Increased risk of recurrence after hormone replacement therapy in breast cancer survivors.
BACKGROUND
Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up.


METHODS
HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone.


RESULTS
Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test).


CONCLUSIONS
After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.
Holmberg
Lars
L
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. lars.holmberg@kcl.ac.uk
Iversen
Ole-Erik
OE
Rudenstam
Carl Magnus
CM
Hammar
Mats
M
Kumpulainen
Eero
E
Jaskiewicz
Janusz
J
Jassem
Jacek
J
Dobaczewska
Daria
D
Fjosne
Hans E
HE
Peralta
Octavio
O
Arriagada
Rodrigo
R
Holmqvist
Marit
M
Maenpaa
Johanna
J
Maenpa
Johanna
J
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced* / Q000453:epidemiology*; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects; D016017:Odds Ratio; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D017741:Survivors / Q000706:statistics & numerical data*
D004958:Estradiol; D009640:Norethindrone