| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Environmental Risk Research Division, National Institute for Environmental Studies, Ibaraki 305-0053, Japan [M. K.]; Departments of Epidemiology [S. A.] and Clinical Studies [K. N.], Radiation Effects Research Foundation, Hiroshima 732-0815, Japan; Department of Public Health, Faculty of Medicine, Kagoshima University, Kagoshima 890-0075, Japan [S. A.]; Pacific Northwest National Laboratory, Richland, Washington 99352 [R. G. S.]; and Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7362 [C. E. L.]
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
RERF4 and its predecessor, Atomic Bomb Casualty Commission, in Hiroshima and Nagasaki, Japan have studied mortality and morbidity in a large study cohort of atomic bomb survivors and have solicited a subcohort (AHS) for biennial clinical examinations since 1958. Serum samples have been collected, frozen, and stored at Atomic Bomb Casualty Commission/RERF since the 1968–1970 examination cycle. This repository of stored samples and clinical records provides for focused studies of cancer cases and appropriately chosen controls using serum samples collected before disease onset.
We report here the results of a nested case-control study of serum hormones collected prior to breast cancer development. The prior hypothesis of primary interest was that high levels of biologically available E2 in serum may predispose women to develop breast cancer. The serum constituents assayed were total E2, SHBG, bioavailable E2 (not bound to SHBG), prolactin, progesterone, and DHEA-s. Case-control differences were evaluated for each hormonal component, alone and in combination with other risk factors including reproductive history, other medical history, and radiation dose.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Participation in the biennial AHS clinical examination program has been
consistently 
85% of the surviving subcohort members still resident
in the two cities. Clinical examinations are given at RERF or at home
if the subject is physically unable to come to RERF. The examinations
involve clinical history, physical examination, blood work-up, and, if
held at RERF, chest X-ray or other radiography as appropriate.
Beginning with the 1968–1970 examination cycle, serum samples have
been frozen and stored at -60o to
-70o C, except for a 4-day period in July 1982,
when the freezer malfunctioned and the temperature eventually reached
25–35oC.
Individual, organ-specific radiation dose estimates have been calculated for most (86%) exposed cohort members using the dosimetry system (DS86) introduced in 1986 (2) that replaced the T65D system introduced in 1965. Both systems were based on individual shielding histories and mathematical models for radiation yield from the bombs and its attenuation over distance and by materials and tissue. Cancer cases are identified by death certificate and through the RERF Tumor Registry (3) . Diagnosis date was confirmed for all cases in the current study on the basis of pathology or clinical records. Three cases were diagnosed in 1973, five in 1974, and the remainder in 1975 or later.
Selection of Cases and Controls.
All women in the AHS subcohort diagnosed with breast cancer between
1973 and 1983 and recorded as having at least 1.0 ml of stored serum
from the 1970 to 1972 examination cycle were selected from the RERF
tumor registry and mortality files. Initially, two control women
satisfying the same sample and serum availability criteria and matched
with respect to city, age (±3 years), date (±3 months) of blood
collection, and radiation dose in Gy
(nonexposed/<0.01/0.01–0.49/0.50–0.99/
1.00/unknown dose) were
selected for each case. A control woman must have been alive and cancer
free at the date of case diagnosis. Cases and controls were matched on
dose to remove dose as a possible confounder and (more importantly) to
improve power for analyses of possible interactions between hormonal
effects and radiation dose (4)
. Case and control selection
for this study was conducted in 1985, prior to the availability of DS86
estimates. Matching was therefore based on breast tissue dose according
to the T65D system, which is highly correlated with the DS86 dose.
Subsequently, based on visual inspection of the samples, 12 cases and about twice as many controls were found to have insufficient volumes of serum (i.e., <1.0 ml) and were dropped from the study. Later, based on results from hormone assays, 5 cases and 10 controls were dropped because of suspected pregnancy at blood drawing. For 1 additional case and 4 additional controls, total E2 could not be evaluated, and these subjects were dropped from analysis. Seventy-two breast cancer cases with 150 controls remained. Because losses of cases and controls left some of the original matched sets without a case or control, a modified version of the original matching criteria was applied to the remaining cases and controls without knowledge of assay results. The modified criteria involved a relaxation of the criterion for matching on radiation dose to allow exposed subjects without DS86 dose estimates to be included in matched sets of exposed subjects if other matching criteria were met. This procedure resulted in 72 new matched sets, 52 of which had 1 case and 2 controls, and the remainder had a single case and 1, 3, 4, or 5 controls.
Laboratory Analysis.
Hormonal assays were carried out by one of us (M. K.) at Nagasaki
University in 1986 under blind conditions, using samples (including
control samples) identified only by number. The choice of assays was
governed both by the study purposes and the limited serum available for
most subjects. RIA was performed using commercially available kits to
determine E2 levels (Dai-ichi Radioisotope
Institute) and prolactin and progesterone (Amersham International Plc).
Levels of bioavailable E2 were calculated by
multiplying total (i.e., free plus albumin-bound plus
SHBG-bound) E2 values by percentage of
bioavailable E2, which was estimated using a
modified version of the charcoal method reported by Vermulen et
al. (5)
.
The intra-assay coefficients of variation based on control pools were 9.8% for E2, 5.3% for SHBG, and 7.5% for progesterone. In a pilot study on 10 males and 10 females, repeated serum samples were collected for four periods between 1969 and 1983, and very good stability of the mean values was obtained for DHEA-s, prolactin, and E2. All assays were performed blind. Assay materials from several lots were mixed and applied to all subjects to avoid kit-to-kit variation.
DHEA-s levels were measured by RIA for 11-deoxy-17 ketosteroid with DHEA-s as standard. Antisera for this assay was obtained from the Third Department of Internal Medicine of the University of Tokyo. SHBG was measured by RIA kit using a specific monoclonal antibody (Farmos Diagnostica, Oulansalo, Finland).
Information from RERF Data Files.
Blood pressure, height, weight, and cholesterol levels were measured at
the time of blood collection and included in the clinical record of
each subject. Obstetrical-gynecological histories were gathered from
various RERF files, including medical records, interviews at the RERF
clinics in the mid 1960s, 1978 mail survey data files (6)
,
X-ray film records, and PAP smear records (7)
. Variables
of particular interest as possible risk or modifying factors include
number of deliveries, age at first marriage, age at first delivery,
cumulative months of lactation, age at menarche, age at menopause, and
smoking history.
There were seven subjects whose ages at menopause, i.e., 1 year after the last menstrual period, were uncertain. These women were all categorized as postmenopausal for events (diagnosis or blood drawing) occurring after 55 years of age. One case, diagnosed at age 46, was treated as premenopausal, and one control, examined at age 44, was treated as premenopausal at blood drawing. Also, the exact timing of cancer diagnosis relative to menopause was difficult to determine for some cases. In the analysis, cases diagnosed within 1 year after menopause were treated as premenopausal cases.
Statistical Analysis.
Measured levels of total E2, SHBG, prolactin, and
bioavailable E2 were transformed to their
logarithms (base 10) because the distributions of the transformed
values were more nearly symmetric than in the original scale, whereas
DHEA-s and progesterone were analyzed in the original scale.
The primary analyses were comparisons of serum hormone levels between
cases and individually matched controls, using the PECAN algorithm for
conditional logistic analysis from the Epicure package of generalized
regression programs for epidemiological data analysis (8)
.
The results changed only slightly when analyses were conducted using a
conventional logistic analysis that ignored the matching scheme but
adjusted for age and the DS86 breast dose. In all regression analyses,
the logarithm of the OR was modeled as a linear function of the
hormonal variable of interest, with separate intercepts for
premenopausal and postmenopausal serum. Slope coefficients were
calculated both with and without regard for menopausal status at the
time of blood drawing, e.g.,
 |
or
 |
where 
1, 2, ß,
ß1, and ß2 are unknown
parameters, X is the variable of immediate interest, and
I1 and
I2 are indicator functions for
premenopausal and postmenopausal serum, respectively
(I1 = 1 and
I2 = 0 for premenopausal serum, and
I1 = 0 and
I2 = 1 for postmenopausal serum).
In other analyses, X was replaced by a categorical variable (Y, Y1, or Y2) with levels denoting placement of the observed value by quintile among observations based on assays of all serum (Y), premenopausal serum only (Y1), or postmenopausal serum only (Y2). Ps presented correspond to likelihood ratio tests.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
, by menopausal status at examination. Missing values include one
control for whom SHBG could not be evaluated. With that exception and
the subjects excluded from the analysis for other reasons, it appears
that serum hormone levels accord well with normal ranges and did not
deteriorate under storage conditions, including the 4 days of freezer
malfunction in 1982. Correlations between pairs of hormones are shown
in Table 2
, separately by menopausal status at examination. As expected,
bioavailable E2 and SHBG were inversely related
in both premenopausal and postmenopausal serum.
|
|
shows the ORs estimated from conditional logistic regression (using
PECAN) for bioavailable E2, SHBG, DHEA-s, total
estrogen, and prolactin. These ORs apply to a unit change in the
logarithm or, in the case of DHEA-s, the untransformed level of the
hormone in question. Bioavailable E2 was
significantly associated with risk (OR, 2.24 with 95% CI, 1.02–5.30);
separate estimates for premenopausal and postmenopausal serum were
similar, but with wider confidence limits. For SHBG, the overall OR was
0.58 (95% CI, 0.14–2.26), and 1.00 (95% CI, 0.19–5.45) and 0.21
(95% CI, 0.02–1.88) based on premenopausal and postmenopausal serum,
respectively. Total E2 was suggestively related
to risk [OR, 2.22 (95% CI, 0.85–6.17); however, there was no
association after adjustment for bioavailable E2
(adjusted OR, 1.05 (95% CI, 0.20–5.16)]. Prolactin was not related
to subsequent breast cancer risk. Risk increased with increasing
DHEA-s, but not significantly (P = 0.15).
|
.
|
Case-Control Comparisons: Epidemiological Variables.
Analyses with respect to epidemiological variables provided little
insight into the relationships between breast cancer risk and serum
hormone levels. In these data, having delivered a child (OR, 0.26; 95%
CI, 0.10–0.63; P = 0.006) and cumulative lactation
(OR, 0.49 per year; 95% CI, 0.21–0.89; P = 0.013)
were significantly and inversely related to breast cancer risk.
Information on parity was available for most subjects (67 cases and 141
controls; 66 informative data sets), but information on lactation was
available for fewer than half of the subjects (32 of 72 cases and 62 of
150 controls; 20 informative data sets), and therefore, no adjustment
was considered for this variable. Adjustment for parity had little or
no effect on the main associations demonstrated in Tables 3
4
. No
suggestive or statistically significant associations were observed
between cigarette smoking and hormone levels, nor did adjustment for
smoking affect observed associations, or lack thereof, between breast
cancer risk and serum hormone levels.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Toniolo et al. (12) conducted a nested case-control study based on 14,291 women in the prospective New York University Women’s Health Study. Among 130 cases of breast cancer in postmenopausal women, they found a strong trend of increasing risk with increasing quartile of bioavailable E2 and a strong decreasing risk with increasing quartile of SHBG-bound E2 after adjustment for Quetelet’s index. They also found positive associations of total E2 and estrone with risk. In addition, they found a strong negative correlation of Quetelet’s index with percent SHBG-bound E2. Similarly, Key et al. (13) conducted a prospective study of urinary estrogens and subsequent risk of breast cancer in 1000 women. Among 31 postmenopausal cases, there was a statistically significant association of urinary E2 concentration and of total estrogen concentration and subsequent risk. Among 38 premenopausal cases, there were no significant associations. Two more prospective studies reported an association of biologically available E2 and risk and strong associations of androgens and risk (14 , 15) . The studies were methodologically strong but had small numbers of cases (71 and 25, respectively). In Dorgan et al. (14) , the association with androgens was restricted to cases occurring within 2 years of blood draw.
Three recent studies have reported associations of elevated serum E2 with risk of postmenopausal breast cancer (16, 17, 18) . Cauley et al. (16) studied 97 women with breast cancer from a cohort of 9704 women of ages 65+ in the United States. They reported a relative risk of 3.6 for women in the highest quartile of bioavailable E2 compared with the lowest quartile. They also found a strong association of free testosterone and risk; however, this did not attain statistical significance after adjustment for bioavailable E2. Hankinson et al. (17) used the Nurses’ Health Study to examined plasma hormone levels and risk of breast cancer in the United States. Among 156 women diagnosed over the study period, 1989–1994, total E2, estrone, estrone sulfate, and DHEA-s were each significantly associated with risk. Bioavailable E2 and testosterone were also marginally significant. In multivariate analyses, adjustment for total E2 substantially reduced risk associated with testosterone, and it became nonsignificant. Thomas et al. (18) reported a strong association of total circulating E2 concentration and breast cancer risk in a nested case-control study of 61 cases and 179 control chosen from within a prospective follow-up of 6127 women from the island of Guernsey in the United Kingdom (OR, 5.0 for highest tertile compared with lowest). E2 was strongly associated even after adjustment for testosterone and SHBG; however, after adjustment for E2, testosterone and SHBG were not significantly associated with risk. In a review of epidemiological studies published from 1966 to 1996, Thomas et al. (19) reported that the results from prospective studies supported an association of high total E2 (serum or urinary, depending upon the study) and risk of breast cancer in postmenopausal women. There was no significant heterogeneity among these studies.
In the present study, we distinguished between cases who had serum drawn before and after menopause because of the impact of menopause on hormone levels. In this prospective study, cases with postmenopausal serum were all diagnosed after menopause, whereas among the women with premenopausal serum, there were cases diagnosed both before and after menopause. There were too few cases diagnosed before menopause to be separately informative about the association of hormones and risk.
Unfortunately, no record was kept of stage of menstrual cycle at time of clinical examination, nor was time of day recorded for blood drawing. The problem here is not a possible bias attributable (for example) to an association between subsequent development of breast cancer and stage of the menstrual cycle at time of blood drawing, but one of reduced ability to do refined statistical analyses with respect to hormone levels in premenopausal serum.
We were concerned about the reliability of the measurement of
bioavailable E2 in sera that had been stored for
as long as 15+ years. We were encouraged by the facts that:
(a) age-specific levels of bioavailable
E2 among control subjects were comparable with
those reported by other researchers; and (b) bioavailable
E2 levels showed a strong positive correlation
with total E2 and strong negative correlation
with SHBG (Table 2)
. There is high variability among women in total
E2 level (20)
and lower levels in
Japanese than American women (21)
. Given this variability,
our values are in the same range as studies published previously.
A case-control interview study (4 , 22) , based on 196 cases and 566 controls from the full cohort of the RERF Life Span Study, reported a strong, positive association of risk with age at first full-term pregnancy. Inverse associations were observed for number of births and total period of breastfeeding, even after adjustment for age at first birth. The present study was conducted separately, with subjects drawn from those members of the Life Span Study clinical subsample for whom stored serum was available. However, the findings with respect to epidemiological factors were comparable with respect to those in the interview study given the smaller numbers of cases and controls. The interview study also investigated interactions between radiation dose and reproductive factors and found a generally multiplicative relationship; for example, early age at first full-term pregnancy was found to be protective against both baseline and radiation-related breast cancer to about the same degree. The relationships between risk and serum hormone levels were not sufficiently clear in these data to yield clear results with respect to interaction with radiation dose.
In summary, our study showed a positive association of bioavailable E2 with risk of breast cancer in Japan, despite the fact that Japanese women have lower bioavailable E2 and higher SHBG than Caucasian women (21) .
|
Acknowledgments |
|---|
|
Footnotes |
|---|
1 This publication is based on research performed
at the RERF, Hiroshima and Nagasaki. RERF is a private nonprofit
foundation funded jointly by the Japanese Ministry of Health and
Welfare and the United States Department of Energy through the National
Academy of Sciences. R. G. S. was supported by the United States
Department of Energy under contract DE-AC06-76RLO 1830. 
2 Present address: University of Connecticut
Health Center, Department of Community Medicine, 263 Farmington Avenue,
Farmington, CT 06030-6205.
3 To whom requests for reprints should be
addressed, at Department of Clinical Studies, Radiation Effects
Research Foundation, Hijiyama Koen, Minami-Ku, Hiroshima 732-0815,
Japan. Phone: 81-82-261-3131; Fax: 81-82-263-7279; E-mail
neriishi@rerf.or.jp.
4 The abbreviations used are: RERF, Radiation
Effects Research Foundation; SHBG, sex hormone binding globulin;
DHEA-s, dehydroepiandrosterone sulfate; E2, estradiol; AHS,
Adult Health Study; OR, odds ratio; CI, confidence interval.
Received 10/11/99; revised 3/15/00; accepted 3/27/00.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  F. Xue and K. B Michels Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence Am. J. Clinical Nutrition, September 1, 2007; 86(3): 823S - 835S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Tworoger, A. H. Eliassen, P. Sluss, and S. E. Hankinson A Prospective Study of Plasma Prolactin Concentrations and Risk of Premenopausal and Postmenopausal Breast Cancer J. Clin. Oncol., April 20, 2007; 25(12): 1482 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Tworoger, A. H. Eliassen, S. A. Missmer, H. Baer, J. Rich-Edwards, K. B. Michels, R. L. Barbieri, M. Dowsett, and S. E. Hankinson Birthweight and Body Size throughout Life in Relation to Sex Hormones and Prolactin Concentrations in Premenopausal Women Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2494 - 2501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Michels, K. L. Terry, and W. C. Willett Longitudinal Study on the Role of Body Size in Premenopausal Breast Cancer Arch Intern Med, November 27, 2006; 166(21): 2395 - 2402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Eliassen, S. A. Missmer, S. S. Tworoger, D. Spiegelman, R. L. Barbieri, M. Dowsett, and S. E. Hankinson Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst, October 4, 2006; 98(19): 1406 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Russo, S. V. Fernandez, P. A. Russo, R. Fernbaugh, F. S. Sheriff, H. M. Lareef, J. Garber, and I. H. Russo 17-Beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells FASEB J, August 1, 2006; 20(10): 1622 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Eliassen, S. A. Missmer, S. S. Tworoger, and S. E. Hankinson Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer: Does the Association Vary by a Woman's Predicted Breast Cancer Risk? J. Clin. Oncol., April 20, 2006; 24(12): 1823 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Tworoger, P. Sluss, and S. E. Hankinson Association between Plasma Prolactin Concentrations and Risk of Breast Cancer among Predominately Premenopausal Women Cancer Res., February 15, 2006; 66(4): 2476 - 2482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Kaaks, S Rinaldi, T J Key, F Berrino, P H M Peeters, C Biessy, L Dossus, A Lukanova, S Bingham, K-T Khaw, et al. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition Endocr. Relat. Cancer, December 1, 2005; 12(4): 1071 - 1082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S A Khan, D Bhandare, and R T Chatterton Jr The local hormonal environment and related biomarkers in the normal breast Endocr. Relat. Cancer, September 1, 2005; 12(3): 497 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kaaks, F. Berrino, T. Key, S. Rinaldi, L. Dossus, C. Biessy, G. Secreto, P. Amiano, S. Bingham, H. Boeing, et al. Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk Within the European Prospective Investigation into Cancer and Nutrition (EPIC) J Natl Cancer Inst, May 18, 2005; 97(10): 755 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Goffin, S. Bernichtein, P. Touraine, and P. A. Kelly Development and Potential Clinical Uses of Human Prolactin Receptor Antagonists Endocr. Rev., May 1, 2005; 26(3): 400 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Geisler and P. E. Lonning Aromatase Inhibition: Translation into a Successful Therapeutic Approach Clin. Cancer Res., April 15, 2005; 11(8): 2809 - 2821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Lonning Exemestane for Breast Cancer Prevention: A Feasible Strategy? Clin. Cancer Res., January 15, 2005; 11(2): 918s - 924s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Missmer, A. H. Eliassen, R. L. Barbieri, and S. E. Hankinson Endogenous Estrogen, Androgen, and Progesterone Concentrations and Breast Cancer Risk Among Postmenopausal Women J Natl Cancer Inst, December 15, 2004; 96(24): 1856 - 1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Hilakivi-Clarke, C Wang, M Kalil, R Riggins, and R G Pestell Nutritional modulation of the cell cycle and breast cancer Endocr. Relat. Cancer, December 1, 2004; 11(4): 603 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. McDonald, M. G. Mandel, P. A. Marchbanks, S. G. Folger, J. R. Daling, G. Ursin, M. S. Simon, L. Bernstein, B. L. Strom, S. A. Norman, et al. Alcohol Exposure and Breast Cancer: Results of the Women's Contraceptive and Reproductive Experiences Study Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2106 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Maskarinec, A. A. Franke, A. E. Williams, S. Hebshi, C. Oshiro, S. Murphy, and F. Z. Stanczyk Effects of a 2-Year Randomized Soy Intervention on Sex Hormone Levels in Premenopausal Women Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1736 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Tworoger, A. H. Eliassen, B. Rosner, P. Sluss, and S. E. Hankinson Plasma Prolactin Concentrations and Risk of Postmenopausal Breast Cancer Cancer Res., September 15, 2004; 64(18): 6814 - 6819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B Cologne, G. B Sharp, K. Neriishi, P. K Verkasalo, C. E Land, and K. Nakachi Improving the efficiency of nested case-control studies of interaction by selecting controls using counter matching on exposure Int. J. Epidemiol., June 1, 2004; 33(3): 485 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Endogenous Hormones and Breast Cancer Collaborativ Free Estradiol and Breast Cancer Risk in Postmenopausal Women: Comparison of Measured and Calculated Values Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1457 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bernichtein, C. Kayser, K. Dillner, S. Moulin, J. J. Kopchick, J. A. Martial, G. Norstedt, O. Isaksson, P. A. Kelly, and V. Goffin Development of Pure Prolactin Receptor Antagonists J. Biol. Chem., September 19, 2003; 278(38): 35988 - 35999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ahsan and A. G. Rundle Measures of genotype versus gene products: promise and pitfalls in cancer prevention Carcinogenesis, September 1, 2003; 24(9): 1429 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Endogenous Hormones Breast Cancer Collaborative Gr Body Mass Index, Serum Sex Hormones, and Breast Cancer Risk in Postmenopausal Women J Natl Cancer Inst, August 20, 2003; 95(16): 1218 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Clevenger, P. A. Furth, S. E. Hankinson, and L. A. Schuler The Role of Prolactin in Mammary Carcinoma Endocr. Rev., February 1, 2003; 24(1): 1 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The Endogenous Hormones and Breast Cancer Collabor Endogenous Sex Hormones and Breast Cancer in Postmenopausal Women: Reanalysis of Nine Prospective Studies J Natl Cancer Inst, April 17, 2002; 94(8): 606 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Stevens and L. Hilakivi-Clarke Alcohol exposure in utero and breast cancer risk later in life Alcohol Alcohol., May 1, 2001; 36(3): 276 - 277. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||
