© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Response: Re: Age-Related Lobular Involution and Risk of Breast Cancer
Affiliations of authors: Division of Medical Oncology (LCH), Mayo Medical School (TRM), and Divisions of Epidemiology (CMV) and Biostatistics (RAV), Mayo Clinic, College of Medicine, Rochester, MN
Correspondence to: Lynn C. Hartmann, MD, Mayo Clinic and Foundation, Medical Oncology, 200 First St SW, Rochester, MN 55905 (e-mail: hartmann.lynn{at}mayo.edu).
We appreciate the interest of Ferretti et al. in the complex arena of age-related lobular involution, parity, and breast cancer risk. In our cohort of women with benign breast disease, we found that pregnancies were associated with persistence of lobular structures. In the cohort overall, persistence of lobules (i.e., no involution) was associated with an increased risk of breast cancer. We concluded that "breast cancer risk modification associated with parity is independent of involution status." We realize that our definition of involution is a histologic one. Ferretti et al. rightly point out that protection from breast cancer may also be conferred at the cellular or molecular level and may not be registered histologically as involution. And we certainly concur.
In Table 1, we provide data regarding the effect of involution in parous women in our cohort specifically. We observed a stepwise reduction in risk of breast cancer with progressive degrees of involution. Thus, even in breast tissue from parous women, which is already at reduced risk of breast cancer, completing the process of involution appears to be associated with further risk reduction.
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The mechanism(s) by which pregnancy exerts a protective effect on breast tissue remains unknown (1–3). The most widely cited explanation is that parity induces terminal differentiation of stem cells and/or early progenitors in the mammary gland, rendering them resistant to transforming stimuli (4). However, this hypothesis is based on chemically induced rodent models of mammary cancer. Not all subscribe to this model (1), and it has not been studied in humans. Interestingly, transgenic rodent models that express oncogenes driven by hormone-responsive promoters develop pregnancy-induced mammary cancers (5). Clinical data show that, although pregnancy is associated with a lower lifetime risk of breast cancer, it is associated with an increased risk during pregnancy and for the next several years (6). These trends also vary by age(s) at pregnancy and the interval between pregnancies. We certainly concur with Ferretti et al. that the intersection of parity and age-related involution in humans provides fertile ground for new ideas in risk reduction.
REFERENCES
(1) Medina D. Mammary developmental fate and breast cancer risk. Endocr Relat Cancer (2005) 12:483–95.
(2) Blakely CM, Stoddard AJ, Belka GK, Dugan KD, Notarfrancesco KL, Moody SE, et al. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat stains and identifies a core gene expression signature induced by pregnancy. Cancer Res (2006) 66:6421–31.
(3) National Cancer Institute. Summary report: early reproductive events and breast cancer workshop. Available at: http://www.cancer.gov/cancertopics/ere-workshop-report. Updated March 25, 2003. [Last accessed: February 23, 2007].
(4) Russo J, Russo IH. Role of differentiation in the pathogenesis and prevention of breast cancer. Endocr Relat Cancer (1997) 4:7–12.[CrossRef]
(5) Henry MD, Triplett AA, Oh KB, Smith GH, Wagner KU. Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene (2004) 23:6980–5.[CrossRef][ISI][Medline]
(6) Albrektsen G, Heuch I, Thoresen S, Kvale G. Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones? Cancer Epidemiol Biomarkers Prev (2006) 15:65–9.
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J Natl Cancer Inst 2007 99: 571-572.
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