"Patients with aggressive subtypes of locallyadvanced breast cancer may have new treatment options on the horizon according to two reports published in July in the New England Journal of Medicine. Results of two different investigational arms of a multidrug phase II trial conducted in part by researchers at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center show that use of new targeted therapies neratinib or a combination of veliparib and carboplatin improves outcomes when used in addition to standard chemotherapy before surgery for patients with HERpositive and triplenegative breast cancer respectively. The results are part of the multiinstitutional ISPY  study. Related Links Perelman School of Medicine at the University of Pennsylvania http University of Pennsylvania Health System http Compared to standard therapies alone the drugs tested in the trial substantially reduced the presence of residual disease in the breast tissue and lymph nodes known as achieving pathological complete response or pCR when administered before surgery said Angela DeMichele MD MSCE a professor of HematologyOncology and Epidemiology at the Perelman School of Medicine at the University of Pennsylvania a coinvestigator and Chair of Trial Operations for the study known as ISPY . pCR strongly predicts prevention of later recurrence of incurable metastatic disease.  These results suggest that neratinib and veliparibcarboplatin are very promising treatment options for patients with HERpositive and triplenegative breast cancer respectively. In addition the platform used for the ISPY  trial allows the research team to test these and other new therapies simultaneously targeting tumor subtypes that would be most likely to benefit from the therapies minimizing the exposure of patients to treatments that are not likely to work for their disease subtype and accelerating drug development The data presented in the two NEJM articles shows that when added to standard neoadjuvant chemotherapy the combination of the molecularly targeted experimental drug veliparib plus carboplatin showed sufficient improvement to meet the prespecified threshold for graduation from the trial signifying a high likelihood for success in a modest confirmatory phase  neoadjuvant trial in the triple negative subset. Likewise the experimental drug neratinib was found to have sufficient improvement in the pCR rate for patients in the HERpositiveHRnegative subset that it too was graduated from the ISPY  trial. Because there are so many subtypes of breast cancer and because we always test drugs in the metastatic and then adjuvant setting finding effective therapies is a very difficult and long process. The ISPY  platform allows therapies to be tested and evaluated in more expeditious costeffective ways said Laura J. Esserman MD MBA a professor of Surgery and Radiology and director of the Carol Franc Buck Breast Care Center at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco Principal Investigator on the ISPY  trial and a senior author on the reports. These results provide valuable information on which drugs should proceed to confirmatory trials to improve outcomes for patients with extremely aggressive cancers that put women at risk for early recurrence and death. For these patients time is of the essence. In particular finding drug combinations that are effective and less toxic is extremely important. The new studies show that by using the ISPY  model to match therapies with biomarker subsets we can create trials that are more focused smaller and faster thereby exposing more patients to effective treatments. A major achievement in the progression of ISPY  has been significantly reducing the time it takes to move forward from initiation of discussions with drug companies to enrollment of the first patients. ISPY  has compressed this timeline from an average timeframe of    months to five months. The ISPY  study startup period takes approximately  days with more than  percent of the sites opening and enrolling patients as opposed to the traditional study startup timing of  to  months with less than  percent of the sites opening and enrolling. More than  investigators from the nations most prestigious and innovative cancer research centers coauthored the two NEJM articles with hundreds of staff and investigators involved in ISPY  overall. In addition to Dr. Esserman the Principal Investigators for ISPY  is Donald A. Berry PhD a professor in the department of Biostatistics at The University of Texas MD Anderson Cancer Center and founder of Berry Consultants. A complete list of the participating centers and investigators is provided in a Supplementary Appendix available at NEJM.org. The ISPY  Trial is sponsored by QuantumLeap Healthcare Collaborative a nonprofit foundation that was established in  as a collaboration between medical researchers at University of California at San Francisco and Silicon Valley entrepreneurs. QuantumLeaps mission is to accelerate transfer of highimpact research in clinical processes and systems technology into widespread adoption so that patients and physicians can benefit from the research as soon as practicable. QuantumLeap provides operational financial and regulatory oversight to ISPY  and is also the sponsor of the ISPY Phase  program and ISPY  a companion phase  confirmatory trial that is in development."