Tau protein expression predicts breast cancer survival -- though not as expected

December 14, 2008

Expression of the microtubule-binding protein Tau is not a reliable means of selecting breast cancer patients for adjuvant paclitaxel chemotherapy, according to research led by The University of Texas M. D. Anderson Cancer Center.

Presented today, Dec. 13, at the CRTC-AACR San Antonio Breast Cancer Symposium, the researchers found that Tau expression does predict survival, yet in an unexpected way.

In earlier neoadjuvant studies, investigators from M. D. Anderson found that low levels of Tau predicted a good response to pre-operative chemotherapy. In vitro studies had shown that down-regulation of Tau expression increased the sensitivity of breast cancer cell lines to paclitaxel. Other studies suggested that high levels of Tau partially protect microtubules from paclitaxel binding and that low levels of the protein leave microtubules more accessible and vulnerable to the drug.

"If you treat patients who have a low level of Tau protein expression with pre-operative chemotherapy in neo-adjuvant studies, they are very likely to have a good response to the chemotherapy," said Lajos Pusztai, M.D., D. Phil, associate professor of medicine in the Department of Breast Medical Oncology at M. D. Anderson and the study's first author. "We wanted to see if this correlation would hold up in predicting survival in adjuvant studies."

Working with researchers from the National Surgical Adjuvant Breast and Bowel Project (NSABP), the investigators assessed Tau protein expression in primary breast cancer specimens from 1,942 patients in the NSABP-B28 clinical trial. The goal was to evaluate the prognostic value of Tau in these patients, who were treated with four courses of doxorubicin/cyclophosphamide (AC) or AC followed by four courses of paclitaxel. All hormone receptor-positive patients in the trial also received adjuvant endocrine therapy.

The hypothesis was that patients whose tumors expressed low levels of Tau would preferentially benefit from the addition of paclitaxel to their adjuvant regimen, Pusztai explained. Univariate and multivariate analyses found that both Tau-positive status (high Tau expression) and estrogen receptor (ER) -positive status were associated with better disease-free and overall survival. However, the researchers found no significant correlation between Tau expression and benefit from paclitaxel in the total population or among estrogen receptor (ER) -positive or ER-negative patients.

"We eventually found that Tau is very predictive of survival but in the opposite manner than we initially thought," Pusztai said. "Low Tau expression was actually associated with a relatively poor survival despite a higher sensitivity to chemotherapy."

"On the other hand," he continued, "patients with high levels of Tau-and we knew these patients were not particularly sensitive to chemotherapy-actually did very well. They had a significantly better survival in this large randomized study."

Pusztai noted that survival is determined by baseline prognosis, endocrine sensitivity and sensitivity to chemotherapy-and that Tao is a marker of receptivity for two of these important variables.

"It's receptive to chemotherapy sensitivity but also to endocrine therapy sensitivity," he added, "and the receptivity is in an opposite manner: Low Tau means higher chemotherapy sensitivity, but it also means lesser sensitivity to endocrine therapy and vice versa. Patients with high Tau expression do very well because they all tend to be ER-positive and very sensitive to endocrine treatment."

This complex interaction between Tau and outcome is not unique, according to Pusztai. It is the same association as with many other biomarkers, including the Oncotype DX breast cancer assay and the proliferation marker Ki-67-an inverse relationship between chemotherapy sensitivity and endocrine sensitivity.

The issues would be far less complicated, Pusztai added, if ER-negative and ER-positive breast cancer were treated as distinct entities. "The most important thing we've learned is that we need to develop prognostic markers, response markers, or any type of biomarker separately for the ER-negative and ER-positive tumors."

Source: University of Texas M. D. Anderson Cancer Center

Explore further: 'Microtentacles' on tumor cells appear to play role in how breast cancer spreads (w/ Video)

Related Stories

Protein inhibitor helps rid brain of toxic tau protein

September 29, 2009

Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer's disease when it builds up abnormally inside nerve cells affecting memory, neuroscientists at the University of South ...

An individualized approach to breast cancer treatment

January 26, 2009

Not all breast cancers are the same, and not all will have fatal consequences. But because clinicians find it difficult to accurately determine which tumors will metastasize, many patients do not receive the therapy fits ...

Young blood fights cancer

December 30, 2008

"New blood" can revitalize a company or a sports team. Recent research by Tel Aviv University finds that young blood does a body good as well, especially when it comes to fighting cancer.

Scientists discover class of potent anti-cancer compounds

March 7, 2011

Working as part of a public program to screen compounds to find potential medicines and other biologically useful molecules, scientists from The Scripps Research Institute and Massachusetts Institute of Technology (MIT) have ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.