The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35–64 years were participants in the National Institute of Child Health and Human Development Women’s Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9–1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5–8.1; nulliparous OR = 0.5, 95% CI = 0.04–5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer.

A relationship between thyroid disease and risk of breast cancer is supported by experiments suggesting a role for thyroid hormones (1), insulin, and insulin-like growth factor-1 (2) on the regulation of breast epithelial cell growth. Even so, evidence regarding a relationship between diseases of the thyroid and breast cancer risk is, on the whole, not compelling (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). Several epidemiological studies have found no significant relationship between either thyroid disorders (3) or treatment for thyroid disorders (12) and breast cancer risk, but others have found modest effects for hyperthyroidism (13), thyroid hormone treatment (4), and radioactive iodine treatment (13). In addition, a protective effect was found for untreated goiters (4). Limitations in the literature investigating relationships between breast cancer and thyroid disorders include small samples (4) and a lack of information of the specific types of thyroid disorder (6) or treatment (3).

We examined whether thyroid disorders and/or treatment of these disorders affect the risk of breast cancer. We used data from a large case-control study of invasive breast cancer in which participants were asked about their history of several medical conditions potentially related to use of female hormones. That study ascertained data on specific thyroid conditions and treatments, as well as the timing of disease onset and duration of treatment.

Participants were enrolled in the National Institute of Child Health and Human Development Women’s CARE4 Study, a population-based, case-control study that was carried out at five sites in the United States. Four of the sites were affiliated with cancer registries funded through the National Cancer Institute’s SEER Program (Atlanta, Detroit, Los Angeles, and Seattle/Puget Sound); the fifth site had no SEER affiliation (Philadelphia; Ref. 14).

As described previously in detail, United States-born white and black women aged 35–64 years who were newly diagnosed with invasive breast cancer in July 1994 to April 1998 were eligible to serve as cases in the Women’s CARE Study (14). Cases were identified through rapid ascertainment systems at the SEER-affiliated sites and by field staff in Philadelphia. Controls were chosen from the same counties as the cases, selected by random-digit dialing, and were frequency matched to cases based on 5-year age groups, race, and geographic site. Younger cases, and black cases and controls were oversampled to approximate a uniform distribution across age and race groups with the goal of efficiently assessing effect modification.

Exposure information was obtained during in-person interviews conducted by trained interviewers. Completed interviews were obtained for 4575 of the 5982 eligible cases (76.5%) and 4682 of the 5956 randomly selected controls (78.6%). The interview instrument included detailed questions on the previous use of oral contraceptive pills, HRT, fertility drugs, and other hormones. It also included questions on many other potential risk factors for breast cancer, including: (a) reproductive; (b) exercise; (c) health and family histories; (d) smoking and alcohol exposures; (e) demographics; and (f) medical history. Exposure information was collected for the time period preceding a set reference date, which was the date of diagnosis for cases and of initial household screening for controls.

All respondents were asked, “Before (reference date), did a doctor or other health professional ever tell you that you had a thyroid problem or any condition requiring thyroid medication or treatment?” Those who answered “yes” were shown a list of thyroid-associated conditions, including: (a) Graves’ disease; (b) Hashimoto’s disease (chronic thyroiditis); (c) overactive (hyperactive) thyroid; (d) under active (hypoactive); (e) goiter; (f) nodules; (g) cancer; and (h) other conditions. They were then asked, “What type of problem or condition was this?” Subsequently, respondents were asked, “Before (reference date), have you been hospitalized, had surgery, been prescribed medications, or been treated for any thyroid problem or condition?” Those who answered “yes” were shown a list of thyroid-associated medications, including: (a) thyroid USP or equivalent; (b) Synthroid or equivalent; (c) thyroid gland inhibitors; and (d) other medications. They were also shown a list of thyroid-associated procedures, including: (a) thyroid surgery; (b) radioactive iodine treatment; (c) X-ray or radiation treatment; and (d) other treatments. We evaluated whether a history of a thyroid disorder was associated with breast cancer risk and whether risk varied by time since first diagnosis, type of thyroid disorder, or treatments and duration of treatments.

ORs and 95% CIs were calculated using unconditional multivariate logistic regression methods (15). Models included adjustment for age (5-year groups), race (white or black), and study site. We examined other variables as potential confounding factors. None of the factors we considered changed the ORs by ≥10%, including: (a) first-degree family history of breast cancer (except in the analysis of thyroid cancer); (b) BMI at reference date minus 5 years; (c) number of full-term pregnancies (>26 weeks); (d) age at first full-term pregnancy; (e) education; (f) income; (g) age at menarche; (h) menopausal status; (i) mammogram screening history in the past 2 years; (j) alcohol consumption; (k) smoking history; (l) duration of oral contraceptive use; and (m) duration of HRT. In analyzing the association between preexisting thyroid cancer and risk of breast cancer, we adjusted for family history of breast cancer because the adjusted and unadjusted effect estimates as noted differed by ≥10%. Stratified analyses were conducted using likelihood tests for heterogeneity to the regression models to assess effect modification by menopausal status, race, and parity (16).

Demographic and risk factor characteristics of 4575 cases and 4682 controls in the Women’s CARE Study, which have been described elsewhere (14), are presented in Table 1. The study population was approximately one-third black, and just over half was premenopausal. On average, controls in our study had more full-term pregnancies than did the cases and were less likely than the cases to have had a first-degree family history of breast cancer.

The relationship between a history of thyroid disorders and risk of breast cancer is shown in Table 2. A history of any thyroid disorder was not associated with breast cancer (OR = 1.1, 95% CI = 0.9–1.2). There were no significant associations by time since first diagnosis of any of the thyroid disorders. An increased risk of breast cancer was detected among women with a history of thyroid cancer (OR = 2.7, 95% CI = 1.2–5.9), although this risk was restricted to parous women (OR = 3.4, 95% CI = 1.5–8.1). On the basis of the small number of women (one case and two controls), thyroid cancer was not found to be associated with risk of breast cancer for nulliparous women. We observed no association between breast cancer risk and type of thyroid medication, duration of thyroid medication use, or exposure to other thyroid procedures or treatments (Table 3). Finally, no statistical interaction was seen by race, menopausal status, or parity (data not shown).

The largely negative results of this study support the majority of reports in the literature and provide additional reassurance that neither disorders of the thyroid nor treatment for these conditions substantially alters the risk for breast cancer among women aged 35–64 years. This study was large and population based, providing an advantage over studies that are hospital based (8, 10). Although two other studies included some data on minority populations (12, 13), no other investigations had a sample large enough to evaluate differences in risk by race. In addition, we tried to evaluate issues not completely addressed in previous publications, such as the potential elevation in risk associated with specific thyroid disorders and treatments and the recency of diagnoses and duration of treatments. This is potentially important because these conditions probably operate via different mechanisms, and group analysis could mask true findings. Limitations inherent in the design of a case-control study, such as selection bias, have been discussed previously, although our high-response rates argue against much selection bias (14). Other limitations that are specific to our analysis include the lack of provisions to confirm diagnoses of medical conditions other than breast cancer and the fact that subject recall was the only basis for data on previous medications or treatments.

Even though there is in vitro evidence for an effect of thyroid hormones on breast epithelial proliferation (1, 17, 18), the epidemiological literature provides little support for an association between thyroid disorders and breast cancer risk (3, 6, 12). In one large population-based, case-control study, there was a protective effect associated with untreated goiters (OR = 0.34, 95% CI = 0.1–0.8; Ref. 4), but this finding was based on small numbers. Other researchers have not identified associations for a history of goiters or untreated goiters (8), and analysis of our data supports these earlier findings (data not shown; Ref. 13). Data from another hospital-based, case-control study showed a small protective effect for thyroid adenomas diagnosed among premenopausal women (OR = 0.4, 95% CI = 0.1–0.7) or among women aged <35 (OR = 0.4, 95% CI = 0.2–0.8; Ref. 8). Our study was not able to evaluate the risk of breast cancer for women aged <35 years. However, we found no association for thyroid adenomas (nodules) among premenopausal women (OR = 1.1, 95% CI = 0.6–2.1). Others who have evaluated time since diagnosis of thyroid disease found no significant effects (3, 12, 13). One other report found a relationship between hyperthyroidism and breast cancer risk, but it was based on only 17 cases and 19 controls (OR = 2.2, 95% CI = 1.1–4.4; Ref. 13), and this finding has not been replicated by us or by others (3, 4, 8). Thus, although some studies suggest a protective effect of goiters or adenomas, our results, as well as much of the published literature on this issue, do not substantiate these findings.

Epidemiological support is also scant for an association between treatments for thyroid disorders and breast cancer risk (3, 6, 8, 10). One study showed a decrease in risk for women with untreated goiters and an increase in risk after 5–9 years of thyroid medication use, but no time trends were seen, and no significant effects were observed for euthyroid women who used thyroid medications for other reasons (4). Our results are consistent with those from other large studies in which no significant effects have been found for specific thyroid treatments, particularly I131 and X-ray treatment, on breast cancer risk (9, 11, 13).

Our finding of a significant association between a history of thyroid cancer and breast cancer risk has been reported by others (19, 20). In our study, the direction and strength of this association varied by parity, although the interaction was not found to be statistically significant and could very well have been attributable to chance. The relationship between thyroid cancer and breast cancer may reflect the influence of shared hormonal or genetic factors and should be studied further.

In conclusion, although there is laboratory evidence that thyroid hormones, insulin, and other growth factors can influence the growth and regulation of breast epithelial cells in vivo, we found no evidence of a positive association between risk of breast cancer and thyroid disease or its treatment, among women aged 35–64 years, except for thyroid cancer.

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.

1

Supported by the National Institute of Child Health and Human Development, with additional support from the National Cancer Institute, through contracts with Emory University (N01-HD-3-3168), Fred Hutchinson Cancer Research Center (N01-HD-2-3166), Karmanos Cancer Institute at Wayne State University (N01-HD-3-3174), University of Pennsylvania (N01-HD-3-3176), and University of Southern California (N01-HD-3-3175) and through an intra-agency agreement with the Centers for Disease Control and Prevention (Y01-HD-7022). The Centers for Disease Control and Prevention contributed additional staff and computer support.

4

The abbreviations used are: CARE, Contraceptive and Reproductive Experiences; SEER, Surveillance, Epidemiology, and End Results; OR, odds ratio; BMI, body mass index; HRT, hormone replacement therapy; CI, confidence interval.

Table 1

Demographic and risk factor characteristics of 4575 cases and 4682 controls in the Women’s CARE Study

CharacteristicCases (n = 4575)Controls (n = 4682)
n%n%
Age (yrs)     
 35–39 689 15.1 666 14.2 
 40–44 758 16.6 832 17.8 
 45–49 782 17.1 857 18.3 
 50–54 844 18.5 825 17.6 
 55–59 770 16.8 801 17.1 
 60–64 732 16.0 701 15.0 
Race     
 White 2953 64.5 3021 64.5 
 Black 1622 35.5 1661 35.5 
Study site     
 Atlanta 881 19.3 895 19.1 
 Detroit 679 14.8 779 16.6 
 Los Angeles 1242 27.2 1255 26.8 
 Philadelphia 707 15.5 736 15.7 
 Seattle 1066 23.3 1017 21.7 
Educationa     
 Less than high school 399 8.7 444 9.5 
 High school 1335 29.2 1350 28.8 
 Some college 1483 32.4 1495 31.9 
 College graduate or more 1357 29.7 1393 29.8 
BMI (kg/m2)b     
 <21.5 1130 24.8 1104 23.7 
 21.5 to <28.5 2409 53.0 2413 51.8 
 28.5+ 1011 22.2 1145 24.6 
Age at menarche (yrs)c     
 <12 1197 26.2 1262 27.0 
 12–13 2528 55.4 2464 52.7 
 >13 840 18.4 950 20.3 
Number of full-term pregnanciesd,e     
 0 890 19.5 805 17.2 
 1 770 16.8 717 15.3 
 2 1371 30.0 1355 29.0 
 3+ 1541 33.7 1796 38.4 
Age at first full-term pregnancy (yrs)f     
 <20 1046 28.4 1191 30.8 
 20–24 1368 37.1 1461 37.8 
 25–29 777 21.1 718 18.6 
 ≥30 492 13.4 497 12.9 
Menopausal statusg     
 Premenopausal 2116 52.4 2061 50.4 
 Postmenopausal 1924 47.6 2029 49.6 
Use of oral contraceptivesh     
 Never 1042 22.8 990 21.2 
 <6 months 512 11.2 508 10.9 
 6 mos to <5 yrs 1488 32.6 1612 34.5 
 ≥5 years 1525 33.4 1566 33.5 
HRT for menopausal usee,i     
 Never 2837 62.1 2749 58.7 
 <6 months 318 7.0 388 8.3 
 6 mos to <5 yrs 610 13.3 716 15.3 
 ≥5 years 807 17.7 827 17.7 
First degree family history of breast cancere,j     
 No 3616 82.3 4050 89.9 
 Yes 778 17.7 453 10.1 
CharacteristicCases (n = 4575)Controls (n = 4682)
n%n%
Age (yrs)     
 35–39 689 15.1 666 14.2 
 40–44 758 16.6 832 17.8 
 45–49 782 17.1 857 18.3 
 50–54 844 18.5 825 17.6 
 55–59 770 16.8 801 17.1 
 60–64 732 16.0 701 15.0 
Race     
 White 2953 64.5 3021 64.5 
 Black 1622 35.5 1661 35.5 
Study site     
 Atlanta 881 19.3 895 19.1 
 Detroit 679 14.8 779 16.6 
 Los Angeles 1242 27.2 1255 26.8 
 Philadelphia 707 15.5 736 15.7 
 Seattle 1066 23.3 1017 21.7 
Educationa     
 Less than high school 399 8.7 444 9.5 
 High school 1335 29.2 1350 28.8 
 Some college 1483 32.4 1495 31.9 
 College graduate or more 1357 29.7 1393 29.8 
BMI (kg/m2)b     
 <21.5 1130 24.8 1104 23.7 
 21.5 to <28.5 2409 53.0 2413 51.8 
 28.5+ 1011 22.2 1145 24.6 
Age at menarche (yrs)c     
 <12 1197 26.2 1262 27.0 
 12–13 2528 55.4 2464 52.7 
 >13 840 18.4 950 20.3 
Number of full-term pregnanciesd,e     
 0 890 19.5 805 17.2 
 1 770 16.8 717 15.3 
 2 1371 30.0 1355 29.0 
 3+ 1541 33.7 1796 38.4 
Age at first full-term pregnancy (yrs)f     
 <20 1046 28.4 1191 30.8 
 20–24 1368 37.1 1461 37.8 
 25–29 777 21.1 718 18.6 
 ≥30 492 13.4 497 12.9 
Menopausal statusg     
 Premenopausal 2116 52.4 2061 50.4 
 Postmenopausal 1924 47.6 2029 49.6 
Use of oral contraceptivesh     
 Never 1042 22.8 990 21.2 
 <6 months 512 11.2 508 10.9 
 6 mos to <5 yrs 1488 32.6 1612 34.5 
 ≥5 years 1525 33.4 1566 33.5 
HRT for menopausal usee,i     
 Never 2837 62.1 2749 58.7 
 <6 months 318 7.0 388 8.3 
 6 mos to <5 yrs 610 13.3 716 15.3 
 ≥5 years 807 17.7 827 17.7 
First degree family history of breast cancere,j     
 No 3616 82.3 4050 89.9 
 Yes 778 17.7 453 10.1 
a

Data missing for one case.

b

Quetelet’s Index calculated as weight (kg)/height (m)2 and based on weight 5 years before the participant’s reference date. Data were missing for 26 cases and 21 controls.

c

Data were missing for 10 cases and 6 controls.

d

Includes all pregnancies lasting >26 weeks. Data were missing for three cases and nine controls.

e

Statistically significant with a P < 0.01.

f

Data were missing for 2 cases and 10 controls.

g

Unknown or unable to classify menopausal status for 535 cases and 592 controls.

h

Data were missing for three cases and four controls.

i

Data were missing for one case and one control.

j

First-degree family includes mother, full sister(s), and daughter(s). Data were missing for 181 cases and 179 controls who were either adopted or had unknown family history of breast cancer.

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Table 2

Relationship between history of thyroid disorders and breast cancer risk

Cases (n = 4571)Controls (n = 4677)ORa95% CI
n%n%
History of thyroid disorderb       
 Never 3751 82.1 3876 82.9 1.0  
 Ever 820 17.9 801 17.1 1.1 0.9–1.2 
Years since first diagnosis of thyroid disorderc       
 0 to <10 292 6.4 283 6.1 1.1 0.9–1.2 
 10 to <25 279 6.1 288 6.2 1.0 0.8–1.2 
 ≥25 332 7.3 373 8.0 0.9 0.7–1.03 
Type of thyroid disorder       
 Graves disease 39 0.9 33 0.7 1.2 0.8–1.9 
 Hashimoto’s disease 34 0.7 37 0.8 0.9 0.6–1.5 
 Hyperactive 125 2.7 141 3.0 0.9 0.7–1.1 
 Hypoactive 465 10.2 530 11.3 0.9 0.8–1.02 
 Goiter 120 2.6 119 2.5 1.0 0.8–1.3 
 Nodules 71 1.6 63 1.4 1.1 0.8–1.6 
 Thyroid cancerd 23 0.5 10 0.2 2.7 1.2–5.9 
 Other problem(s) 42 0.9 52 1.1 0.8 0.5–1.2 
Cases (n = 4571)Controls (n = 4677)ORa95% CI
n%n%
History of thyroid disorderb       
 Never 3751 82.1 3876 82.9 1.0  
 Ever 820 17.9 801 17.1 1.1 0.9–1.2 
Years since first diagnosis of thyroid disorderc       
 0 to <10 292 6.4 283 6.1 1.1 0.9–1.2 
 10 to <25 279 6.1 288 6.2 1.0 0.8–1.2 
 ≥25 332 7.3 373 8.0 0.9 0.7–1.03 
Type of thyroid disorder       
 Graves disease 39 0.9 33 0.7 1.2 0.8–1.9 
 Hashimoto’s disease 34 0.7 37 0.8 0.9 0.6–1.5 
 Hyperactive 125 2.7 141 3.0 0.9 0.7–1.1 
 Hypoactive 465 10.2 530 11.3 0.9 0.8–1.02 
 Goiter 120 2.6 119 2.5 1.0 0.8–1.3 
 Nodules 71 1.6 63 1.4 1.1 0.8–1.6 
 Thyroid cancerd 23 0.5 10 0.2 2.7 1.2–5.9 
 Other problem(s) 42 0.9 52 1.1 0.8 0.5–1.2 
a

OR was relative to never having had a thyroid disorder, adjusted for age, race, and study site.

b

Excludes nine women that did not know if they had a history of a thyroid disorder.

c

Five cases and five controls were missing because of unknown diagnosis year.

d

OR adjusted for age, race, study site, and first-degree family history of breast cancer.

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Table 3

Relationship between use of thyroid medications and procedures and breast cancer riska

Case (n = 4502)Control (n = 4604)ORb95% CI
n%n%
Thyroid medications       
 Never 3791 84.2 3867 84.0 1.0  
 Ever 711 15.8 737 16.0 1.0 0.9–1.1 
Type of medicationsc       
 Thyroid USP/equivalent       
  Everd 87 1.9 93 2.0 0.9 0.7–1.3 
  ≤1 yr 21 0.5 23 0.6 0.9 0.5–1.7 
  >1 yr, ≤10 yrs 32 0.8 33 0.8 1.0 0.6–1.6 
  >10 yrs 34 0.9 35 0.9 1.0 0.6–1.6 
 Synthyroid/equivalent       
  Evere 499 11.1 537 11.7 0.9 0.8–1.1 
  ≤1 yr 81 1.9 100 2.3 0.8 0.6–1.1 
  >1 yr, <10 yrs 232 5.4 244 5.6 1.0 0.8–1.2 
  >10 yrs 184 4.3 189 4.3 1.0 0.8–1.2 
 Thyroid gland inhibitor       
  Ever 23 0.5 26 0.6 0.9 0.5–1.6 
  ≤1 yr 16 0.4 14 0.4 1.1 0.6–2.4 
  >1 yr 7 0.2 12 0.3 0.6 0.2–1.5 
 Other medication(s)       
  Everf 22 0.5 25 0.5 0.9 0.5–1.6 
  ≤1 yr 12 0.3 8 0.2 1.5 0.6–3.7 
  >1 yr 9 0.2 17 0.4 0.6 0.2–1.3 
Other thyroid proceduresg       
 Never 4333 94.9 4433 95.1 1.0  
 Ever 231 5.0 231 5.1 1.0 0.8–1.2 
 Types       
  Thyroid surgery 136 3.0 114 2.4 1.2 0.9–1.6 
  Radioactive iodine 102 2.2 105 2.3 1.0 0.8–1.3 
  X-ray/radiation 29 0.6 35 0.8 0.9 0.5–1.4 
  Other treatment(s) 20 0.4 20 0.4 1.1 0.6–2.0 
Case (n = 4502)Control (n = 4604)ORb95% CI
n%n%
Thyroid medications       
 Never 3791 84.2 3867 84.0 1.0  
 Ever 711 15.8 737 16.0 1.0 0.9–1.1 
Type of medicationsc       
 Thyroid USP/equivalent       
  Everd 87 1.9 93 2.0 0.9 0.7–1.3 
  ≤1 yr 21 0.5 23 0.6 0.9 0.5–1.7 
  >1 yr, ≤10 yrs 32 0.8 33 0.8 1.0 0.6–1.6 
  >10 yrs 34 0.9 35 0.9 1.0 0.6–1.6 
 Synthyroid/equivalent       
  Evere 499 11.1 537 11.7 0.9 0.8–1.1 
  ≤1 yr 81 1.9 100 2.3 0.8 0.6–1.1 
  >1 yr, <10 yrs 232 5.4 244 5.6 1.0 0.8–1.2 
  >10 yrs 184 4.3 189 4.3 1.0 0.8–1.2 
 Thyroid gland inhibitor       
  Ever 23 0.5 26 0.6 0.9 0.5–1.6 
  ≤1 yr 16 0.4 14 0.4 1.1 0.6–2.4 
  >1 yr 7 0.2 12 0.3 0.6 0.2–1.5 
 Other medication(s)       
  Everf 22 0.5 25 0.5 0.9 0.5–1.6 
  ≤1 yr 12 0.3 8 0.2 1.5 0.6–3.7 
  >1 yr 9 0.2 17 0.4 0.6 0.2–1.3 
Other thyroid proceduresg       
 Never 4333 94.9 4433 95.1 1.0  
 Ever 231 5.0 231 5.1 1.0 0.8–1.2 
 Types       
  Thyroid surgery 136 3.0 114 2.4 1.2 0.9–1.6 
  Radioactive iodine 102 2.2 105 2.3 1.0 0.8–1.3 
  X-ray/radiation 29 0.6 35 0.8 0.9 0.5–1.4 
  Other treatment(s) 20 0.4 20 0.4 1.1 0.6–2.0 
a

Data were missing for 73 cases and 78 controls.

b

ORs were relative to never using any thyroid medications (except for other thyroid procedures), adjusted for age, race, and study site.

c

Some women took more than one type of thyroid medications. These data reflects duration of use.

d

Duration of USP use was unknown for two women.

e

Duration of synthyroid use was unknown for six women.

f

Duration of other thyroid medication use was unknown for one woman.

g

Some women received more than one procedure. OR was relative to never having any procedures.

View Large

We thank all past and present members of the Women’s CARE Study team for their important contributions to this project.

Investigators in the National Institute of Child Health and Human Development Women’s CARE Study include: Project Officer Dr. Robert Spirtas; Principal Investigators Drs. Leslie Bernstein, Janet R. Daling, Jonathan M. Liff, Polly A. Marchbanks, Brian L. Strom, and Linda K. Weiss; Coprincipal Investigators Drs. Dennis M. Deapen, Elaine W. Flagg, Jill A. McDonald, Sandra A. Norman, Michael F. Press, Hoyt G. Wilson; Coinvestigators Drs. Jesse A. Berlin, Ronald T. Burkman, Ralph J. Coates, Suzanne G. Folger, Kathleen E. Malone, Michael S. Simon, Giske Ursin, and Phyllis Wingo. Members of the Scientific Advisory Committee include Drs. Barbara S. Hulka, Carrie Hunter, Dennis Lezotte, and James Schlesselman.

1
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