Surgical Treatment for Primary Lymphedema: A Systematic Review of the Literature.

This is a retrospective review of surgical management for primary lymphedema. Data were extracted from 55 articles from PubMed MEDLINE, Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials between the database inception and December 2022 to evaluate the outcomes of lymphaticovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT), and outcomes of soft tissue extirpative procedures such as suction-assisted lipectomy (SAL) and extensive soft tissue excision. Data from 485 patients were compiled; these were treated with LVA ( n = 177), VLNT ( n = 82), SAL ( n = 102), and excisional procedures ( n = 124). Improvement of the lower extremity lymphedema index, the quality of life (QoL), and lymphedema symptoms were reported in most studies. LVA and VLNT led to symptomatic relief and improved QoL, reaching up to 90 and 61% average circumference reduction, respectively. Cellulitis reduction was reported in 25 and 40% of LVA and VLNT papers, respectively. The extirpative procedures, used mainly in patients with advanced disease, also led to clinical improvement from the volume reduction, as well as reduced incidence of cellulitis, although with poor cosmetic results; 87.5% of these reports recommended postoperative compression garments. The overall complication rates were 1% for LVA, 13% for VLNT, 11% for SAL, and 46% for extirpative procedures. Altogether, only one paper lacked some kind of improvement. Primary lymphedema is amenable to surgical treatment; the currently performed procedures have effectively improved symptoms and QoL in this population. Complication rates are related to the invasiveness of the chosen procedure.

Single versus Double Drainage for Immediate Two-Stage Implant-Based Breast Reconstruction: A Propensity Score-Matched Analysis.

BACKGROUND: Reports evaluating plastic surgeons' practices indicate there are conflicting trends regarding the use of one or two drains for implant-based breast reconstruction (IBBR). Our study aimed to perform a matched cohort analysis to examine the postoperative outcomes and complications of immediate IBBR with tissue expander (TE) using two drains versus a single drain. METHODS: A propensity score-matched analysis (nearest neighbor, 1:1 matching) of immediate reconstructions using two versus one drain was conducted. Female patients undergoing immediate two-stage IBBR with TEs between January 2011 and May 2021 were included. The covariables were as follows: BMI, mastectomy weight, lymph node surgery, TE surface, plane of reconstruction, use of acellular dermal matrix products, fluorescence imaging use, and intraoperative TE volume. RESULTS: After matching using propensity scores, 192 reconstructions were included in the final analysis: 96 in each group. The rate of 30-day complications and overall complications during the first phase of IBBR were comparable between groups. The time for drain removal, time to initiate and finalize expansions, and time for TE-to-implant exchange were comparable between groups. Diabetes (OR 3.74, p = 0.025) and an increased estimated blood loss (OR 1.004, p = 0.01) were the only independent predictors for seroma formation. CONCLUSION: In this matched cohort analysis evaluating the role of one versus two drains for two-stage IBBR, we found a comparable rate of complications and surgical outcomes between the two cohorts. Using two drains for immediate IBBR needs to be tailored depending on intraoperative findings. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Two-Stage Implant-Based Breast Reconstruction Using Intraoperative Fluorescence Imaging: A Propensity Score-Matched Analysis.

BACKGROUND: Limited comparability between study groups can generate significant selection and observer bias when evaluating the efficacy of the SPY system and fluorescence imaging for implant-based breast reconstruction. In this study, the authors compared the surgical outcomes and complications during the first stage of reconstruction between reconstructions evaluated intraoperatively with fluorescence imaging using the SPY system and clinical assessment using a matched analysis. METHODS: The authors conducted a retrospective review of patients undergoing total mastectomy and immediate two-stage implant-based breast reconstruction with TEs from January of 2011 to December of 2020. The rate of complication, time for TE-to-implant exchange, and time to start radiotherapy were compared between groups (intraoperative fluorescence imaging versus clinical assessment) using a propensity score-matched analysis. RESULTS: After propensity score matching, 198 reconstructions were evaluated. There were 99 reconstructions in each group. The median time for TE-to-implant exchange (140 days versus 185 days; P = 0.476) and time to initiate adjuvant radiotherapy (144 days versus 98 days; P = 0.199) were comparable between groups. The 30-day rate of wound-related complications (21% versus 9%; P = 0.017) and 30-day rate of wound-related unplanned interventions were significantly higher in reconstructions evaluated with clinical assessment when compared with the SPY system (16% versus 5%; P = 0.011). A higher 30-day rate of seroma (19% versus 14%; P = 0.041) and hematoma (8% versus 0%; P = 0.004) were found in reconstructions assessed intraoperatively with the SPY system. CONCLUSIONS: After matching, reconstructions evaluated with fluorescence imaging exhibited a lower incidence of early wound-related complications when compared with clinical evaluation alone. Nonetheless, the Wise pattern for mastectomy was found to be the only independent predictor associated with early wound-related complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

HER2 categorical changes after neoadjuvant chemotherapy: A study of 192 matched breast cancers with the inclusion of HER2-Low category.

Understanding the changes of HER2 expression after neoadjuvant chemotherapy (NAC) in breast cancer (BC) is more important than ever, since it may allow more patients to access the effective therapeutic drugs targeting HER2-low BC. 192 matched pre- and post-NAC BCs were analyzed. HER2 immunohistochemistry (IHC) was re-evaluated with consensus according to the current ASCO/CAP guidelines. Tumors were categorized into HER2-0 (IHC0+), HER2-low (IHC1+ or IHC2+/ISH-) and HER2-positive (IHC3+ or IHC2+/ISH+) subgroups. 55 (28.6 %) patients achieved pathologic complete response (pCR). HER2-low BC accounted for 75/192 (39.1 %) baseline tumors, and 48/133 (36.1 %) residual tumors. In the non-pCR cohort, 53 (39.9 %) patients had HER2 categorical change after NAC, most commonly converting from HER2-low to HER2-0 (20.3 %, n = 27). Among patients with residual tumor, 25.6 % (11/43) of patients with baseline HER2-0 expression experienced a categorical change to HER2-low after NAC, significantly higher (p < 0.05) in the hormone receptor (HR) positive (9/23, 39.1 %) compared to the HR negative tumors (10 %, 2/20). Exploratory analysis failed to reveal a statistically significant difference in disease free survival and overall survival in non-pCR patients with or without HER2 change. Our results suggest that a substantial number of patients may experience HER2 categorical change after NAC, supporting re-testing of HER2 status in post-NAC residual tumors. Retesting HER2 status may be particularly important for evaluating post-NAC HER2-low status, in order to better assess which patients will more likely benefit from therapeutic drugs targeting HER2-low BC.

Wise Pattern versus Transverse Pattern Mastectomy in Two-Stage Implant-Based Breast Reconstruction: A Propensity Score-Matched Analysis.

BACKGROUND: The Wise pattern adapted to mastectomy incisions has become a valuable asset for breast reconstruction in patients with large and ptotic breasts. The authors compared the time for exchange, time to initiate postmastectomy radiotherapy, and complication rates between Wise pattern and transverse incision pattern reconstructions. METHODS: Records of patients who underwent immediate, two-stage, implant-based breast reconstruction (IBBR) between January of 2011 and December of 2020 were retrospectively reviewed. Two cohorts were compared according to the incision pattern: Wise pattern versus transverse incision pattern. Complications were compared after propensity score matching. RESULTS: The authors initially analyzed 393 two-stage immediate IBBRs in 239 patients [91 IBBRs (23.2%) in the Wise pattern group and 302 (76.8%) in the transverse pattern group]. Expansion time (53 days versus 50 days, P = 0.9), time for tissue expander-to-implant exchange (154 versus 175 days, P = 0.547), and time to initiate postmastectomy radiotherapy (144 days versus 126 days, P = 0.616) were not different between groups. Before propensity score matching, the 30-day rate of wound-related complications (32% versus 10%, P < 0.001) and the 30-day rate of wound complications requiring excision/débridement and closure procedures (20% versus 7%, P < 0.001) were significantly higher in the Wise pattern group. After propensity score matching, the 30-day rate of wound complications was persistently higher (25% versus 10%, P = 0.03) in the Wise pattern group. CONCLUSIONS: The Wise pattern mastectomy independently increases the incidence of wound-related complications versus only transverse patterns during two-stage IBBR, even after propensity score matching. Delayed tissue expander placement may improve the safety profile of this procedure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The Rochester Modified Magee Algorithm (RoMMa): An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX® Testing.

INTRODUCTION: Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER+, HER2- breast cancer (BC) patients, with Oncotype DX® (ODX) emerging as the genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER+, HER2- BC patients to ODX testing. The Magee equationsTM use standard histopathologic data in a set of multivariable models to estimate the ODX recurrence score. Our group published the first outcome data in 2019 on the Magee equationsTM, using a modification of the Magee equationsTM combined with an algorithmic approach-the Rochester Modified Magee algorithm (RoMMa). There has since been limited published outcome data on the Magee equationsTM. We present additional outcome data, with considerations of the TAILORx risk-stratification recommendations. METHODS: 355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy. RESULTS: There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence (p > 0.05) or log-rank test (p > 0.05). Using the RoMMa, we estimate that at least 17% of individuals can safely avoid ODX testing. CONCLUSION: Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equationsTM. The RoMMa can be helpful in the initial clinical risk-assessment and risk-stratification of BC patients, providing increased opportunities for cost savings in the health care system, and for clinical risk-assessment and risk-stratification in less-developed geographies where multigene testing might not be available.

Subpectoral versus prepectoral two-stage breast reconstruction: A propensity score-matched analysis of 30-day morbidity and long-term outcomes.

BACKGROUND: Approximately 80% of patients undergoing total mastectomy in the US opt for implant-based breast reconstruction (IBBR). A two-stage reconstruction with tissue expander (TE) remains the most common technique. Since the implementation of ADMs, a prepectoral approach has gained popularity and is becoming the standard of care. Herein, we compared the surgical and postoperative outcomes of prepectoral versus subpectoral two-stage IBBR. METHODS: A retrospective chart review was performed between January 2011 and December 2020. We included female patients undergoing immediate two-stage IBBR. The primary outcomes of this study were to compare the 30-day morbidity and the overall rate of complications during the first and second stages of reconstruction, and to compare the time to initiate postmastectomy radiotherapy (PMRT). Propensity score matching was implemented. RESULTS: After matching, 154 reconstructions were analyzed, 77 in each group. The two matched groups exhibited comparable (p > 0.05) characteristics for all analyzed demographic and intraoperative independent variables. Reconstructions in the prepectoral group had a shortened median time for drain removal (13-days vs. 15-days, p = 0.001). The intraoperative expansion volumes were higher in the prepectoral group (300 ml versus 200 ml, p = 0.025). The 30-day morbidity and first- and second-stage complication rates were not significantly different between groups. The time to start postmastectomy radiation therapy (PMRT) was not significantly different between groups (134-days versus 126.5-days, p = 0.58). CONCLUSION: Prepectoral and subpectoral TE placement had comparable complication rates during the first and second stages of IBBR. Timing for TE-to-Implant exchange and initiation of PMRT were comparable between the two approaches.

Simultaneous Fat Grafting During Tissue Expander-to-Implant Exchange: A Propensity Score-Matched Analysis.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most common technique for breast reconstruction. The primary resource for correcting deformities, once patients have achieved an adequate volume with two-stage IBBR, is autologous fat grafting. We compared the surgical outcomes of simultaneous fat grafting during TE-to-implant exchange (SFG + TtIE) versus no fat grafting during TE-to-implant exchange (No-FGX). METHODS: A retrospective review was performed of all consecutive patients undergoing two-stage implant-based breast reconstruction with TE from January 2011 to December 2020. Propensity score matching was implemented to optimize comparability. The control group did not receive fat grafting at the time of TE-to-implant exchange. RESULTS: After propensity score matching, 196 reconstructions were evaluated, 98 in each group. Reconstructions in the SFG + TtIE received larger implants during exchange in comparison with the No-FGX group (539 ± 135.1-cc versus 495.97 ± 148-cc, p=0.035). The mean volume of fat lipoinjected during TE-to-implant exchange in the SFG + TtIE group was 88.79 ± 41-ml. A higher proportion of reconstructions in the SFG + TtIE group underwent additional fat grafting after exchange versus the No-FGX group (19% versus 9%, p = 0.041). After propensity score matching, only the rate of fat necrosis after exchange was significantly higher in the SFG + TtIE group (10% versus 2%, p = 0.017). The rate of breast cancer recurrence (3% versus 5%, p = 1.00) was comparable between the groups. CONCLUSION: SFG + TtIE is a safe procedure to improve the envelope of reconstructed breasts during two-stage IBBR. SFG + TtIE does not increase the rate of periprosthetic infection or wound-related complication versus no fat grafting during TE-to-implant exchange, but increases the rate of fat necrosis. LEVEL OF EVIDENCE III: Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Detailed Morphologic Evaluation of Breast Papillary Lesions on Core Biopsy Is Critical for Accurate Classification and Clinical Management: The Experience of an Academic Institute.

BACKGROUND: Distinguishing between a breast intraductal papilloma and a papillary lesion with atypia or malignancy can be very challenging on core biopsy. There has been a long ongoing debate over whether or not it is necessary for breast papillary lesions diagnosed on core biopsies to be surgically excised, and the upgrading rate after excision varies. METHOD AND/OR RESULT: This study was carried out in a subspecialized academic pathology department, with well-formed criteria established among the faculty for the categorization of breast papillary lesions, with emphasis on the morphology evaluation of cellular features. A total of 320 breast core biopsies with follow-up excisions were identified. Of these, 286 cases had concordant results between the biopsy and excision, giving a concordance rate of 89.4%, with 98% concordance (143/146) in benign papilloma, 100% (111/111) in papillary carcinoma, and 51% (32/63) in papilloma with atypia. Of the upgraded cases, two were upgraded from benign to atypical, 11 from atypia to malignancy, and only one from benign to malignant. The overall average upgrading rate was 4.4% (14/320), with the critical upgrading (from benign to atypia or malignancy) rate of 0.94% (3/320). Downgrading was only identified in the group of papilloma with atypia, with 20 of 63 cases downgraded to benign papilloma on excision. CONCLUSION: Our study indicates that surgical excision may not be necessary for all papillary lesions after detailed evaluation of the morphology on core biopsies. Assessing the morphological features of the epithelial cells is critical for the accurate classification and clinical management of papillary lesions.

Intraoperative neurophysiologic monitoring prevented iatrogenic spinal cord injury during robotic-assisted transabdominal adrenalectomy: a case report.

Cervical spondylotic myelopathy (CSM) is the most common disease of the cervical spinal cord in patients older than 55 and is characterized by an initial asymptomatic period followed by progressive neurological deficit from degenerative changes of the cervical vertebrae. These changes cause compression and vascular compromise to the cervical spinal cord. Because there are no pathognomonic symptoms, its diagnosis is commonly delayed. Herein we report the first case of the use of IONM during a transabdominal adrenalectomy in a patient with CSM, which prevented an iatrogenic spinal cord injury (SCI). The patient is a 74-year-old male with what was proven later as cervical spinal stenosis who presented for robotic-assisted transabdominal adrenalectomy. When positioned supine on the operating table, he exhibited upper and lower extremity neurological symptoms, prompting awake fiberoptic intubation and the use of IONM secondary to suspicion for CSM. After being positioned into lateral decubitus, IONM showed a loss of transcranial motor evoked potentials (TcMEP) and attenuated somatosensory evoked potentials (SSEP) from the right lower extremities and the procedure was aborted and the patient returned supine. TcMEPs returned to baseline, but SSEPs remained attenuated. The patient exhibited normal movement and sensation in post-anesthesia care. A high index of suspicion for CSM is required for older patients, as early diagnosis allows for spinal surgery treatment before acute worsening during anesthesia or non-spinal surgery. Furthermore, a low threshold for the use of IONM in patients with a high likelihood of CSM who require a non-spinal surgery can successfully prevent iatrogenic SCI.

Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.

The skyrocketing cost of health-care demands that we question when to use multigene assay testing in the planning of treatment for breast cancer patients. A previously published algorithmic model gave recommendations for which cases to send out for Oncotype DX® (ODX) testing. This study is a multi-institutional validation of that algorithmic model in 620 additional estrogen receptor positive breast cancer cases, with outcome data on 310 cases, named in this study as the Rochester Modified Magee algorithm (RoMMa). RoMMa correctly predicted 85% (140/164) and 100% (17/17) of cases to have a low- or high-risk ODX recurrence score, respectively, consistent with the original publication. Applying our own risk stratification criteria, in patients who received appropriate hormonal therapy, only one of the 45 (2.0%) patients classified as low risk by our original algorithm have been associated with a breast cancer recurrence over 5-10 years of follow-up. Eight of 116 (7.0%) patients classified as low risk by ODX have been associated with a breast cancer recurrence with up to 11 years of follow-up. In addition, 524 of 537 (98%) cases from our total population (n = 903) with an average modified Magee score ≤18 had an ODX recurrence score <26. Patients with an average modified Magee score ≤18 or >30 may not need to be sent out for ODX testing. By avoiding these cases sending out for ODX testing, the potential cost savings to the health-care system in 2018 are estimated to have been over $100,000,000.

Comparison of single-injection ultrasound-guided approach versus multilevel landmark-based approach for thoracic paravertebral blockade for breast tumor resection: a retrospective analysis at a tertiary care teaching institution.

BACKGROUND: The role of thoracic paravertebral blockade (TPVB) in decreasing opioid requirements in breast cancer surgery is well documented, and there is mounting evidence that this may improve survival and reduce the rate of malignancy recurrence following cancer-related mastectomy. We compared the two techniques currently in use at our institution, the anatomic landmark-guided (ALG) multilevel versus an ultrasound-guided (USG) single injection, to determine an optimal technique. METHODS: We retrospectively reviewed records of patients who received TPVB from January 2013 to December 2014. Perioperative opioid use, post anesthesia care unit (PACU) pain scores and length of stay, block performance, and complications were compared between the two groups. RESULTS: We found no statistical difference between the two approaches in the studied outcomes. We did find that the number of times attending physicians in the ALG group took over the blocks from residents was significantly greater than that of the USG group (p=0.006) and more local anesthetic was used in the USG group (p=0.04). CONCLUSION: This study compared the ALG approach with the USG approach for patients undergoing mastectomy for breast cancer. Based on our observations, an attending physician is more likely to take over an ALG injection, and more local anesthetic is administered during USG single injection.

p53 alteration in morphologically normal/benign breast luminal cells in BRCA carriers with or without history of breast cancer.

Germline mutations in BRCA genes have been shown to predispose patients to breast cancer. Studies have suggested that p53 alteration is a necessary step in tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in morphologically normal/benign breast luminal cells in sporadic breast cancer patients, the so-called breast p53 signature. Here, we studied p53 status in 66 BRCA1/2 carriers' breasts: 29 patients with breast carcinoma (2 patients with bilateral breast carcinomas) and 37 without. Seven of the 12 (58%) triple-negative breast carcinomas in BRCA carriers were positive for p53 alteration (immunohistochemical stain and/or sequencing), the same frequency as in sporadic triple-negative breast carcinomas. Focal p53 positivity in adjacent normal/benign luminal cells was identified in 4 of the 7 cases with p53-positive carcinomas but not in breasts with p53-negative carcinomas, indicating that p53 positivity in normal/benign breast luminal cells is not a random event. Furthermore, in BRCA carriers' prophylactic mastectomies, 12 of the 94 (12.77%) breasts had focal p53 positivity in normal/benign luminal cells, with 2 cases in bilateral breasts, significantly higher than in previously studied mammoplasty specimens (0%). Our study suggests that germline BRCA gene mutations could result in genomic instability and an elevated gene mutation rate (such as the p53 gene) in breast luminal cells compared with the general population, predisposing BRCA carriers to develop p53-positive/triple-negative breast carcinomas.

p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma.

Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score.

Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P<0.0001). 100% of cases with an average modified Magee recurrence score>30 (n=8) or an average modified Magee recurrence score<9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS<6) with an ER and PR≥150, and a Ki-67<10%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.

Pathological features and clinical outcomes of breast cancer according to levels of oestrogen receptor expression.

AIMS: Historically, nuclear staining of ≥10% of invasive tumour cells has been used for oestrogen receptor (ER) positivity. In 2010, ASCO/CAP guidelines recommended the cut-off value be changed to nuclear staining of ≥1%. This study will analyse the relationships between levels of ER expression and clinicopathological features and clinical outcomes, with an emphasis on the ER 1-10% subgroup. METHODS AND RESULTS: We analysed clinicopathological features in five subgroups based on ER expression levels in 1700 consecutive invasive breast cancer patients diagnosed and treated at our institution between 2000 and 2011. Of the cases, 24% had ER expression <1%, 2% were ER 1-10%, 5% were 11-50%, 5% were 51-70% and 64% were 71-100%. We observed four subgroups of patient cohorts (ER <1%, 1-10%, 11-70% and 71-100%) that were unique in Nottingham grade, nuclear grade, progesterone receptor expression and disease-free survival. Of the 341 patients with follow-up data, we found no significant differences in pathological features between patients in the ER 11-50% and ER 51-70% subgroups. CONCLUSION: These data support the important role of ER in breast cancer, and the importance of accurate testing and quantitative reporting for ER. Tumours with ER 1-10% are not common, and further studies are needed to understand more clearly this subgroup of breast cancer.

Dedicated Breast CT: Feasibility for Monitoring Neoadjuvant Chemotherapy Treatment.

OBJECTIVES: In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated. MATERIALS AND METHODS: Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points - pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologist's segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined. RESULTS: Tumor volumes from automated and radiologist's segmentations were correlated (Pearson's r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%. CONCLUSIONS: This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.

Folate receptor α associated with triple-negative breast cancer and poor prognosis.

CONTEXT: Folate receptor α (FRA) has been shown to be selectively expressed in several types of human cancer, including breast cancer. Currently, several FRA target therapies are under intensive study. OBJECTIVE: To investigate the expression pattern of FRA in a large cohort of patients with breast cancer and analyze its relationship with different clinicopathologic features, with expression of several key biomarkers, and with clinical outcome. DESIGN: Four hundred forty-seven cases of infiltrating ductal carcinoma diagnosed between 1997 and 2008 at the University of Rochester Medical Center were identified and reviewed, and 25 blocks of tissue microassays were constructed. The association between expression of FRA and clinicopathologic features; expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67; and clinical outcome of these tumors were evaluated. RESULTS: The expression of FRA was significantly associated with tumors with high histologic grade, higher nodal stages, ER/PR negativity, and high proliferative activity (Ki-67 ≥ 15%), and was independent of HER2/neu overexpression. In all, 74% of ER/PR-negative and 80% of triple-negative breast cancers expressed FRA. The expression of FRA was significantly associated with a worse disease-free survival. CONCLUSIONS: Our data demonstrate that a significant subgroup of ER/PR-negative and triple-negative breast cancers express FRA, and its expression is associated with worse clinical outcome.

The association between breast cancer prognostic indicators and serum 25-OH vitamin D levels.

BACKGROUND: Studies show that women with low vitamin D levels have an increased risk of breast cancer (BC) incidence and mortality, but there is a lack of research examining vitamin D levels and prognostic variables in BC patients. The aim of this study is to examine 25-OH vitamin D levels between BC cases and controls and by prognostic indicators among BC cases. METHODS: 25-OH vitamin D levels were collected from 194 women who underwent BC surgery and 194 cancer-free (CF) controls at the University of Rochester between January 2009 and October 2010. Mean 25-OH vitamin D levels and odds ratios (OR) were calculated by case/control status for the overall cohort and by prognostic indicators (invasiveness, ER status, triple-negative status, Oncotype DX score, molecular phenotype) for BC cases. RESULTS: BC cases had significantly lower 25-OH vitamin D levels than CF controls (BC: 32.7 ng/mL vs. CF: 37.4 ng/mL; P = .02). In case-series analyses, women with suboptimal 25-OH vitamin D concentrations (<32 ng/mL) had significantly higher odds of having ER- (OR = 2.59, 95% confidence interval [95% CI] = 1.08-6.23) and triple-negative cancer (OR = 3.15, 95% CI = 1.05-9.49) than those with optimal 25-OH D concentrations. Women with basal-like phenotype had lower 25-OH vitamin D levels than women luminal A phenotype (basal-like: 24.2 ng/mL vs. luminal A: 32.8 ng/mL; P = 0.04). CONCLUSIONS: BC patients with a more aggressive molecular phenotype (basal-like) and worse prognostic indicators (ER- and triple-negative) had lower mean 25-OH vitamin D levels. Further research is needed to elucidate the biological relationship between vitamin D and BC progression.

Predictors of nipple-areolar complex involvement by breast carcinoma: histopathologic analysis of 787 consecutive therapeutic mastectomy specimens.

BACKGROUND: Breast-conserving therapy (BCT) is an accepted therapeutic option for most breast cancer patients. However, mastectomy is still performed in 30-50% of patients undergoing surgeries. There is increasing interest in preservation of the nipple and/or areola in hopes of achieving improved cosmetic and functional outcomes; however, the oncologic safety of nipple-areolar complex (NAC) preservation is a major concern. We sought to identify the predictive factors for NAC involvement in breast cancer patients. METHODS: We analyzed the rates and types of NAC involvement by breast carcinoma, and its association with other clinicopathologic features of the tumors in 787 consecutive therapeutic mastectomies performed at our institution between 1997 and 2009. RESULTS: Among these, 75 cases (9.5%) demonstrated NAC involvement. Only 21 (28%) of 75 of cases with NAC involvement could be identified grossly by inspection of the surgical specimen (seven of these had been clinically identified). NAC involvement was most significantly associated with tumors located in all four quadrants (P<0.0001), tumors>5 cm in size (P=0.0014 for invasive carcinoma and P=0.0032 for in-situ carcinoma), grade 3 tumors (P=0.0192), tumors with higher nuclear grades (P=0.0184), and tumors with HER2 overexpression (P=0.0137). CONCLUSIONS: On the basis of our findings, we have developed a mathematical model that is based on the extent and location of the tumor, HER2 expression, and nuclear grade that predicts the probability of NAC involvement by breast cancer. This model may aid in preoperative planning in selecting appropriate surgical procedures based on an individual patient's relative risk of NAC involvement.