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 Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Puglisi, F. Articles by Demonty, G. Search for Related Content PubMed PubMed Citation Articles by Puglisi, F. Articles by Demonty, G. Related Articles Related Reply Social Bookmarking                            What's this?

Shrinking the Tumor, Shrinking the Patient Sample Size: The Early Disclosure Dilemma

Department of Clinical Oncology, University of Udine, Udine, Italy

Evandro de Azambuja, Gilberto de Castro, Jr, Gaston Demonty

Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium

To the Editor:

We read with great interest the article by Buzdar et al on their randomized study comparing neoadjuvant chemotherapy (NAC) consisting of sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide versus the same chemotherapy plus trastuzumab in patients with stage II-IIIA HER-2–positive breast cancer (BC).¹

On the basis of preliminary results from the first 42 patients, the study was prematurely closed. Pathologic complete response (pCR), defined as the absence of residual invasive cancer both in breast and axilla, was chosen as the primary end point of the study. pCR rates of 65.2% and 26.3% were observed in the trastuzumab-containing arm and in the control arm, respectively (P = .016).

Those patients who were clinically node-negative after NAC could proceed to sentinel lymph node biopsy (SLN) without axillary dissection if the SLN was negative. Although several studies reported an acceptable accuracy of SLN biopsy after NAC, the ability of this technique to predict the status of the remaining non-SLNs is still a matter of debate.² In a previous study, Breslin et al³ reported an overall false-negative rate of 12% with SLN biopsy performed after NAC. This figure decreased to an acceptable 4.3% when only patients who were clinically node-negative after treatment were considered in the analysis. However, the false-negative rates reported for SLN biopsy studies after NAC can be as high as 25%, as reported by Kuerer and Newmann.⁴

This trial was terminated early and will perhaps add fuel to the fire of the ongoing debate about early disclosure of results and trial termination. In the last paragraph, the authors state that additional studies are needed to better define the pCR rate and cardiac risk, while establishing whether this higher-than-expected pCR rate has an impact on survival. But, by stopping recruitment on the control arm, comparisons will no longer be possible. In other words, if continued, this trial could have been able to answer at least some of these questions. With only 42 patients in the database, we think that despite the P value of .016 (which might be considered insufficient because it was obtained in an unplanned analysis using a small sample size), a random effect cannot be completely excluded, neither for overestimating the pCR rate in the experimental arm nor for lowering it in the control arm. Although there are studies supporting a link between pCR and clinical outcome, we cannot assume that the higher than expected pCR rate obtained in the experimental arm will translate into an overall survival benefit. An example of this can be found in the recently presented National Surgical Adjuvant Breast and Bowel Project B-27 trial results.⁵ Bearing this in mind, it is reasonable to disagree with the decision to stop this trial.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Buzdar A, Ibrahim NK, Francis D, et al: Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: Results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23:3676-3685, 2005[Abstract/Free Full Text]

2. Pendas S, Jakub J, Giuliano R, et al: The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ or with locally advanced breast cancer receiving neoadjuvant chemotherapy. Cancer Control 11:231-235, 2004[Medline]

3. Breslin TM, Cohen L, Sahin A, et al: Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 18:3480-3486, 2000[Abstract/Free Full Text]

4. Kuerer HM, Newmann LA: Lymphatic mapping and sentinel lymph node biopsy for breast cancar: Developments and resolving controversies. J Clin Oncol 23:1698-1705, 2005[Free Full Text]

5. Bear HD, Anderson S, Smith RE, et al: A randomized trial comparing preoperative (preop) doxorubicin/cyclophsophamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative T in patients with operable carcinoma of the breast: Results of NSABP B-27. Breast Cancer Res Treat 88:S16, 2004 (suppl 1)

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

Related Reply

• In Reply:
  Aman U. Buzdar, Kelly K. Hunt, Donald Berry, and Gabriel N. Hortobagyi
  JCO 2005 23: 6804-6805 [Full Text]

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 Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Puglisi, F. Articles by Demonty, G. Search for Related Content PubMed PubMed Citation Articles by Puglisi, F. Articles by Demonty, G. Related Articles Related Reply Social Bookmarking                            What's this?