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The DCIS Dilemma: Time to Change The Name?

by GoozNews ~ 04 Oct 2009 08:01am

In 2007, the American College of Physicians issued controversial new guidelines suggesting women under 50 could skip routine mammograms. Just five years earlier, the U.S. Preventive Services Task Force had recommended that women start the annual or bi-annual chest x-rays to look for breast cancer at age 40, making the U.S. the only country in the world to endorse the procedure in women that young.

Clinicians debated the issue. The American Cancer Society put its heavy foot down on the side of the earlier annual screens. Virtually every media outlet carried stories (most of them emphatically endorsing early screening).(1) Only a handful of women's health advocacy groups, who knew routine mammograms were lifesavers for women over 50, allowed that the tradeoff in risks and benefits for women under that age were about even unless they were particularly high risk, such as having a family history.(2)

Lost in the uproar was any significant discussion of the troubling conundrum facing many of the women -- young or old -- whose routine mammograms turned up an unwanted growth. In one out of five cases, the ultimate verdict revealed that the tiny tumor was confined to their milk ducts and did not invade the surrounding breast tissue. It's called ductal carcinoma in situ (DCIS).

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Comments

Ductal carcinoma in situ

Sun, 10/04/2009 - 13:49 — gpawelski

Ductal carcinoma in situ (DCIS) is described as pre-cancerous, pre-invasive, non-invasive or intraductal cancer. It is not harmful at this stage. Not every woman with DCIS will go on to develop breast cancer if it is left untreated.

If one has a colonoscopy and the physician spots a pre-cancerous polyp, the doctor excises the lesion. That's what one does (surgery). No adjuvant treatment.

It's not possible to predict which women with DCIS will develop breast cancer. Sometimes scans cannot pick up breast malignancies in detail because of the opaqueness. Is that nodularity an indication that should be looked at with more clarity? Only a pathologist would know well.

For years, physicians have settled on the smallest amount of tumor tissue possible, often with a fine needle aspirate that collects just a few cells for biopsy analysis. Larger bore needles are needed to perform core biopsies or even remove entire lymph nodes, so that they can collect enough live (fresh) tissue to more reliably determine the histologic and molecular features of a specimen. Imaging technologies cannot substitute for the biologist's thorough examination of the features of a cell.

The headlong rush to develop commercialized multigene prognostic and predictive tests (companion disgnostics) to identify high risk breast cancer patients who would likely benefit from chemotherapy (identify patients who are likely to have a recurrence if treated with surgery alone) and which ones do not need to be unnecessarily exposed to toxic chemotherapy cocktails, still does not guarantee that a cancer drug will be effective for an "individual" patient (if found positive). Nor can they, for any patient or even large group of patients, descriminate the potential for clinical activity among different cancer agents of the same class.

Microarray profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, still cannot work successfully in predicting treatment response for individual patients. Perhaps this is because they are performed on formalin-fixed, paraffin-embedded tissues or fresh-frozen tissue samples or unfrozen samples stored in RNA-preserving solution that were never actually exposed to the drugs whose activity they are trying to assess.

It will never be as effective as the cell-based functional profiling, which exists today and is not hampered by the problems associated with gene or protein expression tests. That is because functional methodology measures the net effect of all processes within the cancer, acting with and against each other in real-time, and it tests living (fresh) cells actually exposed to drugs and drug combinations of interest.

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DCIS

Sun, 10/04/2009 - 17:37 — mgoozner

I'm surprised to learn there are already ways to test excised DCIS samples from a lumpectomy to determine if chemo is necessary (cell-based functional profiling). Neither of the government-funded physician thought leaders I interviewed mentioned it to me. They both seemed to suggest such tests were not available.

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Cell-based vs Genetic-based Assays

Sun, 10/04/2009 - 21:23 — gpawelski


 



There are new "gene expression profiling tests" that enable oncologists and breast cancer surgeons to more accurately determine who should be treated and who should not be treated with chemotherapy (Oncotype DX, MammaPrint, Mammostrat), but they cannot predict chemo response (clinical responders) as "cell-based functional profiling tests."

The molecular-based profiling tests can enhance the ability to distinguish between "low" risk and "high" risk patients. Patients in the "low" risk group can be spared from unnecessary chemotherapy.

Patients in the "high" risk group, who would benefit from chemotherapy, can then be pre-tested to see what treatments have the best opportunity of being successful, and offer a better chance of tumor response resulting in progression-free and overall survival.

Oncotype DX looks at 21 genes that influence the behavior of breast cancer cells. MammaPrint looks at the expression of 70 genes linked to breast cancer, and Mammostrat utilizes five immunohistochemical (IHC) biomarkers to classify patients into high, moderate, or low-risk categrories for disease recurrence.

Cell-based functional profiling analyzes the systems' response to drug treatments, not just one or a few genetic targets or pathways (does the cell express a particular target that the drug is supposed to be attacking). Even if a genetic test can fine one type of gene or protein expressed, they will not be able to know if a targeted drug against those targets will actually benefit an individual cancer patient. Molecular assays are never tested in the presence of cancer cells.

Cell-based functional profiling of human tumor cells measures the actual response of tumor cells to drug exposure. Following this exposure, they measure both metabolic (cell metabolism) and cell morphology (structure). 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 or proteins are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead. It can measure the net effect of everything which goes on in the entire genome of a cancer cell. It can look at both the anti-tumor and anti-microvasular effects of cancer drugs. Are the cells ultimately killed, or aren't they?

Sources:

Genomic Health, Inc.

Agendia

Applied Genomics, Inc.

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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