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Old 10-14-2009, 10:43 PM
Dross Dross is offline
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Default Study examines mastectomy and breast-conserving surgery rates

There is concern that mastectomy is over-utilized in the United States, which raises questions about the role of surgeons and patient preference in treatment selection for breast cancer. New data from an observational study found that breast-conserving surgery was presented and provided in the majority of patients evaluated. Surgeon recommendations, patient decisions, and failure of breast-conserving surgery were all found to be contributing factors to the mastectomy rate. The findings are published in the October 14 issue of the Journal of the American Medical Association (JAMA), a theme issue on surgical care.

The study was lead by Monica Morrow MD, Chief of the Breast Service in the Department of Surgery at Memorial Sloan-Kettering Cancer Center, along with Steven Katz MD, MPH, and colleagues at the University of Michigan Comprehensive Cancer Center. Dr. Morrow and colleagues were interested in investigating the factors responsible for the overall mastectomy rate in the United States and why women undergo mastectomy for the initial treatment of breast cancer.

The findings suggest that surgeons are appropriately recommending breast-conserving surgery and that patient preferences play an important role in shaping the pattern of surgical treatment for breast cancer, especially in the absence of a surgeon recommendation favoring one procedure over another. This is consistent with previous studies performed by these investigators that have shown that when both procedures are medically appropriate, increased patient involvement in breast surgery decisions is associated with greater probability of mastectomy. In this study, one-third of patients appear to choose mastectomy as initial treatment when not given a specific recommendation for mastectomy by their surgeons. Researchers speculate that patients may prefer mastectomy for "peace of mind" or to avoid radiation and are often strongly influenced by concerns about disease recurrence and fear. "Women need to understand that although it intuitively seems obvious that a bigger surgery is a better surgery-it may not be the case here. There are some patients for whom mastectomy is the best medical treatment, but when it is not indicated, women need to make sure that if they are choosing mastectomy as a matter of preference that they understand that it is not going to improve the likelihood of breast cancer survival. The risk of cancer recurring in the breast after a lumpectomy is basically no different than the risk of cancer recurring in the scar tissue of a mastectomy," said Dr. Morrow.

Concerns about the excessive use of mastectomy for patients with breast cancer have been raised for decades despite a marked increase in breast-conserving surgery in recent years. According to a 2008 study (by the Mayo Clinic), mastectomy rates were 45 percent in 1997, dropped to 30 percent in 2003, but then increased to 43 percent in 2006.

In this new study, Dr. Morrow and colleagues found that of 1984 women aged 20 to 79 years with stage 1 and 2 breast cancer that was diagnosed between June,2005 and February,2007: 67 percent of women reported that their first surgeon recommended breast-conserving surgery and that they had successful procedures; 13 percent had mastectomies after initial surgical recommendation; 8.8 percent had mastectomies when there was no clear surgical recommendation for either procedure; and finally, an additional 8.8 percent reported having unsuccessful breast-conserving surgery that required revision with mastectomy. The results are based on data reported to the metropolitan Los Angeles and Detroit Surveillance, Epidemiology and End Results (SEER) registries.

"Our results and those from other studies we performed suggest that surgeons face special challenges in how they discuss treatment options and elicit the treatment preferences of their patients with breast cancer. Our results reinforce that both patient preferences and surgeon recommendations are powerful determinants of treatment," said Dr. Katz, who is a professor of internal medicine and health management and policy at the University of Michigan.

"This study suggests that breast-conserving surgery has been appropriately adopted by surgeons and for most women- if they are given a specific reason why they are not a good candidate for breast-conserving surgery, a second opinion is not likely to change that," said Dr. Morrow.

Talking With the Doctor About Breast Surgery Options

[url]http://www.cancer.net/print/24393

Last edited by gdpawel : 08-22-2012 at 09:47 AM. Reason: correct url address
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Old 02-19-2011, 09:18 AM
gdpawel gdpawel is offline
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Default Surgical Specimen Is the Personalized Part of Personalized Cancer Medicine

In this dawning era of molecular medicine, surgeons and pathologists are playing a more pivotal role in cancer medicine. They are the custodians of the specimens and therefore the molecules that represent the personalized part of personalized cancer medicine. Surgeons will continue to cure cancer with greater success rates through earlier detection and excision, but as the custodiams of the tissue, they will also be central to improving cancer management through molecularly targeted interventions.

Ann Surg Oncol. 2009 August; 16(8): 2079–2080.
Published online 2009 May 27. doi: 10.1245/s10434-009-0526-1. PMCID: PMC2711907

Society of Surgical Oncology 2009

The Surgical Specimen Is the Personalized Part of Personalized Cancer Medicine

Carolyn C. Compton, MD, PhD

Office of Biorepositories and Biospecimen Research, National Cancer Institute, Bethesda, MD USA
Carolyn C. Compton, Email: [email]comptcar@mail.nih.gov[/email]

Received March 15, 2009

As a pathologist, I have been evaluating cancer resection specimens throughout my career and have come to have a deep appreciation of the challenges of surgical oncology. Happily for patients, surgeons cure cancer on a fairly regular basis by excising it with expert technique and detailed knowledge of human anatomy and tumor biology. The tissue resected by the surgeon and analyzed by the pathologist is the source of crucial information that, in turn, informs the decisions and actions of our medical oncology colleagues.

As cancer medicine looks forward to a new era of molecularly defined cancer subtypes and targeted therapies, however, the role of both surgeon and pathologist is evolving to require an ever greater degree of professional attention towards the surgical resection specimen. It is the surgically resected tissue that possesses the molecular information needed to define the specific molecular characteristics of the patient’s tumor, the specific therapies to which the tumor would be expected to respond, and even the specific risks of adverse reactions to given therapies predicted by the patient’s genetic make-up. This molecular information forms the basis of the “personalized” approaches envisioned for cancer patients in an age of molecular medicine. The professional responsibility to assure that the specimen’s molecular composition and integrity are safeguarded is shared by both the surgeon and the pathologist. Current momentum towards molecular medicine is rapidly elevating this professional responsibility to one of the most important aspects of cancer patient care.

Currently, however, safeguarding the molecular integrity or documenting surgical variables that impact the molecular composition of the resection specimen is not widely considered to be primary aspects of the surgeon’s professional responsibility. Manipulations of the tissue within the surgical procedure itself may have dramatic effects on the molecular make-up of that tissue. However, these manipulations are neither recorded nor controlled when and where possible. Variables such as anesthesia type and duration, drugs administered preoperatively and intraoperatively, and devascularization/ischemia time for the resected tissue may dramatically alter molecular profiles and/or molecular integrity. Once successfully resected, the specimen may spend varying amounts of time at room temperature in the surgical suite and/or holding unit before being delivered to Pathology, which may further alter the molecular composition and quality of the tissue.

Without the surgeon’s extension of professional responsibility to the resected tissue to control, when feasible, and track such variables, the advantages of personalized adjuvant approaches may be lost to the patient. In molecular medicine, the resected tissue becomes the major determinant of all downstream therapy. Therefore, the care of the specimen must be addressed co-equally with the care of the patient. This elevated bar for ensuring tissue integrity and molecular quality also must be addressed by pathologists. The fresh specimen will need to be overseen by the pathologist with the same immediacy and professional attention. More than ever, surgeons and pathologists will be required to work together closely to achieve the goal of meeting the new standards of “specimen care” required for molecular analysis.

Our knowledge about the affects of iatrogenic variables such as surgical manipulation, intraoperative drug delivery, and pathological handling on the molecular profiles that reflect the biology in resected tissues is growing rapidly.1–5 Postoperative tissue ischemia time, for example, has been shown to alter gene and protein expression profiles within minutes following surgical excision in colectomy specimens and prostatectomy specimens.1–3 Not surprisingly, even before resection has been completed, intraoperative manipulations have been shown to markedly alter gene transcription levels during radical prostatectomies.4 The effects of different peri- and intraoperative variables on molecular profiles in different types of tissues are just beginning to be understood, but it is clear that surgeons and pathologists alike contribute significantly to the final molecular composition and integrity of the resected tissue.5

Procedures that maximize specimen quality respect the fact that resected tissues are vital and biologically reactive. Until they are fixed or frozen, biospecimens are viable and capable of reacting to physiological stress. They are a living part of the patient from which they come and are responsive to changes in temperature, perfusion, oxygenation, and other physiological and biochemical variables, both pre- and intraoperatively as well as postoperatively. Typically, once a tumor is successfully resected, the surgeon’s attention turns to patient and relatively little is directed towards the specimen. Unless an intraoperative consultation such as a frozen section is requested and the specimen is immediately addressed for this purpose, it may sit unattended for varying periods of time before being prepared for delivery to the pathology laboratory. The conditions of delivery itself may vary, as may the immediacy of the specimen handling once it has arrived in the pathology laboratory. Furthermore, some of the newer surgical techniques, such as robotically assisted prostate resections, may further compromise the quality of the resection specimen if it is allowed to remain in the operative site at body temperature for significant amounts of time after devascularization.

In this emerging age of molecular medicine, a new level of awareness of and attention to “the state of the specimen” will be required by surgeons, operating room staff, pathologists, and pathology staff. All play essential roles in the series of events leading up to stabilization of the tissue that impact its molecular make-up and molecular integrity. Surgeons are the initiators and controllers of many of these events and therefore represent the “gatekeepers.” The powerful molecular analysis technologies now at our disposal and the increasingly sensitive and specific analysis platforms under development provide us with unprecedented abilities to define the molecular features of cells and tissues. However, they also pose new risks by providing us with the ability to derive the wrong answer with even greater speed and accuracy unless the analytes are of high quality and are derived from high-quality specimens. It is our joint professional responsibility to follow procedures that will ensure the quality of the biospecimen and to document the specimen handling history for the patient’s record.

In this dawning era of molecular medicine, where a hard-won understanding of the molecular details of cancer is leading to more powerful and accurate diagnostics and therapeutics, I foresee surgeons and pathologists playing a new and more pivotal role in cancer medicine. They are the custodians of the specimens and therefore the molecules that represent the personalized part of personalized medicine. Surgeons will continue to cure cancer with greater success rates through earlier detection and excision; but as the custodians of the tissue, they will also be central to improving cancer management through molecularly targeted interventions.

References

1. Spruessel A, Steimenn G, Jung M, Lee SA, Carr T, Fentz A-K, et al. Tissue ischemia time affects gene and protein expression patterns within minutes following surgical excision. BioTechniques. 2004;30:1030–7.

2. Dash A, Maine IP, Varambally S, Shen R, Chinnaiyan AM, Rubin MA. Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens. Am J Pathol. 2002;161:1743–8.

3. Lin DW, Coleman IM, Hawley S, Huang CY, Dumpit R, Gifford D, et al. Influence of surgical manipulation on prostate gene expression: implications for molecular correlates of treatment effects and disease prognosis. J Clin Oncol. 2006;23:3763–70.

4. Schlomm T, Näkel E, Lübke A, Buness A, Chun FK-H, Steuber T, et al. Marked gene transcript level alterations occur early during radical protatectomy. Eur Urol. 2008;53:333–46.

5. Signoretti S, Bratslavsky G, Waldman FM, Reuter VE, Haaga J, Merino M, et al. Tissue-based research in kidney cancer: current challenges and future directions. Clin Cancer Res. 2008;14:3699–705.
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Old 02-19-2011, 09:19 AM
gdpawel gdpawel is offline
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Default Personalized Cancer Medicine Is Here, Now

As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis is needed matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden and the Annual Meeting of the American Assoication for Cancer Research (AACR) in San Diego, CA concluded that "functional profiling" with cell-based assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity) in primary cultures of "fresh" human tumors.

Cell-based Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.

Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.

There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell-based assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

Funtional profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.

The funtional profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.

This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a pre-test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Literature Citation:

Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007

Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)
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Old 09-13-2011, 03:07 PM
gdpawel gdpawel is offline
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Default Personalized Oncology Care: A New Paradigm For The Onocologist And Patient

Cary Presant, M.D.
Wilshire Oncology Medical Group

Personalized Cancer Care was the theme of the American Society of Clinical Oncology meeting in 2009, a theme chosen by ASCO president Dr. Richard Schilsky. In his article in the Journal of Clinical Oncology (Volume 27, Page 3725, 2009), Dr. Schilsky emphasized the reasons why personalized oncology care is so important. Other articles on Medscape also confirm that personalized oncology is a new paradigm for practicing oncologists, and patients are beginning to understand and expect this individualized planning as well. What are the implications for the oncology practice today?

The first implication is that the way in which we communicate with patients has to change. Because patients are seeing personalized cancer care as a recurring emphasized theme in newspapers and television, it is important for each oncologist to assure patients that their treatment plans are optimized for personalized therapy. It is also important that patients understand that the tests necessary to personalize therapy may necessitate some delay while results are obtained, and that the tests necessary may involve additional authorizations and payments. By knowing that the physician is giving the best and most up-to-date care, confidence and trust will help the doctor/patient relationship.

Next, it is important that clinical needs for personalized treatment plans be met by the oncology office. New tests will have to be implemented by pathology departments, for example advanced immunohistochemistry and gene array testing (especially in breast, lung, lymphoma and colon). Oncologists will have to alert the laboratory as to the types of specialized testing that will be requested (such as SNPs, the single nucleotide polymorphisms that are becoming important in colon cancer therapy and breast cancer therapy).

In addition, surgeons must be informed to understand that biopsy for tumor diagnosis or excision for cure can also be important for specialized testing that allows personalized therapy, such as fresh tissue for microarray DNA testing, or for cellular assays (for example chemotherapy sensitivity or drug induced apoptosis which can personalize care for patients with leukemia and solid tumors). Such advanced planning before surgery may necessitate special handling of the tissue (for example, fresh and sterile, sometimes in special media) so as to produce optimal results. Identifying resources within a practice allows personalized treatment plans to be efficiently coordinated.

Personalized care also implies adequate surveillance after actual drug treatments have concluded. This includes monitoring blood or organ function (such as blood levels of vitamin D which are associated with cancer outcomes, as shown by Pamela Goodwin in the Journal of Clinical Oncology, Volume 27, page 3757, 2009 in early breast cancer), and newer techniques of monitoring such as circulating tumor cells. Patients who are under surveillance have to be monitored for newly identified unusual organ side effects not previously appreciated, such as osteoporosis, renal dysfunction, deterioration of cardiac risk factors, long-term fatigue, second cancers in uterus, bone marrow, and bladder, thrombotic complications and infectious complications.

Lastly, personalized care implies adequate prevention of new cancers, and screening to detect any new cancers at early stages. Prevention includes drug therapy and lifestyle modification. Sometimes this is important not only for the patient, but also for the patient s family members who may be at increased risk of the very same tumor that the patient had.

My take home recommendations from today s blog for physicians are to be certain that treatment plans are comprehensive and personalized, which requires more frequent high level visits. Seek out the resources necessary to utilize personalized treatment planning. In that regard, State Oncology Associations may be of particular assistance. Lastly, use guidelines, such as NCCN, to determine if a personalized treatment program is recommended for your patients.

If you are a patient reading this blog, consider asking these questions of your oncologist: Are there any tests which need to be done to personalize my therapy? Have you checked me completely for recurrences and side effects of medications which I have received? Have you checked my vitamin levels to be certain that they are optimal? Have you discussed prevention and screening in me and in my family members with me so I know how frequently I need to be coming for visits to get results?

[url]http://boards.medscape.com/forums?128@593.Snv2ayvEtJr@.29f5f8dc!comment=1
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Last edited by gdpawel : 01-16-2013 at 01:02 AM. Reason: correct url address
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