Racial Disparities in the Use of Peripheral Nerve Blocks for Postoperative Analgesia After Total Mastectomy: A Retrospective Cohort Study.

BACKGROUND: Peripheral nerve blocks (PNBs) are used to provide postoperative analgesia after total mastectomy. PNBs improve patient satisfaction and decrease postoperative opioid use, nausea, and vomiting. Few studies have examined whether there is racial-ethnic disparity in the use of PNBs for patients having total mastectomy. We hypothesized that non-Hispanic Asian, non-Hispanic Black, non-Hispanic patients of other races, and Hispanic patients would be less likely to receive a PNB for postoperative analgesia compared to non-Hispanic White patients having total mastectomy. Secondarily, we hypothesized that PNBs would be associated with reduced odds of major complications after total mastectomy. METHODS: We performed a retrospective cohort study using National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2019. Patients were included if they underwent total mastectomy under general anesthesia. Unadjusted rates of PNB use were compared between race-ethnicity groups. Multivariable logistic regression was performed to determine whether race-ethnicity group was independently associated with receipt of a PNB for postoperative analgesia. Secondarily, we calculated crude and risk-adjusted odds ratios for major complications in patients who received a PNB. RESULTS: There were 64,103 patients who underwent total mastectomy and 4704 (7.3%) received a PNB for postoperative analgesia. Patients who received a PNB were younger, more commonly women, were less likely to have diabetes and hypertension, and had less disseminated cancer (all P < .05). In our regression analysis, the odds of receiving a PNB differed significantly by race-ethnicity group (P < .001). Non-Hispanic Asian and non-Hispanic Black patients had reduced odds of receiving a PNB compared to non-Hispanic White patients (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.33-0.49 and OR, 0.37 [0.32-0.44]), respectively. Non-Hispanic patients of other races, including American Indian, Alaskan Native, and Pacific Islander, also had reduced odds of receiving a PNB (OR, 0.73 [95% CI, 0.64-0.84]) compared to non-Hispanic White patients, as did Hispanic patients (OR, 0.62 [0.56-0.69]). Patients who received a PNB did not have reduced odds of major complications after mastectomy (crude OR, 0.83 [0.65-1.08]; P = .17 and adjusted OR, 0.85 [0.65-1.10]; P = .21). CONCLUSIONS: Significant disparity exists in the use of PNBs for postoperative analgesia in patients of different race-ethnicity who undergo total mastectomy in the United States. Continued efforts are needed to better understand the causes of disparity and to ensure equitable access to PNBs.

Comparative Diagnostic Utility of Low-Dose Breast-Specific Gamma Imaging to Current Clinical Standard.

To retrospectively compare low-dose (7-10 mCi) to high-dose (15-30 mCi) breast-specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low-dose and high-dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow-up imaging to establish true-negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low-dose group and 114 patients with 145 lesions in the high-dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9-99.6%) and 94.6% (95% CI = 84.2-98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2-70.3%) and 50.5% (95% CI = 40.6-60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2-98.3%) and 92.5% (95% CI = 78.5-98.0%, p = 0.781) in the low-dose and high-dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low-dose group and 116 patients with 132 lesions in the high-dose group, with a specificity of 53.7% (95% CI = 39.7-67.1%) and 66.3% (95% CI = 56.2-75.2%%, p = 0.143), respectively. Low-dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false-positives.

miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targets BRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment. METHODS: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays. RESULTS: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells. BRCA1 was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulated BRCA1 expression. CONCLUSIONS: Our findings suggest that miR-638 plays an important role in TNBC progression via BRCA1 deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.

Breast-specific gamma imaging for the detection of breast cancer in dense versus nondense breasts.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity of breast-specific gamma imaging (BSGI) for the detection of breast cancer in dense versus nondense breasts. MATERIALS AND METHODS: This was a retrospective study of 341 women with biopsy-proven breast cancer diagnosed from January 2004 to August 2009 who underwent BSGI before surgical excision. Patients with predominantly fatty replaced (BI-RADS density 1) or scattered fibroglandular tissue (BI-RADS density 2) breasts were classified as nondense, and those with heterogeneously dense (BI-RADS density 3) or extremely dense tissue (BIRADS density 4) were classified as dense. BSGI examinations exhibiting focal increased radiotracer uptake in the area of biopsy-proven cancer were classified as positive according to BSGI reports in the medical record. The sensitivity of BSGI was calculated using Microsoft Excel 2003. Between-group differences were evaluated statistically using the Student t test for continuous variables and the chi-square test for categoric variables, with p < 0.05 considered statistically significant. RESULTS: The overall sensitivity of BSGI for breast cancer detection was 95.4%. Positive BSGI examinations were present in 136 of 142 nondense breast cancers and 195 of 205 dense breast cancers, for sensitivities of 95.8% and 95.1%, respectively. There was no significant difference in BSGI breast cancer detection and parenchymal breast density (p = 0.459). CONCLUSION: BSGI has high sensitivities for the detection of breast cancer in women with dense and nondense breasts and is an effective adjunct imaging modality in women with both dense and nondense breasts.

Breast-specific gamma imaging influences surgical management in patients with breast cancer.

Breast-specific gamma imaging (BSGI) is a physiologic breast imaging modality that provides more sensitive detection of breast lesions than mammography or ultrasound, and appears to have greater specificity than breast MRI. The purpose of this study was to evaluate how often BSGI changed surgical management in patients with breast cancer. Charts were reviewed from 218 consecutive eligible patients who had preoperative evaluation with BSGI or MRI before surgery for breast cancer from January 2008 to May 2010. Patients who were initially considered eligible for breast-conserving therapy (BCT) were evaluated to determine how many ultimately had mastectomies. Patients who underwent mastectomy because of personal choice or ineligibility for BCT were excluded. Management was changed to mastectomy in 11.9% of those who had BSGI and 28.9% of those who had MRI. Review of pathology demonstrated that all patients who underwent mastectomies were not candidates for breast conservation. 15.4% of patients who underwent BCT based on BSGI findings required a single re-excision due to positive surgical margins. 14.4% required mastectomy. In the MRI group, 18.8% required a single re-excision, and 6.3% required mastectomy. Evaluation with BSGI changed management to mastectomy in a substantial proportion of patients believed to be eligible for BCT following standard imaging. BSGI is effective in evaluation of extent of disease in patients with breast cancer, and is comparable to MRI in terms of its influence on surgical management.

Mastectomy and contralateral prophylactic mastectomy rates: an institutional review.

BACKGROUND: Breast conservation surgery (BCS) followed by radiation is as effective as mastectomy for long-term survival and is considered standard of care for early-stage breast cancer. An increasing number of patients are opting for cancer-side mastectomies (CM) and often contralateral prophylactic mastectomies (CPM). Our study investigates if there are increasing trends in our patient population toward CM and CPM and identifies common factors associated with those electing to have more extensive surgery. METHODS: A retrospective analysis was performed on 812 breast cancer surgeries between January 2001 and December 2009 at The George Washington University Breast Care Center. BCS-eligible patients who elected to have BCS were compared with those who chose CM. Patients who underwent CM were compared with patients undergoing CM and CPM. RESULTS: A personal or family history of breast cancer and larger tumor size were positively associated with choosing CM in BCS-eligible patients. A nonstatistically significant trend toward CM was seen in younger patients. Age, family history, fewer children, Caucasian race, and reconstructive surgery were positively associated with choosing CPM. CONCLUSION: Mastectomy rates at this institution have not shown the recent sharp increase observed by some authors. The association of age, race, family history, and parity with CPM has been corroborated in multiple studies. However, there is disagreement between statistically significant findings among investigators evaluating factors associated with CPM, and there is limited data in the literature characterizing BCS-eligible patients who chose CM. Larger prospective studies are necessary to further evaluate CM and CPM rates.

Factors associated with re-excision in patients with early-stage breast cancer treated with breast conservation therapy.

One of the risks of breast conservation surgery is local recurrence, which predominantly occurs as a result of inadequate surgical margins. The purpose of this study was to identify factors associated with close or positive surgical margins leading to reexcision (RE). The charts of 532 consecutive breast cancer patients treated at our center between September 2001 and June 2007 were reviewed to evaluate patients who opted for breast conservation surgery and needed reexcision. A total of 351 patients were treated with breast conservation, of which 118 (34%) had positive or close surgical margins and went on to RE. On univariate analysis, factors that significantly correlated with RE (P < 0.05) were preoperative diagnosis, final pathology, size of tumor, and presentation with nipple discharge. RE was necessary in 53 per cent of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS), 57 per cent of patients diagnosed by surgical excision, 86 per cent of patients presenting with nipple discharge, and 87 per cent of patients with DCIS or invasive carcinoma with extensive intraductal component in the final pathology. Additionally, 53 per cent of patients with T3 tumors required RE. Age, race, and grade of tumor had no effect on RE rates. Most (75%) patients were able to ultimately have breast conservation.

Breast-specific gamma imaging as an adjunct imaging modality for the diagnosis of breast cancer.

PURPOSE: To retrospectively determine the sensitivity and specificity of breast-specific gamma imaging (BSGI) for the detection of breast cancer by using pathologic results as the reference standard. MATERIALS AND METHODS: This study was Institutional Review Board approved and Health Insurance Portability and Accountability Act compliant. Informed consent was obtained for participants who were not imaged as part of their clinical protocol but were participating in other Institutional Review Board-approved studies that used BSGI. A retrospective review of 146 women (aged 32-98 years) undergoing BSGI and breast biopsy was performed. Patients underwent BSGI with intravenous injection of 30 mCi (1110 MBq) of technetium 99 ((99m)Tc)-sestamibi and were imaged in craniocaudal and mediolateral oblique projections. Study images were assigned scores, and scores were classified as positive (focal increased radiotracer uptake) or negative (no uptake or scattered heterogeneous physiologic uptake) and compared with biopsy results. The sensitivity, specificity, and positive and negative predictive values were determined. RESULTS: In 146 patients, 167 lesions underwent biopsy, of which 83 (16 ductal carcinoma in situ [DCIS] and 67 invasive cancers) were malignant. Of 84 nonmalignant lesions, 82 were benign and two showed atypical histologic results (one atypical lobular hyperplasia and one lobular carcinoma in situ). BSGI helped detect cancer in 80 of 83 malignant lesions with a sensitivity of 96.4% (95% confidence interval [CI]: 92%, 99%) and correctly identified 50 of 84 nonmalignant lesions as negative for cancer with a specificity of 59.5% (95% CI: 49%, 70%). The positive predictive value for 80 of 114 malignant lesions with a BSGI examination with findings positive for cancer was 68.8% (95% CI: 60%, 78%) and the negative predictive value for 50 of 53 nonmalignant lesions was 94.3% (95% CI: 88%, 99%). The smallest invasive cancer and DCIS detected were both 1 mm. BSGI helped detect occult cancer not visualized at mammography or ultrasonography in six patients. CONCLUSION: BSIG has high sensitivity (96.4%) and moderate specificity (59.5%) helping detect breast cancers.

Beta protein 1 homeoprotein induces cell growth and estrogen-independent tumorigenesis by binding to the estrogen receptor in breast cancer.

Expression of Beta Protein 1 (BP1), a homeotic transcription factor, increases during breast cancer progression and may be associated with tumor aggressiveness. In our present work, we investigate the influence of BP1 on breast tumor formation and size in vitro and in vivo. Cells overexpressing BP1 showed higher viability when grown in the absence of serum (p < 0.05), greater invasive potential (p < 0.05) and formed larger colonies (p < 0.004) compared with the controls. To determine the influence of BP1 overexpression on tumor characteristics, MCF-7 cells transfected with either empty vector (V1) or overexpressor plasmids (O2 and O4) were injected into the fat pads of athymic nude mice. Tumors grew larger in mice receiving O2 or O4 cells than in mice receiving V1 cells. Moreover, BP1 mRNA expression levels were positively correlated with tumor size in patients (p = 0.01). Interestingly, 20% of mice injected with O2 or O4 cells developed tumors in the absence of estrogen, while no mice receiving V1 cells developed tumors. Several mechanisms of estrogen independent tumor formation related to BP1 were established. These data are consistent with the fact that expression of breast cancer anti-estrogen resistance 1 (BCAR1) was increased in O2 compared to V1 cells (p < 0.01). Importantly, O2 cells exhibited increased proliferation when treated with tamoxifen, while V1 cells showed growth inhibition. Overall, BP1 overexpresssion in MCF-7 breast cancer cells leads to increased cell growth, estrogen-independent tumor formation, and increased proliferation. These findings suggest that BP1 may be an important biomarker and therapeutic target in ER positive breast cancer.

miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer.

MicroRNA (miRNA) dysfunction is associated with a variety of human diseases, including cancer. Our previous study showed that miR-671-5p was deregulated throughout breast cancer progression. Here, we report for the first time that miR-671-5p is a tumor-suppressor miRNA in breast tumorigenesis. We found that expression of miR-671-5p was decreased significantly in invasive ductal carcinoma (IDC) compared to normal in microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. cDNA microarray data revealed that differentially expressed genes when miR-671-5p was transfected are associated with cell proliferation, invasion, cell cycle, and EMT. These data indicate that miR-671-5p functions as a tumor suppressor miRNA in breast cancer by directly targeting FOXM1. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.

Correlation of lymphoscintigraphy with the number of sentinel lymph nodes identified intraoperatively in patients with breast cancer.

BACKGROUND: Numerous studies have evaluated the benefit of performing lymphoscintigraphy for the sentinel lymph node procedure in breast cancer patients. The purpose of this study is to determine if lymphoscintigraphy accurately predicts the number of radioactive sentinel lymph nodes (SLNs) identified during surgery for breast cancer patients. METHODS: From October 2001 to June 2004, SLN biopsy was attempted in 112 patients with breast cancer using a combination of blue dye and radioisotope. Lymphoscintigraphy was performed in 98 of the patients. A lymph node was considered an SLN when it was stained with blue dye, had a blue lymphatic afferent, had increased radioactivity, or was abnormal by palpation. RESULTS: Lymphoscintigraphy accurately predicted the number of radioactive SLN identified intraoperatively in 47 patients. In 44 of the patients who did not have concordance, there were more SLN identified intraoperatively than were seen on lymphoscintigraphy. In the other 8 patients, there were fewer SLN identified intraoperatively than seen on lymphoscintigraphy. CONCLUSIONS: Lymphoscintigraphy accurately predicted the number of SLN identified intraoperatively in only 47% of the patients in this study. In a majority of the patients in whom the lymphoscintigraphy was not concordant, the number of SLN identified intraoperatively was underestimated. Thus, although lymphoscintigraphy is beneficial in showing that at least 1 radioactive SLN will be identified intraoperatively, it does not accurately predict the number.

A retrospective study of the impact of 21-gene recurrence score assay on treatment choice in node positive micrometastatic breast cancer.

To assess clinical utility of the 21-gene assay (Oncotype DX® Recurrence Score®), we determined whether women with HER2(-)/ER+ pN1mi breast cancer with low (<18) Recurrence Scores results are given adjuvant chemotherapy in a lower proportion than those with high scores (≥31). This was a multicenter chart review of ≥18 year old women with pN1mi breast cancer, HER2(-)/ER+ tumors, ductal/lobular/mixed histology, with the assay ordered on or after 1 January 2007. One hundred and eighty one patients had a mean age of 60.7 years; 82.9% had ECOG performance status 0; 33.7% had hypertension, 22.7% had osteoporosis, 18.8% had osteoarthritis, and 8.8% had type-2 diabetes. Mean Recurrence Score was 17.8 (range: 0-50). 48.6% had a mastectomy; 55.8% had a lumpectomy. 19.8% of low-risk group patients were recommended chemotherapy vs. 57.9% in the intermediate-risk group and 100% in the high-risk group (p < 0.001). A total of 80.2% of the low-risk group were recommended endocrine therapy alone, while 77.8% of the high-risk group were recommended both endocrine and chemotherapy (p < 0.001). The Oncotype DX Recurrence Score result provides actionable information that can be incorporated into treatment planning for women with HER2(-)/ER+ pN1mi breast cancer. The Recurrence Score result has clinical utility in treatment planning for HER2(-)/ER+ pN1mi breast cancer patients.

Role of deregulated microRNAs in breast cancer progression using FFPE tissue.

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-ß pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.

Breast-specific gamma imaging in the detection of atypical ductal hyperplasia and lobular neoplasia.

RATIONALE AND OBJECTIVES: Atypical lesions such as atypical ductal hyperplasia (ADH) and lobular neoplasia are nonmalignant lesions that are associated with significant increased risk of developing breast cancer. Atypical lesions have been reported to present with focal increased radiotracer uptake on breast-specific gamma imaging (BSGI) examination, a novel physiologic tool for the detection of breast cancer. To date the sensitivity of BSGI in the detection of atypical lesions has not been reported. The purpose of this study is to determine the sensitivity of BSGI in detecting ADH and lobular neoplasia. MATERIALS AND METHODS: A total of 1316 patients who received a BSGI exam between January 2006 and July 2009 were retrospectively reviewed. All patients who underwent minimally invasive biopsy and subsequent surgical excision where the highest pathology was solely ADH or lobular neoplasia (reported as ALH, lobular carcinoma in situ or lobular neoplasia), according to the pathology database were included (n = 15). The sensitivity was determined as the percentage of positive BSGI exams out of all patients diagnosed with ADH or lobular neoplasia who received a BSGI. RESULTS: Patient ages ranged from 39 to 67 (mean, 52). Eight of 15 patients had ADH, 6/15 lobular neoplasia, and 1/15 ADH and lobular neoplasia in one lesion. Fifteen of the 15 (100%) patients with surgically confirmed ADH or lobular neoplasia had a positive BSGI, with focally increased radiotracer uptake at the site of the verified high-risk lesion. CONCLUSION: BSGI has a high sensitivity for the detection of atypical, high-risk breast lesions. A diagnosis of an atypical lesion is concordant with focal increased radiotracer uptake with BSGI and can identify women at increased risk for breast cancer.

Mastectomy and contralateral prophylactic mastectomy rates: an institutional review.

Background. Breast conservation surgery (BCS) followed by radiation is as effective as mastectomy for long-term survival and is considered standard of care for early-stage breast cancer. An increasing number of patients are opting for cancer-side mastectomies (CM) and often contralateral prophylactic mastectomies (CPM). Our study investigates if there are increasing trends in our patient population toward CM and CPM and identifies common factors associated with those electing to have more extensive surgery.Methods. A retrospective analysis was performed on 812 breast cancer surgeries between January 2001 and December 2009 at The George Washington University Breast Care Center. BCS-eligible patients who elected to have BCS were compared with those who chose CM. Patients who underwent CM were compared with patients undergoing CM and CPM.Results. A personal or family history of breast cancer and larger tumor size were positively associated with choosing CM in BCS-eligible patients. A nonstatistically significant trend toward CM was seen in younger patients. Age, family history, fewer children, Caucasian race, and reconstructive surgery were positively associated with choosing CPM.Conclusion. Mastectomy rates at this institution have not shown the recent sharp increase observed by some authors. The association of age, race, family history, and parity with CPM has been corroborated in multiple studies. However, there is disagreement between statistically significant findings among investigators evaluating factors associated with CPM, and there is limited data in the literature characterizing BCS-eligible patients who chose CM. Larger prospective studies are necessary to further evaluate CM and CPM rates.

Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function.

BACKGROUND: Approximately half of hereditary breast cancers have mutations in either BRCA1 or BRCA2. BRCA1 is a multifaceted tumor suppressor protein that has implications in processes such as cell cycle, transcription, DNA damage response and chromatin remodeling. This multifunctional nature of BRCA1 is achieved by exerting its many effects through modulation of transcription. Many cellular events are dictated by covalent modification of proteins, an important mechanism in regulating protein and genome function; of which protein methylation is an important posttranslational modification with activating or repressive effects. METHODS/PRINCIPAL FINDINGS: Here we demonstrate for the first time that BRCA1 is methylated both in breast cancer cell lines and breast cancer tumor samples at arginine and lysine residues through immunoprecipitation and western blot analysis. Arginine methylation by PRMT1 was observed in vitro and the region of BRCA1 504-802 shown to be highly methylated. PRMT1 was detected in complex with BRCA1 504-802 through in vitro binding assays and co-immunoprecipitated with BRCA1. Inhibition of methylation resulted in decreased BRCA1 methylation and alteration of BRCA1 binding to promoters in vivo as shown through chromatin immunoprecipitation assays. Knockdown of PRMT1 also resulted in increased BRCA1 binding to particular promoters in vivo. Finally, following methylation inhibition, Sp1 was found to preferentially associate with hypo-methylated BRCA1 and STAT1 was found to preferentially associate with hyper-methylated BRCA1. CONCLUSIONS/SIGNIFICANCE: These results suggest that methylation may influence either the ability of BRCA1 to bind to specific promoters or protein-protein interactions which alters the recruitment of BRCA1 to these promoters. Thus, given the importance of BRCA1 to genomic stability, methylation of BRCA1 may ultimately affect the tumor suppressor ability of BRCA1.

Detection of occult foci of breast cancer using breast-specific gamma imaging in women with one mammographic or clinically suspicious breast lesion.

RATIONALE AND OBJECTIVES: The aim of this study was to determine how often breast-specific gamma imaging (BSGI) identifies occult cancerous lesions in women with one suspicious lesion detected on mammography or physical exam. MATERIALS AND METHODS: A retrospective review was performed of the records of all patients who underwent BSGI between January 1, 2004, and June 4, 2007. Included in the study were 159 women who had one suspicious breast lesion on physical exam and/or mammography and who underwent BSGI to evaluate for occult lesions in the breast. All patients had one or more foci of cancer proven pathologically. BSGI findings were classified as normal or abnormal on the basis of the presence of focal radiotracer uptake. RESULTS: BSGI detected additional suspicious lesions occult to mammography and physical exam in 46 of 159 women (29%). BSGI identified occult cancer in 14 of 40 women (35%) who underwent biopsy or excision because of BSGI findings and in 14 of the 159 (9%) women in this study. In nine women, the occult cancer was present in the same breast as the index lesion (6%), and in five women, the occult cancer was found in the contralateral breast (3%). CONCLUSIONS: BSGI is an effective imaging modality in the identification of mammographically and clinically occult cancer in women with one suspicious breast lesion.

BP1, a putative signature marker for inflammatory breast cancer and tumor aggressiveness.

Our previous studies revealed that beta protein 1 (BP1) was barely detectable in normal human breasts, but was seen in 21%, 46%, and 81% of hyperplastic, in situ, and invasive breast lesions, respectively. Our current study attempted to assess BP1 expression in inflammatory breast cancer (IBC), a very aggressive subtype of breast cancers characterized by extensive lympho-vascular invasion and involvement of dermal lymphatics. Paraffin-embedded tissue sections from 45 cases of IBC (nine with paired metastatic lymph nodes) and different controls were assayed immunohistochemically for BP1 expression. Positive BP1 immunoreactivities were present in all IBC cases. Strikingly, all cancer cells metastasized to lymph nodes and cells within lymphatic channels were uniformly and strongly immunoreactive to BP1. The percentage of BP1 positive cells and the intensity of BP1 immunostaining in IBC cases were significantly greater than those in non-IBC cases. Our findings suggest that BP1 may possess properties of onco-proteins that promote tumor progression, invasion, and metastasis, representing a putative signature marker for IBC and tumor aggressiveness.