Re-Excision Rates of Invasive Ductal Carcinoma with Lobular Features Compared with Invasive Ductal Carcinomas and Invasive Lobular Carcinomas of the Breast

Background

Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies.

Methods

Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed.

Results

For T2 tumors (2.1–5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L.

Conclusions

Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.     

Invasive Lobular vs. Ductal Breast Cancer: A Stage-Matched Comparison of Outcomes

Background  

Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC), more difficult to detect mammographically, and usually diagnosed at a later stage. Does delayed diagnosis of ILC affect survival? We used a national registry to compare outcomes of patients with stage-matched ILC and IDC.     

25-Hydroxyvitamin D Status Does Not Affect Intraoperative Parathyroid Hormone Dynamics in Patients with Primary Hyperparathyroidism

Background  

Deficiency of 25-hydroxyvitamin D (25OHD) is a stimulus for the secretion of parathyroid hormone (PTH). During surgery for primary hyperparathyroidism, 25OHD deficiency may artificially elevate PTH, decreasing the sensitivity of intraoperative PTH (ioPTH) measurements.     

Lymph Node Status in Breast Cancer Does Not Predict Tumor Biology

Background/Objective

The 21-gene Oncotype DX^® Breast Recurrence Score^® (RS) assay has been prospectively validated as prognostic and predictive in node-negative, estrogen receptor-positive (ER+)/HER2? breast cancer patients. Less is known about its prognostic role in node-positive breast cancer. We compared RS results among patients with lymph node-negative (N0), micrometastatic (N1mi), and macrometastatic (N+) breast cancer to determine if nodal metastases are associated with more aggressive biology, as determined by RS.

Methods

Overall, 610,350 tumor specimens examined by the Genomic Health laboratory from February 2004 to August 2017 were studied. Histology was classified centrally, while lymph node status was determined locally. RS distribution (low: <?18; intermediate: 18–30; high: ≥?31) was compared by nodal status.

Results

Eighty percent (n = 486,013) of patients were N0, 4% (n = 24,325) were N1mi, 9% (n = 56,100) were N+, and 7% (n = 43,912) had unknown nodal status. Mean RS result was 18, 16.7, 17.3 and 18.9 in the N0, N1mi, N+, and unknown groups, respectively. An RS?≥?31 was seen in 10% of N0 patients, 7% of N1mi patients, and 8.0% of N+ patients. The likelihood of an RS ≥ 31 in N1mi and N+ patients varied with tumor histology, with only 2% of patients with classic infiltrating lobular cancer having an RS?≥?31, versus 7–9% of those with ductal carcinoma.

Conclusions

RS distribution among N0, N1mi, and N+ patients is similar, suggesting a spectrum of biology and potential chemotherapy benefit exists among node-negative and node-positive ER+/HER2? breast cancer patients. If RxPONDER does not show a chemotherapy benefit in N+ patients with a low RS result, our findings indicate that substantial numbers of patients could be spared the burden of chemotherapy.

     

Predictors of Breast Cancer Development in Women with Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia

Background

Atypical ductal hyperplasia and atypical lobular neoplasia are common benign breast diseases that increase breast cancer risk. We performed a cohort analysis that compared atypia patients for additional risk factors to asses the effect on breast cancer risk by atypia status.

Methods

This longitudinal cohort study used data from the Women At Risk High-Risk Registry at Columbia University Medical Center, New York. Women with atypia were compared to women without atypia across known risk factors to determine the combined effect on breast cancer development. Odds ratios (ORs) stratified by atypia status were calculated for each risk factor of interest with 95% confidence intervals (95% CIs). P values were calculated to determine statistical significance.

Results

The study population included 1598 high-risk women, 921 (57.6%) of whom had a history of biopsy-proven atypia. The remaining 677 high-risk women (42.4%) did not have atypia. Fifty women (3.1%) developed breast cancer. Alcohol was significantly associated with the development of breast cancer (P = 0.02) and increased breast cancer risk among women with atypia (OR, 2.13; 95% CI, 0.95–4.81) compared to women without atypia (OR, 1.71). The odds of breast cancer were higher for atypia patients with first-degree relatives (OR, 1.48; 95% CI, 0.64–3.35) compared to women with a relative and no atypia diagnosis (OR, 0.98; 95% CI, 0.41–2.63). The other risk factors of interest did not differ significantly by atypia status.

Conclusions

Atypia patients who drank alcohol and had a first-degree relative with breast cancer have an increased risk of breast cancer compared to those without atypia. Continued understanding of the high-risk population will lead to more individualized protocols for risk reduction and prevention.     

Palpable Adenopathy Does Not Indicate High-Volume Axillary Nodal Disease in Hormone Receptor-Positive Breast Cancer

Annals of Surgical Oncology - Axillary metastases in the form of palpable adenopathy indicate the need for neoadjuvant chemotherapy or axillary lymph node dissection (ALND). Patients with hormone...     

Low-dose Interleukin-2 Administered Pre-operatively to Patients with Gastric Cancer Activates Peripheral and Peritumoral Lymphocytes But Does Not Affect Prognosis

Background There is evidence that cancer is immunogenic under certain situations. IL-2 is described to stimulate an effective antitumor immune response in vitro and in vivo. The ability of cancer patients to undergo surgical resection is still the most important prognostic factor for many solid tumors, including gastric adenocarcinoma. The host immune system may be further compromised by surgical procedures leading to a generalized state of immunodepression in the post-operative period. The aim of this randomized case–control study is to evaluate the effects of pre-operative low-dose IL-2 treatment on patients with gastric adenocarcinoma who undergo surgery. Methods Sixty-eight patients with gastric adenocarcinoma were enrolled in the study and randomized in two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery without any treatment. Total peripheral WBC, neutrophils, CD3+ T, CD4+ T, CD8+ T and NK cells were obtained before and after surgery, at different times. Peritumoral infiltration was analyzed on all surgical specimens. Overall survival and relapse-free survival were studied with a median follow-up of 51 months. Results Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic and eosinophilic infiltrations and in a minor decrease in CD3+ T and CD4+ T cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that overall survival and relapse-free survival were affected only by stage of tumor and age of patients. Conclusions According to our data low-doses of IL-2 administered pre-operatively to patients with gastric cancer activate peripheral and peri-tumoral lymphocytes but did not affect prognosis.     

Hormone Receptor Status of Breast Cancer in the Himalayan Region of Northern India

The role of hormone receptors as a prognostic and therapeutic tool in breast cancer is widely accepted. The frequency of nonreactivity of estrogen and progesterone receptors in breast cancer patients of India is much more common than in the West. This study was conducted with the aim of analysis of steroid receptor status in breast cancer with clinico-pathological characteristics from the northern hilly state of Himachal Pradesh, India located in the region of the Western Himalayas. Fifty five consecutive patients with the diagnosis of breast cancer were included in this study. Detailed clinical and histopathologic data was recorded in all cases. Estrogen receptor and progesterone receptor status was evaluated by immunohistochemistry. Chi-square test was used for statistical analysis. On immunohistochemical staining, 34.5% cases proved to be estrogen receptor positive and 36.4% cases progesterone receptor positive. The results in the present study documented low estrogen receptor and progesterone receptor positivity in breast cancer from this region of India.     

Prognosis of Japanese Breast Cancer Based on Hormone Receptor and HER2 Expression Determined by Immunohistochemical Staining

BACKGROUND: We classified Japanese breast cancer patients based on estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression and compared their prognoses. METHODS: We compared the background and prognostic factors of 600 patients with breast cancer who were assigned to the following groups: luminal A (ER + and/or PR + and HER2-; n = 431; 71.8%), luminal B (ER + and/or PR + and HER2 + ; n = 27; 4.5%), HER2 (ER-, PR-, and HER2 + ; n = 39; 6.5%) and basal-like (BBC; ER-, PR-, and HER2-; n = 103; 17.2%). RESULTS: Background factors did not significantly differ among the groups. Disease-free survival rates were significantly lower for the luminal B, HER2, and BBC subtypes than for the luminal A subtype. Cancer tended to recur earlier and overall survival was significantly lower for the BBC than for the luminal A and HER2 subtypes. Overall survival rates for the luminal B, HER2, and luminal A subtypes were comparable. CONCLUSIONS: The subtype distribution for Japanese and Caucasian patients was comparable. The prognosis for the BBC subtype was poorest among all subtypes. Breast cancer tended to recur earlier for the luminal B and HER2 subtypes than for the luminal A subtype; however, overall survival did not significantly differ among them.     

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

BackgroundInvasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis.MethodsWe evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson''s χ² test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS).ResultsOverall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2− subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2− subtype (OS, hazard ratio: 1.501, 95% CI 1.270–1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281–1.825, p < 0.001), lower histological grade (I–II) (OS, hazard ratio: 1.411, 95% CI 1.184–1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235–1.791, p < 0.001), or tumor burden, such as T_0–2 (OS, hazard ratio: 1.693, 95% CI 1.368–2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405–2.205, p < 0.001) and N_1–2 (OS, hazard ratio: 1.451, 95% CI 1.171–1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187–1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T_3–4 and N₃), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients.ConclusionPatients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.     

Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation

BackgroundDonors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients.MethodsAdults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor–recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used.ResultsMeeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41).ConclusionsUse of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.     

The Prognostic Significance of Micrometastases in Breast Cancer: A SEER Population-Based Analysis

Introduction The prognostic significance of lymph node micrometastases in breast cancer is controversial. We hypothesized that the survival of patients with solely micrometastatic disease (N1mi) would be intermediate to patients with 1–3 tumor-positive lymph nodes (N1) and those with no positive lymph nodes (N0). Methods We queried the surveillance, epidemiology and end results (SEER) database for all patients between 1992 and 2003 with invasive ductal or lobular breast cancer without distant metastases and ≤3 axillary nodes with macroscopic disease. Patients were stratified by nodal involvement and compared using the Kaplan–Meier method. Cox proportional hazards regression was utilized to compare survival after adjusting for patient and tumor characteristics. Results Between 1992 and 2003, N1mi diagnoses increased from 2.3% to 7% among the 209,720 study patients (p < 0.001). In a T-stage stratified univariate analysis, N1mi patients had a worse prognosis in T2 lesions. On multivariate analysis, N1mi remained a significant prognostic indicator across all patients (p < 0.0001) with a hazard ratio of 1.35 compared to N0 disease and 0.82 compared to N1 disease. Other negative prognostic factors included male gender, estrogen-receptor negativity, progesterone-receptor negativity, lobular histology, higher grade, older age, higher T-stage, and diagnosis in an earlier time period. Conclusion Nodal micrometastasis of breast cancer carries a prognosis intermediate to N0 and N1 disease, even after adjusting for tumor- and patient-related factors. Prospective study is warranted and the results of pending trials are highly anticipated. Until then adjuvant therapy trials should consider using N1mi as a stratification factor when determining nodal status.     

Outcome of Pure Mucinous Breast Carcinoma Compared to Infiltrating Ductal Carcinoma: A Population-based Study from China

Purpose

Pure mucinous breast carcinoma (PMBC) is a rare pathologic finding. Few studies have addressed the biologic features of PMBC and prognostic factors among patients with this disease. We performed a study to compare PMBC and invasive ductal carcinoma (IDC) by means of a large database to reliably assess the biologic phenotype and clinical behavior of PMBC.

Methods

A total of 2,511 patients who met the inclusion criteria were identified from 1999 to 2010; 2,202 patients had pure IDC and 309 had PMBC. Clinical and biologic features, overall survival, and recurrence/metastasis-free survival (RFS) were compared for both groups.

Results

PMBC had favorable characteristics including smaller size, lower rates of lymph node positivity, lower stage, higher expression of hormone receptors, and less HER2 overexpression. Patients with PMBC had better 10-year RFS (71?%) than patients with IDC (64?%). Multivariate analysis revealed that node status and tumor, node, metastasis system (TNM) stage were statistically significant prognostic factors for survival. RFS curves stratified for node status revealed a highly significant difference between node negative and node positive patients. Additionally, patients with PMBC underwent breast-conserving surgery (BCS) more frequently than patients with IDC, and the 5-year overall survival rate of the BCS group was not significantly different from the total mastectomy group.

Conclusions

PMBC in Chinese women showed less aggressive behavior and had a better prognosis than IDC, and this favorable outcome was maintained after 10?years. Node status and TNM stage appeared to be the most significant predictors of worse prognosis. BCS should be preferred over mastectomy in the treatment of early-stage PMBC.     

Steroid Hormone Receptor Immunohistochemistry in Breast Cancer: Past, Present, and Future

This article reviews the development of steroid hormone receptor detection using the biochemical approach and the disadvantages inherent in these systems. The early history of methods for the in situ detection of receptors is related, culminating in the development of histologic immunoassays using monoclonal antibodies. Correlation of the latter with disease-free and overall survival and with clinical endocrine response are presented together with preliminary findings utilizing a new generation of antireceptor antibodies. Current problems with test scoring and interpretation are detailed with a section devoted to image analysis for assay quantification. Emphasis is placed on the fact that because so many different antibodies and tissue substrates have been employed in the past, these histologic receptor immunoassays cannot yet be considered to be fully validated. It is stressed that different laboratories must employ the same antibodies, substrates, detection systems and methods of scoring, and then correlate findings with measurable clinical end points. Only then can the assays be included in the brief list of approved breast cancer prognostic and predictive markers to eventually replace the routine biochemical methods of steroid receptor detection. ▪     

Trends in Incidence and Management of Lobular Carcinoma In Situ: A Population-Based Analysis

Purpose

Lobular carcinoma in situ (LCIS) is a marker of increased risk of breast cancer. Current guidelines do not recommend mastectomy as a strategy for risk reduction for most patients with LCIS. We conducted a population-based study to evaluate national trends in incidence and management of LCIS.

Methods

Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of women diagnosed with microscopically confirmed LCIS from 2000 through 2009. We excluded patients with invasive breast cancer or ductal carcinoma in situ. We evaluated variation in treatment, including biopsy alone, excision, excision with radiation therapy, and mastectomy. We utilized logistic regression to identify time trends, demographics, and patient factors associated with mastectomy.

Results

We identified 14,048 patients diagnosed with LCIS from 2000 to 2009. The rate of LCIS incidence increased from 2.0 per 100,000 in 2000 to 2.75 per 100,000 in 2009 (38 % increase). Of these patients, 10 % underwent biopsy only, 73 % underwent excision alone, 1 % underwent excision with radiation, and 16 % underwent mastectomy. Mastectomy rates were significantly higher among white and younger women. The proportion of women with LCIS to receive mastectomy increased by 50 % from 2000 to 2009 (p < 0.01). Mastectomy rates varied significantly based on geographic region ranging from 12 to 24 %.

Conclusions

This is the first population-based analysis evaluating patterns and trends in surgical management of LCIS. Despite current recommendations, risk-reduction surgery is increasingly performed in the United States for women with LCIS.     

Factors Associated with Breast MRI Use: A Population-Based Analysis

Introduction

Although controversial, the use of breast magnetic resonance imaging (MRI) is widespread. We sought to determine factors that influenced its use in a population-based sample.

Methods

The National Health Interview Survey is conducted annually by the Centers for Disease Control and is designed to be representative of the American population. Data from 2010 were queried for the use of breast MRI and associated sociodemographic and risk characteristics.

Results

Of the 11,222 women aged ≥30 years who were surveyed, 4.7 % reported ever having a breast MRI. Nearly a quarter were done as part of a “routine exam” and <5 % were done for “family history” or for “high risk.” Factors correlating with MRI use on univariate analysis included age, race, personal and/or family history of breast cancer, history of benign breast biopsy, perceived risk, and insurance. On multivariate analysis, African-American race (p = 0.001), personal history (p < 0.001), history of benign biopsy (p < 0.001), and high perceived risk (p < 0.001) were significantly associated with increased MRI use. In a cohort without a personal history of breast cancer, race, history of benign biopsy, and perceived risk were independent correlates of breast MRI, whereas family history, age, and insurance were no longer significant.

Conclusions

Personal history is the strongest factor associated with breast MRI use. However, whereas race, history of benign biopsy, and perceived risk were independently associated with MRI use, family history was not. These findings call into question whether current practice patterns follow evidence-based guidelines.     

Early Detection of Breast Cancer through Population-Based Mammographic Screening in Asian Women: A Comparison Study between Screen-Detected and Symptomatic Breast Cancers

Abstract: The first nation‐wide mammographic screening program in Asia, BreastScreen Singapore (BSS), was launched in Singapore in January 2002. This study compared the presentation and results of screen‐detected breast cancers with symptomatic breast cancers in two affiliated high‐volume institutions, one of which was an assessment centre for BSS. The medical records of patients diagnosed with primary breast cancer at the Department of General Surgery, Singapore General Hospital and the Department of Surgical Oncology, National Cancer Centre, Singapore, during the period January 2002 to December 2003 were reviewed. Clinical and pathological comparisons were made between screen‐detected lesions and symptomatic lesions. Of a total of 767 cases, 640 (83.4%) were invasive carcinomas and 127 (16.6%) were ductal carcinoma in‐situ (DCIS) lesions. Only 13.4% of them were screen‐detected. Compared to symptomatic cancers, screen‐detected lesions were of smaller size (median size 18 versus 23 mm), a lower stage (stages 0–2, 95 versus 83.2%) and histologic grade (grade 1–2, 71 versus 60%), with a higher incidence of DCIS (31.0 versus 14.3%) and had higher rates of breast conservation (45.6 versus 28.2%) (all p‐values <0.05). By multivariate analysis, tumor palpability, tumor size >20 mm, nodal involvement, cerbB2 overexpression, and advanced disease stage were independent poor prognostic factors for disease‐free survival, whereas nodal involvement, advanced disease, and recurrence predicted poor cancer‐specific survival. However, there was no statistically significant difference in disease‐free survival or cancer‐specific survival between the two groups at a median follow‐up of 38 months. Screening mammography has allowed the detection of smaller and hence oncologically more favorable lesions in Asian women. Although no significant survival benefit was demonstrated in our study, a longer period of follow‐up is essential before the benefit of mortality reduction, as a result of mammography screening becomes evident in our population.     

Characteristics and Treatment of Metaplastic Breast Cancer: Analysis of 892 Cases from the National Cancer Data Base

Background Metaplastic breast cancer (MBC) is characterized by various combinations of adenocarcinoma, mesenchymal, and other epithelial components. It was officially recognized as a distinct pathologic diagnosis in 2000. With few published reports, we hypothesized that MBC may have markedly different characteristics at presentation than typical infiltrating ductal carcinoma (IDC) and may be managed differently. Methods Data from patients with MBC and IDC reported to the National Cancer Database from January 2001 through December 2003 were reviewed for year of diagnosis, patient age, race/ethnicity, tumor size, nodal status, American Joint Committee on Cancer (AJCC) stage, tumor grade, hormone receptor status, and initial treatment, and were analyzed statistically by the Pearson χ² test. Results A total of 892 patients with MBC and 255,164 patients with IDC were identified. The group with MBC was older (mean age, 61.1 vs. 59.7 years; P = .001), had a significantly increased proportion of African American (14.1%, 126 of 892, vs. 10.2%, 25,900 of 255,164; odds ratio [OR], 1.455, P = .001) and Hispanic patients (5.5%, 49 of 892 vs. 3.9%, 9,947 of 255,164; OR, 1.817, P = .001), had fewer T1 tumors (29.5% vs. 65.2%), more N0 tumors (78.1% vs. 65.7%, OR, .5, P = .001), more poorly or undifferentiated tumors (67.8% vs. 38.8%), and fewer estrogen receptor–positive tumors (11.3% vs. 74.1%, OR, 22.4, P = .001) than the IDC group. Patients with MBC were treated with breast-conserving surgery less frequently than patients with IDC (38.5% vs. 55.8%, OR, 2.0, P = .001) because of the larger tumor size. Chemotherapy was used more often for patients with MBC (53.4% vs. 42.1%, OR, 1.6, P = .001) because of more advanced AJCC stage. Conclusions MBC is a rare tumor with different characteristics than IDC: it presents with larger tumor size, less nodal involvement, higher tumor grade, and hormone receptor negativity. Patients with MBC are treated more aggressively than IDC (more often with mastectomy and chemotherapy) because of a higher stage at presentation, but are being treated by the same principles as IDC. Follow-up will determine the long-term results of the current treatment. *Members of the Breast Disease Site Team are listed in Appendix 1.     

Recombinant Human Hemoglobin Does Not Affect Renal Function in Humans: Analysis of Safety and Pharmacokinetics

Background: Recombinant human hemoglobin (OptroD; rHb1.1) is a genetically engineered protein produced in Escherichia coli. The two alpha-globin polypeptides are genetically joined, resulting in a stable tetramer that does not dissociate into dimers or monomers. Historically, infusion in humans of acellular hemoglobin preparations has resulted in renal toxicity. This study was performed to evaluate the safety and pharmacokinetics of rHb1.1 when infused in humans.

Methods: After giving informed consent, 48 healthy male volunteers were randomly assigned to receive either 0.015-0.32 g/kg 5% rHb1.1 (n = 34) or an equivalent amount of 5% human serum albumin (HSA; n = 14) infused intravenously over 0.8-1.9 h. Serum creatinine, creatinine clearance, urine N-acetyl-beta-glucosaminidase, and serum rHb1.1 concentrations were measured before and at timed intervals after infusion.

Results: Postinfusion urine N-acetyl-beta-glucosaminidase activity did not exceed preinfusion values at any interval in either group. Serum creatinine did not differ from preinfusion values at 1 day, 2-3 days, or 7 days after infusion for either group. Creatinine clearance increased significantly for the HSA group 12 h after infusion (138 +/- 16 ml/min, means +/- SE) and in the rHb1.1 group 1 day after infusion (112 +/- 5 ml/min; P < 0.05). Values for creatinine clearance did not differ from preinfusion values for either group at any other postinfusion interval; serum creatinine and creatinine clearance did not differ between groups at any time. The amount of hemoglobin excreted in the urine did not exceed approximately 0.04% of the administered rHb1.1 dose in any volunteer. Plasma clearance of rHb1.1 decreased and half-life increased as a function of increasing plasma concentration (e.g., the half-life was 2.8 h at a plasma concentration of 0.5 mg/ml and 12 h at 5 mg/ml). The incidence of gastrointestinal symptoms, fever, and chills was greater after infusion of rHb1.1 than after HSA (P < 0.05).