavity with 5/18 (28%) DTC pts being symptomatic at follow-up versus 5/33 (15%) without DTC (P = 0.296). At 6 months, DTC resulted in smaller seroma cavity volumes compared to those without DTC (P = 0.03). CONCLUSION: Presence of a seroma is commonplace post BCT/IORT; symptomatic seromas are uncommon. DTC generated smaller seromas. Longer follow-up with serial US performed in all BCT/IORT pts could be considered to document natural progression/regression of symptoms and seromas.

Factors affecting lymph node yield in patients undergoing axillary node dissection for primary breast cancer: a single-institution review.

BACKGROUND: A minimum of 10 level I/II axillary nodes is recommended for accurate breast cancer staging. The goal of this study was to assess the effect of neoadjuvant chemotherapy on lymph node yield at axillary lymph node dissection. METHODS: A single-institution National Comprehensive Cancer Network (NCCN) breast cancer database was queried for cases with axillary node dissection from 2000 to 2008. All dissections were performed at the same institution. Demographic, chemotherapy, and clinicopathologic data were collected. Age and body mass index at diagnosis were calculated for subset analyses. Statistical analyses used Student's t-test or analysis of variance with Tukey multiple comparison and Fisher's exact test. RESULTS: Two hundred forty patients had axillary node dissection after neoadjuvant chemotherapy; an additional 903 women with primary lymph node dissection were identified as contemporaneous control subjects. There was a far lower nodal yield in patients undergoing axillary dissection after neoadjuvant chemotherapy than those undergoing primary surgery. Patients with pathologic stage II or III disease undergoing primary surgery had more lymph nodes at axillary dissection than stage I disease. CONCLUSIONS: Age, type of breast surgery, body mass index, and clinical stage have no effect on yield of lymph nodes at axillary lymph node dissection. Neoadjuvant chemotherapy, however, is associated with a far fewer nodes at axillary dissection, and alteration of the guidelines should be considered for this population of patients.

Ipsilateral nodal recurrence after axillary dissection for breast cancer.

INTRODUCTION: Level I/II axillary lymph node dissection (ALND) is the standard operation for patients with node-positive breast cancer. The objective of this study was to assess the incidence of regional nodal recurrence (RNR) after ALND performed for definitive operative treatment for primary breast cancer. MATERIALS AND METHODS: A retrospective, Institutional Review Board-approved query of our single-institution National Comprehensive Cancer Network database was performed for patients undergoing ALND who developed subsequent RNR. All patients were treated from 1999 to 2009. A detailed chart review was performed and clinical, pathologic, treatment, and outcome data were collected. RESULTS: A total of 1614 patients had an ALND for initial staging; 14/1614 (0.9%) patients had RNR. Two other patients had contralateral breast/axillary recurrences and were excluded. The mean age at diagnosis for the sample group was 52.7 y (range 34-77); mean follow-up time was 47.1 mo (range 12.6-114.6). The median number of nodes for ALND was 16 (range 8-27). The median number of positive nodes was 2.5 (range 0-7). Nine (64.3%) cases were estrogen receptor/progesterone receptor negative. Twelve (85.7%) patients had axillary recurrences, and six of 12 (50.0%) had concurrent chest wall lesions. Twelve patients (85.7%) had distant metastases; nine of 12 (75.0%) died; two were lost to follow-up. Mean time from RNR to distant recurrence was 6.0 mo (range 0-29.3 mo). CONCLUSIONS: RNR after ALND is rare but a harbinger of poor outcome. This is apparent regardless of treatment used for initial disease or recurrence. Specifically, RNR after primary ALND is related to increased risk of mortality and distant metastatic disease.

Pathologic tumor response of invasive lobular carcinoma to neo-adjuvant chemotherapy.

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.

Teaching medical students how to break bad news with standardized patients.

One of the biggest challenges that a physician will face is conveying difficult news (CDN) to a patient.The ability to provide this information may either strengthen or destroy the patient­physician relationship. Despite the importance of this skill, formal education for medical students has been limited. To improve upon skill building in the medical student experience, fourth year medical students(on their oncology clerkship) spent 3 hours partaking ina CDN session. During this session, each student had a videotaped encounter with a standardized patient, followed by a small group discussion and review of the tape with other students and a clinician. We evaluated the experience with pre- and post-questionnaires assessing overall knowledge,satisfaction, and specific components of the curriculum. The objective of this study was to review our institution's educational program focused on teaching techniques for CDN.

Effect of Microporous Polysaccharide Particles in Patients Undergoing Mastectomy.

BACKGROUND: Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation. PATIENTS AND METHODS: A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables. RESULTS: One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001). CONCLUSION: Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Selective application of routine preoperative axillary ultrasonography reduces costs for invasive breast cancers.

PURPOSE: Preoperative axillary sonography with fine needle aspiration (FNA) in patients with invasive breast cancer identifies patients with nodal metastasis who can be spared further surgery. Indiscriminate use of the diagnostic modality can increase costs and yield inaccurate results. We evaluate the costs associated with the use of highly sensitive axillary ultrasonography in patients with stage ≥T2 tumors. PATIENTS AND METHODS: We constructed a decision analysis tree using TreeAge Pro 2009 software comparing direct hospital charges between patients with and without routine use of axillary ultrasound. Base case estimates were derived from our institutional data and compared with those derived from the literature. One- and two-way sensitivity analyses were performed to check the validity of our inferences. RESULTS: We found that, for the base case estimate with 35% lymph node positivity in stage ≥T2 tumors and sensitivity of the axillary ultrasound set at 86% with a specificity of 40%, the strategy to perform preoperative axillary ultrasound yielded rollback costs of $15,215, compared with $15,940 for surgery plus sentinel lymph node biopsy (cost difference, $725 per patient favoring axillary ultrasound). On two-way sensitivity analysis, the cost benefit for axillary ultrasound was not seen in patients with a low risk for nodal metastasis. CONCLUSION: The adoption of routine preoperative axillary sonography with FNA is a lower-cost strategy than conventional strategies in patients with stage ≥T2 invasive breast cancer.

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.

Axillary recurrence rate following negative sentinel node biopsy for invasive breast cancer: long-term follow-up.

OBJECTIVE: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the definitive nodal staging procedure for breast cancer. SLN biopsy has been proven to cause less morbidity and be more cost effective than complete ALND. Short-term follow-up has shown that lymphatic mapping and SLN have a low false-negative rate, but there is limited data demonstrating long-term outcomes within a large consecutive series of patients. METHODS: Retrospective review of a prospective database of breast cancer patients at our institution was performed. The initial mapping of 1,530 patients with invasive breast cancer who demonstrated a negative sentinel node biopsy and no axillary dissection between January 1995 and June 2003 were collated and reviewed to achieve a long-term follow-up. These 1,530 patients were reviewed for follow-up time, local recurrences, distant metastases, and survival. RESULTS: 1,530 consecutively mapped invasive breast cancer patients had a negative SLN biopsy and no ALND. The mean invasive tumor size was 1.40 cm. Of 1,530 patients, 73% (1,121) underwent lumpectomy and 27% (409) underwent mastectomy. Mean follow-up was 4.92 years (range 0-12.0 years). There have been 4 (0.26%) patients presenting with local axillary recurrences, 54 (3.53%) patients presenting with local recurrences in the ipsilateral breast/chest wall, and 24 (1.57%) presenting with distant metastases. CONCLUSION: These data confirm that SLN biopsy is an effective and safe alternative to ALND for detection of nodal metastases in patients with invasive breast cancer and should be used as the standard tool for nodal staging.