Research Advances Presented At 2009 Breast Cancer Symposium
Main Category: Breast CancerAlso Included In: Cancer / Oncology
Article Date: 09 Oct 2009 - 4:00 PDT
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Five additional studies on the early detection, treatment and evaluation of breast cancer were highlighted today by the co-sponsoring organizations of the 2009 Breast Cancer Symposium. The symposium, occurring this year during Breast Cancer Awareness Month, is being held October 8-10, 2009, at the San Francisco Marriott.
The additional studies being highlighted feature a short summary and perspective from Lori Pierce, MD, professor of radiation oncology at the University of Michigan School of Medicine, and chair of the symposium news planning team.
Click here to view the additional studies and the complete release.
To view the complete 2009 Breast Cancer Symposium press kit, visit http://www.asco.org/BCSpresskit09.
Source
ASCO
Visit our breast cancer section for the latest news on this subject.
MLA
13 Feb. 2012. <http://www.medicalnewstoday.com/releases/166850.php>
APA
http://www.medicalnewstoday.com/releases/166850.php.
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Drug Selection Through The Use Of Molecular Profiling
posted by Gregory D. Pawelski on 14 Oct 2009 at 5:36 amAt the 2009 American Society of Clinical Oncology (ASCO) breast cancer symposium, in San Francisco, the Keynote Address (by Martine PIccart-Gebhart of the Jules Bordet Institute) was very relevant to Individualized Tumor Response Testing.
The speaker made the point that only 8% of new drugs entering Phase I trials ever make it to marketing and that this percentage is even lower for cancer drugs, because current drug testing is inefficient, with many drugs failing late in development, with these expensive failures owing, in large measure, to ineffective drugs and poor patient selection (i.e, lack of prognostic and predictive markers for response to therapy).
The speaker went on to note that little progress has been made in identifying which therapeutic strategies are likely to be effective for individual patients. The speaker concluded that identifying markers that can predict response to a particular drug remains a great challenge.
Why was nothing being presented at this meeting which reports any progress at all in drug selection through the use of molecular profiling? When microarrays and high throughput RT-PCR emerged some years back, you'd think that there would be quite a bit of progress by now. Sad to say, there has not.
Drug Selection Through The Use Of Cell-based Functional Profiling
posted by Gregory D. Pawelski on 16 Oct 2009 at 4:53 pmA study was presented at the symposium about progress in drug selection through the use of cell-based functional profiling. It delt with the so-called "triple negative" breast cancer (TNBC), which is estrogen receptor negative (ER-), progesterone receptor negative (RP-), and Her2 negative (H2-).
When breast cancer presents as locally advanced disease, it is customarily treated with neoadjuvant (preoperative) chemotherapy, followed by definitive surgery. At the time of surgery, the specimen is assessed to determine if all visible tumor has been destroyed by chemotherapy. When this happens, it is said to be a “pathological complete response” (pCR).
Data shows that obtaining a pCR is everything. Get a pCR, and the survival is excellent. Don’t get a pCR and the survival, especially for TNBC patients, is very poor. How can the pCR rate be improved in TNBC?
The speaker went through all the database of breast cancer cell culture assays (using cell death endpoints) and tried to see if there were any drugs which appeared to be uniquely active in TNBC vs non-TNBC.
There were no major differences between the activity of most drugs in TNBC vs non-TNBC, with one glaring exception: cisplatin, which was dramatically more active in TNBC than in non-TNBC.
The speaker went on to present a lot of data further dissecting which specific markers were most associated with TNBC sensitivity to cisplatin. The data will shortly appear on the ASCO website.
But, essentially, the major markers for platinum sensitivity in breast cancer were estrogen receptor negativity and very poorly differentiated tumors. The minor markers for platinum sensitivity in breast cancer were Her2 negativity and progesterone receptor negativity.
The data compared TNBC to other types of tumors. It’s known that renal cell carcinomas are very resistant to cisplatin (less than 10% response rate), and that is reflected by the cell culture (cell death endpoint) data. It’s known that previously-untreated, poorly differentiated ovarian cancers tend to be very sensitive to cisplatin (70% response rate), and that’s also reflected by the cell culture data. When ovarian cancer patients relapse soon (0 to 6 months) after discontinuation of chemotherapy, they have only a 25% response rate to re-treatment with platinum. When ovarian cancer patients relapse greater than 6 months following discontinuation of chemotherapy, they have a 50% response rate to re-treatment with platinum. These clinical findings are also nicely recapitulated by the cell culture assay data.
Now, breast cancers which are either estrogen receptor positive and/or more than very poortly differentiated (Bloom Richardson score of 4 to eight) tend to be even more resistant to cisplatin than are previously treated ovarian cancer which relapse soon (0 to 6 months) after discontinuation of chemotherapy. In contrast, Triple Negative Breast Cancers tend to be as sensitive or more sensitive (especially when also Bloom Richardson 9/9) to cisplatin than are previously-untreated, poorly-differentiated ovarian cancers.
The data clearly showed the utility of cell culture assays in “targeting” chemotherapy to patient sub-groups who are most likely to benefit from treatment with given individual drugs. It is hard to see how molecular profiling tests could have produced similar insights.
Genomics is far too limited in scope to encompass the vagaries and complexities of human cancer biology when it comes to drug selection. Efforts to administer targeted therapies in randomly selected patients often result in low response rates at significant toxicity and cost.
While researchers continue to develop molecular probes to select candidates, the cell culture analysis platform serves as a functional profile capable of examining the nuances of cellular response to drugs. To exploit the full potential of targeted anticancer therapies, physicians will need laboratory tests that match patients to specific drugs.
Cell culture assays are able to accurately predict how an individual patient's cancer cells will respond to an array of drug combinations. It is able to quantify synergistic drug combinations and individually tailor treatment.
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