This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jones, S. E. Search for Related Content PubMed Articles by Jones, S. E. Social Bookmarking                            What's this?

In Reply

US Oncology Research, Houston, TX, and Dallas, TX

Drs Ferrario and Panasci have raised an important issue regarding HER-2 status in the interpretation of our trial results.¹ We studied a group of women with early-stage breast cancer without regard to HER-2 status. We can presume that the usual approximately 20% of these cancers overexpressed HER-2. Our efforts to obtain paraffin blocks or slides from these patients, registered between 1997 and 1999, resulted in a small number of samples, which were inadequate to evaluate HER-2 status. Updated 7-year results of this trial will be available shortly, but alas without knowledge of the patients' HER-2 status and how it impacted patient outcome.

Considerable research has linked anthracycline sensitivity to HER-2 status, as well as to topoisomerase II (TOPO2A) status. For example, the MA5 trial recently reported the benefit of anthracyclines only in the HER-2 overexpressing population and, then more recently, in the TOPO2A overexpressing population.^2,3 As it turns out, TOPO2A and HER-2 coexist and there is very little, if any, TOPO2A overexpression in the population of patients screened as HER-2 negative. Because TOPO2A is the target of anthracycline therapy, it seems likely that a treatment like our docetaxel and cyclophosphomide (TC) regimen would be equally effective to one containing an anthracycline in a population of women where the cancer does not overexpress TOPO2A (ie, HER-2–negative disease). We were sufficiently intrigued by this hypothesis to have launched a new clinical trial in early breast cancer (US Oncology Research trial 06090) for 2,000 women with HER-2–negative breast cancer (80% of all invasive cancer) to test a proven anthracycline/taxane combination regimen (docetaxel, doxorubicin, and cyclophosphamide [TAC]), compared to our TC regimen for six cycles of treatment. This study should provide a definitive answer to whether anthracyclines are needed if there is not a proper target (TOPO2A) available. If TC proves to be as effective and less toxic than TAC, then it may well be possible to spare many women the potential toxicities of anthracyclines (cardiomyopathy, increased nausea and vomiting, and leukemogenesis). Our better understanding of the biology of breast cancer is leading to more specific and directed therapy with either better outcome or less toxicity.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Jones SE, Savin MA, Holmes FA, et al: Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381-5387, 2006[Abstract/Free Full Text]

2. Pritchard KI, Sheperd LE, O'Malley F, et al: HER2 and responsiveness of breast cancer to adjuvant therapy. N Engl J Med 354:2103-2111, 2006[Abstract/Free Full Text]

3. O'Malley FP, Chia S, Tu D, et al: Topoisomerase II alpha protein overexpression has predictive utility in a randomized trial comparing CMF to CEF in premenopausal women with node positive breast cancer (NCIC CTG MA. 5). Presented at the San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-17, 2006. Http://www.abstracts2view.com/sabcs06/view.php?nu=SABCS06L_712

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Jones, F. A. Holmes, J. O'Shaughnessy, J. L. Blum, S. J. Vukelja, K. J. McIntyre, J. E. Pippen, J. H. Bordelon, R. L. Kirby, J. Sandbach, et al. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735 J. Clin. Oncol., March 10, 2009; 27(8): 1177 - 1183. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jones, S. E. Search for Related Content PubMed Articles by Jones, S. E. Social Bookmarking                            What's this?