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San Antonio Breast Symposium News Tips from M. D. Anderson Cancer Center

San Antonio Breast Symposium News Tips from M. D. Anderson Cancer Center
The University of Texas M. D. Anderson Cancer Center offers these news items presented at the San Antonio Breast Symposium meeting.
M. D. Anderson News Release 12/13/04

ABSTRACT #201 New Molecular Classification of Breast Cancer Predicts Response to Chemotherapy

Different molecular subtypes of breast cancer respond differently to chemotherapy, a research team from The University of Texas M. D. Anderson Cancer Center reported at the annual San Antonio Breast Cancer Symposium meeting.

The findings reinforce the emerging notion that breast cancer should be classified according to its gene expression profile, in order to make accurate predictions about the outcome of the disease and select the optimal treatment for patients, says the senior investigator, Lajos Pusztai, M.D., Ph.D., an associate professor in the Department of Breast Medical Oncology.

Four major molecular subgroups of breast cancer ¯ normal-like, luminal (ER-positive), basal-like (mostly ER-negative), or erbb2+ (mostly HER-2 amplified) ¯ have been previously defined, based on expression of 424 genes involved in cancer development. Scientists have already shown that each subgroup has a different prognosis. In this recent study Pusztai and his group looked at whether these molecular subgroups also respond differently to chemotherapy that is delivered before surgery.

The research team obtained  tumor tissue biopsies from 82 patients with newly diagnosed breast cancer before they were given a commonly used chemotherapy (Taxol/FAC). Patients with basal-like and erbb2+ subgroups were found to have the highest rates (45 percent each) of a pathological complete response, while only 6 percent of luminal tumors had a complete response. Among the normal-like cancers, no response was seen.

They then looked at the genes associated with response in basal-like and erbb2+ patients and found that they were different, “suggesting that the mechanisms of chemotherapy sensitivity may be unique to a subgroup,” Pusztai says.

“This is of great interest because it suggests that stratification of patients into molecular subgroups may be needed in order to develop the most accurate predictors of treatment response,” he says. “Different sets of genes present in different molecular subgroups may determine the response to a particular regimen of chemotherapy.”

 

ABSTRACT #112 Cell Marker Identifies Patients Who Are More Likely to Respond to Taxol

Researchers at The University of Texas M. D. Anderson Cancer Center have found a potential predictor of response to the chemotherapy drug Taxol, which is commonly used before or after surgery for stage I-III breast cancers, even though only a subset of women ultimately benefit from this treatment. 

Patients whose breast cancer cells have lost their ability to express a protein called “tau” are twice as likely to have a good response to Taxol treatment, the researchers report at the annual San Antonio Breast Cancer Symposium meeting.

The finding makes sense because tau promotes the assembly of microtubules, which provide structure to the cell and help it divide. Taxol works by binding to microtubules to form an inappropriately stable structure which ultimately leads to cell death. “In the absence of tau, Taxol stabilizes microtubules more easily,” says the study’s lead researcher, Lajos Pusztai, M.D., Ph.D., an associate professor in the Department of Breast Medical Oncology.

If validated in larger studies, the finding suggests that tumor tissue could be screened to predict if it will respond to Taxol, says Pusztai. “If it doesn’t, perhaps other chemotherapy regimens would work better.”

The results also suggest a way to improve the use of Taxol, Pusztai says. “If you block the effect of tau with an agent, you could possibly increase the effectiveness of Taxol in more patients, making them super responders.”

The researchers came up with their discovery after examining breast cancer biopsy samples taken from 82 patients, 21 of whom had a complete disappearance of their cancer after Taxol-containing treatment. They looked at the difference between these responders and non-responders in 22,000 genes, and found that tumors were highly sensitive to treatment that had low levels of tau messenger RNA (mRNA) expression in their cancer cells. This observation was confirmed by examining tau protein expression using a routine pathological assay, immunohistochemistry, in 122 additional patients. Then, research in breast cancer cell lines in the laboratory were undertaken to look at how low expression of tau leads to increased sensitivity to Taxol.

Pusztai says that about 25 percent of all patients show very high sensitivity to the Taxol-containing chemotherapy, and respond with complete disappearance of cancer after treatment.

“Assessment of tau expression at the time of diagnosis could identify a group of patients who are at least twice as likely to have high sensitivity to the treatment,” he says. “The rest of the patients may not benefit much from the drug because none of the patients who had high levels of tau mRNA expression in their cancer experienced complete response to therapy.

Before routine use of such a test can be recommended, investigators say these findings will need to be examined in a larger, randomized study to accurately determine the clinical value of tau as a predictive marker.

 

ABSTRACT #29 Re-analysis of Large Trials Shows Greatest Benefit of Chemotherapy in
ER-negative Tumors

Despite the common belief in the oncology community that cancer research and treatment have focused on breast tumors that are estrogen receptor (ER)-positive, a researcher from The University of Texas M. D. Anderson Cancer Center maintains that clinicians have made “enormous strides” in treating patients with tumors that are ER-negative.

In a presentation at the annual meeting of the San Antonio Breast Cancer Symposium, Donald Berry, Ph.D., a professor and chair of the Department of Biostatistics and Applied Mathematics, looked at decades of breast cancer clinical trial experience and found that “the benefit of chemotherapy advances over the last 20 years to ER-negative patients has been surprisingly dramatic.”

In examining the impact of chemotherapy treatment of node-positive breast cancer in three national clinical trials, which enrolled more than 6,000 patients cumulatively, Berry found that chemotherapy has reduced the risk of death in ER-negative patients by 56 percent. “The absolute benefit has been similarly impressive, especially in comparison with the corresponding absolute benefit of chemotherapy to ER-positive patients,” he says.

The studies, conducted by the Cancer and Leukemia Group B (CALGB) and the U.S. Breast Intergroup, all tested different chemotherapy regimens and doses in women whose cancer had spread to their lymph nodes, and all three showed statistically significant results. But, patients were treated “irrespective of hormone sensitivities or whether they had received tamoxifen or not,” Berry says. In women who are ER-positive, tamoxifen and other SERMs (selective estrogen receptor modulators) have been shown to help prevent cancer development or recurrence.

The impact of such preventive treatments, however, was not “weighted” in these trials, he says. “People accept and act as though chemotherapy is equally beneficial independent of ER status,” he says. In his analysis, Berry found that all three studies show that chemotherapy provided a statistically significant benefit for patients with ER-negative tumors, but “only a little bit of an effect for ER-positive tumors that had been treated with tamoxifen, and none of the trials showed a statistically significant benefit for higher doses of chemotherapy in ER-positive patients.”

Berry says that the results will likely surprise oncologists “because everyone has assumed that ER status doesn’t matter in chemotherapy treatment, but here we show it does.” That doesn’t mean, however, that patients with ER-positive tumors should not receive chemotherapy, Berry warns.

He adds that the study proves that breast cancer patients of both hormonal types are being aided by clinical advances. “The prevailing wisdom has been that science has focused on ER-positive tumors, with development of SERMs and now aromatase inhibitors, but ER-negative patients have been left in the lurch,” Berry says. “Not so. This analysis demonstrates that chemotherapy use has more than doubled survival rates in women with ER-negative tumors.”

 

ABSTRACT #4026 Celecoxib Shows Surprising Activity Against Estrogen Receptors

Six months of treatment with celecoxib (Celebrex) in women at risk of developing breast cancer results in the reduction of estrogen receptor expression in breast cells, a research team at The University of Texas M. D. Anderson Cancer Center has found.

The surprising insight ¯ that celecoxib may regulate a cell’s use of estrogen ¯ could help explain the drug’s observed anticancer properties, says the study’s lead author, Banu Arun, M.D., associate professor in the Department of Breast Medical Oncology.

“Since estrogen receptor expression is a marker of proliferation, this finding confirms celecoxib’s antiproliferative properties,” she says. “This is a preliminary, but exciting, finding that has not been reported in clinical chemoprevention studies before.”

To date, the study has enrolled 40 women at high risk of developing breast cancer. Each woman agreed to undergo a fine needle aspiration and ductal lavage to remove breast epithelium cells both before and after six months of celecoxib treatment. These samples were available for analysis in 26 high-risk women. The researchers assessed the difference in estrogen receptor levels before and after treatment.

They found that the average pre- and post-treatment estrogen receptor expression was 30.8 percent and 21.8 percent, respectively, which is a statistically significant difference. Arun says they are continuing to examine the impact of celecoxib on other cancer risk markers in breast cells, such as EGFR, HER2, Ki-67 and Bcl-2. 


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