Avoiding mastectomy: accelerated partial breast irradiation for breast cancer patients with pacemakers or defibrillators.

INTRODUCTION: The objective of this study was to evaluate the safety, toxicity, and planning concerns involved in accelerated partial breast irradiation (APBI) for patients with breast cancer who have a pacemaker or an automatic implantable cardioverter-defibrillator (AICD) and who desire breast conservation. METHODS: We performed a review of prospectively obtained data for patients with early-stage breast cancer with a pacemaker or AICD treated between April 2007 and July 2010. Patients were treated with either 3D conformal external beam irradiation (3D-CRT) or high-dose rate balloon brachytherapy (HDRBB) as performed in the National Surgical Adjuvant Breast and Nowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 protocol. Device interrogation was performed after the first and last radiation treatment, with comparative cardiac monitoring performed before and after the first three treatments. RESULTS: Eight patients were treated and have a mean follow-up of 6 months. Three patients received HDRBB delivering 34 Gy in 10 fractions. Mean planning target volume for evaluation (PTV_EVAL) coverage was 93.6%. The maximum radiation dose delivered to any device was 1.03 Gy, with a mean pacemaker distance to lumpectomy cavity (DLC) of 9.1 cm. Five patients received 3D-CRT consisting of 38.5 Gy in 10 fractions. The mean 90% PTV_EVAL coverage was 97.3%. Maximum dose delivered to any device was 1.68 Gy at a DLC of 9 cm. Local toxicity did not exceed grade 1, and no adverse device events were noted. CONCLUSIONS: APBI in patients with pacemakers or AICDs who desire breast preservation seems to be a technically safe and reasonable application of targeted radiation therapy.

Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients.

BACKGROUND: To determine the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of clinical examination and breast imaging techniques in determining pathologic complete response in patients with locally advanced breast cancer after neoadjuvant therapy. METHODS: A retrospective review was performed of data collected from patients treated with either neoadjuvant hormonal or chemotherapy between January 2005 and September 2010. Patients were evaluated by one of three surgical breast oncologists before neoadjuvant therapy and within 1 month before surgery by clinical breast examination (CBE), digital mammogram, breast ultrasound, and/or magnetic resonance imaging (MRI). The accuracy, NPV, and PPV of each modality was calculated on the basis of the final pathologic report. Available data from the literature was synthesized. RESULTS: Sixty-two tumors in 61 patients with a mean age of 56 (range 34-87) years were evaluated. Overall accuracy ranged from 54% (CBE) to 80% (breast ultrasound). All modalities had a PPV greater than 75% for identifying the presence of residual disease. The PPV of each modality was generally higher in the younger patients. The NPV of all methods was less than 50%. The accuracy and NPV were compromised even further in younger patients. The combination of our own data with data available from the literature revealed MRI to be superior with regard to accuracy and PPV, but the NPV of MRIs remained poor at 65%. CONCLUSIONS: All measured tests are good at predicting the presence of disease on final pathology, but none are able to reliably predict a pathologic complete response.

The need for axillary dissection in patients with positive axillary sentinel lymph nodes.

The need for completion axillary dissection after a positive sentinel node biopsy continues to be challenged. In the 2 years since we last reviewed this subject, a number of authors have shared their experiences about micrometastatic disease and isolated tumor cells, opining both for and against axillary treatment. Data from the ACOSOG Z0011 trial and other small studies do not appear to support the use of completion axillary dissection even for macro-metastatic disease in patients with clinically node-negative (N0) disease. While existing guidelines still recommend axillary dissection for patients with clinically positive nodes, even when conversion to clinically negative disease following neoadjuvant chemotherapy has occurred, this concept is being questioned in ACOSOG Z1071 and in several other recent small trials. The surgical approach to the treatment of breast cancer continues to move away from the traditional Halstedian concept.

Laparoscopic-assisted percutaneous endoscopic gastrostomy: its role in providing enteric access when percutaneous endoscopic gastrostomy is not possible.

Percutaneous endoscopic gastrostomy (PEG) replaced open surgical gastrostomy (OSG) as the preferred method for enteric access soon after its introduction in 1980. Since that time, laparoscopic gastrostomy (LG), percutaneous radiologic gastrostomy (PRG), and laparoscopic-assisted PEG (LAPEG) have been introduced. PEG and PRG have been found to be over 95 per cent successful, convenient, economical, and associated with less morbidity than OSG. However, there are patients that are not appropriate candidates for, or have failed attempts at, PEG or PRG placement. At one time, OSG was the only option left for these patients, but they may be better served by LAPEG or, in some cases, LG. LAPEG offers less morbidity than OSG by having less pain and wound complications, and potentially may avoid the use of general anesthesia. We present a series of patients that underwent successful LAPEG placement after an unsuccessful attempt at PEG placement, and we describe its role in patient care.

Prophylactic and Therapeutic Breast Conservation in BRCA1/2 Mutation Carriers.

Breast-conserving therapy (BCT) for sporadic breast cancer has been widely accepted by surgeons and patients alike. While BCT is associated with a higher risk of ipsilateral breast tumor recurrence (IBTR), it has not been shown to decrease overall survival (OS) in comparison with mastectomy. Many women with a BRCA1/2 mutation opt for mastectomy instead of breast-conserving measures at the time of a breast cancer diagnosis. In some cases, this is due to fear of aggressive disease, but to date, there have been no studies offering strong evidence that breast conservation should not be offered to these women. BRCA1/2-associated breast cancer has not been found to be more aggressive or resistant to treatment than comparable sporadic tumors, and no study has shown an actual survival advantage for mastectomy in appropriately treated affected mutation carriers. This paper reviews the available literature for breast conservation and surgical decision making in BRCA1/2 mutation carriers.

A gene expression classifier of node-positive colorectal cancer.

We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10(-6)). We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.

Somatic mutations to CSMD1 in colorectal adenocarcinomas.

The short arm of chromosome 8 is frequently deleted in advanced human colorectal cancers, suggesting the presence of one or more tumor suppressor genes having a major role in tumor progression and metastasis. Comprehensive sequencing of over 18,000 genes in colon and breast cancers identified somatic mutations in CUB and Sushi Multiple Domains 1 Gene (CSMD1)which is located on the p arm of chromosome 8. In this report, we describe a novel, robust, high-throughput gene mutation profiling strategy based on massively parallel picotiter plate pyrosequencing and have used this approach to identify additional somatic mutations to CSMD1 in early and late stage colorectal cancers. Using this strategy, we identified five nonsynonymous somatic mutations in CSMD1 among 26 colorectal cancers. Interestingly, these mutations occurred predominantly in advanced colorectal tumors,suggesting a role for CSMD1 in the development of late-stage metastatic disease.

The genomic landscapes of human breast and colorectal cancers.

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.