Featured Research

from universities, journals, and other organizations

Tau Protein Expression Predicts Breast Cancer Survival -- Though Not As Expected

Date:
December 25, 2008
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Expression of the microtubule-binding protein Tau is not a reliable means of selecting breast cancer patients for adjuvant paclitaxel chemotherapy, according to new research.

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.

Related Articles


Presented 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."

This research was supported by a grant to Pusztai from the Breast Cancer Research Foundation and by the Nellie B. Connally Breast Cancer Research Fund.

In addition to Pusztai, other M. D. Anderson co-authors include: Gabriel N. Hortobagyi, M.D., professor and chair, Department of Breast Medical Oncology; W. Fraser Symmans, M.D., and Yun Gong, M.D., Department of Pathology; Other authors include: Jong-Hyeon Jeong of the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Biostatistical Center; Jeffrey S. Ross of the Department of Pathology, Albany Medical College, Albany, NY and Chungyeul Kim and Soonmyung Paik of the Departments of Biostatistics and Pathology at the University of Pittsburgh.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Tau Protein Expression Predicts Breast Cancer Survival -- Though Not As Expected." ScienceDaily. ScienceDaily, 25 December 2008. <www.sciencedaily.com/releases/2008/12/081213130055.htm>.
University of Texas M. D. Anderson Cancer Center. (2008, December 25). Tau Protein Expression Predicts Breast Cancer Survival -- Though Not As Expected. ScienceDaily. Retrieved March 1, 2015 from www.sciencedaily.com/releases/2008/12/081213130055.htm
University of Texas M. D. Anderson Cancer Center. "Tau Protein Expression Predicts Breast Cancer Survival -- Though Not As Expected." ScienceDaily. www.sciencedaily.com/releases/2008/12/081213130055.htm (accessed March 1, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, March 1, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Could a $34 Smartphone Device Improve HIV Diagnosis in Africa?

Reuters - Innovations Video Online (Feb. 27, 2015) A dongle that plugs into a Smartphone mimics a lab-based blood test for HIV and syphilis and can detect the diseases in 15 minutes, say researchers. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
Doctor Says Head Transplants Possible Within Two Years

Doctor Says Head Transplants Possible Within Two Years

Buzz60 (Feb. 27, 2015) An Italian doctor is saying he could stick someone&apos;s head onto someone else&apos;s body. Patrick Jones (@Patrick_E_Jones) reports. Video provided by Buzz60
Powered by NewsLook.com
How Your Dentist Could Help Screen You For Diabetes

How Your Dentist Could Help Screen You For Diabetes

Newsy (Feb. 27, 2015) A new study from researchers at New York University suggests dentists could soon use blood samples taken from patients&apos; mouths to test for diabetes. Video provided by Newsy
Powered by NewsLook.com
The Best Tips to Makeover Your Health

The Best Tips to Makeover Your Health

Buzz60 (Feb. 27, 2015) If you&apos;re looking to boost your health this season, there are a few quick and easy steps to prompt you for success. Krystin Goodwin (@Krystingoodwin) has the best tips to give your health a makeover this spring! Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins