To the Editor,
We appreciate Drs. Sun and Long’s interest in our work. We cannot agree with them more that it will be of considerable benefit if we can identify biomarkers for the chemotherapeutic efficacy and prevention of relapse. Indeed, the ear wax phenotype and osmidrosis are phenotypes associated with the functional, 538G>A (Gly180Arg) single-nucleotide polymorphism in ABCC11 [7]. Multiple epidemiologic studies have attempted to clarify the link between functional ABCC11 and the risk of breast tumorigenesis; however, the relationship remains controversial and inconclusive [8–10]. The essential difference between these studies and our article published in February issue of Breast Cancer Research and Treatment [11] is that we analyzed the ABCC11 expression in the tumor, and not in the patients’ stromal tissue. We found that ABCC11 expression in the tumor is associated with low disease-free survival, but we also did not find any association between the tumor ABCC11 expression and the ear wax type. Therefore, from our observation, we cannot conclude that the ear wax phenotype and osmidrosis can be used as prognostic factors of breast cancer. On the other hand, we did find that ABCC11 positive tumors tend to have a low response to neoadjuvant chemotherapy. ABCC11 is known to efflux 5-fluorouracil (5-FU); however, 5-FU is not the most commonly used drug for breast cancer in the latest regimen, and only 30.9 % of our cohort received it. Therefore, efflux of 5-FU alone cannot entirely explain the association of ABCC11 expression in the tumor with poor disease-free survival, and it is more likely that some other function of ABCC11 may contribute to the phenomenon. Given the recent advances in the understanding of the role of cancer stem cells in breast cancer survival, it is tempting to speculate that ABCC11 expression may be related to drug resistance in cancer stem cells, which is the case in some ABC transporters [12]. Along this line of investigation, we are planning to explore the mechanism by which the expression of ABCC11 in tumors is associated with poor prognosis utilizing in vitro and in vivo systems.
Acknowledgments
Kazuaki Takabe is supported by NIH (R01CA 160688) and a Susan G. Komen for the Cure Investigator Initiated Research Grant (IIR12222224).
Contributor Information
Akimitsu Yamada, Department of Clinical Oncology and Breast Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan.
Takashi Ishikawa, Email: tishik@urahp.yokohama-cu.ac.jp, Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan.
Kazuaki Takabe, Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 7-402 West Hospital, 1200 E Broad Street, Richmond, VA, USA.
Itaru Endo, Department of Clinical Oncology and Breast Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan.
References for Rebuttal letter
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