EPIDEMIOLOGY

Ovarian cysts and breast cancer: results from the Women’sContraceptive and Reproductive Experiences Study

Julia A. Knight Æ Maia Lesosky Æ Kristina M. Blackmore Æ Lynda F. Voigt ÆVictoria L. Holt Æ Leslie Bernstein Æ Polly A. Marchbanks Æ Ronald T. Burkman ÆJanet R. Daling Æ Alice S. Whittemore

Received: 25 April 2007 / Accepted: 30 May 2007 / Published online: 7 July 2007

� Springer Science+Business Media B.V. 2007

Abstract A diagnosis of ovarian cysts is likely an

indicator of hormonal milieu and thus may be related to

breast cancer risk. Recent studies have reported an inverse

relationship between prior ovarian cyst diagnosis and

breast cancer risk. We evaluated this relationship in the

Women’s Contraceptive and Reproductive Experiences

(CARE) Study, a population-based case–control study

conducted in Atlanta, Detroit, Philadelphia, Los Angeles,

and Seattle. Cases had first primary invasive breast cancer

diagnosed between 1994 and 1998 at ages 35–64 years.

African American women were over-sampled. Controls

were identified through random digit dialling and were

frequency matched to cases on centre, race, and five-year

age group. A total of 4575 cases and 4682 controls were

interviewed. We used unconditional logistic regression

adjusted for age and study centre within racial groups to

estimate the odds ratio (OR) and 95% confidence interval

(CI) for the relationship between prior ovarian cysts and

breast cancer. Ovarian cyst diagnosis was associated with

a significantly reduced risk among Caucasians (OR =

0.85, 95% CI 0.76–0.96) and among African Americans

(OR = 0.68, 95% CI 0.57–0.81). The association in

Caucasians was not significant within subgroups defined

by menopausal status, hormone use, or gynecological

surgery while the OR estimates in African Americans

were consistently lower and frequently significant. These

data are consistent with the previously reported inverse

association between ovarian cysts and breast cancer, but

the evidence for a relationship was stronger in African

Americans than Caucasians. Additional studies are

required to determine the specific cyst type(s) responsible

for the observed relationship.

Keywords Breast cancer � Ovarian cysts � Case–control

study � Race � Hormone receptor status

Introduction

The hypothesis that a history of ovarian cysts is associated

with breast cancer risk is plausible as these cysts are likely

an indicator of hormonal milieu. Initial reports were largely

null [1–3], but two recent studies with larger samples have

reported a reduced risk of breast cancer significantly

associated with a diagnosis of ovarian cysts [4, 5].

J. A. Knight (&) � M. Lesosky � K. M. Blackmore

Prosserman Centre for Health Research, Samuel Lunenfeld

Research Institute, Mount Sinai Hospital, 60 Murray Street, Box

18, Toronto, ON, Canada M5T 3L9

e-mail: knight@mshri.on.ca

L. F. Voigt � V. L. Holt � J. R. Daling

Division of Public Health Sciences, Fred Hutchinson Cancer

Research Centre, Seattle, WA, USA

L. F. Voigt � V. L. Holt

Department of Epidemiology, University of Washington, Seattle,

WA, USA

L. Bernstein

Department of Preventive Medicine, Keck School of Medicine,

University of Southern California, Los Angeles, CA, USA

P. A. Marchbanks

Division of Reproductive Health, Centers for Disease Control

and Prevention, Atlanta, GA, USA

R. T. Burkman

Department of Obstetrics and Gynecology, Bay State Medical

Center, Springfield, MA, USA

A. S. Whittemore

Department of Health Research and Policy, Stanford University

School of Medicine, Stanford, CA, USA

123

Breast Cancer Res Treat (2008) 109:157–164

DOI 10.1007/s10549-007-9634-4

A diagnosis of ovarian cysts can arise from a number of

cyst types. Functional cysts, which may or may not be

symptomatic, are the most common type and they frequently

resolve without intervention. Less common are endometri-

omas occurring as a manifestation of endometriosis. Benign

neoplastic tumours such as cystic teratomas and serous

cystadenomas are sometimes grouped with other ovarian

cyst types. Polycystic ovary syndrome (PCOS), with multi-

ple small cysts associated with high levels of androgens, has

been evaluated as a potential risk factor for breast cancer

with mixed results with findings of both increased and

decreased risk as well as null results [6–9].

The etiology of ovarian cysts and benign ovarian tumours

is not well understood and evidence suggests that the risk

factors for the various entities that make up this group of

conditions differ [10]. In addition, some ‘‘risk factors’’ such

as menstrual irregularity, impaired fertility, and oral con-

traceptive use may occur as a result of the condition rather

than as a predisposing factor. Oral contraceptives have been

used to prevent functional cysts, although modern, low-dose

oral contraceptives do not appear to affect the risk of

developing ovarian cysts [11, 12]. However, functional and/

or other types of cysts may be a marker of a particular state of

the hypothalamic-pituitary-gonadal axis that is associated

with reduced breast cancer risk.

Here, we report results from the Women’s Contraceptive

and Reproductive Experiences (CARE) Study, a large,

multi-site case–control study of breast cancer conducted in

the US. This study collected information on ovarian cysts,

ovarian surgery, and other breast cancer risk factors prior to

breast cancer from 4,575 cases and 4,682 controls, pro-

viding an additional opportunity to evaluate a potential

inverse relationship between ovarian cysts and breast

cancer risk.

Material and methods

Study design and population

The Women’s CARE Study, which is funded by the

National Institute of Child Health and Human Develop-

ment, is a population-based case–control study conducted

in Atlanta, Detroit, Philadelphia, Los Angeles, and Seattle.

The study design has been described in detail elsewhere

[13]. Protocols were approved by the institutional review

boards at each site and all the women provided a signed

informed consent form. The study was restricted to Cau-

casian and African American women able to speak English

who were born in the US.

Cases were randomly sampled from women with inci-

dent, histologically confirmed, first primary invasive breast

cancer diagnosed between July 1, 1994 and April 30, 1998

at ages 35–64 years who resided within the geographic

area covered by each participating centre. At all centres

except Philadelphia, women were identified through local

cancer registries that participated in the Surveillance,

Epidemiology, and End Results (SEER) Program. In

Philadelphia cases were identified through area medical

facilities by study personnel. Younger cases and African

American cases were over-sampled to approximate a

uniform distribution across age groups and groups of

Caucasian and African American women. Of the 5,982

eligible cases identified, 4,575 (76.5%) were interviewed.

The controls were women without invasive or in situ

breast cancer who were living in the same geographic loca-

tions as the cases. Random-digit dialling of residential

households was used to identify eligible controls. Through-

out the study, women were randomly sampled from the

eligible controls in order to frequency match the controls to

the cases on study centre, race, and five-year age group.

Approximately 82% of residential households contacted

were successfully screened. Of the 5,956 eligible women

selected as controls, 4,682 (78.6%) were interviewed.

In-person interviews were conducted within 18 months

(most were within six months) of the reference date, which

was defined as date of diagnosis for cases and date of first

household contact for controls. Information was collected

on reproductive and medical history, family history of

cancer, and demographic and lifestyle variables. Respon-

dents were asked whether they had ever had a diagnosis of

ovarian cysts before the reference date and a complete

ascertainment of ovarian and other gynecological surgeries

was obtained.

Statistical analysis

Analyses were based on the 4,555 cases and 4767 controls

with information on a diagnosis of ovarian cysts. Reference

age was defined as age at diagnosis for cases and age at first

household contact for controls. We estimated odds ratios

(ORs) and 95% confidence intervals (CIs) using uncondi-

tional logistic regression. The main variable of interest was

ever having been diagnosed with ovarian cysts prior to the

reference date. Information on type of cysts was not col-

lected. All analyses were performed separately for Cau-

casians and African Americans as the interaction between

cysts and race was statistically significant (P = 0.03). All

models included reference age as a continuous variable and

also study centre (Atlanta, Detroit, Philadelphia, Los

Angeles, and Seattle). We individually tested the following

variables as potential confounders: Hispanic ancestry (yes/

no), education (three categories), oral contraceptive use

(ever/never), breastfeeding (at least two weeks/never or

less than two weeks), hormone therapy (HT) use (never and

ever any estrogen plus progestin, estrogen only, progestin

158 Breast Cancer Res Treat (2008) 109:157–164

123

only), first degree family history of breast cancer (yes/no),

menopausal status (premenopausal, postmenopausal,

unknown), menopausal status with age at menopause

(premenopausal, unknown, and age at menopause in four

categories), body mass index (BMI, kg/m2) five years prior

to the reference date (four categories), BMI at age 18 years

(three categories), age at menarche (three categories),

income (five categories), parity (five categories including

nulliparous), age at first birth (five categories including

nulliparous), alcohol use (never/former/current), smoking

(never/former/current), hysterectomy (ever/never), number

of ovaries removed (none, one, both). None of these vari-

ables altered the OR for ovarian cysts by 10% or more in

either race except for number of ovaries removed in

Caucasians, which increased the OR by 10%. We then

estimated ovarian cyst ORs within each of the following

subgroups: menopausal status (premenopausal and post-

menopausal), HT (never, ever any estrogen plus progestin,

estrogen only, progestin only), hysterectomy (never/ever),

ovaries removed (none, one, two). The associations

between breast cancer and age at cyst diagnosis (no cysts,

age <30 years, age ‡30 years) and time since cyst diag-

nosis (no cysts, <20 years, ‡20 years) were also estimated.

Finally we estimated the ORs for ovarian cysts within

subsets of cases based on estrogen receptor (ER) and

progesterone receptor (PR) status using all controls. All

analyses were carried out using SAS version 9 and with a

two-tailed P-value <0.05 to define statistical significance.

Results

Table 1 describes cases and controls separately among the

5,954 Caucasians (2,938 cases and 3,016 controls) and

among the 3,277 African Americans (1,617 cases and

1,660 controls). Cases and controls were similar for a

number of factors including age, income, and education. As

expected, controls tended to have a higher parity and they

were also more likely to have breastfed. Cases were less

likely to have had a hysterectomy or ovaries removed.

Among Caucasians, ER status was available for 90% of

cases and PR status was available for 87% of cases. The

proportion was somewhat lower for African American

cases in whom ER was available for 81% and PR was

available for 76%.

Among all Caucasians and among all African Americans

ovarian cysts were statistically significantly associated with a

reduced risk of breast cancer, although the effect was greater

among African Americans (Table 2). Among Caucasians,

the OR estimate was less than 1.0 in all subgroups (according

to menopausal status, HT use, hysterectomy status, and

oophorectomy status), but was not more than marginally

statistically significant in any subgroup. In contrast, African

Americans had consistently lower OR estimates and these

were significantly below 1.0 in a number of subgroups. We

found no statistically significant interactions between cysts

and menopausal status, HT use, hysterectomy, or removal of

ovaries in either racial group. There was also no evidence of a

difference between cysts diagnosed before age 30 and those

diagnosed at an older age. Among Caucasians, a statistically

significant inverse association with cysts was only observed

for cysts diagnosed 20 years or more before the reference

date, but time since the reference date did not have much

impact in African Americans. From Table 3 it appears that

the difference between the races is confined to ER or PR

positive breast cancers as there was little difference in the

relationship of cysts to either ER or PR negative tumours,

although none of the differences reach statistical significance

(P = 0.10 and 0.15 for ER positive and PR positive,

respectively and P = 0.87 and 0.88 for ER negative and PR

negative, respectively).

Discussion

In this analysis we found some evidence, using the

Women’s CARE Study, to support the hypothesis that a

history of ovarian cysts is associated with a reduced risk of

breast cancer. Consistent with recent reports from two

other large studies [4, 5], we observed significant inverse

associations between a reported diagnosis of ovarian cysts

and breast cancer. However, in the present study the evi-

dence for an association was stronger in African Americans

than in Caucasians. The relationship between prior ovarian

cysts and breast cancer in African Americans has not

previously been evaluated in the published literature.

Initial reports relating ovarian cysts to breast cancer risk

were largely null. A case–control study of 354 cases and

747 controls identified from women undergoing breast

screening in the US had an OR of 1.1 (95% CI 0.7–1.6) for

a report of cystic ovary [1]. Another US case–control study

of 2,173 cases and 1990 controls under age 55 observed an

OR of 1.16 (95% CI 0.8–1.7) for a history of ovarian cyst

treated with surgery [3]. The risk was significantly elevated

in those who had surgery for the cysts, but had not had

oophorectomy. In a cohort study of women who had

undergone oophorectomy and/or hysterectomy in Sweden

295 cases of breast cancer occurred and the observed

standardized incidence ratio was 0.8 (95% CI 0.5–1.5) for

having ovarian cyst as an indication for surgery [2].

Recently, data from Caucasians from three study sites in

the US, Canada, and Australia were pooled yielding 3,049

cases, 2,344 population controls, and 1,934 sister controls

[4]. An OR of 0.71 (95% CI 0.61–0.81) was observed for a

reported diagnosis of ovarian cysts and the result was

consistent across study sites and was also consistent

Breast Cancer Res Treat (2008) 109:157–164 159

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Table 1 Characteristics of Caucasian and African American cases and controls with information on ovarian cysts from the CARE study

Caucasian African American

Cases N = 2938 (%) Controls N = 3016 (%) Cases N = 1617 (%) Controls N = 1660 (%)

Age in years (mean and sd) 50 (8.5) 49 (8.3) 49 (8.1) 49 (8.1)

Income ($)

0–19,999 311 (11) 308 (10) 544 (35) 561 (35)

20,000–34,999 513 (18) 516 (18) 375 (24) 407 (25)

35,000–49,999 534 (19) 529 (18) 269 (17) 260 (16)

50,000–69,999 503 (18) 595 (20) 188 (12) 212 (13)

70,000 + 975 (33) 987 (34) 192 (12) 180 (11)

Site

Atlanta 559 (19) 551 (18) 321 (20) 343 (21)

Seattle 997 (34) 960 (32) 61 (4) 54 (3)

Detroit 400 (14) 446 (15) 278 (17) 333 (20)

Philadelphia 315 (11) 345 (11) 387 (24) 391 (24)

Los Angeles 667 (23) 714 (24) 570 (35) 539 (32)

Education

High school or less 948 (32) 1025 (34) 780 (48) 769 (46)

Tech school or some college 945 (32) 924 (31) 529 (33) 567 (34)

College graduate 1045 (36) 1067 (35) 307 (19) 324 (20)

Menopause status

Premenopausal 1368 (47) 1361 (45) 739 (46) 695 (42)

Postmenopausal 1273 (43) 1323 (44) 668 (41) 738 (44)

Unknown 297 (10) 332 (11) 210 (13) 227 (14)

Number of births

None 658 (22) 572 (19) 220 (14) 223 (13)

One 424 (14) 432 (14) 320 (20) 278 (17)

Two 957 (33) 922 (31) 396 (25) 415 (25)

Three 546 (19) 611 (20) 295 (18) 299 (18)

More than three 353 (12) 474 (16) 383 (24) 443 (27)

Oral contraceptive use

Never 652 (22) 608 (20) 386 (24) 382 (23)

Ever 2285 (78) 2406 (80) 1229 (76) 1276 (77)

Age at first birth (years)

<20 392 (13) 513 (17) 665 (41) 689 (42)

20–24 899 (31) 981 (33) 453 (28) 475 (29)

25–29 596 (20) 551 (18) 177 (11) 166 (10)

30 + 393 (13) 394 (13) 100 (6) 104 (6)

No births 658 (22) 572 (19) 220 (14) 223 (13)

Ever breastfed ‡2 weeks

Never 1616 (55) 1480 (49) 1071 (67) 1021 (62)

Ever 1320 (45) 1525 (51) 538 (33) 629 (38)

Age at menarche (years)

<12 731 (25) 777 (26) 459 (28) 482 (29)

12 1673 (57) 1674 (56) 845 (52) 790 (48)

‡13 526 (18) 561 (19) 311 (19) 386 (23)

HT use

Never 1661 (57) 1619 (54) 1166 (72) 1125 (68)

Estrogen + progestin 741 (25) 705 (23) 151 (9) 155 (9)

Estrogen only 449 (15) 600 (20) 256 (16) 332 (20)

160 Breast Cancer Res Treat (2008) 109:157–164

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regardless of control group used. More recently, data from

two previously published Italian case-case control studies

were pooled along with an additional Swiss study [5].

Among the 6,315 cases and 6,038 controls, an OR of 0.72

(95% CI 0.62–0.85) was observed for a reported history of

ovarian cysts. The estimates of effect changed little

according to menopausal status, age at menarche, parity,

BMI, oophorectomy status, or other factors. The overall

results from these two most recent large pooled studies are

virtually identical. Previous studies have included only or

mostly Caucasian women. The present study is the first to

specifically report on the relationship between ovarian

cysts and breast cancer in African Americans.

Data from the Women’s CARE Study are consistent

with the two recent pooled analyses in that all the OR

estimates were less than 1.00. The results for the African

American women are quite similar to the recent pooled

analyses [4, 5]. Although the OR estimates for ovarian

cysts in Caucasians were also less than 1.0 in all subgroups,

the effect was not significant or was marginally significant

except for the significant OR of 0.85 (95% CI 0.76–0.96)

among all Caucasians combined. African Americans

overall had an OR of 0.68 (95% CI 0.57–0.81) for ovarian

cysts and the estimate was lower than the estimate in

Caucasians in all subgroups except for the small number of

women using progesterone only. As an ovarian cyst

Table 1 continued

Caucasian African American

Cases N = 2938 (%) Controls N = 3016 (%) Cases N = 1617 (%) Controls N = 1660 (%)

Progestestin only 85 (3) 88 (3) 43 (3) 48 (3)

Hysterectomy

Never 2318 (79) 2214 (73) 1129 (70) 1080 (65)

Ever 619 (21) 802 (27) 488 (30) 579 (35)

Number of ovaries removed

None 2559 (87) 2489 (83) 1329 (83) 1309 (79)

One 123 (4) 150 (5) 112 (7) 120 (7)

Two 255 (9) 373 (12) 168 (10) 224 (14)

BMI 5 years before reference date (kg/m2)

0–19.99 416 (14) 437 (15) 71 (4) 78 (5)

20.00–24.99 1519 (52) 1445 (48) 550 (34) 555 (34)

25.00–29.99 637 (22) 696 (23) 553 (34) 559 (34)

30.00 + 353 (12) 425 (14) 431 (27) 461 (28)

BMI at age 18 (kg/m2)

0–19.99 1581 (54) 1538 (51) 743 (46) 729 (44)

20.00–24.99 1188 (41) 1255 (42) 707 (44) 727 (44)

25.00 + 163 (6) 215 (7) 150 (9) 196 (12)

Smoking

Never 1334 (45) 1373 (46) 752 (46) 729 (44)

Former 1044 (36) 1012 (34) 445 (28) 454 (27)

Current 558 (19) 630 (21) 420 (26) 476 (29)

Alcohol use

Never 946 (32) 977 (32) 842 (52) 920 (55)

Former 506 (17) 546 (18) 313 (19) 277 (17)

Current 1482 (50) 1489 (49) 461 (29) 463 (28)

ER status

Positive 1907 (65) 733 (45)

Negative 733 (25) 578 (36)

Not available 298 (10) 306 (19)

PR status

Positive 1678 (57) 646 (40)

Negative 865 (29) 588 (36)

Not available 395 (13) 383 (24)

Breast Cancer Res Treat (2008) 109:157–164 161

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Table 2 Odds ratios and 95% confidence intervals for the association between an ovarian cyst diagnosis and breast cancer incidence in all

Caucasian and African American women and selected subgroups in the CARE study

Caaucasian African American

Cases N (%) Controls N (%) ORa (95% CI) Cases N (%) Controls N (%) ORa (95% CI)

All

No cysts 2306 (78) 2281 (76) 1.00 1374 (85) 1315 (79) 1.00

Ovarian cysts 632 (22) 735 (24) 0.85 (0.76, 0.96) 243 (15) 345 (21) 0.68 (0.57, 0.81)

Premenopausal

No cysts 1109 (81) 1071 (80) 1.00 637 (86) 584 (84) 1.00

Ovarian cysts 259 (19) 278 (20) 0.91 (0.75, 1.10) 102 (14) 111 (16) 0.85 (0.63, 1.14)

Postmenopausal

No cysts 981 (77) 970 (73) 1.00 569 (85) 572 (77) 1.00

Ovarian cysts 292 (23) 353 (27) 0.86 (0.72, 1.03) 99 (15) 166 (23) 0.65 (0.49, 0.86)

Never used HT

No cysts 1353 (81) 1296 (80) 1.00 1009 (87) 926 (82) 1.00

Ovarian cysts 308 (19) 323 (20) 0.92 (0.78, 1.10) 157 (13) 199 (18) 0.73 (0.58, 0.91)

Estrogen + progestin

No cysts 589 (79) 551 (78) 1.00 124 (82) 120 (77) 1.00

Ovarian cysts 152 (21) 154 (22) 0.96 (0.75, 1.24) 27 (18) 35 (23) 0.78 (0.44, 1.37)

Estrogen only

No cysts 301 (67) 375 (62) 1.00 204 (80) 231 (70) 1.00

Ovarian cysts 148 (33) 225 (38) 0.82 (0.64, 1.07) 52 (20) 101 (30) 0.61 (0.42, 0.91)

Progestin only

No cysts 61 (72) 57 (65) 1.00 36 (84) 38 (79) 1.00

Ovarian cysts 24 (28) 31 (35) 0.67 (0.34, 1.33) 7 (16) 10 (21) 0.80 (0.26, 2.50)

No hysterectomy

No cysts 1901 (82) 1798 (81) 1.00 997 (88) 918 (85) 1.00

Ovarian cysts 417 (18) 416 (19) 0.97 (0.83, 1.13) 132 (12) 162 (15) 0.76 (0.59, 0.97)

Hysterectomy

No cysts 405 (65) 483 (60) 1.00 377 (77) 396 (68) 1.00

Ovarian cysts 214 (35) 319 (40) 0.80 (0.65, 1.00) 111 (23) 183 (32) 0.64 (0.49, 0.85)

No ovaries removed

No cysts 2134 (83) 2046 (82) 1.00 1186 (89) 1124 (86) 1.00

Ovarian cysts 425 (17) 443 (18) 0.94 (0.81, 1.09) 143 (11) 185 (14) 0.74 (0.58, 0.93)

One ovary removed

No cysts 88 (72) 109 (73) 1.00 67 (60) 64 (53) 1.00

Ovarian cysts 35 (28) 41 (27) 0.93 (0.54, 1.61) 45 (40) 56 (47) 0.55 (0.31, 0.96)

Both ovaries removed

No cysts 137 (54) 192 (51) 1.00 116 (69) 129 (58) 1.00

Ovarian cysts 118 (46) 181 (49) 0.93 (0.67, 1.29) 52 (31) 95 (42) 0.69 (0.44, 1.06)

Age at cyst diagnosis (years)

No cysts 2306 (79) 2281 (76) 1.00 1374 (85) 1315 (79) 1.00

<30 294 (10) 347 (12) 0.84 (0.71, 1.00) 95 (6) 142 (9) 0.64 (0.49, 0.84)

‡30 336 (11) 385 (13) 0.87 (0.74, 1.01) 147 (9) 202 (12) 0.70 (0.56, 0.88)

Time since cyst diagnosis (years)

No cysts 2306 (78) 2281(76) 1.00 1374 (85) 1325 (79) 1.00

<20 368 (13) 405 (13) 0.92 (0.79, 1.08) 159 (10) 215 (13) 0.71 (0.57, 0.89)

‡20 262 (9) 327 (11) 0.78 (0.65, 0.92) 83 (5) 129 (8) 0.61 (0.46, 0.82)

a Odds ratio and 95% confidence interval adjusted for age and study site

162 Breast Cancer Res Treat (2008) 109:157–164

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diagnosis may be the cause or result of ovarian surgery, it

is difficult to separate any effects of the surgery or sub-

sequent menopausal status or use of HT from the effects of

the cysts. Although estimates varied slightly according to

menopausal, hormonal, or surgical subgroup, there was no

evidence for an interaction with any of these. Sampling

variation may be responsible for the variation in results

across different study populations. It is also interesting to

note, however, that in the Women’s CARE study, the racial

differences were restricted to ER and/or PR positive

tumours.

A biological explanation for an inverse relationship

between reported ovarian cysts and breast cancer is com-

plicated by the fact that ovarian cysts are heterogeneous and

the definition varies across studies. The term ‘‘ovarian

cysts’’ includes common functional cysts, which are most

frequently follicular cysts, but can also occur as luteal cysts

and theca lutein cysts [14]. Other types of cysts include

benign cystic teratomas, serous cystadenomas, and benign

serous tumours [14]. In addition, women with endometriotic

cysts or with PCOS may respond positively when queried

about a history of ovarian cysts. A major limitation in all

reports is their inability to distinguish among these condi-

tions. One exception is PCOS, which has been specifically

addressed in some studies. A report of increased risk asso-

ciated with PCOS in postmenopausal women in a cohort with

chronic anovulation [6] was followed by an inverse finding in

younger women [9] and two null reports [7, 8]. In general, the

prevalence of PCOS was quite low in these studies.

The literature on attributes associated with ovarian cysts

is sparse. Smoking has been associated with an increased

risk of unspecified ovarian cysts as well as with functional

cysts [15, 16], although BMI may modify the effect [16].

Functional cysts have also been associated with tubal

sterilization [11]. Endometriotic cysts have been associated

with regular periods, lower parity, and lower BMI while

serous and mucinous cysts have been associated with later

age at first birth, earlier menarche, and higher meat and

lower green vegetable consumption [10, 17]. The infor-

mation is currently insufficient to draw conclusions

with respect to a possible explanation for a relationship

with breast cancer. It is likely that the hypothalamic-

pituitary-gonadal axis plays a role in the development of

functional cysts, one of the more common types of ovarian

cysts, since it is responsible for follicular development. It

may be involved in other cyst types as well.

To confirm and make use of a finding of reduced breast

cancer risk associated with a diagnosis of ovarian cysts it

will be necessary to determine whether this reduced risk is

associated with one or more specific types of cyst, which

may act as a marker of the hormonal milieu. Such an

investigation would be possible in a large cohort of women

with detailed medical record information. This more spe-

cific knowledge would allow further research to determine

the protective mechanism.

Acknowledgements This study was funded by the National Insti-

tute of Child Health and Human Development, with additional sup-

port 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 Pennsyl-

vania (NO1-HD-3-3276), and University of Southern California

(N01-HD-3-3175) and through an interagency 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. General support through SEER contracts

N01-PC-67006 (Atlanta), N01-CN-65064 (Detroit), N01-PC-67010

(Los Angeles), and N01-CN-0532 (Seattle) is also acknowledged.

Table 3 Odds ratios and 95% confidence intervals for the association between an ovarian cyst diagnosis and breast cancer incidence in

Caucasian and African American women according to the ER and PR status of the cases in the CARE study

Caucasian African American

Cases N (%) ORa (95% CI) Cases N (%) ORa (95% CI)

ER+

No cysts 1505 (79) 1.00 626 (85) 1.00

Ovarian cysts 402 (21) 0.84 (0.73, 0.97) 107 (15) 0.67 (0.53, 0.85)

ER-

No cysts 578 (79) 1.00 475 (82) 1.00

Ovarian cysts 155 (21) 0.84 (0.69, 1.03) 103 (18) 0.82 (0.64, 1.05)

PR+

No cysts 1333 (79) 1.00 552 (85) 1.00

Ovarian cysts 345 (21) 0.82 (0.70, 0.94) 94 (15) 0.66 (0.52, 0.85)

PR-

No cysts 672 (78) 1.00 478 (81) 1.00

Ovarian cysts 193 (22) 0.90 (0.75, 1.08) 110 (19) 0.87 (0.69, 1.11)

a Odds ratio and 95% confidence interval adjusted for age and study site

Breast Cancer Res Treat (2008) 109:157–164 163

123

The findings and conclusions in this report are those of the authors

and do not necessarily represent the views of the Centers for Disease

Control and Prevention.

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