Personalized Medicine Helps Breast, Colorectal & Ovarian Cancer Patients Survive

“Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations. The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors. Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator. … Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients. …” [Emphasis added by Libby’s H*O*P*E*™]


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“Personalized medicine helps cancer patients survive – TGen, Scottsdale Healthcare and Caris Dx clinical trial shows molecular profiling can result in specific treatments for individual patients that significantly limit the growth and spread of tumors

PHOENIX, Ariz. – April 19, 2009 – Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations.

The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors.

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Daniel Von Hoff, M.D., F.A.C.P., Physician in Chief & Senior Investigator, The Translational Genomics Research Institute; Chief Scientific Officer, TGen Clinical Research Services, Scottsdale Healthcare; Clinical Professor of Medicine, University of Arizona Department of Medicine

Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator.

The study included 66 patients at nine centers across the United States, including Scottsdale Heathcare. Dr. Von Hoff also is the Chief Scientific Officer of TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare that is administered by the Scottsdale Clinical Research Institute (SCRI) at Scottsdale Healthcare.

All of the patients had previously experienced growth of their tumors while undergoing as many as two to six prior cancer treatments, including conventional chemotherapy.

However, after molecular profiling identified precise targets, new treatments were administered that resulted in patients experiencing significant periods of time when there was no progression of their cancer.

This clinical trial was unique because patients acted as their own control,’ said Dr. Von Hoff. ‘We compared each patient’s progression-free survival, following treatment based on molecular profiling, to how their tumors progressed under their prior treatment regimens, before molecular profiling.’

In a significant number of patients, the targeted treatments provided significantly longer periods when tumors did not progress, or even shrunk, said Dr. Von Hoff, who also is a Medical Director of US Oncology and a former Director of the Arizona Cancer Center at the University of Arizona.

Dr. Von Hoff said the new study was done in a way that avoided issues surrounding tumor subtypes and differences in individual biology, which have confounded other clinical trials.

He said this clinical trial demonstrated the value of personalized medicine, in which treatments are prescribed based on an individual’s specific genetic makeup. The type of drugs, dosages, their delivery and other treatment aspects – all are based on each patient’s individual medical needs.

Among the patients, 27 percent had breast cancer, 17 percent had colorectal cancer, 8 percent had ovarian cancer and 48 percent had cancers that were classified as miscellaneous.

Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients.

‘With this trial, we are showing the power of personalized medicine using the tools we already have available to us. As these tools become more precise and more effective, the value of personalized medicine will increase,’ Dr. Von Hoff said.

The molecular profiling for this research study was performed by Caris Diagnostics (Caris Dx) in Phoenix.

These results are the first in a series of studies in support of Target NowTM, a commercially-available oncology testing service offered exclusively by Caris Dx. Target Now uses cutting-edge molecular profiling techniques, including both DNA microarray and immunohistochemical (IHC) analysis, to provide individualized information about a patient’s tumor as an aid to the treating oncologist.

‘This trial is evidence of an important breakthrough in the treatment of cancer. We are excited to work with Dr. Von Hoff and TGen as we make this important molecular diagnostic information available to physicians to aid in therapy-selection decision making,’ said David D. Halbert, Chairman and CEO of Caris Diagnostics. ‘The valuable information provided through the Target Now panel of tests improves patient care while reducing costs for the payer.’

Clinical studies were conducted by TCRS at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center. Scottsdale Healthcare is a primary clinical research site for TGen.

‘Patients in our community have access to ground-breaking, world-class research right in their own backyard thanks to this collaboration,’ said Tom Sadvary, president and CEO of Scottsdale Healthcare. ‘Our goal is reducing the time it takes to get new treatment discoveries from the research lab to the patient. We are thrilled to see these advances in personalized medicine taking place right here in Scottsdale.’

The recent clinical study was dubbed the Bisgrove Trial, after longtime Scottsdale Healthcare supporter Jerry Bisgrove. The trial was funded through a $5 million grant from Mr. Bisgrove’s Stardust Foundation to the Scottsdale Healthcare Foundation. Mr. Bisgrove has been a patient at Scottsdale Healthcare and is a member of the Scottsdale Healthcare Foundation Board of Trustees. In honor of the Stardust gift, the research building at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center is named the Debi and Jerry Bisgrove Research Pavilion.

‘The Stardust Foundation is proud to have played a key role in the advancements in cancer research represented by Dr. Von Hoff’s clinical trial. We believe we are closer than ever to finding a cure for this devastating disease that affects so many millions,’ Mr. Bisgrove said.

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About Scottsdale Healthcare
Scottsdale Healthcare is a primary clinical research site for TGen. TGen Clinical Research Services (TCRS) at Scottsdale Healthcare is housed in the Virginia G. Piper Cancer Center at Scottsdale Healthcare, located on the Scottsdale Healthcare Shea medical campus. Scottsdale Healthcare is the not-for-profit parent organization of the Scottsdale Healthcare Shea, Scottsdale Healthcare Osborn and Scottsdale Healthcare Thompson Peak hospitals, Virginia G. Piper Cancer Center, Scottsdale Clinical Research Institute, TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale Healthcare Home Health Services, Scottsdale Healthcare Community Health Services, and Scottsdale Healthcare Foundation. For additional information, visit www.shc.org.

About Scottsdale Clinical Research Institute (SCRI)
SCRI, established in 2005, provides infrastructure and support for the clinical research at Scottsdale Healthcare. Start-up funding for SCRI was provided by a lead gift of $4.5 million from the Virginia G. Piper Charitable Trust in 2005. An additional $5 million was provided by the Stardust Foundation to support this multi-site molecular profiling study of targeted therapies for treatment refractory cancers coordinated by SCRI. A defining feature of SCRI is a focus on genomics and personalized medicine as well as clinical and translational research. The basic science arm of SCRI is provided by a partnership with the Translational Genomics Research Institute (TGen). Innovations from TGen’s laboratory are taken to the bedside at SHC by our joint clinical research program, TGen Clinical Research Services (TCRS) at Scottsdale Healthcare. Additional research collaborations include the University of Arizona, Arizona State University, other local health care delivery systems and participation in the Arizona NIH Clinical and Translational Science Award (CTSA) program initiative. Areas of study at SCRI include Cancer, Cardiovascular, Trauma, Metabolic and Nanomedicine.

Press Contact:
Keith Jones
Public Relations Director
Scottsdale Healthcare
480-882-4412
kjones@shc.org

About TGen
The Translational Genomics Research Institute (TGen) is a non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.

Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

About Caris Diagnostics
Caris Diagnostics (Caris Dx) is a leading provider of the highest quality diagnostic, translational development and pharmaceutical services encompassing anatomic pathology and molecular testing. Caris Diagnostics provides world-class pathology services to physicians who treat patients in the community setting. The company provides academic-caliber medical consults through its industry-leading team of subspecialty fellowship and expert-trained pathologists in gastrointestinal and liver pathology, dermatopathology and hematopathology. Caris Diagnostics provides the highest levels of service to its customers and their patients through its state-of-the-art laboratories; proprietary, advanced clinical and technology solutions; and rigorous quality assurance programs. Through the molecular testing expertise of the Caris Molecular Profiling Institute (Caris MPI) at Caris Dx, the company also offers advanced molecular analyses of patient samples through prognostic testing services and genomic and proteomic profiling to provide critical information to physicians treating cancer and other complex diseases. In addition, Caris MPI supports pharmaceutical companies and other researchers in their clinical trials for targeted therapeutics with custom genomic and proteomic analyses, analyte preservation, tissue procurement and comprehensive reporting services. The company has strategic relationships with the International Genomics Consortium, US Oncology, the Translational Genomics Research Institute, and the Biodesign Institute of Arizona State University. More than 2,000 physicians nationally use Caris Diagnostics. Formed in 1996, the company is headquartered in Irving, Texas and operates four laboratories: Irving, Texas; Phoenix, Arizona (2 sites); Newton, Massachusetts. Additional information is available at www.carisdx.com.

Press Contact:
Brian Wright
Caris Dx
(602) 358-8916
bwright@carismpi.com”

Sources:

European Researchers Find Estrogen Receptor Gene Amplification Occurs Rarely in Ovarian Cancer

“… ESR1 [gene] amplification is an uncommon mechanism for estrogen receptor overexpression in ovarian cancer occurring in about 2.1% of the total number of ovarian cancers. In general, this frequency parallels the fraction of ovarian cancers reported to show complete response to antiestrogenic [anti-hormonal] therapies. Given the strong predictive power of ESR1 [gene] amplification for response to tamoxifen in breast cancer, an evaluation of such treatments in ESR1 [gene] amplified ovarian cancers appears justified.”

Abstract:

“Amplification of the gene encoding estrogen receptor-alpha occurs in about 20% of breast cancers and is an important mechanism for estrogen receptor overexpression in this tumor type. In ovarian cancer, overexpression of estrogen receptor protein has been described in more than two thirds of cases.

To study a potential role of estrogen receptor-alpha gene amplification for estrogen receptor overexpression in ovarian cancer, a tumor tissue microarray containing 428 ovarian cancers was analyzed by fluorescence in situ hybridization [FISH] for estrogen receptor-alpha gene amplification and immunohistochemistry [IHC] for estrogen receptor expression. The estrogen receptor-alpha gene status was successfully determined in 243 of 428 arrayed cancers.

Estrogen receptor gene amplification was found in 5 of 243 (2%) of tumors. Amplification levels were usually low, with 4-8 estrogen receptor-alpha gene copies. However, one case had a high-level amplification, with more than 30 estrogen receptor-alpha gene copies. All five amplified tumors were estrogen receptor positive, with 3 of 5 tumors showing highest (Allred score, 7-8) estrogen receptor levels. The data demonstrate that estrogen receptor-alpha amplification occurs only rarely in ovarian cancer.”

Article Discussion Points:

  • “The results of this study show that ESR1 amplification is rare in ovarian cancers (2.1%). More than one-third of ovarian tumors showed immunohistochemically detectable estrogen receptor protein expression, most abundant in serous and endometroid subtypes. This is in line with previous studies done on the classical paraffin blocks. The good concordance between our data and previous studies demonstrates the representation of our tumor tissue microarray data obtained on a 0.6 mm tissue spot per tumor and enhances the results of other studies used in this method.”
  • “A small subset of ESR1 [gene] amplified estrogen receptor-positive cases was indeed found in ovarian cancers. In comparison, some other genes showed higher rates of amplifications in these cancers. For example, the amplification of ERBB2 ranges (0-66%),  EGFR (3.65-12%),  CCND1 (0-19%), C-MYC up to 54.5,  and KRAS (31%).”
  • “The significant frequency of estrogen receptor positivity in ovarian cancers had prompted treatment efforts using hormonal therapy early on. In addition their relatively little toxicity was another provoking factor to continue going on to achieve more advance in this therapeutic field. Monotherapy studies using tamoxifen, aromatase inhibitors, and GnRH analogues had yielded variable results with objective response rates ranging between 0 and 56%.  Combinatorial treatment regimens combining tamoxifen and goserelin or tamoxifen and Gefitinib had obtained results with objective response rates of up to 11.5%.”
  • “The role of estrogen receptor expression for response prediction to anti-hormonal drugs has been much better studied in breast cancer, where a strong association between estrogen receptor positivity and response to anti-hormonal drugs is well established. … More than 20% of breast cancers had amplified or at least elevated ESR1 [gene] copy number. Possible explanations for the predictive effect of ESR1 [gene] amplification could be a particularly high expression of amplified as compared to non-amplified cancers. Alternatively, it could be speculated, that ESR1 [gene] amplified are more dependent on the estrogen receptor pathway than other tumors that express estrogen receptors together with many other growth receptors. If this latter hypothesis was true, visualization of ESR1 [gene] amplification would pinpoint toward an ‘Achilles tendon‘ of a tumor that could be most successfully targeted.”
  • “The frequency of ESR1 [gene] amplified ovarian cancers (2.1%) is much lower than that in breast cancer. Interestingly, this fraction somehow parallels the percentage of ovarian cancers reported to show strong responses to hormonal therapies.”
  • “For example, in retrospective analysis was conducted of patients who received tamoxifen at a dose 20 mg twice daily for the treatment of advanced epithelial ovarian cancer,
    • Karagol et al found that out of 29 eligible patients included in the study, there were 1 (3%) complete response, 2 (7%) partial response, 6 (21%) stable disease, and 20 (69%) progressive disease.
    • Papadimitriou et al have studied response rate in 27 patients treated with letrozole at a dose of 2.5 mg once a day. Patients with measurable or evaluable disease (n=21) and those with only increasing CA-125 serum levels (n=6) were eligible. Among the 21 patients with measurable or evaluable disease, 1 complete response (5%) and 2 partial responses were observed (10%) for an objective response rate of 15%.
    • Other studies, in which the combined regiment had been implicated, patients were given oral tamoxifen 20 mg twice daily on a continuous basis and subcutaneous goserelin 3.6 mg once a month until disease progression. In total, 26 patients entered this study, of which 17 had platinumresistant disease, using the definition of endocrine response that included patients with stable disease of 6 months or greater, the overall response rate (clinical benefit rate) was 50%. This included one complete response (3.8%), two partial responses (7.7%), and 10 patients with stable disease (38.5%).”
  • “In summary, ESR1 [gene] amplification is an uncommon mechanism for estrogen receptor overexpression in ovarian cancer occurring in about 2.1% of the total number of ovarian cancers. In general, this frequency parallels the fraction of ovarian cancers reported to show complete response to antiestrogenic [anti-hormonal] therapies. Given the strong predictive power of ESR1 [gene] amplification for response to tamoxifen in breast cancer, an evaluation of such treatments in ESR1 [gene] amplified ovarian cancers appears justified.”

Quoted SourceEstrogen receptor gene amplification occurs rarely in ovarian cancer, Issa RM et. al., Mod Pathol. 2009;22(2):191-196, reprinted in From Modern Pathology, Medscape Today, February 18, 2009. [Free Medscape subscription required to view full text article.]

Comment:  This study indicates that the occurrence of estrogen positivity (ER+)/ESR1 gene amplification with respect to ovarian cancer is significantly lower than such occurrence in the breast cancer area.  Nevertheless, it is prudent to request your doctor to have your ovarian cancer tumor tissue tested by a pathologist for estrogen positivity or ESR1 gene amplification (through IHC or FISH testing, respectively).  If your ovarian cancer tissue tests ER+, you may respond to anti-estrogen drugs.  Although this type of pathology testing is commonplace in the breast cancer area, it is not in the ovarian cancer area due to the much lower percentage of ER+ ovarian cancer tumors.  As the study above notes, further research of anti-estrogen therapy use within the area of ovarian cancer is needed, especially given the potential high effectiveness and low toxicity of such therapies.