Dr. Weisenthal Replies

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Dr. Mason states that I implied that Dr. Telli supports the routine application of chemosensitivity assays. I have no knowledge regarding Dr. Telli’s views on this subject, nor did I in any way attempt to represent her views, much less imply that she was supportive of anything relating to chemosensitivity assays.

Dr. Mason also raises the issue of conflict of interest. I am an expert in chemosensitivity testing, with 35 years of largely full-time experience with the relevant technologies. Dr. Telli stated that her group was working on predictive markers to identify the best candidates for platinum treatment in breast cancer. I quoted our data presented at the 2009 Breast Cancer Symposium, which prospectively identified the best candidates for such treatment as being patients with triple-negative disease and a Bloom-Richardson score of 9/9. My laboratory provides neither marker studies for triple-negative disease nor Bloom-Richardson scoring.

Obvious vs Nonobvious Conflicts

Let’s imagine that I were a pathologist, who pointed out to Dr. Telli that there was prior work suggesting that the above routine pathology markers could be useful in identifying candidates for platinum treatment. Would this be a conflict of interest?

Dr. Mason seems to be implying that any expert/specialist who provides a service related to his/her comment should declare a conflict of interest. Thus, a radiotherapist commenting on a surgical study should declare a conflict of interest, a chemotherapist commenting on a radiotherapy study should declare a conflict of interest, and so forth.

In my case, it was obvious from my letter that I performed chemosensitivity testing, as I quoted my own work in this field! In a similar vein, pathologists, radiotherapists, and chemotherapists generally make note of their own specialties in their comments, as workers in a particular field typically have the most relevant knowledge base, and their conflicts of interest are likewise obvious. One generally makes a formal conflict of interest declaration when one’s conflict is not obvious, eg, most typically in disclosing a relationship to an entity not obviously related to one’s medical practice, such as a relationship with an outside pharmaceutical company. 

I am going to hazard a guess that Dr. Mason would state that the difference between an oncologist providing chemosensitivity testing and a pathologist providing estrogen receptor testing is that the former testing is considered to be “investigational/not recognized by ASCO,” whereas the latter is considered to be noninvestigational/recognized. But is this a fair distinction?

Double Standard?

To date, ASCO has provided two formal reviews of chemosensitivity testing.1,2 In both reviews, the sole criterion being assessed was “efficacy,” meaning the existing data relating to the question of whether the use of this testing improves clinical outcomes. In both reviews, no attempt was made to assess the considerable data documenting the accuracy of chemosensitivity testing, where test accuracy is the only criterion ever used to “validate” any predictive laboratory technology, specifically including the triple-negative tests (ie, for estrogen receptor, progesterone receptor, and HER2).

This double standard has had the effect of halting virtually all progress in the field of chemosensitivity testing since the late 1980s. Critics have labeled the technology “investigational” and have then failed to support the investigations they have demanded, as readily evidenced by the complete absence of NIH grant–supported publications in the American literature over the past 2 decades. The technologies are largely in the public domain and labor-intensive, and there has accordingly been no serious private sector money to compete with pharmaceutical company funding for clinical trials.

New Development

Just this year, however, there has been a new development. A large-scale (777-patient) prospective, randomized trial in chronic lymphocytic leukemia was published, supported by the British Leukemia Research Fund.3 I would ask fair reviewers to compare and contrast the quality and results of this trial with what is the self-proclaimed “best” trial ever performed to “validate” estrogen receptor testing4 (estrogen receptor negativity being the most powerful contributor to platinum sensitivity in patients with triple-negative disease in our 2009 study).5

Comparing the chemosensitivity test study with the estrogen receptor study, the former had a greater number of patients and stronger predictive correlations, and used real-world test conditions (real-time processing and prospective reporting, as opposed to post hoc batch-processing and retrospective reporting). Additionally, for the first time ever in all studies of predictive markers used for treatment selection in cancer, the chemosensitivity study showed an improved clinical outcome for patients randomly assigned to test-guided treatment selection vs non–test-guided treatment selection. (Patients in the empiric therapy arm had a 2.5-fold greater probability of being dead at 1 year, compared to the patients in the test-directed arm.)

Lost Opportunity

I view the lack of support and overt hostility to chemosensitivity testing as being the single greatest lost opportunity in clinical cancer research over the past 25 years.

As a postscript, there was a nonfunctioning link to our 2009 ASCO Breast Symposium presentation relating to platinum therapy in triple-negative breast cancer in my original comment, as published. Here is the correct link, presenting our abstract and most important data: http://meetinglibrary.asco.org/content/40486-70 ■

—Larry Weisenthal, MD
Huntington Beach, California


1. Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology Technology Assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22:3631-3638, 2004.

2. Burstein HJ, Mangu PB, Somerfield MR, et al: American Society of Clinical Oncology clinical practice guideline update on the use of chemotherapy sensitivity and resistance assays. J Clin Oncol 29:3328-3330, 2011.

3. Matutes E, Bosanquet AG, Wade R, et al: The use of individualized tumor response testing in treatment selection: Second randomization results from the LRF CLL4 trial and the predictive value of the test at trial entry. Leukemia 27:507-510, 2013.

4. Elledge RM, Green S, Pugh R, et al: Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: A Southwest Oncology Group Study. Int J Cancer 89:111-117, 2000.

5. Weisenthal L: Activity of cisplatin in triple-negative breast cancer in comparison to other cancer types in fresh tumor cell culture assay using a cell death endpoint. 2009 Breast Cancer Symposium. Abstract 61. Presented October 8-10, 2009.

Disclaimer: This letter represents the views of the author and may not necessarily reflect the views of ASCO.




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