The association between oral contraceptive use and lobular
and ductal breast cancer in young women
Sarah J. Nyante1*, Marilie D. Gammon1, Kathleen E. Malone2, Janet R. Daling2and Louise A. Brinton3
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC
2Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA
3Division of Cancer Epidemiology and Genetics, Department of Health and Human Services,
National Cancer Institute, National Institutes of Health, Bethesda, MD
Recent reports indicate that the incidence of lobular breast cancer
is increasing at a faster rate than ductal breast cancer, which may
be due to the differential effects of exogenous hormones by histol-
ogy. To address this issue, we examined whether the relationship
between oral contraceptive use and incident breast cancer differs
between lobular and ductal subtypes in young women. A popula-
tion-based sample of in situ and invasive breast cancer cases
between ages 20 and 44 were recruited from Atlanta, GA; Seattle-
Puget Sound, WA and central New Jersey. Controls were sampled
from the same areas by random-digit dialing, and were frequency
matched to the expected case age distribution. Odds ratios (ORs)
and 95% confidence intervals (95% CIs) were calculated using
polytomous logistic regression. Among the 100 lobular cancers,
1,164 ductal cancers, and 1,501 controls, the odds ratios for oral
contraceptive ever use were 1.10 (95% CI 5 0.68–1.78) for lobular
cancers and 1.21 (95% CI 5 1.01–1.45) for ductal cancers,
adjusted for study site, age at diagnosis, and pap screening history.
Our results suggest that the magnitude of the association between
ever use of oral contraceptives and breast cancer in young women
does not vary strongly by histologic subtype. These results are
similar to previous studies that report little difference in the effect
of oral contraceptive use on breast cancer by histology.
' 2007 Wiley-Liss, Inc.
Key words: breast cancer; ductal carcinoma; lobular carcinoma; oral
Recent reports indicate that the incidence rate of invasive lobular
breast cancer is increasing faster than invasive ductal breast can-
cer,1–4but few epidemiologic studies have focused on identifying
breast cancer risk factors by histologic subtype. Among the studies
that have, the association between combination hormone replace-
ment therapy and risk of invasive breast cancer differed for ductal
and lobular cancers in most studies,5–10but not all.11These findings
suggest that the effects of other exogenous hormonal treatments,
such as oral contraceptives, may also differ by histologic type.
Ithasbeenconsistently shownthatoralcontraceptive useis associ-
ated with anincreased riskof breast cancer in young women,12–25but
not older women.21,23–25Recently, Newcomer et al.26reported that
current oral contraceptive use, recent use, and older age at first use
are associated with an increased risk of invasive lobular breast can-
cer, but not invasive ductal breast cancer in a population of middle-
aged women, suggesting that oral contraceptives may have effects
related to specific histologic subtypes. It is unknown whether the
associations between oral contraceptive use and breast cancer differs
by histologic subtype among younger women—the age group most
likely to experienceincreased risk of breastcancer due to oralcontra-
ceptive use.25To determine this, we explored the relationship of oral
contraceptive use and lobular and ductal breast cancer subtypes
within a population of young women. Previously, we reported an
odds ratio (OR) of 1.2 for the association between oral contraceptive
use and all breast cancers in this population,22which is consistent
with other results in the literature for women lessthan 45 years old.24
Material and methods
Study data were originally collected as part of the Women’s
Interview Study of Health (WISH), a population-based case–con-
trol study designed to investigate the effects of oral contraceptives,
alcohol consumption and dietary intake during adolescence on
breast cancer risk in young women.22Cases were recruited from
metropolitan Atlanta, GA, Seattle-Puget Sound, WA, and a 5-
county area in central New Jersey and were defined as any woman
between 20 and 44 years of age who was diagnosed with incident
in situ or invasive breast cancer between May 1, 1990 and Decem-
ber 31, 1992. Eligible cases were identified using rapid reporting
systems established in each of the 3 geographic areas and checks
were made against population-based cancer registries in these
same areas. Controls were randomly selected from the same geo-
graphic regions as cases using 13 cycles of random-digit dialing,
and were matched to the expected age distribution of the cases.
Cases and controls were asked to give written informed consent,
and then complete an in-person interview. During the interview,
information was collected by a trained interviewer about demo-
graphic characteristics, lifestyle, medical history, contraceptive
use, diet, reproductive and menstrual histories, physical activity,
smoking habits, occupation, exogenous hormone use, alcohol con-
sumption and family history of cancer. Anthropometric measures
were also obtained. A book of color photographs and descriptions
of oral contraceptive pills organized by brand, name and dose, cor-
responding packaging, and years the pill was available in the
United States were shown to study subjects to help identify spe-
cific formulations they used. Additionally, a monthly reproductive
history calendar marked with pregnancies, other reproductive
events, and contraceptive use since menarche was used to aid in
the recall of dates of oral contraceptive use. Interviews were com-
pleted for 86.4% of eligible cases and 78.1% of eligible controls.
Clinical and histopathologic information for cases was obtained
from hospital and medical records and classified according to the
International Classification of Diseases.27Cases with an ICD-O
behavior code of 2 were classified as in situ, and cases with a
behavior code of 3 were classified as invasive. To facilitate com-
parisons with a previously published study of the effect of oral
contraceptive use on lobular and ductal breast cancer incidence,26
we limited our analysis to cases of ductal carcinoma, NOS (ICD-
O-2 code 8500) and lobular carcinoma (ICD-O-2 code 8520). Ta-
ble I shows the histologic classification of all cases in the study
population. There were 1,164 ductal cases with a mean age at di-
agnosis of 39 years and 100 lobular cases with a mean age at diag-
nosis of 41 years. The 1,501 controls had a mean age of 38 years
old at the time of the telephone screening interview.
The association between oral contraceptive use and lobular and
ductal breast cancers was estimated using polytomous logistic
Grant sponsor: National Cancer Institute; Grant numbers: NCI-NO1-CP-
95671, N01-CN-0532, 5-T32-CA009330. Grant sponsor: the National
Institutes of Environmental Health Sciences; Grant number: P30ES10126;
Grant sponsor: NCI Intramural Research Program.
*Correspondence to: CB# 7435, UNC-Chapel Hill, Chapel Hill, NC
27599, USA. E-mail: email@example.com
Received 10 April 2007; Accepted after revision 16 August 2007
Publishedonline 23October 2007inWileyInterScience (www.interscience.
Int. J. Cancer: 122, 936–941 (2008)
' 2007 Wiley-Liss, Inc.
Publication of the International Union Against Cancer
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ORAL CONTRACEPTIVE USE AND BREAST CANCER