Short-Duration Rapid Chilling of Mastectomy Specimens Does Not Interfere With Breast Cancer Biomarker and Molecular Testing.

CONTEXT.­: A thorough gross examination of specimens for breast cancer requires the tissue to be very thinly sectioned, which is often difficult in large mastectomy samples. We have implemented rapid chilling of mastectomy specimens before formalin fixation. OBJECTIVE.­: To evaluate the effects of rapid chilling of breast tissue on subsequent biomarker and molecular testing. DESIGN.­: Mastectomy specimens were chilled at -80°C for 20 minutes to facilitate uniform sectioning of tissue at 4-mm intervals and enhance proper fixation and identification of small lesions. The integrity of chilled tissue for ancillary and molecular testing was assessed. We identified patients who were diagnosed with breast cancer on biopsy at outside institutions and subsequently underwent mastectomy at our institution during 2010-2014. We compared the results of biomarker testing performed on biopsy tissue with those performed on mastectomy tissue. The quantity and quality of DNA extracted from formalin-fixed, paraffin-embedded (FFPE) mastectomy tissue with invasive carcinoma were assessed by using spectrophotometry and polymerase chain reaction. All Oncotype DX reports from 2011-2014 were reviewed to identify any documented evidence of assay interference caused by rapid chilling of tissue. RESULTS.­: We found essentially 100% concordances in estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 gene ERBB2 (HER2/neu) studies. Extracted tumor DNA showed suitable purity and concentration that produced amplified fragments of 300 to 400 base pair lengths by polymerase chain reaction of FFPE tissue. No documented assay interferences were found in the Oncotype DX reports. CONCLUSIONS.­: Short-duration rapid chilling of mastectomy tissue improves gross examination, optimally preserves DNA, allows for molecular testing, and does not interfere with biomarker assessment.

Silicone breast implant associated fibromatosis.

Extra-abdominal desmoid tumors, also known as aggressive or deep fibromatosis, are uncommon soft tissue tumors that rarely involve the breast. Although the exact etiology is unknown, the development of these tumors has been correlated with sites of previous trauma, surgery or in association with familial adenomatous polyposis. Clinically, breast fibromatosis is often mistaken for carcinoma but lacks metastatic potential. It is locally aggressive with high rates of recurrence. The treatment is primarily wide local excision with negative margins. Adjuvant treatments have been suggested and include radiotherapy, chemotherapy and hormonal therapy, however, there are no evidence-based treatment protocols to support their use. Here, we describe a case of fibromatosis that developed within the capsule around a silicone breast implant treated with surgical excision alone. The patient remains recurrence free at 3 months post-operative magnetic resonance imaging.

Cholangiocarcinoma Presenting as Linitis Plastica with Unusual Metastases to the Psoas Muscle and Urinary Bladder.

Cholangiocarcinoma offers poor prognosis. Infrequent sites of metastasis are poorly described and often diagnostically delayed or missed. Bile duct brush cytologies provide poor diagnostic sensitivity/specificity. We present an unusual case of cholangiocarcinoma in a 34-year-old woman with rare distant metastasis to the psoas muscle and urinary bladder. It is the first case of metastatic cholangiocarcinoma presenting as linitis plastica, and our patient is the youngest to be described with metastatic cholangiocarcinoma to the psoas muscle leading to diagnosis. We conclude that seemingly idiopathic biliary strictures that fail to respond to testing should prompt alarm and referral for cholangioscopy, where available.

Assessment of gut microbiota populations in lean and obese Zucker rats.

Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.

Effects of Obesity on Pro-Oxidative Conditions and DNA Damage in Liver of DMBA-Induced Mammary Carcinogenesis Models.

The prevalence of the overweight and obesity is on the rise worldwide. Obesity can increase the risk of certain cancers and liver steatosis development. Previously, we reported that obesity increased liver steatosis in a mammary tumor model, but little is known about the effects of obesity in the liver in regard to global DNA methylation, DNA damage, and oxidative/nitrosative stress. Using a mammary tumor model, we investigated the effects of obesity on oxidative stress and DNA reaction. Five-week-old lean and obese female rats were used. At 50 days of age, all rats received 7,12-dimethylbenz(α)anthracene (DMBA) and were sacrificed 155 days later. HPLC with electrochemical and ultraviolet detection and LC-MS were used. Obesity caused higher (p < 0.0004) methionine levels, had no effect (p < 0.055) on SAM levels, caused lower (p < 0.0005) SAH levels, caused higher (p < 0.0005) SAM/SAH ratios, and increased (p < 0.02) global DNA methylation. Levels of free reduced GSH were not significantly lower (p < 0.08), but free oxidized GSSG was higher (p < 0.002) in obese rats. The GSH/GSSG ratio was lower (p < 0.0001), and oxidized guanosine was higher (p < 0.002) in DNA of obese rats compared to lean rats. Obesity caused significant oxidative/nitrosative stress, oxidative DNA damage, and change of DNA methylation pattern in the liver, and these changes may contribute to the development of liver steatosis in breast cancer models.

Dehydroepiandrosterone (DHEA) Feeding Protects Liver Steatosis in Obese Breast Cancer Rat Model.

Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels. Female Zucker rats were randomly assigned to either a control diet or a control diet with DHEA supplementation for 155 days. Livers were collected for histological examination. Serum was collected to measure DHEA, DHEA-S, IGF-1, and IGFBP-3. Our results show that DHEA-fed rats had significantly less liver steatosis (p < 0.001) than control-fed rats and gained less weight (p < 0.001). DHEA feeding caused significant decreases (p < 0.001) in the serum levels of IGF-1 and IGFBP-3 and significantly increased (p < 0.001) serum levels of DHEA and DHEA-S. Our results suggest that DHEA feeding can protect against liver steatosis by reducing body weight gain and modulating serum IGF-1 and IGFBP-3 levels in an obese breast cancer rat model.

Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?

BACKGROUND: We hypothesized that disconcerting lymphedema rates in both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may be because of unrecognized vunerable variations in arm lymphatic drainage within the axilla. Axillary reverse mapping (ARM) facilitates identification and avoidance of arm lymphatics within the axilla and its use may reduce lymphedema. METHODS: This institutional review board-approved study from June 2007 to December 2013 involved patients undergoing SLNB with or without ALND, or ALND alone. Technetium is injected subareolarly for localization of the breast SLN and isosulfan blue dye (5 mL) is injected in the ipsilateral upper arm for localization of nonbreast lymphatics. Data were collected on identification and preservation of arm lymphatics, crossover rates, blue node metastases, axillary recurrence, and lymphedema as measured by volume displacement. RESULTS: A total of 654 patients prospectively underwent 685 ARM procedures with a SLNB and/or ALND. Objective lymphedema rates for SLNB and ALND were 0.8% and 6.5% respectively, with 26-month median follow up. Blue lymphatics were identified in 29.2% (138/472) of SLNB and 71.8% (153/213) of ALND. Crossover was seen in 3.8% (18/472) of SLNB and 5.6% (12/213) of ALND. Blue node metastases rate was 4.5% (2/44). Axillary recurrence rate was 0.2% and 1.4% for SLNB and ALND, respectively. CONCLUSIONS: ARM allows frequent identification of arm lymphatics in the axilla, which would have been transected during routine surgery. Rates of metastases in noncrossover nodes and axillary recurrences are low. Lymphedema rates are dramatically reduced using ARM when compared with accepted standards.

Rapid onsite evaluation: A comparison of cytopathologist and pulmonologist performance.

BACKGROUND: Rapid onsite evaluation (ROSE) has several potential benefits but also can prolong procedures if one must wait for a cytopathologist, and it can involve a considerable time commitment on the part of the cytopathologist. At the University of Arkansas for Medical Sciences, interventional pulmonologists have routinely reviewed cytology specimens. This study was performed to determine prospectively how accurately pulmonologists could perform ROSE and whether they could contribute to the efficiency of the process. METHODS: For sequential cases, the procedural pulmonologist documented a ROSE reading before the reading by the cytopathologist. Readings were compared between the two for agreement and for accuracy. The time commitment for the cytopathologist was also recorded. RESULTS: One hundred sixty-four sites were biopsied in 102 patients. With respect to onsite adequacy, there was a high level of concordance between pulmonology and cytopathology as evidenced by the κ score ( ± standard error) of 0.72 ± 0.15 and by disagreement in only 3 cases (2%). For the diagnostic category, there was once again a high level of concordance; there was agreement in 141 of the 164 cases (86%), and the weighted κ score was 0.89 ± 0.02. The cytopathologist's time in the endoscopy suite averaged 4.02 ± 6.9 minutes per procedure. CONCLUSIONS: Procedural pulmonologists can effectively learn enough cytology to be able to make ROSE a collaborative process and to greatly increase the efficiency of the cytopathologist.

Short- and Long-Term Soy Diet Versus Casein Protects Liver Steatosis Independent of the Arginine Content.

Nonalcoholic fatty liver disease, a major cause of abnormal liver function, is often associated with obesity. Arginine (ARG) plays a role in modulating body weight/fat, but limited data exist as to the role of ARG in soy protein's ability to protect from liver steatosis. We investigated the role of native ARG in the soy protein isolate (SPI) in reducing liver steatosis in male obese Zucker rats. Rats (N=48; 6 weeks old) were randomly assigned to one of three diets for 8 or 16 weeks: the casein (CAS) diet as control (0.6% ARG), CAS diet supplemented to contain 1.3% ARG, or an SPI diet containing isoflavones (1.3% ARG). SPI and ARG rats gained significantly more weight (P<.05) than CAS rats after 16 weeks only. The SPI rats had lower liver steatosis scores after 8 and 16 weeks (P<.05 and P<.001, respectively) compared to CAS and ARG rats. SPI rats had lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P<.05) compared to CAS after 16 weeks, and AST was lower (P<.05) compared to ARG rats. After 16 weeks, the SPI rats had lower (P<.05) serum ALT and AST levels than at 8 weeks. Our results suggest that a longer period of SPI feeding results in lower liver steatosis and serum ALT and AST levels, while the ARG diet had no effect on steatosis or ALT and AST levels. We found that the SPI diet reduced (P<.001) serum tumor necrosis factor-α (TNF-α) compared to CAS and ARG diets after 8 and 16 weeks. The SPI diet significantly reduced (P<.001) interleukin-6 (IL-6) when compared to the CAS diet at 8 weeks, but there was no significant difference at 16 weeks. Based on the findings of our study, the protective effect of SPI in reducing liver steatosis is not modulated by its native arginine content.

Whey Protein Hydrolysate but not Whole Whey Protein Protects Against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats.

Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44-49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified.

The SAVE review: sonographic analysis versus excision for axillary staging in breast cancer.

BACKGROUND: Health care reform goals involve more cost-effective methods of delivering health care. The cost-effectiveness of axillary ultrasound-guided core needle biopsy (AUS-CNB) was compared with sentinel lymph node biopsy (SLNB) when evaluating the status of the axilla in operable invasive breast cancer. STUDY DESIGN: We performed an IRB-approved retrospective review of patients undergoing ultrasound of the axilla plus core needle biopsy at our institution from 2007 to 2012. An accuracy of technique and cost analysis (TreeAge Pro 2009) of AUS-CNB vs SLNB was conducted. RESULTS: The cohort of 95 patients was divided into 2 groups: clinically positive (CP) (32%) and negative (CN) (68%) axilla. In the CP group, 83% had a suspicious AUS, of which 90% were positive. In the CN group, AUS was suspicious in 70%, with a positive biopsy in 59%. The sensitivity and specificity of AUS-CNB were 90% (95% CI 84.8% to 98.8%) and 100% (95% CI 27% to 59.1%), respectively. Cost estimates comparing AUS-CNB with SLNB demonstrated a cost saving of $236,517 in the CP axilla and $248,490 in the CN axilla, for a total cost savings of $485,007. CONCLUSIONS: Axillary ultrasound-guided core needle biopsy is a sensitive, diagnostic, surgeon-performed procedure. It is time-saving, cost-efficient, and less invasive, making it a viable option when evaluating the status of the axilla in invasive breast cancer or staging before neoadjuvant chemotherapy.

CHST11 gene expression and DNA methylation in breast cancer.

Our previously published data link P-selectin-reactive chondroitin sulfate structures on the surface of breast cancer cells to metastatic behavior of cells. We have shown that a particular sulfation pattern mediated by the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness of human breast cancer cell lines. The present study was performed to evaluate the prognostic value of CHST11 expression and determine whether aberrant DNA methylation controls CHST11 expression in breast cancer. Publicly available datasets were used to examine the association of CHST11 expression to aggressiveness and progression of breast cancer. Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2'-deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation bisulfite sequencing was performed in the CpG island of CHST11 with a minimum coverage of 10. Quantitative real-time RT-PCR was employed to confirm the expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS-A). The expression of CHST11 was significantly higher in basal-like and Her2-amplified cell lines compared to luminal cell lines. CHST11 was also highly expressed in cancer tissues compared to normal tissues and the expression levels were significantly associated with tumor progression. We observed very low levels of DNA methylation in a CpG island of CHST11 in basal-like cells but very high levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal cell line with very low expression of CHST11, with 5AzadC increased the expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner. These results suggest that CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the methylation status of this gene also has potential as a prognostic biomarker.

Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer.

OBJECTIVES: To evaluate the pathologic complete response (pCR) and safety of bevacizumab (B) with chemotherapy in the neoadjuvant setting of breast cancer (BC). METHODS: A prospective single-arm, single-institution phase II trial for women with stage IIA-B/IIIA-B-C BC. Patients received neoadjuvant docetaxel, cyclophosphamide, B every 3 weeks for 4 cycles followed by doxorubicin every 3 weeks for 4 cycles followed by surgery. After healing, B was given every 3 weeks for 9 cycles. Radiation therapy, trastuzumab and endocrine therapy were given as indicated. RESULTS: Thirty-nine of 40 patients were evaluable. Median age of participants was 45 years (range, 26 to 72 y). The most serious grade ≥3 adverse events were infection (4), congestive heart failure (2), and pulmonary embolism (1). Thirty-eight of 39 patients underwent surgery. The pCR rate was 41% (16/39), significantly higher than the null-hypothesis rate of 25% (P=0.0204). Rates of pCR were 52% (15/29) in ductal carcinoma compared with 10% (1/10) in nonductal disease (P=0.021), and 59% (10/17) in estrogen receptor-/progesteron receptor- patients compared with 27% (6/22) among patient with at least one positive hormone receptor (P=0.047). African Americans (AA) had 75% pCR (9/12), whereas Whites had only 28% pCR (7/25; P=0.0069), possibly in part because 100% of AA (12/12) had ductal carcinoma compared with only 64% (16/25) of Whites (P=0.017). CONCLUSIONS: Chemotherapy with B improved pCR in BC patients, but was associated with significant toxicity and rare but very serious complications. The improvement was more pronounced in AA patients, those with ductal carcinoma, and those with estrogen receptor-/progesteron receptor - BC.ClinicalTrials.gov Identifier: NCT00203502.

Axillary reverse mapping: five-year experience.

BACKGROUND: We hypothesize that mapping the lymphatic drainage of the arm with blue dye (axillary reverse mapping [ARM]) during axillary lymphadenectomy decreases the likelihood of disruption of lymphatics and subsequent lymphedema. METHODS: This institutional review board-approved study involved 360 patients undergoing sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) from May 2006 to October 2011. Technetium sulfur colloid (4 mL) was injected subareolarly, and 5 mL of blue dye was injected subcutaneously in the volar surface ipsilateral upper extremity (ARM). Data were collected on variations in lymphatic drainage, successful identification and protection of arm lymphatics, crossover, and occurrence of lymphedema. RESULTS: A group of 360 patients underwent SLNB and/or ALND, 348 of whom underwent a SLNB. Of those, 237 (68.1%) had a SLNB only, and 111 (31.9%) went on to an ALND owing to a positive axilla. An additional 12 of 360 (3.3%) axilla had ALND owing to a clinically positive axilla/preoperative core needle biopsy. In 96% of patients with SLNB (334/348), breast SLNs were hot but not blue; crossover (SLN hot and blue) was seen in 14 of 348 patients (4%). Blue lymphatics were identified in 80 of 237 SLN incisions (33.7%) and in 93 of 123 ALND (75.4%). Average follow-up was 12 months (range, 3-48) and resulted in a SLNB lymphedema rate of 1.7% (4/237) and ALND of 2.4% (3/123). CONCLUSION: ARM identified substantial lymphatic variations draining the upper extremities and facilitated preservation. Metastases in ARM-identified lymph nodes were acceptably low, indicating that ARM is safe. ARM added to present-day ALND and SLNB may be useful to lesser rates of lymphedema.

Long-term results of phase II ablation after breast lumpectomy added to extend intraoperative margins (ABLATE l) trial.

BACKGROUND: Excision followed by radiofrequency ablation (eRFA) is an intraoperative method that uses intracavitary hyperthermia to create an additional tumor-free zone around the lumpectomy cavity in breast cancer patients. We hypothesized that eRFA after lumpectomy for invasive breast cancer could reduce the need for re-excision for close margins as well as potentially maintain local control without the need for radiation. STUDY DESIGN: This prospective phase II institutional review board-approved study was conducted from March 2004 to April 2010. A standard lumpectomy was performed, then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 °C for 15 minutes. Validated Doppler sonography was used to intraoperatively determine adequacy of ablation. RESULTS: One hundred patients were accrued to the trial, with an average age of 65.02 years ± 10.0 years. The stages were Tis (n = 30); T1mic (n = 1); T1a (n = 9); T1b (n = 27); T1c (n = 22); T2 (n = 10) ; and T3 (n = 1). Grades were I (n = 48); II (n = 29); and III (n = 23). Seventy-eight subjects had margins >2 mm (negative), 22 patients had margins ≤ 2 mm, of which 12 were close and 3 focally positive, which, at our institution, would have required re-excision (only 1 patient in this group had re-excision). There were 6% postoperative complications, and 24 patients received radiation therapy (XRT). During the study mean follow-up period of 62 months ± 24 months (68-month median follow-up) in patients not treated with XRT, there were 2 in-site tumor recurrences treated with aromitase inhibitor, 3 biopsy entrance site recurrences treated with excision and XRT to conserve the breast, and 2 recurrences elsewhere and 1 contralateral recurrence; all 3 treated with mastectomy. CONCLUSIONS: Long-term follow-up suggests that eRFA may reduce the need for re-excision for close or focally positive margins in breast cancer patients, and eRFA may be a valuable tool for treating favorable patients who desire lumpectomy and either cannot or do not want radiation. A multicenter trial has been initiated based on these results.

Surgeon-performed touch preparation of breast core needle biopsies may provide accurate same-day diagnosis and expedite treatment planning.

BACKGROUND: We aimed to determine the accuracy of surgeon-performed touch-preparation cytology (TPC) of breast core-needle biopsies (CNB) and the ability to use TPC results to initiate treatment planning at the same patient visit. METHODS: A single-institution retrospective review of TPC results of ultrasound-guided breast CNB was performed. All TPC slides were prepared by surgeons performing the biopsy and interpreted by the pathologist. TPC results were reported as positive/suspicious, atypical, negative/benign, or deferred; these were compared with final pathology of cores to calculate accuracy. Treatment planning was noted as having taken place if the patient had requisition of advanced imaging, referrals, or surgical planning undertaken during the same visit. RESULTS: Four hundred forty-seven CNB specimens with corresponding TPC were evaluated from 434 patient visits, and 203 samples (45.4 %) were malignant on final pathology. When the deferred, atypical, and benign results were considered negative and positive/suspicious results were considered positive, sensitivity and specificity were 83.7 % (77.9-88.5 %) and 98.4 % (95.9-99.6 %), respectively; positive and negative predictive values were 97.7 % (94.2-99.4 %) and 87.9 % (83.4-91.5 %), respectively. In practice, patients with atypical or deferred results were asked to await final pathology. An accurate same-day diagnosis (TPC positive/suspicious) was hence feasible in 83.7 % (170 of 203) of malignant and 79.5 % (194 of 244) of benign cases (TPC negative). Of patients who had a same-day diagnosis of a new malignancy, 77.3 % had treatment planning initiated at the same visit. CONCLUSIONS: Surgeon-performed TPC of breast CNB is an accurate method of same-day diagnosis that allows treatment planning to be initiated at the same visit and may serve to expedite patient care.

Nipple skin-sparing mastectomy is feasible for advanced disease.

BACKGROUND: Skin-sparing mastectomy (SSM) or nipple skin-sparing mastectomy (NSSM) are procedures commonly offered as part of the surgical treatment for breast cancer. Each involves a mastectomy with preservation of the skin overlying the breast (in SSM) and often also the skin overlying the nipple-areolar complex (NSSM). At the time of mastectomy, immediate reconstruction with a tissue expander or implant is performed for a more favorable cosmetic outcome. Until now, these procedures have been reserved for low-risk patients and are rarely offered to patients with advanced disease where neoadjuvant chemotherapy and postmastectomy radiation are a planned part of the treatment. We report our experience of SSM and NSSM in such high-risk patients. METHODS: This retrospective study from 2001 to 2012 evaluates the outcomes of 527 patients who underwent SSM or NSSM. Sixty patients with advanced disease who underwent neoadjuvant chemotherapy followed by SSM or NSSM with immediate reconstruction and subsequent radiotherapy (RT) were identified. The cosmetic and oncologic outcomes of this patient group were noted. RESULTS: A total of 527 patients in our study group had a total of 1,035 skin-sparing mastectomies (558 NSSM and 477 SSM; 444 patients with bilateral and 83 with unilateral procedures). Of the 60 patients with locally advanced disease, 39 underwent NSSM and 21 underwent SSM. All patients received RT to the diseased side. Mean age of the group was 50.2 ± 10.8 years, with a range of 27-75 years for NSSM and 29-73 years for SSM. The lymph node status was positive in 71.8 % with an average tumor size of 3.8 ± 2.5 cm. The overall radiation-induced complication rate was 38.1 % (8 of 21) in the SSM group and 30.8 % (12 of 39) in the NSSM group. Wound infections and tissue necrosis occurred at a rate of 16.7 %. The implant was removed in 5 % of these cases. Capsular contracture occurred at a rate of 10.2 %. Radiation-related nonbreast complications occurred in 6.7 % of the cases. Examples of these radiation-related nonbreast complications included radiation pneumonitis, stenosis of the superior vena cava requiring venoplasty and severe atypical chest pain thought to be consistent with osteochondritis. The locoregional recurrence rate (median follow-up of 18 months) was 14.3 % (3 of 21) in the SSM group and 10.3 % (4 of 39) in the NSSM group. CONCLUSIONS: SSM and NSSM have been offered to patients with relatively low-risk breast cancer as oncologically safe while affording superior cosmesis with one-step immediate reconstruction. Our series demonstrates that either procedure can be offered to patients with more advanced cancers requiring postoperative RT. The complication rates are comparable to those reported for patients undergoing RT after traditional mastectomies.

Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy. METHODS: Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003). RESULTS: A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal. CONCLUSIONS: Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.

Race is not a factor in overall survival in patients with triple negative breast cancer: a retrospective review.

The purpose of this study was to determine if race is a factor on overall survival when stage at diagnosis is compared. In this study, a total of 93 women with triple negative breast cancer (TNBC) were evaluated for survival outcomes after diagnosis between the year 2000 through 2010. Thirty-five patients (38%) were African American (AA), and 58 patients (62%) were Caucasian. Overall survival rates were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Student's t-test was used to calculate differences in cancer recurrence and mortality rates by stage and race. Cox proportional hazards ratios were used to determine the association of patient and variables with clinical outcome. Of women diagnosed with stage 1 breast cancer, the overall survival rates for AAs was 100% compared to Caucasians at 94% (95% CI, 0.003 to 19; P = 0.5). For women with stage 2 breast cancer, overall survival for AA women was 85% and for Caucasian women was 86% (HR = 0.8; 95% CI, 0.3 to 2.6; P = 0.73). For advanced stages (stage 3 and 4), survival for AA women were 78% and 40% for Caucasian women (HR = 0.6; 95% CI 0.2 to 1.98; P = 0.43). Rates of recurrence and mortality were not significantly different between AA and Caucasian TNBC patients. After controlling for patient variables, race was not significantly associated with OS (HR = 1.24; 95% CI, 0.32 to 5.08; P = 0.74) when comparing AA to Caucasian patients. Our study suggests that race does not have an effect on overall survival in African American and Caucasian women diagnosed with TNBC in Arkansas.

Long-term results of excision followed by radiofrequency ablation as the sole means of local therapy for breast cancer.

INTRODUCTION: Clinical trials have yet to find a size or grade of invasive cancer which can be treated with lumpectomy alone due to the higher local recurrence (LR) rate without radiation (XRT). Excision followed by radiofrequency ablation (eRFA) is an intraoperative method which utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA after lumpectomy for invasive breast cancer could reduce the need for re-excision in close margins and potentially maintain local control without the need for XRT. METHODS: This institutional review board-approved study from July 2002 to December 2010 involved patients undergoing eRFA. A standard lumpectomy was performed and then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 °C for 15 min. Validated doppler sonography was used to determine final ablation size. RESULTS: Seventy-three patients (mean age of 68.8 ± 10.9 years) with invasive cancer who had an average tumor size of 1.0 ± 0.54 cm (range of 0.2-2.6 cm) underwent eRFA. Margins were negative in 54, close in 10, focally positive in 6, and grossly positive in 3 patients. Sixteen out of 19 (84 %) of patients with close or positive margins were spared of re-excision. Median follow-up was 55 ± 21 months. Only one patient (1.3 %) developed an in site recurrence. There were three recurrences, elsewhere. CONCLUSIONS: Long-term follow-up suggests that eRFA may reduce the need for re- excision as well as reduce LR for invasive breast cancer treated without XRT.