Androgen receptor expression in patients with triple negative breast cancer treated with neoadjuvant chemotherapy: a single institution study.

Background: Androgen receptor (AR) expression has emerged as a potential prognostic and predictive marker in patients with triple negative breast cancer (TNBC). We conducted a retrospective analysis to evaluate pathologic complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS) in patients with AR positive and AR negative TNBC treated with neoadjuvant chemotherapy. Methods: 107 patients with TNBC subtype, treated with neoadjuvant chemotherapy between June 2006 and March 2016 were evaluated for AR expression. Androgen receptors were evaluated by immunohistochemical staining (clone AR441, Dilution 1:50, Dako-Agilent, Santa Clara, CA) using whole tissue sections from archived paraffin-embedded formalin-fixed (FFPE) blocks. AR positive was defined as ≥10% nuclear stained cells. Correlation of AR expression was examined with age, BMI, race, menopausal status, tumor grade, tumor size, and lymph node involvement, and response and outcomes. Univariate and multivariate analyses were performed to determine an association with AR expression and pathologic response and survival outcomes. Results: Fifty-eight patients with available tumor specimens were stained, with twenty (34.5%) being AR-positive and thirty-eight (65.5%) being AR negative. Median age was 49 years and median follow up was 5.7 years. All patients received anthracycline based neoadjuvant chemotherapy with 13 patients (23%) receiving an additional platinum chemotherapy. BRCA mutation positivity was 7% for the entire group. No differences in age, menopausal status, BMI, race, tumor size and lymph node involvement were observed between the two groups. However, there was a statistically significant difference in tumor grade between the two groups (p=0.008). Overall pCR rate was 28% with no difference between the two groups (30% vs 26%, p=0.56). There was no statistically significant difference in median DFS (5.9 years vs 5.2 years (p=0.94) and median OS (6.2 years vs 5.4 years, p=0.98) between the AR positive and AR negative groups. Conclusions: Our study did not find an association of AR status and the pathologic responses or survival outcomes in patients with TNBC treated with neoadjuvant chemotherapy. Further studies exploring the prognostic and predictive role of AR in patients with TNBC are warranted.

Unusual presentation of lepidic adenocarcinoma in a healthy female.

BACKGROUND: Lepidic adenocarcinoma represents a histologic pattern of non-small cell lung cancer that characteristically arises in the lung periphery with tracking alongside pre-existing alveolar walls. Noninvasive and invasive variants of lepidic adenocarcinoma are dependent on parenchymal destruction, vascular, or pleural invasion. The lepidic-predominant lung malignancies are collectively recognized as slow growing with rare metastasis and excellent prognosis. The World Health Organization classification of lung malignancies depends on molecular and histopathological findings. CT findings most commonly include ground-glass characteristics, commonly mistaken for inflammatory or infectious etiology. These tumors are generally surgically resectable and associated with better survival given infrequent nodal and extrathoracic involvement. Rarely these tumors present with diffuse pneumonic-type involvement associated with worse outcomes despite lack of nodal and distant metastases. CASE PRESENTATION: A 63-year-old Caucasian athletic immunocompetent female presented with 2 months of progressive shortness of breath, fatigue, loss of appetite and 15 pound weight loss. History was only notable for well controlled essential hypertension and hypothyroidism. Contrast computed tomography angiogram and positron emission tomography revealed diffuse hypermetabolic interstitial and airspace abnormalities of the lungs without lymphadenopathy (or distant involvement) in addition to right hydropneumothorax and left pleural effusion. Baseline laboratory testing was unremarkable, and extensive bacterial and fungal testing returned negative. Bronchoscopy and video-assisted thoracoscopic surgery was subsequently performed with pleural fluid cytology, lung and pleural biopsies returning positive for lepidic adenocarcinoma with 2% programmed death ligand 1 expression and genomic testing positive for PTEN gene deletion. Prior to treatment, the patient perished on day 15 of admission. CONCLUSION: We present a rare case of lepidic predominant adenocarcinoma with extensive bilateral aerogenous spread in the context of no lymphovascular invasion in a healthy, low risk patient. This case presentation may add to the body of knowledge regarding the different behavior patterns of lepidic predominant adenocarcinomas.

A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology.

AIMS: Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC. METHODS AND RESULTS: We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively. CONCLUSIONS: High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.

High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature.

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.

Evaluation of a two-sample process for prevention of ABO mistransfusions in a high volume academic hospital.

BACKGROUND: Acute haemolytic transfusion reactions due to ABO incompatible blood transfusion remain a leading cause of transfusion-associated morbidity and mortality in the USA. Erroneous patient identification and specimen labelling account for many errors that lead to ABO mistransfusions; these errors are largely preventable. METHODS: Our hospital requires a two-sample process of ABO/Rh typing prior to transfusion. Both samples must be drawn independently. To prevent simultaneous sample draw, our second sample tube has a unique pink top that is only available from the blood bank and can only be sent to the patient's floor once the first sample arrives in the lab. We performed an audit of this process from 19 March to 30 July 2014 and 19 March to 30 July 2015. RESULTS: We reviewed type and crossmatch orders for 2702 new patients during the audit period and 824 patients (30.5%) required transfusion. All patients evaluated received compatible blood, and no mistransfusions were recorded using this method. Three per cent of testing was performed incorrectly, which safely defaulted to giving type O blood. CONCLUSIONS: The two-sample protocol used by our institution can decrease the risk of mistransfusion. Our protocol was relatively inexpensive, safe, efficient and practical for adaptation by other hospitals.

Does Progesterone Receptor Matter in the Risk of Recurrence for Patients With Ductal Carcinoma in Situ?

BACKGROUND: Local recurrence is a major concern in patients diagnosed with ductal carcinoma in situ (DCIS). In invasive breast cancers, estrogen receptor (ER) (+)/progesterone receptor (PR) (-) subtype is considered more aggressive with poorer prognosis as compared to ER+/PR+ tumors. It is unclear whether this holds true in DCIS. METHODS: Six hundred ninety-three patients diagnosed and treated for DCIS at Froedtert and Medical College of Wisconsin Cancer Center (February 2002 to March 2015) were studied to determine if the recurrence rates were significantly different between ER+/PR- and ER+/PR+ tumors. Recurrence was defined as either noninvasive or invasive ipsilateral, contralateral, or distant disease. Probabilities of recurrences were calculated using Kaplan-Meier estimator. Cox proportional hazards model was used to evaluate the effect of prognostic factors on DCIS recurrence. RESULTS: Median follow-up was 5.2 years. The 5-year recurrence-free survival (RFS) was 91% (95% CI, 88.2-93.3) while estimated 7-year RFS was 86% (95% CI, 81.9-89.2). Seventy-five patients had a recurrence during their follow-up. Patients with ER-/PR- tumors (n = 118) had a significantly higher risk of recurrence (Hazard Ratio 3.7, 95% CI, 1.9-7.2, P = 0.0001) whereas those with ER+/PR- subtype (n = 77) did not have a significant difference in recurrence risk (HR 1.75, 95% CI, 0.92-3.32, P = 0.085) when compared to ER+/PR+ tumors (n = 482). No endocrine therapy for ER+ DCIS and lumpectomy alone were also significant predictors of recurrence (P = 0.0073 and P = 0.005, respectively). CONCLUSIONS: ER+/PR- subtype was not a significant predictor of recurrence in DCIS patients. This finding is in contrast to the recurrence risk seen in invasive breast cancers. Mastectomy and postlumpectomy radiation were associated with improved outcomes as was adjuvant endocrine therapy.

Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: A meta-analysis.

BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear. This meta-analysis aims to consolidate previously published data to identify the risk factors most likely leading to TIC. METHODS: A search of the MEDLINE literature database using the keywords trastuzumab/Herceptin, risk factors, outcomes, cardiac, cardiotoxicity, cardiomyopathy, LVEF, and chemotherapy was performed. Only prospective/retrospective human studies were included, with additional studies excluded if they reported baseline LVEF > 68%, a cohort of <50 patients, or results that were not stratified based on cardiotoxic events. Pooled odds ratio (OR) and 95% confidence interval (CI) for each potential risk factor were calculated, with heterogeneity of data and samples explored using random-effects modeling. RESULTS: Data were collected from 17 articles, capturing 6527 patients. Hypertension (OR 1.61, 95% CI 1.14-2.26; P < 0.01), diabetes (OR 1.62; 95% CI 1.10-2.38; P < 0.02), previous anthracycline use (OR 2.14; 95% CI 1.17-3.92; P < 0.02), and older age (P = 0.013) were all shown to be associated with TIC. CONCLUSION: Cardiac performance should be closely monitored in women treated with trastuzumab. Recognizing potential risk factors along with careful attention to symptoms/LVEF measurements could minimize the occurrence of TIC in this population.

Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score.

OBJECTIVE/BACKGROUND: Progesterone-receptor negativity (PR-) is predictive of adverse outcomes in estrogen receptor-positive (ER+) breast cancer. The Oncotype DX assay provides risk stratification for hormone receptor-positive (HR+) invasive breast cancer; however, the association of PR status and Oncotype DX recurrence scores (RSs) is less clear. METHODS: We designed an analysis to determine whether a significant difference exists in the RS for ER+/PR- tumors when compared with ER+/PR+ breast cancer. Three hundred and fifty patients with HR+ invasive breast cancer who underwent Oncotype DX testing at our institution from December 2006 to October 2013 were included. We also examined the concordance in the HR status reported by immunohistochemical (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. The data were analyzed by analysis of variance, F test, t test, and chi-square tests. Multivariate linear regression was used to determine significant predictors of Oncotype DX RS. RESULTS: A total of 301 patients had ER+/PR+ tumors and 47 patients had ER+/PR- tumors by IHC. PR- tumors had a significantly higher RS than PR+ tumors (24.7±8.53 vs. 17.3±7.38; p<.001), predicting a greater 10-year risk of distant recurrence. Multivariate linear regression showed PR status and tumor grade to be significant predictors of Oncotype DX RS (p<.0001). A total of 284 patients had HR status reported by Oncotype DX assay. Concordance between IHC and RT-PCR was 99.3% for ER and 88.7% for PR. CONCLUSION: Our study shows that ER+/PR- breast cancer tumors are associated with a significantly higher Oncotype DX scores; this interprets into a higher risk of recurrence. Our data also show that the concordance between IHC and RT-PCR was 99.3% for ER and lower at 88.7% for PR.

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease.

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty-nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow-up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted.