A Comprehensive Assessment of Radial Scars on Core Needle Biopsy in Patients with or without Breast Cancer: Upgrade Rate and Implications on Management.

BACKGROUND: Radial scars/radial sclerosing lesions (RS) are benign breast lesions identified on core needle biopsy (CNB) which can upgrade to malignancy at excision. There is limited data on RS detection and upgrade rates with more sensitive imaging such as magnetic resonance imaging (MRI) and none during their detection for breast cancer workup and its implication on patient treatment decisions. METHODS: A retrospective institutional study of RS diagnosed on CNB between January 2008 and December 2017 was conducted. Clinicopathologic and radiologic features of RS, patient treatment decisions, upgrade rates and long-term follow-up were examined. RESULTS: We identified 133 patients with RS on CNB, of whom 106 opted for surgery for an upgrade rate to malignancy of 1.9%, 2 patients. Radial scar was diagnosed on mammogram in 60%, MRI in 25% and ultrasound in 15% of patients. In this cohort, 32 patients had their RS detected during breast cancer workup (coexistent group) and they were more likely to have their radial scar detected by MRI (60% vs. 14%, P < .001) and undergo more extensive surgery (94% vs. 75%, P = .02). Among the 27 patients electing observation of their RS, only one (3.7%) developed breast cancer. CONCLUSIONS: Our results show an extremely low upgrade rate to malignancy of RS, regardless if there is coexisting breast cancer elsewhere. Despite this, RS still prompted more extensive surgical excisions. The findings do not support excision of RS even among breast cancer patients when identified at a separate site from their cancer.

Shaves off the Cavity or Specimen in Lumpectomy for Breast Cancer.

INTRODUCTION: Re-excision for positive margins (margins where tumor is positive) after breast conserving surgery (BCS) is common and burdensome for breast cancer patients. Routine shave margins can reduce positive margins and re-excision rates. Cavity shaving margin (CSM) removes margins from the lumpectomy cavity edges, whereas specimen shave margin (SSM) requires ex vivo removal of margins from the resected specimen. METHODS: We assessed breast cancer patients undergoing BCS who received CSM or SSM procedures from 2017 to 2019. CSM and SSM techniques were compared by analyzing positive rates of primary and final shaved margins, re-excision rates, and tissue volumes removed. RESULTS: Of 116 patients included in this study, 57 underwent CSM and 59 underwent SSM. Primary margins were positive or close in 19 CSM patients and 21 SSM patients (33% versus 36%; P = 0.798). Seventeen CSM patients had a tumor in shaved margin specimens, compared to four patients for SSM (30% versus 7%; P < 0.001); however, final shave margins were similar (5% versus 5%; P = 0.983). Volumes of shave specimens were higher with SSM (40.7 versus 13.4 cm3; P < 0.001), but there was no significant difference in the total volume removed (146.8 versus 134.4 cm3; P = 0.540). For tumors 2 cm or larger, the total volume removed (140 versus 206 cm3; P = 0.432) and rates of final margin positivity (7.5% versus 0%; P = 0.684) were similar for both techniques. CONCLUSIONS: CSM and SSM are effective techniques for achieving low re-excision rates. Our findings suggest that surgeons performing either CSM or SSM may maintain operative preferences and achieve similar results.

Hormone replacement therapy after breast cancer: Yes, No or maybe?

Over nine million breast cancer survivors worldwide suffer compromised quality of life attributable to estrogen depletion related symptoms of menopause and side effects of cancer therapy. Hormone Replacement Therapy (HRT) is very effective in managing these symptoms in general population and in breast cancer survivors. However, the concern of breast cancer recurrence as a result of HRT use keeps many oncologists from using this approach in symptom management. Evidence from randomized trials, observational studies and met-analyses on the impact of HRT use on breast cancer recurrence and survival remains controversial. Climacteric symptoms in breast cancer survivors should be delineated for type and severity for methodical management. Lifestyle modifications are effective for mild symptoms, while non-hormonal pharmaceutical approaches can be used as second-line therapy for control of hot flashes, vulvo-vaginal atrophy, arthralgia, mood swings, sleep disturbance, and depression. Evidence does not conclusively render HRT, as a contraindicated approach for these patients; informed consent and shared-decision-making is a reasonable approach for HRT use in symptomatic breast cancer survivors.

Changing practice patterns of adjuvant radiation among elderly women with early stage breast cancer in the United States from 2004 to 2014.

Randomized controlled trials (RCTs) have challenged the need for routine radiation therapy (RT) in women ≥ age 70 with favorable early stage breast cancer (BC) due to modest improvement in local control and no survival benefit. We studied practice patterns in RT among elderly women in the United States. We analyzed data from the National Cancer Database (NCDB) of women ≥age 70 diagnosed with T1 or T2 and N0 invasive BC treated with breast conservation surgery (BCS) between 2004 and 2014. Patients were divided into four groups: (1) no RT, (2) partial breast irradiation (PBI); (3) hypofractionation (HF); and (4) conventional whole breast RT (CWBI). Univariable and multivariable analyses (MVA) were performed to compare characteristics among the four RT groups. A subgroup analysis of women with favorable disease (T1N0 ER + HER2-) was also performed with similar statistical comparisons. Of the 66,126 meeting eligibility, 9,570 (14.5%) had PBI, 16,340 (24.7%) had HF, and 40,117 (60.7%) had CWBI. Only 99 patients (0.15%) had RT omitted. Omission of RT increased marginally from 0.04% in 2004 to 0.24% in 2014. MVA identified older age (OR 1.18, CI 1.08-1.28), more comorbidities (Charlson-Deyo Score of 1) (OR 3.36, CI 1.29-8.72), and no hormone therapy (OR 22.07, CI 5.79-84.07) as more likely to have RT omitted. The use of HF increased from 3.9% to 47.0%, P < .001 with a concomitant decrease in CWBI from 88% to 41%, P < .001. MVA identified older age, treatment location, and omission of chemotherapy as associated with HF. No significant differences from the larger cohort were found among the T1N0 subgroup analysis. Despite RCT evidence, omission of RT was rare in the United States, suggesting that more effective outreach methods to disseminate clinical guideline information may be needed.

Impact of Neoadjuvant Chemotherapy on Breast Cancer Subtype: Does Subtype Change and, if so, How? : IHC Profile and Neoadjuvant Chemotherapy.

BACKGROUND: Breast cancer subtype, as determined by the expression of estrogen receptor (ER) and progesterone receptor (PR), together defined as hormone receptor (HR) status, and the HER2/neu receptor (HER2), is important in predicting prognosis and guiding therapy. Knowledge regarding how tumors evolve during treatment and whether subtype is influenced by neoadjuvant chemotherapy (nCT) is limited. The purpose of this study was to compare the HR and HER2 status between core needle biopsy and residual tumor after surgery of breast cancer patients treated with nCT and to evaluate the impact of status change on therapeutic management. METHODS: After institutional review board approval, we performed a retrospective review of all patients with a diagnosis of breast cancer who received nCT and had their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype between January 2009 and December 2014 at our institution. Immunohistochemistry (IHC) of ER, PR, HER2, and fluorescence in situ hybridization for HER2 expression, when indicated, was performed using identical technique and measured by a single pathologist who specializes in breast pathology. Pre- and post-nCT subtype was cross-tabulated to assess change. Standard diagnostic metrics were computed. RESULTS: Fifty-two patients with 54 cancers were identified to have their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype in identical fashion. There was a complete pathologic response after nCT in 23 cancers (42.6%). Residual disease was noted in 31 cancers (57.4%). Five of these (16.1%) had a change in tumor subtype, of which four changes were based on IHC. HR status changed from positive to negative in two cases and from negative to positive in one case. HER2 status changed from positive to negative in one case and from negative to positive in one case. Subtype change led to treatment change in all five cases, with either the addition or discontinuation of adjuvant therapies. CONCLUSIONS: Patients with breast cancer may experience alterations in their tumor subtype after nCT. At our institution, this led to a change in adjuvant treatment in 100% of such patients. This implies that retesting receptor status of residual tumors after nCT should be routinely performed to tailor adjuvant therapy after nCT.

Reoperative Sentinel Lymph Node Biopsy is Feasible for Locally Recurrent Breast Cancer, But is it Worthwhile?

INTRODUCTION: Reoperative sentinel lymph node biopsy (SLNB) is feasible in patients with local recurrence (LR) of invasive breast cancer but it remains unclear if this procedure affects either treatment or outcome. In this study, we ask whether axillary restaging (vs. none) at the time of LR affects the rate of subsequent events: axillary failure (AF), non-axillary recurrence (NAR), distant metastasis, or death. METHODS: We queried our institutional database to identify patients treated surgically for invasive breast cancer with a negative SLNB (1997-2000) who developed ipsilateral breast or chest wall recurrence as a first event. We excluded those with gross nodal disease at the time of LR. The cumulative incidence of subsequent events was estimated using competing risks methodology. RESULTS: Of 1527 patients with negative SLN at initial surgery, 83 had an ipsilateral breast (79) or chest wall recurrence (4) with clinically negative regional nodes; 47 (57%) were treated with and 36 (43%) without axillary surgery. Primary tumor characteristics were similar between groups, although time to LR was shorter in the no axillary surgery group (median 3.4 vs. 6.5 years; p < 0.05). All patients in the axillary surgery group and 94% of patients in the no axillary surgery group had surgical excision of their LR, and the use of subsequent radiation and systemic therapy was similar between groups. At a median follow-up of 4.2 years from the time of LR, the rates of AF, NAR, distant metastasis and death were low and did not differ between groups. CONCLUSIONS: Among breast cancer patients with LR and clinically negative nodes, our results question the value of axillary restaging but invite confirmation in larger patient cohorts. Since randomized trials support the value of systemic therapy for all patients with invasive LR, reoperative SLNB, although feasible, may not be necessary.

Endovascular approach to acute hemorrhage in locally advanced breast cancer.

We report a case of a woman with recurrent axillary fungating breast cancer who developed catastrophic hemorrhage from tumor erosion of her axillary artery. This was treated successfully with endovascular placement of a covered arterial stent. We discuss the suitability of endovascular therapy for patients with advanced malignancy given its lower morbidity in this population with decreased life expectancy.

Estrogen receptor, progesterone receptor, and HER2 status predict lymphovascular invasion and lymph node involvement.

BACKGROUND: The ACOSOG Z0011 trial demonstrated that axillary dissection (ALND) is not necessary for local control or survival in women with T1/2cN0 cancer undergoing breast-conserving therapy. There is concern about applying these results to triple-negative (TN) cancers secondary to their high local-recurrence (LR) rate. We examined the frequency of lymphovascular invasion (LVI) and nodal metastases in TN cancers to determine whether ALND can be safely avoided in this subtype. METHODS: Data were obtained from a database of patients with invasive breast cancer treated at Memorial Sloan Kettering Cancer Center from January 1998 to December 2010. A total of 11,596 tumors were classifiable into clinical surrogates for molecular subtype by immunohistochemical analysis: hormone receptor (HR)+/HER2+, HR+/HER2-, HR-/HER2+, and TN (HR-/HER2-). Multivariable logistic regression analysis (MVA) was used to determine associations between clinicopathologic variables and subtype. RESULTS: There were differences in age, tumor size, LVI, grade, and nodal involvement among groups. On MVA controlling for size, grade, and age, ER, PR, and HER2 status were significantly associated with LVI (p < 0.0001). Relative to TN tumors, HR+/HER2-, HR+/HER2+, and HR-/HER2+ tumors had higher odds of demonstrating LVI of 1.8 (odds ratio 1.8; 95 % confidence interval 1.6-2.1), 2.5 (2.5; 2.0-3.0), and 1.7 (1.7; 1.4-2.1), respectively. On MVA adjusting for size, grade, LVI, and age, TN tumors had the lowest odds of having any or high-volume nodal involvement (≥4 nodes, p < 0.0001). CONCLUSIONS: LVI and nodal metastases were least frequent in TN cancers compared with other subtypes, despite the uniformly worse prognosis and increased LR rate in TN tumors. This suggests TN cancers spread via lymphatics less frequently than other subtypes and ALND may be avoided in TN patients meeting Z0011 eligibility criteria.

Small RNA sequencing and functional characterization reveals MicroRNA-143 tumor suppressor activity in liposarcoma.

Liposarcoma remains the most common mesenchymal cancer, with a mortality rate of 60% among patients with this disease. To address the present lack of therapeutic options, we embarked upon a study of microRNA (miRNA) expression alterations associated with liposarcomagenesis with the goal of exploiting differentially expressed miRNAs and the gene products they regulate as potential therapeutic targets. MicroRNA expression was profiled in samples of normal adipose tissue, well-differentiated liposarcoma, and dedifferentiated liposarcoma by both deep sequencing of small RNA libraries and hybridization-based Agilent microarrays. The expression profiles discriminated liposarcoma from normal adipose tissue and well differentiated from dedifferentiated disease. We defined over 40 miRNAs that were dysregulated in dedifferentiated liposarcomas in both the sequencing and the microarray analysis. The upregulated miRNAs included two cancer-associated species (miR-21 and miR-26a), and the downregulated miRNAs included two species that were highly abundant in adipose tissue (miR-143 and miR-145). Restoring miR-143 expression in dedifferentiated liposarcoma cells inhibited proliferation, induced apoptosis, and decreased expression of BCL2, topoisomerase 2A, protein regulator of cytokinesis 1 (PRC1), and polo-like kinase 1 (PLK1). The downregulation of PRC1 and its docking partner PLK1 suggests that miR-143 inhibits cytokinesis in these cells. In support of this idea, treatment with a PLK1 inhibitor potently induced G(2)-M growth arrest and apoptosis in liposarcoma cells. Taken together, our findings suggest that miR-143 re-expression vectors or selective agents directed at miR-143 or its targets may have therapeutic value in dedifferentiated liposarcoma.

mRNA and protein levels of FUS, EWSR1, and TAF15 are upregulated in liposarcoma.

Translocations or mutations of FUS, EWSR1, and TAF15 (FET) result in distinct genetic diseases. N-terminal translocations of any FET protein to a series of transcription factors yields chimeric proteins that contribute to sarcomagenesis, whereas mutations in the conserved COOH-terminal domain of wild-type FUS were recently shown to cause familial amyotrophic lateral sclerosis. We thus investigated whether the loss of one FUS allele by translocation in liposarcoma may be followed by mutations in either the remaining FUS allele or the paralogous EWSR1. Furthermore, we investigated the strength of the FET promoters and their contributions to sarcomagenesis given the proteins' frequent involvement in oncogenic translocations. We sequenced the respective genomic regions of both FUS and EWSR1 in 96 liposarcoma samples. Additionally, we determined FET transcript and protein levels in several liposarcoma cell lines. We did not observe sequence variations in either FUS or EWSR1. However, protein copy numbers reached an impressive 0.9 and 5.5 Mio of FUS and EWSR1 per tumor cell, respectively. Compared with adipose-derived stem cells, FUS and EWSR1 protein expression levels were elevated on average 28.6-fold and 7.3-fold, respectively. TAF15 mRNA levels were elevated on average 3.9-fold, although with a larger variation between samples. Interestingly, elevated TAF15 mRNA levels did not translate to strongly elevated protein levels, consistent with its infrequent occurrence as translocation partner in tumors. These results suggest that the powerful promoters of FET genes are predominantly responsible for the oncogenic effect of transcription factor translocations in sarcomas.

Expression profiling of liposarcoma yields a multigene predictor of patient outcome and identifies genes that contribute to liposarcomagenesis.

Liposarcomas are the most common type of soft tissue sarcoma but their genetics are poorly defined. To identify genes that contribute to liposarcomagenesis and serve as prognostic candidates, we undertook expression profiling of 140 primary liposarcoma samples, which were randomly split into training set (n = 95) and test set (n = 45). A multigene predictor for distant recurrence-free survival (DRFS) was developed by the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% versus 45% for high risk score patients (P = 0.001). The HR for high versus low score, adjusted for histologic subtype, was 4.42 (95% CI, 1.26-15.55; P = 0.021). The concordance probability for risk score was 0.732. In contrast, the concordance probability for histologic subtype, which had been considered the best predictor of outcome in liposarcoma, was 0.669. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multigene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. RNAi-mediated knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Taken together, our findings identify genes that seem to be involved in liposarcomagenesis and have promise as therapeutic targets, and support the use of this multigene predictor to improve risk stratification for individual patients with liposarcoma.

Ascaris lumbricoides infection causing respiratory distress after coronary artery bypass grafting.

BACKGROUND: Ascaris lumbricoides infects an estimated 1.2 billion people worldwide, but is usually asymptomatic. Herein we report a case of acute respiratory distress caused by upper airway obstruction due to an adult A. lumbricoides nematodes after cardiac surgery. METHODS: Case report and review of pertinent literature. CASE REPORT: A 70-year old female, until recently a resident of the rural Philippines, underwent coronary bypass grafting in New York City. Nine hours after surgery (one hour after endotracheal extubation), cough and arterial oxygen desaturation prompted airway suctioning, which retrieved an adult nematode from the posterior oroharynx. symptomes abated immediately, after which the patient receive a curative course of mebendazole. CONCLUSION: Although infection with A. lumbricoides is rare in the United States, it may become manifest with severe consequences in the postoperative period.

Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions.

Current preoperative diagnostic procedures for thyroid nodules rely mainly on the cytological interpretation of fine-needle aspirates (FNAs). DNA microarray analysis has been shown to reliably distinguish benign and malignant thyroid nodules in surgically resected specimens, but its diagnostic potential in thyroid FNA has not been examined. In the present study, the expression profiles of 50 benign thyroid lesions and papillary thyroid carcinoma tissue samples were compared, generating a list of 25 differentially expressed genes from this training set. A test set of 22 FNA specimens was evaluated by unsupervised hierarchical cluster analysis using this gene list, and the results were compared to FNA cytology. FNA specimens were found to fall into three clusters: malignant (n = 10), benign (n = 7), and indeterminate (n = 5). The benign and malignant groups showed complete concordance with the final histological diagnosis except for one histologically benign lesion, which was rediagnosed as follicular variant of papillary thyroid carcinoma on histological review. Paired analysis between FNA and matched tissues samples illustrated adequate sampling with FNA. These results illustrate that microarray analysis of FNA is feasible and has the potential to improve the accuracy of FNA in categorizing benign from malignant lesions beyond routine cytological evaluation.

Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer.

OBJECTIVES: To evaluate the expression of the androgen receptor (AR) in transitional cell carcinoma (TCC) of the bladder, and to assess whether its expression correlated with pathologic tumor stage. TCC of the bladder is three times more common in males than in females. The origin of this sex difference in incidence is unknown. METHODS: We evaluated tumor specimens from 49 consecutive patients treated for TCC of the bladder at our institution between July 2002 and June 2003. Immunohistochemistry was performed using a monoclonal mouse anti-AR antibody on paraffin-embedded tissue sections of tumors obtained from transurethral resection, radical cystectomy, or resection of metastases. Specimens were assessed for AR expression, and, in tumors that demonstrated AR staining, the percentage of nuclei that stained positive was recorded. RESULTS: Of the 49 tumors, 26 (53.1%) expressed the AR. The percentage of tumors that expressed the AR decreased with increasing pathologic stage, from 88.9% of pTa lesions to 0% of pT3 tumors. Overall, 75% of superficial tumors (pTa + pT1 + carcinoma in situ) expressed the AR compared with 21.4% of invasive tumors (pT2 + pT3; P = 0.002). In addition, among AR-expressing tumors, the mean percentage of nuclei that stained positive for the AR was significantly greater in pTa tumors (62.5%) than in pT1 (31%) or pT2 (20%) tumors (P = 0.005). CONCLUSIONS: We found a decrease in AR protein expression in tumors with increased pathologic stage. Our data suggest that the loss of AR expression is associated with invasive bladder cancer.