A Single-Center 18-Year Series of 73 Cases of Metaplastic Carcinoma of the Breast.

Aim: To examine the clinical management of metaplastic breast cancer (MeBC), particularly the role of chemotherapy. Methods: This retrospective study included patients with MeBC (n = 73) from a tertiary breast cancer center: the "Centre des Maladies du Sein of the CHU de Québec-Université Laval." The specimens were reviewed by two pathologists. Patient and tumor characteristics, systemic therapy (neoadjuvant and adjuvant), disease-free survival (DFS), and overall survival (OS) were recorded. Results: The median follow-up was 57.2 months. The mean tumor size was 39.5 ± 32.1 (range, 1-200) mm. Most were in grade 3 (75.3%), without evidence of clinical nodal involvement (75.3%), and triple-negative (79.5%). Chemotherapy was given to 49 (67.1%) patients. Thirty-seven patients (50.7%) underwent a mastectomy, and 22/37 (59.5%) received radiotherapy. Adjuvant chemotherapy was given to 36 patients (49.3%), and nine (12.3%) patients were treated with neoadjuvant chemotherapy. The 5-year OS and DFS rates were 60.2% and 66.8%. Among the nine patients who received neoadjuvant chemotherapy, three (33.3%) achieved a partial response, three (33.3%) had stable disease, and three (33.3%) had disease progression. The use of chemotherapy, especially in the adjuvant setting, had a significant positive effect on 5-year OS (P=0.003) and 5-year DFS (P=0.004). Nodal involvement was associated with worse OS (P=0.049) but similar DFS (P=0.157). Lumpectomy was associated with better 5-year OS (P < 0.0001) and DFS (P=0.0002) compared with mastectomy. Conclusion: MeBC represents a rare heterogeneous group of malignancies with poor prognosis. Adjuvant chemotherapy was associated with improved OS and DFS. Patients should be carefully selected for neoadjuvant chemotherapy.

Effect of single-shot intrathecal morphine versus continuous epidural analgesia on length of stay after gastrectomy for cancer: a retrospective cohort study.

BACKGROUND: Single-dose intrathecal opiates (ITO) could shorten the length of hospital stay compared to thoracic epidural analgesia (TEA). This study aimed to compare TEA with TIO in terms of length of hospital stay, pain control, and parenteral opioid consumption in patients undergoing gastrectomy for cancer. METHODS: The patients who underwent gastrectomy for cancer in 2007-2018 at the CHU de Québec-Université Laval were included. The patients were grouped as TEA and intrathecal morphine (ITM). The primary outcome was the length of hospital of stay (LOS). The secondary outcomes were numeric rating scales (NRS) for pain and parenteral opioid consumption. RESULTS: A total of 79 patients were included. There were no differences in preoperative characteristics between the two groups (all P > 0.05). The median LOS was shorter in the ITM group than in the TEA group (median, 7.5 vs. 10 days, P = 0.049). The opioids consumption at 12, 24, and 48 h postoperatively was significantly lower in the TEA group at all time points. The NRS score for pain was lower in the TEA group than in the ITM group at all time points (all P < 0.05). CONCLUSIONS: Patients with ITM analgesia undergoing gastrectomy presented shorter LOS than those with TEA. ITM had an inferior pain control that did not have a clinical impact on recovery in the cohort studied. Given the limitations of this retrospective study, further trials are warranted.

Do Preoperative Prophylactic Antibiotics Reduce Surgical Site Infection Following Wire-Localized Lumpectomy? A Single-Blind Randomized Clinical Trial.

BACKGROUND: Data on the benefits of preoperative prophylactic antibiotics for breast surgery are conflicting, and there is no specific guideline for their use in wire-localized lumpectomy. PATIENTS AND METHODS: This is a proof-of-concept, single-blind randomized controlled trial carried out from April 2018 to June 2019 at the Centre des Maladies du Sein du CHU de Québec - Université Laval. The objectives were to determine whether a single dose of preoperative antibiotics reduces surgical site infection (SSI) after wire-localized lumpectomy and to identify the risk factors for SSI. The patients were randomized to receive preoperative prophylactic antibiotics or not. SSI was defined by positive breast wound cultures, abscess drainage, and/or antibiotics given for clinical signs of breast infection within 30 days of the operation. This study was registered with ClinicalTrials.gov, NCT04818931. RESULTS: A total of 330 patients were enrolled. Eighteen patients were excluded. The SSI rate was 3.1% (5/160) in the antibiotic group versus 5.9% (9/152) in the control group (p = 0.28). Only obesity was a significant risk factor for SSI. All cases of SSI were treated routinely with antibiotics; one patient required wound re-opening. None of the SSIs delayed the adjuvant treatment. CONCLUSION: Preoperative antibiotic prophylaxis does not significantly decrease the occurrence of breast SSI. It is safe to omit prophylactic antibiotics for a wire-localized lumpectomy. This could also decrease the treatment costs and avoid unnecessary side effects.

Impact of the introduction of formal D2 lymphadenectomy for gastric cancer in a Western setting.

Background: Two members from an academic tertiary hospital went to the National Cancer Institute in Tokyo, Japan, to learn how to perform an adequate D2 lymphadenectomy and to then introduce this technique in the surgical care of patients undergoing surgery for gastric cancer at a Western hospital. We aimed to compare the perioperative outcomes and long-term survival of Western patients who underwent gastric resection, performed by these 2 surgeons, before and after the surgeons' shortcourse technical training in Japan. Methods: We conducted a retrospective comparative study of all patients (n = 27 before training and n = 79 after training) who underwent gastric resection for cancer by the same 2 surgeons between September 2007 and December 2017 at the Centre Hospitalier Universitaire de Québec - Université Laval (Québec, Canada). We collected data on patient demographic, clinical, surgical, pathological and treatment characteristics, as well as long-term survival and complications. Results: In the post-training group, the number of sampled lymph nodes was higher (median 33 v. 14, p < 0.0001), but this increase did not result in a higher number of histologically positive lymph nodes (p = 0.35). The rate of complications was lower in the post-training group (15.2% v. 48.2%, p = 0.002). The hospital stay was shorter in the post-training group (11 [standard deviation (SD) 7] v. 23 [SD 45] d, p = 0.03). The median survival was higher in the post-training group (47 v. 29 mo, p = 0.03). Conclusion: These results suggest that a short-course technical training in D2 lymphadenectomy, completed in Japan, improved lymph node sampling, decreased postoperative complications and improved survival of patients undergoing surgery for gastric cancer in a Western setting.

Contexte: Deux membres d'un centre hospitalier universitaire en soins tertiaires se sont rendus à l'Institut national du cancer de Tokyo, au Japon, pour apprendre à effectuer une lymphadénectomie de type D2 et ensuite intégrer cette technique aux interventions chirurgicales visant à contrer un cancer de l'estomac dans un hôpital occidental. L'objectif était de comparer les issues périopératoires et la survie à long terme des patients qui ont subi une gastrectomie réalisée par les 2 chirurgiens, avant et après leur formation technique de courte durée au Japon. Méthodes: Nous avons mené une étude rétrospective comparative portant sur tous les patients (n = 27 avant la formation, et n = 79 après la formation) qui, entre septembre 2007 et décembre 2017, ont subi une gastrectomie pour un cancer réalisée par les 2 chirurgiens au Centre hospitalier universitaire de Québec ­ Université Laval (Québec, Canada). Nous avons recueilli des données démographiques, cliniques, chirurgicales et pathologiques ainsi que des données sur les traitements, la survie à long terme et les complications. Résultats: Dans le groupe de patients opérés après la formation, un plus grand nombre de ganglions lymphatiques a été prélevé (médiane 33 c. 14; p < 0,0001), mais cette augmentation n'était pas accompagnée d'un plus grand nombre d'analyses histologiques positives (p = 0,35). Le taux de complication était plus faible dans ce groupe (15,2 % c. 48,2 %; p = 0,002), et l'hospitalisation, plus courte (11 jours [écart type (É.-T.) 7] c. 23 jours [É.-T. 45]; p = 0,03). De plus, la durée de survie médiane était plus élevée dans ce groupe (47 mois c. 29 mois; p = 0,03). Conclusion: Ces résultats laissent croire qu'une courte formation technique sur la lymphadénectomie de type D2, réalisée au Japon, améliore le prélèvement de ganglions lymphatiques, diminue les complications postopératoires et prolonge la survie des patients qui subissent une chirurgie pour un cancer de l'estomac en Occident.

Is contralateral breast ultrasound worthwhile in preoperative staging of breast cancer?

BACKGROUND: Women with invasive breast cancer are at higher risk of contralateral synchronous cancer. This study aimed at determining if contralateral breast ultrasound (CBUS) examination should be routinely performed in the preoperative evaluation of breast cancer patients. METHODS: This is a retrospective study of preoperative CBUS examinations performed between January 2012 and April 2015. The charts of patients presenting for biopsy of a Breast Imaging Reporting and Data System (BIRADS) 5 lesion and who had undergone a concomitant contralateral breast US examination were reviewed. Index tumor, lymph node status, American College of Radiology (ACR) breast density on mammogram, total scanning time, and results of CBUS were recorded. RESULTS: Of the 3007 patients who underwent breast biopsies during the study period, 360 patients met the inclusion criteria. Index mass size was 19 ± 10 mm. CBUS examination led to 76 biopsies, of which 12 were positive in 11 patients. Detection rate for mammographically occult contralateral invasive cancers was 3.1% (11/360). Contralateral lesion size was 13 ± 10 mm. Breast density was rated ACR C/D for nine women and ACR B for two. In the ACR C/D subgroup (82%), the contralateral cancer detection rate was 4.1%. Average additional scanning time spent required to perform CBUS examination was 3.1 ± 4.9 min. Patients diagnosed with contralateral invasive breast cancer underwent surgery and/or chemotherapy. The treatment strategy was changed in all 11 patients after the detection of a second primary cancer. CONCLUSION: Preoperative CBUS is effective and most beneficial with women presenting ACR C/D breast density. Given its impact on decreasing future morbidity, its routine use should be considered to improve quality healthcare for women diagnosed with breast cancer.

Plasma PCSK9 correlates with apoB-48-containing triglyceride-rich lipoprotein production in men with insulin resistance.

Intestinal triglyceride (TG)-rich lipoproteins (TRLs) are important in the pathogenesis of atherosclerosis in insulin resistance (IR). We investigated the association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations with apoB-48-containing TRL metabolism in 148 men displaying various degrees of IR by measuring in vivo kinetics of TRL apoB-48 during a constant-fed state after a primed-constant infusion of L-[5,5,5-D3]leucine. Plasma PCSK9 concentrations positively correlated with TRL apoB-48 pool size (r = 0.31, P = 0.0002) and production rate (r = 0.24, P = 0.008) but not the fractional catabolic rate (r = -0.04, P = 0.6). Backward stepwise multiple linear regression analysis identified PCSK9 concentrations as a positive predictor of TRL apoB-48 production rate (standard ß = +0.20, P = 0.007) independent of BMI, age, T2D/metformin use, dietary fat intake during the kinetic study, and fasting concentrations of TGs, insulin, glucose, LDL cholesterol, or C-reactive protein. We also assessed intestinal expression of key genes involved in chylomicron processing from duodenal samples of 71 men. Expression of PCSK9 and HMG-CoAR genes was positively associated (r = 0.43, P = 0.002). These results support PCSK9 association with intestinal secretion and plasma overaccumulation of TRL apoB-48 in men with IR.

Characteristics and long-term survival of patients diagnosed with pure tubular carcinoma of the breast.

BACKGROUND AND OBJECTIVES: Pure tubular carcinomas (TC) of the breast are generally considered to have an excellent prognosis. This study aimed to analyze the characteristics and survival of patients with TC. METHODS: This was a retrospective study conducted at the CHU de Québec-Université Laval. Databases were searched for all cases treated between April 1997 and December 2010. Survival was retrieved from the Province of Quebec Ministry of Health. Follow-up was censored on December 31, 2011. Overall survival (OS) was compared to patients with invasive ductal carcinoma (ICD) matched for age, tumor size, lymph node involvement, year of diagnosis, ER, PgR, and HER2, histological grade, lymphovascular invasion, and chemotherapy. RESULTS: The frequency of TC was 2.9% (n = 223/7563). Tumors size was 7.4 ± 8.8 mm, without lymphovascular invasion (95.1%), ER-positive (98.2%), PgR-positive (69.5%), and HER2-negative (100%). Patients were followed up for 7.1 ± 2.7 years. The actuarial 13-year OS was 89.0% for TC, compared to 85.8% for IDC (P = 0.13). For TC, the 13-year OS was 95.8% in NO patients compared to 90.0% for N1-3 (P = 0.01). CONCLUSION: Despite the general popular belief that patients with TC fare better than patients with IDC, the 13-year OS of TC was similar to that of grade I IDC.

The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

BACKGROUND: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH). METHODS: A total of 118 HeFH, 6 HoFH, and 117 controls were included in the study. Plasma PCSK9 and apoB-48 concentrations were measured in the fasting state. RESULTS: Plasma PCSK9 and apoB-48 levels were higher in FH subjects compared with controls (PCSK9: HoFH: 642.6 ± 246.9 vs. HeFH: 324.9 ± 119.8 vs. CONTROLS: 194.5 ± 65.9 ng/mL, P < 0.0001; apoB-48: HoFH: 14.71 ± 4.36 vs. HeFH: 6.55 ± 4.24 vs. CONTROLS: 3.03 ± 2.07 µg/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (ρ = 0.06, P = 0.5) and HeFH subjects (ρ = 0.07, P = 0.4). Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001). CONCLUSIONS: These data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. TRIAL REGISTRATION: NCT02225340 .

Impact of physical activity in group versus individual physical activity on fatigue in patients with breast cancer: A pilot study.

BACKGROUND: Physical activity improves the quality of life of cancer survivors, but whether there is a difference between individual vs. group physical activity is unknown. OBJECTIVES: To compare fatigue at 12 weeks in breast cancer survivors after participation in a program of group vs. individual video-assisted physical activity. METHODS: This was a randomized phase II pilot study carried out in breast cancer survivors at a tertiary breast cancer center. Eligible patients were randomized to individual or group 12-week physical activity program. The primary outcome was fatigue (FACT-F). Aerobic capacity (6-min walk test), muscular strength, and quality-of-life (FACT-G and FACT-B) were assessed. Because of poor accrual, 200 consecutive breast cancer patients were surveyed about their physical activity habits to assess reasons for low recruitment. RESULTS: For all participants (n = 26; n = 12 for group vs. n = 14 for individual), there were some improvement in FACT-F, FACT-G, FACT-B, physical activity level, aerobic capacity, and shoulder strength. Among the 200 patients surveyed, 58% were interested to increase their physical activity level, 15% declared that they were already exercising enough, 9% declared being unable to, 3% declared having no time, and 2% declared having no interest, and other reasons (13%). Among the 200 patients surveyed, 25% preferred in group, 57% preferred alone, and 18% had no preference. CONCLUSION: Low recruitment precluded conclusions about the efficacy of physical activity practiced in group vs. individually, but both groups derived a benefit. Low willingness to change exercising habits could be the biggest barrier to physical activity in breast cancer survivors.

Vacuum-assisted complete excision of solid intraductal/intracystic masses and complex cysts: Is follow-up necessary?

INTRODUCTION: Management of complex cysts and benign intraductal/intracystic masses is controversial. The aim of this study was to determine if the complete removal of the complex cyst lesions with ultrasound-guided vacuum-assisted excision (US-VAE) is sufficient for their safe management when the histological diagnosis obtained at biopsy is benign. SUBJECTS AND METHODS: This is a single institution retrospective study performed on patients who underwent breast biopsy between April 2007 and September 2013. Patients with complete removal of complex cyst lesion of a BIRADS 4 lesion by US-VAE that obtained a benign diagnosis were included. Size, morphology, histological diagnosis, and surgical or imaging follow-up of the lesions were analyzed. RESULTS: During the study period, 131 lesions met the inclusion criteria. Benign papilloma represented 32% (42/131) of the lesions; the remaining lesions had various benign diagnoses. Mean size of the solid mass or the cysts' thickest septum was 7 mm (range, 2-24). Mean imaging follow-up was 34.9 months (24-99 months) in 115 lesions. No recurrence or malignancy in the post-biopsy bed were observed during follow-up. Eleven lesions (8.4%) underwent surgery as follow-up: no cancer was found, but two lesions demonstrated atypia. CONCLUSIONS: Complex cyst lesion image completely excised with US-VAE and with a benign histology at biopsy might not require further imaging follow-up or surgery and a return to routine screening can be safely recommended. In a world where healthcare delivery and accessibility is important, elimination of unnecessary follow-ups is pertinent given its lower cost and lesser social impact.

C-reactive protein levels are inversely correlated with the apolipoprotein B-48-containing triglyceride-rich lipoprotein production rate in insulin resistant men.

The pro-inflammatory state and elevated plasma levels of post-prandial triglycerides (TG) are associated with increased cardiovascular disease risk. Recent studies suggested that the increase in the production rate of post-prandial lipoproteins observed in patients with insulin resistance (IR) may be caused, at least in part, by the dysregulation of intestinal insulin sensitivity triggered by inflammation. OBJECTIVE: The objective of the present study was to evaluate the association between IR, plasma C-reactive protein (CRP) levels and the kinetics of TG-rich lipoprotein (TRL) containing apolipoprotein (apo) B-48 in a large sample of insulin sensitive (IS) and IR men. METHODS: The in vivo kinetics of TRL apoB-48 were measured in 151 men following a primed-constant infusion of l-[5,5,5-D3]leucine. IR subjects (n=91) were characterized by fasting TG levels ≥1.5mmol/L and an index of homeostasis model assessment of IR (HOMA-IR)≥2.5 or type 2 diabetes, while IS subjects (n=24) were characterized by an HOMA-IR index <2.5 and TG levels <1.5mmol/L. RESULTS: IR subjects had higher TRL apoB-48 production rate (+202%; P<0.0001) and CRP levels (+51%; P=0.01) than IS subjects. TRL apoB-48 production rate and CRP levels were inversely correlated in IR subjects (r=-0.32; P=0.002). IR subjects with CRP levels above the median (2.20mg/L) had lower TRL apoB-48 production rate than IR subjects with CRP levels below the median (Δ=-24%; P<0.05). CONCLUSION: Our results confirm that IR is associated with increased TRL apoB-48 secretion and suggest that a higher inflammatory status is associated with decreased TRL apoB-48 secretion among IR subjects.

How Wide Should Margins Be for Phyllodes Tumors of the Breast?

The surgical management of phyllodes tumors (PTs) is still controversial. Some studies have suggested surgical margins ≥1 cm, but recent studies suggested that negative margins could be appropriate regardless of their width. To evaluate recurrence rates of PTs following surgery according to margins. Retrospective study of women who attended a tertiary breast cancer reference center between 1998 and 2010: 142 patients with a PT diagnosis, either at minimally invasive breast biopsy or at surgery, were identified. Clinical, pathologic and follow-up characteristics were assessed. Among 140 patients who underwent surgery, 64.3% of biopsies accurately predicted the final PT diagnosis at surgery. Forty-two (42/87, 48.3%) PTs had positive margins. Twenty-one (21/42, 50.0%) patients had a surgical revision of margins. Only one (1/42, 2.4%) had margins greater or equal to 1 cm. After a median follow-up of 1.29 years in benign PTs, 4.99 years in borderline PTs, and 5.42 years in malignant PTs, there were five local recurrences, three in originally benign PTs and two in borderline PTs. All were managed with surgery. Four had initial margins ≤1 mm. One patient with borderline PT had a local recurrence and later progressed to regional recurrence and metastasis. Free surgical margins are necessary to treat PT, and margins of at least 1 mm might be sufficient to prevent recurrence. Core needle biopsy might not be the best diagnostic tool for PTs.

Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.

BACKGROUND AND OBJECTIVES: Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases. METHODS: Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded. RESULTS: Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC. CONCLUSION: Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. © 2016 Wiley Periodicals, Inc.

n-3 Polyunsaturated Fatty Acid Supplementation Has No Effect on Postprandial Triglyceride-Rich Lipoprotein Kinetics in Men with Type 2 Diabetes.

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been proposed to modulate plasma lipids, lipoprotein metabolism, and inflammatory state and to reduce triglyceride (TG) concentrations. The present double-blind, randomized, placebo-controlled, crossover study investigated the effects of n-3 PUFA supplementation at 3 g/d for 8 weeks on the intravascular kinetics of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins in 10 men with type 2 diabetes. In vivo kinetics of the TG-rich lipoprotein (TRL) apoB-48 and VLDL apoB-100 were assessed using a primed-constant infusion of L-[5,5,5-D3] leucine for 12 hours in a fed state. Compared with the placebo, n-3 PUFA supplementation significantly reduced fasting TG concentrations by -9.7% (P = 0.05) but also significantly increased plasma levels of cholesterol (C) (+6.0%, P = 0.05), LDL-C (+12.2%, P = 0.04), and HDL-C (+8.4, P = 0.007). n-3 PUFA supplementation had no significant impact on postprandial TRL apoB-48 and VLDL apoB-100 levels or on the production or catabolic rates of these lipoproteins. These data indicate that 8-week supplementation with n-3 PUFAs in men with type 2 diabetes has no beneficial effect on TRL apoB-48 and VLDL apoB-100 levels or kinetics.

Validation of EP1 Antibody Clone for Estrogen Receptor Immunohistochemistry for Breast Cancer.

BACKGROUND: SP1 Rabbit monoclonal antibody to estrogen receptor (ER) has long been the standard for determination of ER status in breast cancer but has been replaced by the rabbit EP1 clone. AIM: To validate the EP1 antibody clone for use in determination of breast cancer ER status in a large clinical population against the previous standard SP1. MATERIALS AND METHODS: ER immunohistochemistry was assessed in 523 consecutive cases from a clinical setting using tissue microarrays. RESULTS: The kappa statistic showed that the agreement of ER status between SP1 and EP1 was considered to be almost perfect (kappa=0.97, 95% confidence interval=0.94-1.00). Sensitivity was 99.3%, specificity was 98.6% and overall agreement was 99.2%. CONCLUSION: The EP1 antibody was herein validated regarding its use in breast cancer with almost perfect agreement with the previously used standard SP1 antibody.

Is there an Upgrading to Malignancy at Surgery of Mucocele-Like Lesions Diagnosed on Percutaneous Breast Biopsy?

Management of pure mucocele-like lesion (MLL) diagnosed on percutaneous breast biopsy (PBB) is controversial. To assess surgical upgrade rate and clinical outcome of pure MLL obtained as sole diagnosis on PBB. Patients diagnosed with a MLL as the most advanced lesion on PBB from April 1997 to December 2010 were reviewed for radiologic presentation, biopsy technique, and pathologic and clinical outcomes. Of the 21,340 image-guided PBB performed during the study period, 50 women with 51 MLL (0.24%) were identified. Mean age was 53.1 ± 7.7 years. Radiologic findings were mostly microcalcifications (n = 47, 92.2%). Stereotactic PBB was performed for 49 lesions (96.1%). Surgery was performed shortly after biopsy in 35 women, with benign final pathology in 33, and upgrade to ductal carcinoma in situ (DCIS) in two patients (2/35, 5.7%). Mean follow-up was 4.2 ± 2.5 years (3.7 ± 2.1 years for surgical patients; 5.9 ± 2.9 years for follow-up only patients); three women were lost to follow-up (3/50). Three invasive cancers (3/47, 6.4%) were diagnosed 1.2, 1.2, and 2.8 years after biopsy: two in surgical patients, and one in a follow-up only patient. No cancer occurred at the same site as the original MLL. Pure MLL lesion of the breast is a rare entity and is mostly associated with a benign outcome. We observed an upgrade to DCIS slightly superior to 5%, but no invasive cancer. It is therefore unclear if these lesions should be excised or clinically and radiologically followed up when such lesions are found at PBB.

The contribution of PCSK9 levels to the phenotypic severity of familial hypercholesterolemia is independent of LDL receptor genotype.

UNLABELLED: Autosomal dominant familial hypercholesterolemia (FH) is caused by genetic mutations in the LDL receptor (LDLR), its ligand apolipoprotein (apo) B, or proprotein convertase subtilisin/kexin type 9 (PCSK9). Although PCSK9 levels have been shown to correlate with LDL-cholesterol (LDL-C) levels in FH, the extent to which PCSK9 levels modulate the phenotypic severity of this disease independent of LDLR genotype remains to be clarified. OBJECTIVE: To assess the relationship between LDLR genotype and the plasma levels of PCSK9, LDL-C, and lipoprotein (a) (Lp(a)) in a large cohort of genetically defined FH heterozygotes (HeFH). METHODS: A total of 292 HeFH carrying one of the nine French-Canadian mutations in the LDLR gene were recruited. The cohort included 226 carriers of a negative-receptor (NR) mutation and 66 carriers of a defective-receptor (DR) LDLR gene mutation. Fifty-six control subjects, who were matched with the HeFH subjects based on gender and body mass index, were also recruited. RESULTS: PCSK9 levels were higher in the HeFH group than in the control group (317.9±107.1 ng/mL vs. 203.3±59.8 ng/mL; P<0.0001). The strength of the association between PCSK9 and LDL-C levels was similar among controls (r=0.37; P=0.005) and HeFH (r=0.31; P<0.0001). Furthermore, a multiple linear regression analysis revealed that the positive correlation between PCSK9 and LDL-C levels remained significant after adjusting for LDLR genotype in the HeFH group. CONCLUSION: These results suggested that the contribution of PCSK9 levels to the phenotypic severity in FH heterozygotes is independent of LDLR genotype.

Validation of EP1 antibody clone for estrogen receptor immunohistochemistry in breast cancer.

Estrogen receptor (ER) tumor's status is critical for breast cancer management. A new rabbit antibody clone, EP1, is now available for ER status determination. The objective was to validate the EP1 antibody clone for its use in breast cancer ER status determination in a clinical setting against the previous standard, SP1. EP1 clone was assessed in 130 consecutive cases, including 50 ER-negative (<1% ER expression), 13 ER-low-positive (1% to 9% ER expression), and 67 ER-positive (≥10% ER expression). Using EP1 versus SP1, positive agreement (sensibility) was 92.5% and negative agreement (specificity) was 100%, leading to an overall agreement of 95.4%. All discordant cases (n=6) were ER-low-positive. SP1 was remeasured in 13 ER-low-positive and in 11 ER-negative cases. Overall agreement between SP1 initial tumor status and reassessment was 70.8% in those negative and low-positive cases. In conclusion, EP1 antibody has been validated for use in breast cancer with a positive agreement ≥90% and a negative agreement ≥95%, as recommended. Also, overall agreement between EP1 and SP1 was as good as between the SP1 initial status and SP1 reassessment.