Context Women using combined estrogen and progestin hormone replacement therapy
(CHRT) have an increased risk of breast cancer; however, data on use for long
durations and on risk associated with patterns of use are lacking.
Objective To evaluate relationships between durations and patterns of CHRT use
and risk of breast cancer by histological type and hormone receptor status.
Design Population-based case-control study.
Setting Three counties in western Washington State.
Participants Nine hundred seventy-five women 65-79 years of age diagnosed with invasive
breast cancer from April 1, 1997, through May 31, 1999 (histology: 196 lobular
cases, 656 ductal cases, 114 cases with other histological type, and 9 cases
with an unspecified histological type; estrogen receptor (ER)/progesterone
receptor (PR) status: 646 ER+/PR+ cases, 147 ER+/PR− cases, and 101
ER−/PR− cases [6 ER−/PR+ cases and 75 cases with unknown
ER/PR status were not included in the analyses herein]) and 1007 population
Main Outcome Measures Risks of invasive lobular, ductal, ER+/PR+, ER+/PR−, and ER−/PR−
Results Women using unopposed estrogen replacement therapy (ERT) (exclusive
ERT use), even for 25 years or longer, had no appreciable increase in risk
of breast cancer, although the associated odds ratios were not inconsistent
with a possible small effect. Ever users of CHRT (includes CHRT users who
also had used ERT) had a 1.7-fold (95% confidence interval [CI], 1.3-2.2)
increased risk of breast cancer, including a 2.7-fold (95% CI, 1.7-4.3) increased
risk of invasive lobular carcinoma, a 1.5-fold (95% CI, 1.1-2.0) increased
risk of invasive ductal carcinoma, and a 2.0-fold (95% CI, 1.5-2.7) increased
risk of ER+/PR+ breast cancers. The increase in risk was greatest in those
using CHRT for longer durations (users for 5-14.9 years and ≥15 years had
1.5-fold [95% CI, 1.0-2.3] and 1.6-fold [95% CI, 1.0-2.6] increases in risk
of invasive ductal carcinoma, respectively, and 3.7-fold [95% CI, 2.0-6.6]
and 2.6-fold [95% CI, 1.3-5.3] increases in risk of invasive lobular carcinoma,
respectively. Associations of similar magnitudes were seen among users of
both sequential and continuous CHRT. Risks of ER+/PR− and ER−/PR−
tumors were not increased by use of any form of hormone replacement therapy;
however, small numbers of these tumors limited power to detect possible associations.
Conclusion These data suggest that use of CHRT is associated with an increased
risk of breast cancer, particularly invasive lobular tumors, whether the progestin
component was taken in a sequential or in a continuous manner.