Report from the 2011 Annual Meeting of the American Society of Clinical Oncology, June 3-7

Presided over by BCRF grantee, George W. Sledge, Jr., MD (Indiana University School of Medicine), as he completed his term as ASCO president, the Annual Meeting provided an opportunity for reflection on the progress made in cancer in the 40 years since the passage of the National Cancer Act. More than 32,000 oncologists, researchers, surgeons, and advocates - over half of whom traveled from overseas - attended the conference. In his inspirational Presidential Address Dr. Sledge forecast the direction of cancer medicine and rallied his colleagues to rise to meet the challenges of practicing oncology in an era of increasing molecular science. Reminding his colleagues that a physician should be both skillful and caring, Dr. Sledge said, "As we go forward in the genome era, we must be willing to look back to the humane standards that have forever guided our profession, back to our belief that patients always come first. Back to the realization that all pathways forward flow from that which is best in the human spirit: our thirst for useful knowledge, our compassion for our fellow beings, and our belief in their essential dignity - from our skill and care."

Kathy Miller, MD (Indiana University School of Medicine) was Scientific Program Committee Chair, leading the group who reviewed thousands of abstracts to select the best science to present. Among the most widely reported news in breast cancer was the result of a large trial aimed at prevention. Currently, tamoxifen and raloxifene (Evista®) are approved to prevent breast cancer but their use is limited by concerns that their rare side effects such as uterine cancer and blood clots, may outweigh their benefits for some individuals. Moreover, they are prescribed mostly by oncologists rather than gynecologists or primary care physicians who are the doctors most often seen by healthy women. Hence, while we have had access to drugs proven to prevent breast cancer, their practical impact has been somewhat limited. At ASCO, an international study of 4,560 postmenopausal women at high risk for breast cancer was reported by Paul Goss, MD, PhD; his co-authors included BCRF grantees, James N. Ingle, MD (Mayo Clinic), Judy E. Garber, MD (Dana-Farber Cancer Institute), and Carol Fabian, MD (University of Kansas). The study participants were randomly assigned to take a placebo or exemestane (Aromasin®), one of the three currently available aromatase inhibitors. Importantly, none of these patients had invasive breast cancer, although some had past histories of non-invasive disease (ductal carcinoma in-situ). Exemestane, which lacks some of the more worrisome risks of tamoxifen in particular, was shown to be effective prevention against breast cancer with small increases seen in common side effects such as hot flashes, fatigue and joint pain. "This is a major step forward and, more importantly, provides another option for women at risk," commented Larry Norton, MD of Memorial Sloan-Kettering Cancer Center (MSKCC), BCRF Scientific Director.

Another exciting finding came from the National Cancer Institute of Canada Clinical Trials Group. In an international clinical trial, researchers found that wider radiation fields that treat more of the regional lymph nodes decrease recurrences for women with early-stage breast cancer that has spread or is likely to spread to the lymph nodes, as compared to more limited radiation fields This study, designed to look for a benefit of broadening the area treated with radiation therapy after surgery, may change practice as it matures. It also raises theoretical issues concerning the behavior of cancer cells as seeders of the breast region and, therefore, the rest of the patient's body.

This year's breast cancer sessions were organized according to the four known breast cancer subtypes: luminal A and luminal B (forms of breast cancer marked by the presence of the hormone receptors for estrogen and progesterone), HER2-positive (HER2+), and triple negative (lacking the three receptors). In addition, special sessions on survivorship, clinical science, care for the elderly, and international collaboration were held. Several BCRF grantees participated either as presenters of original research or reviewers of new and past studies. Among the highlights from BCRF investigators at the breast cancer sessions:

At the oral abstract session on luminal and HER2+ breast cancers, Jenny Chang, MD (The Methodist Hospital Research Institute) presented preliminary results from a trial by the Translational Breast Cancer Research Consortium (TBCRC), an initiative co-supported by BCRF since its inception, on the neoadjuvant (pre-operative) use of lapatinib and trastuzumab in patients with HER2+ invasive breast cancer. This is a preliminary step towards the possible elimination of traditional chemotherapy for patients with this kind of breast cancer. Nancy U. Lin, MD (Dana-Farber Cancer Institute) discussed two recent studies on new combinations of drugs for metastatic HER2+ patients. In the same session, Dawn L. Hershman, MD, MS (Columbia University Medical Center) reviewed the challenges facing cancer patients undergoing treatment and emphasized the importance for clinicians to be attuned to patient needs and to work together with patients to avoid therapy non-compliance. The complementary poster session took place a few days later, where Charles Loprinzi, MD (Mayo Clinic) discussed projects on issues faced by patients, such as side effects, compliance, and resistance to therapy.

There was a noticeable emphasis on triple negative breast cancer in this year's breast cancer programming. At the education session entitled "Updates on Triple Negative Breast Cancer," Lisa A. Carey, MD (University of North Carolina, Chapel Hill) reviewed the biology of triple negative breast cancer, the heterogeneity (e.g. basal-like, Claudin-low, non basal-like, etc.) that exists within this group, as well as current treatments. At a later session on metastatic triple negative breast cancer, Dr. Carey discussed results from a phase III clinical trial of iniparib, a PARP inhibitor, when used in combination with standard and platinum-containing chemotherapies. Dr. Carey made several suggestions for future work, including the need to consider whether the effectiveness of PARP inhibitors is influenced by the biologies of the different types of triple negative breast cancer. At the complementary poster session, Fatima Cardoso, MD (Champalimaud Cancer Center) chaired the poster session, which included separate studies by Ana M. Gonzalez-Angulo, MD and W. Fraser Symmans, MD, both of The University of Texas, MD Anderson Cancer Center.

Recent media coverage questioning the effectiveness of bevacizumab (Avastin®), which prevents the growth of blood vessels so that tumors cannot grow or spread, also known as anti-angiogenic therapy, has placed the drug at the forefront of cancer debate. At the ASCO meeting, there were several presentations and posters on recent results, as well as in-depth review of what is currently known. Adding to the discussion, Hope S. Rugo, MD (University of California, San Francisco, UCSF) reviewed several studies on bevacizumab across the different breast cancer subtypes. The varied and seemingly contradictory data were not unexpected, according to Dr. Rugo, who reminded her colleagues of the important impact of differing breast cancer subtypes. Patients with different types of breast cancer will not experience the same benefits from the same drug. "Progress takes time," said Dr. Rugo, "but it does not mean that we should lower our expectations. Treat wisely."

On a promising note, Clifford Hudis, MD of MSKCC, Chairman of BCRF's Scientific Advisory Committee, reported results from a phase II trial on whether sorafenib would help to overcome bevacizumab resistance in women with advanced breast cancer. Preliminary results suggested that adding sorafenib to standard chemotherapy stalled cancer progression. These findings will need to be confirmed in a broader trial but provide additional evidence that this oral drug should be studied further. A randomized phase III clinical trial, presented in ASCO's new Trials In Progress session and led by José Baselga, MD (Massachusetts General Hospital, Harvard University, Boston) was recently launched to resolve this specific question.

Pioneer of post-cancer treatment care and survivorship studies, Patricia Ganz, MD (University of California, Los Angeles), member of BCRF's Scientific Advisory Committee, presented on her BCRF-funded work on "chemo-brain," examining the biological effects of chemotherapy on cognitive function. She also reviewed preliminary results on the ameliorative effects of qigong and yoga therapies after cancer treatment. Teresa Gilewski, MD (MSKCC) was the discussant for a wide variety of survivorship issues facing cancer patients; for example, the psychological effects of disfigurement on pediatric cancer survivors, end of life care, and unique quality of life challenges for elderly patients.

Chairing the clinical science symposium on "Host Genomics and Treatment Outcomes in Breast Cancer," Christos Sotiriou, MD, PhD (Institut Jules Bordet) moderated a panel that also included fellow BCRF grantees, Dr. James N. Ingle and James M. Rae, PhD (University of Michigan). Dr. Ingle presented his BCRF-funded investigation on the actions of tamoxifen and its metabolites on estrogen receptor-positive breast cancer cells, while Dr. Rae discussed the data presented by Dr. Ingle, as well as others, on the relationship between genetics and our responses to different medications.

In the clinical science symposium on biomarkers, Mitch Dowsett, PhD, BSc (Royal Marsden Hospital and Institute of Cancer Research) discussed results from recent studies using Ki67, which is a cellular marker for cell growth and replication. Also, Daniel F. Hayes, MD (University of Michigan) compared two currently available tests that seek to "predict" the likelihood of a patient's breast cancer to recur or to benefit from chemotherapy; one of these tests was developed by fellow grantee, Charles P. Perou, PhD (UNC).

In the session on breast cancer in the elderly, Richard Zellars, MD (Johns Hopkins University) and Hyman B. Muss, MD (UNC) presented two studies demonstrating that older patients often receive less aggressive therapy. Dr. Zellars reported that in several studies taking place at different timeframes, older women tended to receive less standard radiation therapy than younger patients. Dr. Muss contributed results from his own work that chemotherapy was tolerated rather well by older patients.

This year's meeting highlighted the importance of international collaboration and included special joint sessions between ASCO and two international organizations, the European Society for Medical Oncology (ESMO) and the Union for International Cancer Control (UICC). The joint panel with ESMO examined strategies for cancer care in low- and middle-resource countries. Eduardo Cazap, MD of the Latin American and Caribbean Society of Medical Oncology (SLACOM) and President of UICC, chaired the session on the challenges and opportunities in cancer research, treatment, and prevention from an international perspective. Dr. Larry Norton suggested innovative solutions for how the cancer community may be able to overcome barriers to collaboration. Gabriel Hortobagyi, MD (MD Anderson) focused on the care of patients with metastatic breast cancer. He also emphasized the importance of preventive care, especially in light of the anticipated rise in global cancer incidence.

The annual meeting, in addition to presenting new research and treatment progress, offered an opportunity to recognize individuals in the oncology community. Robert Weinberg, PhD (Whitehead Biomedical Institute) was presented with the Science of Oncology Award and delivered the accompanying lecture. Known for his discovery of the first human oncogene, called ras, which causes normal cells to form tumors, and the isolation of the first known tumor suppressor gene, the Rb gene, Dr. Weinberg spoke about his current work, initiated with BCRF funding, exploring whether changes caused by irregularities in cellular development called epithelial mesenchymal transformation (EMT) contribute to the growth and spread of cancer.

Drs. Christine Ambrosone (Roswell Park Cancer Institute), Daniel Hayes, and Larry Norton were among those who led the highly popular "Meet the Professor" sessions. To sold-out crowds of medical professionals, Dr. Ambrosone, who serves on the federal committee for strategic research agenda on environmental and genetic factors related to breast cancer, presented on "Cancer Epidemiology for the Clinical Oncologist: When Should We Have Confidence in Studies and What Should We Tell Our Patients and Colleagues?" Dr. Norton challenged the audience with his presentation on how metastasis arises, while Dr. Hayes provided insights studies on circulating tumor cells, their behavior contributing to breast cancer metastasis, and ways to utilize these cells for patients' benefit.

At a brunch for young investigators awarded grants from the Conquer Cancer Foundation, the grantmaking arm of ASCO, new recipients of BCRF-supported grants were among those announced: Elizabeth Comen, MD (MSKCC), Stephen Shiao, MD, PhD (UCSF), and Benjamin Smith, MD (MD Anderson). Mentored by Drs. Norton and Hudis, Dr. Comen will be working with Robert Benezra, PhD to examine the ability of neutrophils, a type of white blood cell, to inhibit breast cancer metastasis. Dr. Shiao will be researching the effects of combining chemotherapy and radiation with a novel anticancer drug. Dr. Smith will conduct a randomized trial on two forms of radiation therapy for ductal carcinoma in situ and early invasive breast cancer.

With new information coming out of the laboratory, improvements seen in existing treatments, and development of novel therapies, the 2011 ASCO Annual Meeting added to the current optimism in cancer research. This conference attested to BCRF's commitment to the prevention and cure of breast cancer. Strategic investments in genomic science, cancer biology, targeted therapies, personalized medicine, and international collaborations are what will lead us to realize the hopes of those affected by breast cancer.