Taxol and Breast Cancer Abstract

Taxol and Breast Cancer Abstract

Taxol and Breast Cancer Abstract

abstract 6014 (Oncol News Int'l, Vol 14, #5, May '05)

Using a technique that quantifies circulating tumor cells, German investigators have shown that neoadjuvant chemotherapy with paclitaxel (taxol) causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor.


The finding could help explain the fact that complete pathologic responses do not correlate well with improvements in survival.


In the study, breast cancer patients undergoing neoadjuvant chemotherapy gave blood samples in which epithelial antigen-positive cells were isolated. Such cells are detected in most breast cancer patients but are rarely found in normal subjects. The investigators measured the levels of circulating tumor cells before and during primary chemotherapy with several different cytotoxic agents.


Paclitaxel (taxol) produces the greatest degree of tumor shrinkage but also the greatest release of circulating tumor cells. In three different paclitaxel-containing regimens, circulating cell numbers massively increased, whereas tumor size decreased. These cells remained in the circulation for at least five months after surgery.


The tumor shrinks, but more cells are found in the circulation. This corresponds with a high pathologic complete response during paclitaxel treatment, but in the end, this is not reflected in improved survival. These cells are alive in the circulation. The results indicate that monitoring of circulating tumor cells can contribute to understanding of tumor-blood interactions and may provide a valuable tool for therapy monitoring in solid tumors.


What this recent study has shown, so far, that in three different paclitaxel (taxol) containing regimens, as the tumor collapses (a clinical response, not cure), it produces the greatest release of circulating tumor cells. The study has not looked at any other combination regimens.


With these cells being alive in the circulation, it may mean that a patient with invasive breast cancer without lymph node involvement (where systemic treatment "may" benefit), or a patient with invasive breast cancer that involves lymph nodes (where systemic treatment is "usually" recommended), would need additional (anti-estrogen) treatment, such as Tamoxifen (it may be given alone or in addition to chemotherapy, if given).


It has been shown that Tamoxifen treatment will reduce circulating tumor cells in some patients, but not all. It has been shown that Herceptin treatment will reduce circulating tumor cells in patients with HER2-negative tumors, but less pronounced in HER2-positive tumors.


The results of this kind of study are coming out slowly and quietly and indicate that taxol containing regimens didn't prolong survival over other more conventional and less expensive cytotoxic drugs. It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes (taxol) are often dramatic.


Even if one or more chemotherapy regimen is identified as being likely to work on a particular cancer, has the science advanced to tell us whether application of the chosen chemotherapy regimen will not cause other changes that also cause cancer to later return and perhaps be even harder to treat? Is it a case of chemotherapy being bad, in cases where it apparently works? Traditional chemotherapy is mutagenic (changes in form), you might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more agressive fashion.


These studies tell us that much more work needs to be done, and oncologists need to adapt treatment to the patient. There are over 100 chemotherapeutic agents, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing individual properties of each patient's cancer.


Twenty-Seventh Annual San Antonio Breast Cancer Symposium (abstract 6014)


(Oncol News Int'l, Vol 14, #5, May '05)

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