Download Earwax type and osmidrosis: prognostic factor for

Breast Cancer Res Treat (2013) 138:651–653
DOI 10.1007/s10549-013-2450-0
LETTER TO THE EDITOR
Earwax type and osmidrosis: prognostic factor for breast cancer?
Yang Sun • Jianhong Long
Received: 29 January 2013 / Accepted: 15 February 2013 / Published online: 27 February 2013
Ó Springer Science+Business Media New York 2013
To the Editor,
Many women with breast cancer undergoing chemotherapy
suffer from resistance or relapsed disease while other
patients with similar clinical and pathological tumors do
not. Accumulating evidence strongly suggests that this
inter-individual difference is mainly coming from the
genetic variants. However, identification of all the specific
single genes is not only expensive but also unrealistic,
especially in developing countries. Could there be any
highly cost-effective choice for risk assessment?
I have read the article ‘‘High expression of ATP-binding
cassette transporter ABCC11 in breast tumors is associated
with aggressive subtypes and low disease-free survival’’
with great interest. Akimitsu Yamada et al. [1] have suggested the ABCC11 to be a biomarker for prediction of
the recurrence risk and anticancer drug sensitivity. The
underlying molecular mechanism was reported earlier that
one single-nucleotide polymorphism (SNP), 538G[A
(Gly180Arg), in the ABCC11 gene could perturb the
conformation and affects the function and stability of
the protein [2]. The non-functioned protein fail to transport
the anticancer drugs like 5-fluorouracil (5-Fu) [3] and
methotrexate (MTX) [4]. Thus, the SNP (538G[A) of the
ABCC11 gene is suggested to be a clinical biomarker for
prediction of chemotherapeutic efficacy [5].
It is notable that the wet earwax and osmidrosis are the
visible genetic traits of the functional ABCC11 protein [6].
Y. Sun J. Long (&)
Department of Plastic and Aesthetic Surgery, Xiangya Hospital
of Central South University, Changsha 410008, Hunan, China
e-mail: [email protected]
So I wonder if patient with the wet earwax and osmidrosis
is more likely to have a higher level of drug resistance as
the anticancer drugs exportation may comparatively be
more. If so, the earwax type and osmidrosis may be an easy
and visible indicator of patients’ chemotherapeutic efficacy
and may determine the kind and the amount of drug needed
for an efficient therapy while spare the rigors and potential
complications associated with chemotherapy. Although it
is only a hypothesis that should be carefully evaluated by
clinical studies, it would be unfortunate if it is effective but
never attempted.
References
1. Yamada A, Ishikawa T, Ota I et al (2013) High expression of
ATP-binding cassette transporter ABCC11 in breast tumors is
associated with aggressive subtypes and low disease-free survival. Breast Cancer Res Treat 137(3):773–782
2. Toyoda Y, Sakurai A, Mitani Y et al (2009) Earwax, osmidrosis,
and breast cancer: why does one SNP (538G[A) in the human
ABC transporter ABCC11 gene determine earwax type? FASEB J
23(6):2001–2013
3. Oguri T, Bessho Y, Achiwa H et al (2007) MRP8/ABCC11
directly confers resistance to 5-fluorouracil. Mol Cancer Ther
6:122–127
4. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD (2005)
Transport of bile acids, sulfated steroids, estradiol 17-beta-Dglucuronide, and leukotriene C4 by human multidrug resistance
protein 8 (ABCC11). Mol Pharmacol 67(2):545–557
5. Toyoda Y, Ishikawa T (2010) Pharmacogenomics of human ABC
transporter ABCC11 (MRP8): potential risk of breast cancer and
chemotherapy failure. Anticancer Agents Med Chem 10:617–624
6. Yoshiura K, Kinoshita A, Ishida T et al (2006) A SNP in the
ABCC11 gene is the determinant of human earwax type. Nat
Genet 38:324–330
Y. Sun
e-mail: [email protected]
123
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Breast Cancer Res Treat (2013) 138:651–653
Response to Letter to the Editor
REBUTTAL LETTER
Response to Letter to the Editor
Akimitsu Yamada Takashi Ishikawa Kazuaki Takabe Itaru Endo
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).
References for Rebuttal letter
A. Yamada, I. Endo
Department of Clinical Oncology and Breast Surgery,
Yokohama City University, 3-9 Fukuura, Kanazawa-ku,
Yokohama, Kanagawa, Japan
T. Ishikawa (&)
Department of Breast and Thyroid Surgery, Yokohama City
University Medical Center, 4-57 Urafunecho, Minami-ku,
Yokohama, Kanagawa 232-0024, Japan
e-mail: [email protected]
K. 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.
123
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