Overweight and Obese Perimenopausal and
Postmenopausal Women Exhibit Increased
Abnormal Mammary Epithelial Cytology
Victoria L. Seewaldt,1,2,3Vanessa Goldenberg,1Lee W. Jones,3,4Charlotte Peace,1
Gloria Broadwater,3Victoria Scott,1Gregory R. Bean,1Lee Gravit Wilke,4
Carola M. Zalles,6and Wendy Demark-Wahnefried3,4,5
1Department of Medicine,
4Department of Surgery, and
2Department of Pharmacology and Cancer Biology,
5School of Nursing, Duke University Medical Center, Durham, North Carolina;
6Department of Pathology, Yale-New Haven Medical Center, New Haven, Connecticut
3Duke University Comprehensive Cancer Center,
High body mass index (BMI z 25 kg/m2) is associated with
increased postmenopausal breast cancer incidence and
mortality. However, few studies have explored associations
between BMI and direct measures on target tissue. Epithelial
cytology was assessed in 62 high-risk perimenopausal and
postmenopausal women using random periareolar fine
needle aspiration. Masood cytology index scores were signi-
ficantly higher among women with BMIs z25 kg/m2than in
women with BMIs <25 kg/m2(13.9 F 0.42 versus 12.7 F 0.29
kg/m2; P = 0.017). Overweight or obese women also had
significantly higher random periareolar fine needle aspira-
tion epithelial cell counts compared with those who were
normal weight (1,230 F 272 versus 521 F 185; P = 0.028).
These data suggest that overweight in perimenopausal and
postmenopausal women is associated with direct cytologic
abnormalities within the breast. Further research is needed
to confirm these findings and to determine if this potential
biomarker is responsive to changes in body weight resulting
from diet and/or exercise interventions.
Biomarkers Prev 2007;16(3):613–6)
It is estimated that roughly 10 million U.S. women are at high
risk for breast cancer (1). Excessive body weight, as reflected
by a body mass index (BMI z 25 kg/m2), is consistently
associated with postmenopausal breast cancer and increases
the risk of dying from this disease (2-6). Whereas previous
studies have explored associations between body weight and
indirect biomarkers associated with disease risk, such as
circulating hormonal levels or mammographic density, few
have explored associations between BMI and direct measures
on target tissue (7, 8).
Random periareolar fine needle aspiration (RPFNA) is a
research technique developed to sample mammary cells from
the whole breast of asymptomatic women at high risk for
development of breast cancer to assess both (a) breast cancer
risk and (b) response to chemoprevention (9, 10). RPFNA can
be done successfully in a majority of high-risk women (82-89%
cell yield; refs. 9-11). RPFNA has been used successfully to
predict short-term breast cancer risk; the presence of cellular
atypia in a breast RPFNA specimen has been prospectively
validated to confer a 5.6-fold increase in breast cancer risk in
high-risk women (9).
The purpose of this brief communication is to relay findings
obtained from an exploratory study aimed at investigating
whether perimenopausal and postmenopausal women who
are overweight or obese exhibit increased abnormal Masood
Cytology as compared with women of normal weight. The
rationale for undertaking this exploration was driven by the
hypothesis that these direct measures on the target tissue
would indeed be associated with BMI.
Materials and Methods
Informed Consent. This study was conducted among 62
women who underwent RPFNA under an Institutional Review
Board–approved protocol at Duke University Medical Center
(March 2003-August 2005) and who presented sufficient cells
Eligibility. Women were required to have at least one of
the following major risk factors for breast cancer: (a) 5-year
Gail risk calculation z1.7% (12); (b) prior biopsy exhibiting
atypical hyperplasia, lobular carcinoma in situ, or ductal
carcinoma in situ; (c) known BRCA1/2 mutation carrier; or (d)
prior history of contralateral breast cancer. Women were
required to be perimenopausal or postmenopausal, defined as
<6 menstrual periods/y in the absence of pregnancy,
polycystic ovarian syndrome, or thyroid disorder or no
menses for >12 months in the absence of pregnancy and/or
status postsurgical removal of both ovaries, respectively.
Sociodemographic variables (age, race), hormone replacement
therapy (HRT) use, and family history of breast cancer were
collected. Given the potential for HRT to serve as a
confounder of an investigation focused on body weight and
breast cancer risk, all women currently using HRT on a
routine basis were excluded from the analyses.
Cancer Epidemiol Biomarkers Prev 2007;16(3). March 2007
Received 10/13/06; revised 12/12/06; accepted 1/8/07.
Grant support: NIH/National Cancer Institute grants CA68438-AV13 [AVON/National
Cancer Institute Partners in Progress], 2P30CA14236, R01CA088799, R01CA98441, and
R01CA114068 (V.L. Seewaldt); Susan G. Komen Breast Cancer Award BCTR0402720
(V.L. Seewaldt); V-Foundation Award (V.L. Seewaldt); and the American Institute for Cancer
Research (W. Demark-Wahnefried).
The costs of publication of this article were defrayed in part by the payment of page charges.
This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.
Section 1734 solely to indicate this fact.
Requests for reprints: Victoria L. Seewaldt, Duke University Medical Center, Box 2628,
Durham, NC 27710. Phone: 919-668-2455; Fax: 919-668-2458. E-mail: firstname.lastname@example.org
Copyright D 2007 American Association for Cancer Research.