Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy.

PURPOSE: The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer. METHODS: Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years. RESULTS: Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences. CONCLUSION: The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials.

Noninvasive Surface Imaging of Breast Cancer in Humans using a Hand-held Optical Imager.

X-ray mammography, the current gold standard for breast cancer detection, has a 20% false-negative rate (cancer is undetected) and increases in younger women with denser breast tissue. Diffuse optical imaging (DOI) is a safe (nonionizing), and relatively inexpensive method for noninvasive imaging of breast cancer in human subjects (including dense breast tissues) by providing physiological information (e.g. oxy- and deoxy- hemoglobin concentration). At the Optical Imaging Laboratory, a hand-held optical imager has been developed which employs a breast contourable probe head to perform simultaneous illumination and detection of large surfaces towards near real-time imaging of human breast cancer. Gen-1 and gen-2 versions of the handheld optical imager have been developed and previously demonstrated imaging in tissue phantoms and healthy human subjects. Herein, the hand-held optical imagers are applied towards in vivo imaging of breast cancer subjects in an attempt to determine the ability of the imager to detect breast tumors. Five female human subjects (ages 51-74) diagnosed with breast cancer were imaged with the gen-1 optical imager prior to surgical intervention. One of the subjects was also imaged with the gen-2 optical imager. Both imagers use 785 nm laser diode sources and ICCD camera detectors to generate 2D surfaces maps of total hemoglobin absorption. The subjects lay in supine position and images were collected at various locations on both the ipsilateral (tumor-containing) and contralateral (non-tumor containing) breasts. The optical images (2D surface maps of optical absorption due to total hemoglobin concentration) show regions of higher intensity at the tumor location, which is indicative of increased vasculature and higher blood content due to the presence of the tumor. Additionally, a preliminary result indicates the potential to image lymphatic spread. This study demonstrates the potential of the hand-held optical devices to noninvasively image breast cancer in human subjects.

Use of surgisis mesh in laparoscopic repair of hiatal hernias.

BACKGROUND: Breakdown of the crural closure is a frequent reason for failure of antireflux surgical procedures. This retrospective study aimed to determine the effectiveness of using absorbable mesh in preventing recurrence of hiatal hernia after posterior cruroplasty. DESIGN: Comparative retrospective analysis. METHOD: The charts of 220 adults who underwent antireflux surgery with posterior cruroplasty between 1997 and 2005 were retrospectively reviewed. Patients were divided into 2 groups: posterior cruroplasty+absorbable mesh reinforcement (n=127) and posterior cruroplasty alone (n=93). Symptomatic outcome was assessed by telephone interview in 92 patients (72%) in the mesh group at a median of 3.2 years postoperatively and 59 patients (63%) in the no mesh group of men studied at a median of 3.8 years postoperatively. MAIN OUTCOME MEASURES: Incidence of recurrence and persistent symptoms. RESULTS: In the mesh group, 74/92 (80%) patients remained asymptomatic at a median of 3.2 years postoperatively. Of these patients, 31 underwent either an upper endoscopy or an upper gastrointestinal (UGI) series; none had recurrence of hiatal hernia. Of the 18 symptomatic patients, 13 underwent an upper endoscopy or an UGI series to determine the etiology of symptoms; 3 recurrences were confirmed for a 3.3% overall proven recurrence rate. In the no mesh group, 26/59 (44%) patients were symptomatic. Of these, 18 underwent either an upper endoscopy or an UGI series. Recurrence of hernia was confirmed in 12 patients for a 20% overall proven recurrence rate. There were no instances of mesh infection or erosion. CONCLUSIONS: Symptomatic recurrence rates of hiatal hernia after antireflux surgery vary. Recurrence of a hiatal hernia may or may not lead to symptoms. This retrospective analysis demonstrates that absorbable mesh is safe and may lead to a significant reduction in the incidence of symptomatic recurrent hiatal hernia.