Determinants of short and long term outcomes in patients undergoing immediate breast reconstruction following neoadjuvant chemotherapy.

BACKGROUND: We evaluated oncologic outcomes and complications of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction (IR) after neoadjuvant chemotherapy (NAC) in patients with early-stage and locally advanced breast cancer (BC). METHODS: BC patients from 2000 to 2014 treated with NAC followed by SSM/NSM and IR were reviewed. Patient demographics, tumor characteristics, NAC response, complications, and recurrence were analyzed. RESULTS: Two hundred sixty-nine patients with 280 BCs were treated with NAC followed by SSM (94%) or NSM (6%) with IR. Median age was 47 (26-72) years with a median follow-up of 45 months. Pathologic complete response (pCR) was noted in 49 (17.5%) cases. Overall 30-day complication rate was 13.2%. Variables associated with complications included BMI (P < 0.0001), tobacco use (P = 0.015), and adjuvant radiation (P = 0.025). Local-regional recurrence was 3.2% and metastatic recurrence was 13.2%. Variables predicting recurrence risk were pre-NAC tumor size (P < 0.001), residual tumor size (P = 0.002), Grade III (P = 0.002), HER-2 negative (P = 0.025), pre-NAC nodal disease (P = 0.05), and lack of pCR (P = 0.045). CONCLUSION: Following NAC, risk factors for complications in patients undergoing SSM/NSM with IR are high BMI, smoking, and adjuvant XRT. SSM/NSM following NAC is associated with excellent local control. These data support expanding the indications for NSM/SSM to include patients receiving NAC.

Immediate Reconstruction in Inflammatory Breast Cancer: Challenging Current Care.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease that is treated with trimodality therapy consisting of neoadjuvant chemotherapy, surgery, and post-mastectomy radiation therapy (PMRT). Traditionally, modified radical mastectomy without reconstruction has been the operation of choice for patients with IBC due to fears of high rates of margin positivity, risk of local recurrence, and the need for PMRT. METHODS: A retrospective review was performed to evaluate women with IBC at our institution from 2006 to 2014 who completed trimodality therapy. Patients were identified as undergoing reconstruction or no reconstruction (NR), with reconstruction being further classified as immediate (IR) if reconstruction occurred at the initial surgery, or delayed (DR) if initial reconstruction occurred after PMRT. RESULTS: Sixty women with IBC were identified using inclusion criteria. The median follow-up was 2.3 years (range 1.4-4.6). Patients with IR had a statistically significant increased risk (p = 0.006) in postoperative complication rates compared with DR (0 %) and NR (2.6 %). Two patients had positive skin margins on final pathology (one IR, one NR), with both eventually having recurrence. Time to PMRT was delayed 10 days in patients with IR compared with those without IR. No statistically significant difference in recurrence rates was observed (p = 0.86) when comparing patients with IR and those with NR, and no difference in survival was observed between patients who had reconstruction and those without (p = 0.91). CONCLUSION: Performing IR with mastectomy for IBC is associated with increased complications, but is not associated with decreased survival or increased recurrence in selected patients. IR in selected IBC patients can facilitate successful breast reconstruction.

Fertility in Women of Reproductive Age After Breast Cancer Treatment: Practice Patterns and Outcomes.

BACKGROUND: Breast cancer is the most frequently occurring cancer in women of reproductive age, and systemic treatments may adversely affect childbearing plans. Use of assisted reproductive technologies and therapies for ovarian protection improve fertility prospects. We evaluated whether patients had a documented fertility discussion (FD) with their oncology physician prior to therapy, what options were chosen, and if pregnancy was achieved. METHODS: A retrospective chart review from 2006 to 2014 was performed to evaluate women aged 40 years and younger who were diagnosed with breast cancer and treated with chemotherapy and/or antihormonal therapy. Patient demographics, treatment regimens, presence or absence of FD, in vitro fertilization (IVF) consultation, gonadotropin-releasing hormone (GnRH) agonist use, and subsequent successful pregnancy were analyzed. RESULTS: Among 303 patients meeting the inclusion criteria, 80 (26 %) had an FD with their physician documented; 71 of these 80 women (89 %) sought further fertility consultation and options. Sixteen (20 %) women were prescribed a GnRH agonist only for ovarian protection during chemotherapy, 50 (63 %) underwent IVF consultation only, and 5 (6 %) had both a GnRH agonist prescribed and an IVF consultation. The overall pregnancy rate was 7 % at a mean of 3 years post breast cancer treatment. Pregnancy after treatment was more common among those pursuing IVF consultation or prescribed a GnRH agonist. CONCLUSIONS: In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility, and discuss preservation options. Although not every woman in this group desired pregnancy, 71/80 (89 %) women having a documented FD sought further fertility consultation and options.

Time-Related Changes in Yield and Harms of Screening Breast Magnetic Resonance Imaging.

PURPOSE: Breast magnetic resonance imaging (MRI) is accepted as a useful adjunct to screening mammography for women at high risk for breast cancer. Nevertheless, concerns about false-positive findings remain, and data about MRI harms and yields are limited. The aim of this study was to quantify harms and yields of breast MRI over time in a large series of patients. METHODS: A retrospective review was performed of patients at increased risk for breast cancer who underwent annual screening digital mammography and MRI from 2007 to 2013. Harms were defined as events not producing a breast cancer diagnosis (ultrasonography [US], imaging-guided core or surgical biopsy procedure, recommendation for short-term follow-up, or a combination). RESULTS: Of 350 high-risk patients offered MRI screening, 320 underwent 757 screening MRI procedures over time. The median age at the first MRI was 48 years. All patients met American Cancer Society criteria for annual screening breast MRI. Total harms were highest with the first MRI procedure and decreased with subsequent MRI screening. Of 75 biopsy procedures performed, including 58 US- or MRI-guided core biopsy procedures and 17 surgical biopsy procedures, 6 specimens were found to be malignant, including 2 resulting from biopsy procedures performed based on findings from the first MRI scan, 0 from the second MRI scan, 3 from the third MRI scan, and 1 from the fourth MRI scan. CONCLUSION: Among women followed with screening MRI, the number of harms was shown to decrease over time. Breast cancer continued to be detected in MRI studies performed over time. This study demonstrates the utility of MRI screening performed over time in high-risk women.

Conservative axillary surgery in breast cancer patients undergoing mastectomy: long-term results.

BACKGROUND: Recently, the American College of Surgeons Oncology Group Z0011 trial demonstrated that axillary lymph node dissection (ALND) could be safely avoided in selected breast cancer patients with limited nodal disease and having breast conservation therapy. However, for node positive (N+) mastectomy patients, full ALND remains the standard of care. Hypothesizing that omission of complete ALND is safe in many N+ breast cancer patients, a hybrid procedure called conservative axillary regional excision (CARE) was developed, consisting of removal of sentinel nodes and other palpable nodes (without intraoperative frozen section or reoperation for N+). STUDY DESIGN: A retrospective review of patients undergoing mastectomy with CARE between 2002 and 2010 was performed. Data collected included demographics; staging; number of lymph nodes removed; adjuvant, antihormonal, and radiation therapies; recurrence; lymphedema; and survival data. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using Cox proportional hazards. RESULTS: Five hundred and eighty-seven patients underwent mastectomy with CARE. Mean follow-up was 5.1 years. A median of 8 nodes were removed. There were 7 patients with local recurrence, of which 3 were axillary recurrences. Lymphedema developed in 20 (3.4%) patients, 75% of which had neoadjuvant chemotherapy. Lymphedema development was associated with the number of lymph nodes removed (p = 0.05) and radiation therapy (p = 0.004). CONCLUSIONS: Conservative axillary regional excision is an excellent model for understanding the role of limited axillary surgery in mastectomy patients. The locoregional recurrence rate among N1 patients having CARE is low (3.4%). Conservative axillary regional excision is also associated with low rates of lymphedema. These data support the use of limited ALND in selected N+ mastectomy patients.

Optimizing clinical management of surgical margins in breast-conserving therapy for breast cancer.

There has been, and continues to be, significant controversy over the definition of an "optimal" surgical margin in breast-conserving therapy (BCT). The historic basis of this controversy stems from the original trials documenting the safety of BCT and many conflicting retrospective studies that have sought to define the association between surgical margin width and outcomes over the last 20 years. It is important to understand that margin assessment is an inexact science, and current laboratory approaches to surgical-margin assessment represent only a sampling of the surgical margin. Currently available evidence suggests that decisions regarding surgical margins in BCT should be made in the context of what is known about the biology of breast cancer, as well the interactions of tumor biology, adjuvant treatment for breast cancer, and outcomes. Achieving consensus on management of surgical margins in BCT should be a clinical priority as it offers the opportunity to reduce the burden of breast cancer treatment on patients without compromising cancer-related outcomes.

A common copy-number breakpoint of ERBB2 amplification in breast cancer colocalizes with a complex block of segmental duplications.

INTRODUCTION: Segmental duplications (low-copy repeats) are the recently duplicated genomic segments in the human genome that display nearly identical (> 90%) sequences and account for about 5% of euchromatic regions. In germline, duplicated segments mediate nonallelic homologous recombination and thus cause both non-disease-causing copy-number variants and genomic disorders. To what extent duplicated segments play a role in somatic DNA rearrangements in cancer remains elusive. Duplicated segments often cluster and form genomic blocks enriched with both direct and inverted repeats (complex genomic regions). Such complex regions could be fragile and play a mechanistic role in the amplification of the ERBB2 gene in breast tumors, because repeated sequences are known to initiate gene amplification in model systems. METHODS: We conducted polymerase chain reaction (PCR)-based assays for primary breast tumors and analyzed publically available array-comparative genomic hybridization data to map a common copy-number breakpoint in ERBB2-amplified primary breast tumors. We further used molecular, bioinformatics, and population-genetics approaches to define duplication contents, structural variants, and haplotypes within the common breakpoint. RESULTS: We found a large (> 300-kb) block of duplicated segments that was colocalized with a common-copy number breakpoint for ERBB2 amplification. The breakpoint that potentially initiated ERBB2 amplification localized in a region 1.5 megabases (Mb) on the telomeric side of ERBB2. The region is very complex, with extensive duplications of KRTAP genes, structural variants, and, as a result, a paucity of single-nucleotide polymorphism (SNP) markers. Duplicated segments are varied in size and degree of sequence homology, indicating that duplications have occurred recurrently during genome evolution. CONCLUSIONS: Amplification of the ERBB2 gene in breast tumors is potentially initiated by a complex region that has unusual genomic features and thus requires rigorous, labor-intensive investigation. The haplotypes we provide could be useful to identify the potential association between the complex region and ERBB2 amplification.

Impact of postmastectomy radiation on locoregional recurrence in breast cancer patients with 1-3 positive lymph nodes treated with modern systemic therapy.

PURPOSE: Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). METHODS AND MATERIALS: We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. RESULTS: We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonal therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with ≥2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. CONCLUSIONS: PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered for PMRT.

Optimizing surgical margins in breast conservation.

Adequate surgical margins in breast-conserving surgery for breast cancer have traditionally been viewed as a predictor of local recurrence rates. There is still no consensus on what constitutes an adequate surgical margin, however it is clear that there is a trade-off between widely clear margins and acceptable cosmesis. Preoperative approaches to plan extent of resection with appropriate margins (in the setting of surgery first as well as after neoadjuvant chemotherapy,) include mammography, US, and MRI. Improvements have been made in preoperative lesion localization strategies for surgery, as well as intraoperative specimen assessment, in order to ensure complete removal of imaging findings and facilitate margin clearance. Intraoperative strategies to accurately assess tumor and cavity margins include cavity shave techniques, as well as novel technologies for margin probes. Ablative techniques, including radiofrequency ablation as well as intraoperative radiation, may be used to extend tumor-free margins without resecting additional tissue. Oncoplastic techniques allow for wider resections while maintaining cosmesis and have acceptable local recurrence rates, however often involve surgery on the contralateral breast. As systemic therapy for breast cancer continues to improve, it is unclear what the importance of surgical margins on local control rates will be in the future.

Mammary ductoscopy and ductal washings for the evaluation of patients with pathologic nipple discharge.

The majority of breast diseases result from lesions of the ductal epithelium. Mammary ductoscopy allows for visualization of intraductal abnormalities, and ductoscopic lavage provides thousands of cells for analysis. We reviewed our experience of 89 cases of patients with pathologic nipple discharge (PND) undergoing ductoscopy-directed duct excision and collection of ductal washings. Patients undergoing ductoscopy-directed duct excision with ductal washings had an 88% abnormal pathology rate. Most abnormalities were benign (71% papillomas), but the atypia rate for this group was 62%. The combination of visualization and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. Cellular yields for this technique were excellent with most specimens yielding >5,000 epithelial cells per high powered field and with evaluable ductal cells in 82% of specimens. Mammary ductoscopy offers the advantage of a high lesion localization rates with intraoperative guidance. The most accurate tool was the combination of ductal washings and ductoscopic visualization, but preoperative use of these techniques is not helpful in most cases. Greater than 90% of patients with PND are found to have a lesion on pathologic examination when using this technique for directed duct excision. Of interest, ductal washings obtained from symptomatic patients with benign diseases are often atypical.

Guidelines for using breast magnetic resonance imaging to evaluate implant integrity.

The purpose of this report was to review our experience with using breast magnetic resonance imaging to evaluate breast implant integrity and to offer a decision tree to assist physicians in managing these patients. Data were available for 81 patients with 146 implants placed either unilaterally or bilaterally for either cosmesis or breast reconstruction. The chief complaint for a majority of patients (n = 24) was breast pain. Thirty-two patients were found to have 44 ruptured implants, the majority of whom were found to have either contracture (n = 7) or negative findings (n = 7) on physician examination. The likelihood of rupture increased with number of years in place. When a patient presents for a possible implant rupture, the initial concern is to rule out malignancy, but because clinical and radiologic findings are often convoluted and complicated, a decision tree is helpful.

The importance of preoperative breast MRI for patients newly diagnosed with breast cancer.

The use of preoperative breast magnetic resonance imaging (bMRI) for patients newly diagnosed with breast cancer has been criticized for increasing the number of therapeutic mastectomies performed, as well as increasing the cost of treatment. The purpose of this report is to examine one surgeon's practice and to describe the MRI findings for patients with breast cancer to determine if those findings changed the therapeutic options for those patients in. Data were collected prospectively between August 2003 and January 2006 for patients newly diagnosed with breast cancer. Diagnoses were made by core biopsy or fine-needle aspiration; all lesions were intact at the time of MRI. Twenty-five percent of patients were found to have previously occult, but suspicious lesions on MRI that required additional diagnostic evaluation, including ultrasound, core biopsy, excisional biopsy, or any combination; for approximately half of these patients a separate cancer was confirmed. For most of these patients, the new lesion was ipsilateral and multicentric, and most required mastectomy. For the remaining 75% of patients, MRI confirmed the index lesion was the only area of concern, and appropriate surgical treatment was completed. Preoperative bMRI for patients newly diagnosed with breast cancer identified previously occult and separate tumors in 13% of patients, resulting in surgical treatment change for many.

Nipple-sparing mastectomy update: one hundred forty-nine procedures and clinical outcomes.

OBJECTIVES: To describe our experience with patients who underwent the nipple-sparing mastectomy procedure developed and standardized at our institution and to report clinical outcomes for those patients with a breast cancer diagnosis. DESIGN: Prospective study for consecutive nipple-sparing mastectomy procedures. SETTING: Multidisciplinary breast center at a large tertiary care facility. PATIENTS: One hundred ten consecutive patients underwent nipple-sparing mastectomy between July 2001 and June 2007. INTERVENTION: Nipple-sparing mastectomy was offered to carefully screened patients; the nipple-areola tissue was cored and sent for histologic frozen-section analysis intraoperatively. MAIN OUTCOME MEASURES: Assessment of nipple-areola cored tissue for neoplastic involvement; postoperative stability of retained nipple-areola complex; and clinical outcomes. RESULTS: Data were available for 149 nipple-sparing mastectomies performed on 110 patients. No procedure performed for prevention had neoplastic involvement of the cored nipple-areola tissue, while 9 procedures performed for breast cancer treatment were found to have neoplastic involvement. Postoperatively, 2 patients had partial loss of the nipple-areola complex due to sloughing and a third patient developed an infection that required surgical removal of the nipple-areola complex. Among patients with breast cancer, none with ductal carcinoma in situ has developed a recurrence, while 4 patients with infiltrating breast cancer have, including 2 patients with distant metastases only, a third with a chest wall recurrence, and a fourth with an axillary recurrence. CONCLUSION: A low incidence of neoplastic involvement of the nipple-areola cored tissue leads to successful completion of nipple-sparing mastectomy for most patients.

Fluorescence in situ hybridization (FISH) as primary methodology for the assessment of HER2 Status in adenocarcinoma of the breast: a single institution experience.

The demand for both reflexed and primary fluorescence in-situ hybridization (FISH) testing in the clinical setting is increasing. Relevant literature has reported the incidence of HER2 overexpression in 20% to 30% of cases, but some reports suggest that HER2 gene amplification rates are substantially lower. Published data, however, on primary FISH assessment from a single institution is limited, especially information about the frequency of the anomalous genotypes defined by FISH. We report our experience with primary FISH testing in 742 consecutive cases of breast cancer, in the calendar year 2006. Eighty percent (595/742) of the breast cancer cases were not amplified for HER2 (HER2/CEP17=0.8-1.9), whereas 19% (142/742) of cases were HER2 amplified (HER2/CEP17>or=2.0). Among the HER2-amplified cases, 3% (19/742) were low-level amplified (HER2/CEP17 ratio=2.0-2.5). Genotypic heterogeneity, defined as >5% but <50% of the tumor cells demonstrating HER2 gene amplification, was observed in 5% (40/7242) of the cases. HER2 monoallelic deletion (HER2/CEP1780% of tumor cells) was observed in 2% (13/742). Polysomy, if defined as CEP17 spot count 3.0 or more in at least 80% of tumor cells, was observed in 3% (20/742) of the cases. These data may be helpful as benchmarks for other institutions initiating primary FISH analysis for HER2 genotyping.

The expression of the cytoskeletal focal adhesion protein paxillin in breast cancer correlates with HER2 overexpression and may help predict response to chemotherapy: a retrospective immunohistochemical study.

Paxillin, a cytoskeletal focal adhesion adaptor protein, has been shown to be transcriptionally up-regulated and phosphorylated by human epidermal growth factor receptor-2 (HER2) signaling in vitro. Paxillin expression may also correlate with HER2 amplification in breast cancer patients. In the current study, we sought to explore the relationship further between paxillin expression and clinicopathologic features and clinical outcome in breast cancer. A total of 314 primary invasive breast carcinomas were assessed for paxillin expression via immunohistochemistry. Paxillin immunoreactivity was compared with estrogen receptor/progesterone receptor status, HER2 status by silver in situ hybridization, age, tumor size, stage, Bloom-Richardson grade, nodal status, disease-free survival (DFS), and overall survival (OS). Paxillin expression was identified in 27.7% of breast carcinomas as diffuse cytoplasmic staining and the expression correlated with HER2 overexpression (p < 0.001). The influence of paxillin on clinical outcome, in particular the response to chemotherapy, appeared to differ depending on the HER2 status of the tumor. For the subset of HER2 nonamplified cases treated with chemotherapy, patients whose tumor showed a loss of paxillin expression demonstrated a significantly lengthened DFS and OS. In contrast, loss of paxillin expression in the HER2 amplified subset of patients who received chemotherapy correlated with a significantly worse outcome. These data suggest that paxillin up-regulation may be a part of the HER2 pathway in some breast cancers and, furthermore, paxillin expression may also influence the clinical response to chemotherapy, depending upon the HER2 status of a given patient's tumor. Further study of a role for paxillin expression in predicting response to cytotoxic regimens or targeted treatments is warranted.

The 2003 revised TNM staging system for breast cancer: results of stage re-classification on survival and future comparisons among stage groups.

BACKGROUND: Changes to TNM staging criteria for breast cancer, introduced in 2003, have resulted in stage re-classification for some tumors. The most frequently implemented change has resulted in tumors associated with more than three positive axillary nodes being upstaged. We hypothesize these TNM staging changes would result in more TNM Stage IIB, IIIA, and IIIB tumors and that disease-specific survival estimates would change under the new staging system. METHODS: A review of data was completed for patients diagnosed with breast cancer between 1 January 1995 and 31 December 2000. Tumors that would have been staged differently under the 2003 system were identified and re-classified. Clinical outcomes were determined and disease-specific survival estimates were compared relative to TNM Stage using the old and new staging systems. Data were analyzed using the log-rank test and the method of Kaplan and Meier was used to generate survival curves. RESULTS: Data were available for 2492 tumors, of which 919 were candidates for re-classification, including 829 old Stage II, 59 old Stage III, and 31 old Stage IV. Of these 919, 159 (17%) underwent stage re-classification using the new system. Separate survival estimates for patients who had been under old stage IIA/B, IIIA/B were generated; patients upstaged from IIA or IIB demonstrated a significant difference in survival. CONCLUSIONS: Stage specific survival curves indicated decreased survival for patients whose tumors had been upstaged from IIA or IIB under the old system; survival for all other patients remained unchanged.

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.

Identification of breast cancer in patients with pathologic nipple discharge: does ductoscopy predict malignancy?

OBJECTIVE: The purpose of the current study was to review characteristics of patients with nipple discharge who underwent ductoscopy-assisted excisional biopsy who had a final diagnosis of carcinoma. METHODS: A retrospective review was performed of patients presenting with pathologic nipple discharge (PND) who underwent ductoscopy-assisted excisional biopsy and had a final diagnosis of carcinoma. RESULTS: A total of 14 (7%) of 188 patients who underwent ductoscopy-assisted excision had a final pathology of ductal carcinoma-in-situ (DCIS) (12/14, 86%) or invasive breast cancer with DCIS (2/14, 14%). Duct wall irregularities or intraluminal growths were visualized during ductoscopy in 8 of the 14 (57%) breast cancer patients. There were no visual abnormalities noted during ductoscopy that accurately predicted a final diagnosis of malignancy. CONCLUSIONS: Although occult malignancies can be identified in patients undergoing ductoscopy-assisted biopsy for PND, no clear morphologic changes visualized during ductoscopy definitively indicated the presence of malignancy.