UPMC Hillman Cancer Center

September 2013

Golden Gate Bridge, San FranciscoOn this first weekend of September I find myself in San Francisco during two parallel events. The 2013 Breast Cancer Symposium, a multidisciplinary meeting sponsored by six professional societies that are committed to improving breast health and breast cancer prevention, diagnosis and care, has brought together about 800 specialists to explore how we can practice precision or personalized care—the science of bringing the right treatment to the right patient at the right time. Just blocks away the 2013 America's Cup sailing race is also taking place—two high tech sailboats manned by highly experienced and well synchronized teams dueling in the waters inside the Golden Gate Bridge near Alcatraz Island. On the surface these could not be more different events—on the one hand hundreds of doctors sequestered in a dark hotel ballroom for hours watching Powerpoint and poster presentations and participating in debates about best treatments and on the other hand, two crews flying by on futuristic yachts in races that last just a few minutes. But these two seeming disparate events occurring simultaneously have much in common. They are both about how to harness science and technology to achieve a goal. They are both completely reliant on the performance of the multidisciplinary team. They are both about discipline.

This year the dominant theme at the Breast Cancer Symposium is how we can take advantage of our exploding knowledge about the molecular intricacies of breast cancer to improve outcomes for patients. The big debate is how detailed molecular characterization of tumors can be performed and how, or if, it will help. These are vital questions and debates and cancer centers like our own are at the forefront of this important work.

We now know that cancers of all types develop in part because of the accumulation of DNA mutations—changes that promote growth of the cancer cell. We have been evaluating the biological features of some types of cancers to guide treatment for many years—think of estrogen and progesterone receptor and HER-2 expression in breast cancer or EGFR mutations in lung adenocarcinoma—to predict outcome and select therapy. But technical advances have made it possible to assess a very small tumor biopsy for a multitude of changes rather than one candidate gene at a time and we are now bringing this technological advance into practice. In November 2012, the molecular pathology laboratory at UPMC (under the leadership of Yuri Nikiforov, M.D.) brought a next generation sequencing test online for this type of multiplex evaluation of tumor specimens. This Personalized Cancer Mutation Panel (PCMP) uses molecular techniques to interrogate tumor DNA for the presence of about 800 changes in 47 genes that are felt to be critical drivers of cancer, reasoning that such testing should uncover not only the changes that we know but perhaps unexpected changes that can be exploited. The 100th tumor was tested in our laboratory just a few weeks ago.

Introducing a new test is just as complicated as introducing a new drug and we have taken great care to do this in a thoughtful and rigorous fashion. Initially this PCMP test is being focused on biopsies of tumors metastases derived from patients with advanced cancers with limited treatment options, particularly those who are being evaluated as potential participants in clinical trials of new targeted agents. Patients are also asked to participate in a research registry which will allow us to link the PCMP results with the details of their clinical history and response to treatment. We have launched a molecular tumor board so that a panel of experts can help to review and interpret results for the treating physician. After all, such testing will find its true value only if it leads to improved selection of therapy and benefit for the patient. This type of genomic medicine is still in its infancy and we have much to learn. But we feel that we have laid a good foundation to take us forward into this age of molecular cancer medicine.

Here in San Francisco it is day 2 of the Breast Cancer Symposium and the America's Cup. The US team lost both races yesterday and will go up against the New Zealand team again today. We breast cancer specialists are moving into a second day about how to advance personalized cancer care. Our race will of course last long beyond the close of the America's Cup regatta in the San Francisco in just a few short weeks. Though we know that we, too, will face setbacks and “losses” along the way, I am confident we will be successful in harnessing the fruits of our knowledge about the hallmarks of cancer to benefit patients.