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Electronic letters published:
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In Response
High birth weight and secondary breast cancer
This may be due to low DHEA...
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Lisa B Kenney, MD, MPH Dana-Farber Cancer Institute
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Lisa_Kenney{at}DFCI.harvard.edu Lisa B Kenney
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In response to Drs. Rossi and Howard, one of the objectives of our study was to investigate how hormonal and reproductive factors, known to modify breast cancer risk in the general population, modify secondary breast cancer risk in the unique population of childhood cancer survivors. The authors acknowledge that breast carcinogenesis is complex and ovarian steroid hormones are not the only factors that contribute to an individual’s breast cancer risk. However, in our attempt to identify risk factors for secondary breast cancer beyond radiation treatment, we chose to focus on hormonal and reproductive factors that are well established as breast cancer risk factors for the general population (1). In addition, our analysis was limited to data that were available on this cohort. Future studies on secondary breast cancer risk in childhood cancer survivors might address potential risk factors that the readers put forth. Lisa B. Kenney, MD, MPH Dana-Farber Cancer Institute Boston, MA 02115 Lisa_Kenney@DFCI.harvard.edu 1. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl cancer Inst 1989; 81 (24): 1879-86. Conflict of Interest:None declared |
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Gabriele Rossi, M.D. University of Pavia
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gab.rossi{at}tiscali.it Gabriele Rossi
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I read with great interest the original article by Kenney and Collegues regarding the risk factors associated with the development of a secondary breast cancer in a childhood cancer survivors population(1). I would like to ask the Authors if they are able to perform their analysis taking into account the patients’ birth weight. Recently, Ahlgren and Colleagues has emphasized the, already recognized, role of high birth weight as an independent risk factor for breast cancer(2). Moreover, it is known that there is a substantial literature indicating a positive association between high birth weight and the risk of developing some types of cancers (i.e. Wilms tumors, brain tumors, leukemia and lymphoma)(3-5). Theoretically therefore, in the contest of this particular studied population (in which patients suffer from a breast cancer after a childhood cancer), it should be not surprising to argue that high birth weight could somehow influence, in a same patient, the genesis of both tumors. It should be interesting to understand whether high birth weight may be considered as an independent risk factor for secondary breast cancer. In positive case, Clinicians would have a novel element to identify specific subgroup of childhood cancer survivors who, in turn, might benefit from early, vigilant screening for breast cancer. 1)Kenney LB, Yasui Y, Inskip PD, Hammond S, Neglia JP, Mertens AC, et al. Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Intern Med. 2004;141:590-7. 2)Ahlgren M, Melbye M, Wohlfahrt J, Sorensen TI. Growth patterns and the risk of breast cancer in women. New Engl J Med. 2004;351:1619-26. 3)Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J. High-birth weight and other risk factors for Wilms tumour: result of a population- based case-control study. Eur J Pediatr. 2001;160:333-8. 4)Hjalgrim LL, Rostgaard K, Hjalgrim H, Westergaard T, Thomassen H, Forestier E, et al. Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway and Iceland. J Natl Cancer Inst. 2004;96:1549-56. 5)Isager H, Andersen E. Pre-morbid factors in Hodgkin’s disease. Birth weight and growth pattern from 8 to 14 years of age. Scand J Haematol. 1978;21:250-5. Conflict of Interest:None declared |
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James M. Howard, biologist independent
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jmhoward{at}anthropogeny.com James M. Howard
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The findings of Kenney, et al., may be explained. It is my hypothesis that low DHEA may trigger breast cancer and this is often accompanied and caused by high testosterone (1994). My hypothesis has received demonstrable support. Hormone replacement therapy (HRT) increases the probability of breast cancer. I suggest this occurs because HRT and "estrogen replacement therapy" both reduce DHEA (Metabolism. 2001 Apr;50(4):488-93). Also, "…androstenedione and testosterone might be more strongly associated with [breast cancer] risk than estradiol." (J Natl Cancer Inst 2002; 94: 606- 616). Testosterone reduces DHEA. Stahlberg, et al., reported: "In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens…" (Int J Cancer. 2004 May 1;109(5):721-7) I suggest the reason for the increased risk caused by the "testosterone- like progestins" may be due to the possibility that they act like testosterone and reduce overall DHEA. It is also my hypothesis that the “secular trend,” the increase in size and earlier puberty occurring in our children actually is an increase in the percentage of individuals of higher testosterone within our populations. The secular trend is real and robust in the United States (Arch Pediatr Adolesc Med. 2000;154:155-161). More specifically, it is the exposure of fetuses to higher levels of testosterone in utero that is causing the secular trend, including the increase in breast cancer. Kenney, et al., report risk factors for “breast cancer among female survivors of childhood cancer” that may also support my hypothesis. Total body irradiation of girls significantly reduced DHEA levels up to five years following treatment (Horm Res 1995; 43: 279-85). Conversely, in rats “DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced tumorigenesis.” (J Steroid Biochem Mol Biol 1995; 54: 47-53). Thyroid disease, hypo- and hyperthyroid conditions, exhibit decreases and increases in DHEA respectively. Pelvic radiation therapy frequently results in ovarian failure (AJR Am J Roentgenol 1989; 153: 1003-6). This may reduce the production of testosterone in this cohort and, therefore, reduce the effects of testosterone in reducing DHEA. The protective effect of pelvic radiation reported by Kenney, et al., may be due to reduced testosterone. I suggest the findings of Kenney, et al., may represent various phenomena in their cohort which reduce DHEA and, therefore, increase breast cancer with the exception of pelvic radiation which may reduce the negative effect of testosterone , therefore, increasing DHEA. Conflict of Interest:None declared |
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