Link Discovered in Ovarian Cancer Between Adjuvant

Hormonal Therapy and Improved Outcomes

Rosalind Eeles, MD, PhD

A correlation was drawn between adjuvant hormone therapy (AHT) and a 37% reduction in the risk
of death in women with epithelial ovarian cancer, according to results of a 24-year study.
The results natural hormone replacement therapy of the phase III, international, non-blinded,
randomized trial were recently published in the Journal of Clinical Oncology (JCO).1 The study
examined the effects of AHT in 150 pre- and postmenopausal women diagnosed with epithelial
ovarian cancer at 9 or fewer months. From 1990 to 1995 patients from 19 centers in the United
Kingdom, Spain, and Hungary were randomized 1:1 to either AHT for 5 years (n = 75) or no AHT (n
= 75).
"We were really happy to be able to show that hormone replacement therapy (HRT) is safe for
women with the most common type of ovarian cancer. Whether or not to have HRT is a very
important decision for a large proportion of women with ovarian cancer, who will often have to
undergo the menopause due to the cancer treatment at the same time as coping with a cancer
diagnosis, said lead study author Rosalind Eeles, MD, PhD, professor of Oncogenetics, The Institute
of Cancer Research.

"Our results not only suggest HRT is safe for women with this type of ovarian cancer, but that it may
actually improve their chances of long-term survival. We hope our study will inform treatment for
women with ovarian cancer, and the findings could have a big impact on their quality of life."
Patients were due to start treatment within 2 weeks of random assignment in the study and to
continue their treatment for a minimum of 5 years, if tolerated. The median age at random
assignment was 58.7 years.

Of the 75 patients who received AHT, 96% (n = 72)

received at least 1 day of treatment after random
assignment and 4% of patients (n = 3) received no AHT
after random assignment. The types of AHT were
conjugated estrogens (n = 38), conjugated estrogens and
norgestrel (n = 19), estradiol patch (n = 14), and estradiol
implant (n = 1).
The median estimated time receiving AHT for patients allocated to the AHT group was 1.14 years
(IQR, 0.46-5.08 years). Of the 75 patients allocated to the control group, 11% (n = 8) received
hormone therapy during follow-up.
The trials primary endpoint was OS and relapse-free survival. Additional trial endpoints were
compliance to hormone treatment and recording of selected adverse events, such as myocardial
infarction, fracture, transient ischemic attack, cerebrovascular accident, and second cancer.
Median follow-up in living patients was 19.1 years. Patients were observed at 6 and 12 months, and
then annually for a maximum of 15 years. Centers were asked at each follow-up visit whether the
patient was continuing AHT and the date AHT was stopped, if applicable.

In the AHT arm, 71% of patients (n = 53) have died

compared with 91% (n = 68) of patients in the
control arm.
OS was significantly improved in patients who
received AHT (HR, 0.63; 95% CI, 0.44-0.90; P =
.011). For relapse-free survival, a similar effect was
reported (HR, 0.67; 95% CI, 0.47-0.97; P = .032).
Treatment was discontinued for various. reasons,
including adverse events (n = 14),
recurrence/progressive disease (n = 6), patient
choice (n = 4), long duration (n = 4), and second
primary (n = 2), with some patients seeming to have
continued receiving AHT throughout trial follow-up.
HRT does not seem to have a detrimental effect on survival in women with epithelial ovarian cancer,
and there is even the intriguing suggestion that it may be improving their survival chances. We
would like to see more research into this area in the future and hope to see other studies confirm
this finding in larger numbers of women," study scientific lead Judith Bliss, MSc, professor, director
of the Cancer Research UK-funded Clinical Trials and Statistics Unit at the Institute of Cancer
Research, said in a statement.
Eeles et al are to be congratulated for recognizing the importance of this study and observing the
accrued cohort for nearly two decades, Stanley Liplowitz, MD, and Elise C. Kohn, MD, wrote in an
editorial published simultaneously in JCO.2

These findings, unlikely to be repeated, support the hypothesis that HRT improves outcomes in
patients with ovarian cancer by reducing ovarian cancer relapse, ovarian cancer-specific death, and
other causes of death. In the Women's Health Initiative study, estrogen did not significantly affect
all-cause mortality, making the decrease in mortality in the patients studied here of interest,
Liplowitz and Kohn wrote.
These findings demonstrate that women with severe menopausal symptoms following ovarian cancer
treatment are able to safely receive AHT and have survival and quality-of-life benefits, the authors
noted.

Where do we stand in 2015? To treat or not to treat? Lipkowitz and Kohn wrote. Although there are
many unanswered questions [] the data from Eeles et al combined with that of previous studies allow
oncologists to feel comfortable offering patients HRT after the treatment of EOC to reduce
vasomotor and other postmenopausal symptoms and should, therefore, improve the quality of life for
patients with epithelial ovarian cancer.

ReferencesEeles RA, Morden JP, Gore growth hormone therapy M, et al. Adjuvant hormone therapy
may improve survival in epithelial ovarian cancer: results of the AHT randomized trial. J Clin Oncol.
2015;33(35):4138-4144. Lipkowitz S, Kohn EC. To treat or not to treat: the use of hormone
replacement therapy in hormone replacement therapy patients with ovarian cancer. J Clin Oncol.
2015;33 (35):4127-4128.