This article is more than 5 years old. Information may no longer be current.
Endocrine therapy improves long-term ovarian function recovery in breast cancer
The addition of triptorelin pamoate to chemotherapy improved long-term ovarian function recovery among premenopausal women with HR-positive or -negative breast cancer, according to a post hoc analysis of the PROMISE-GIM6 study.
However, the addition of triptorelin pamoate (Trelstar, Actavis) did not appear to significantly impact pregnancy rate or DFS.
The use of luteinizing hormone–releasing hormone analogues (LHRHa) during chemotherapy for women with breast cancer remains controversial, according to study background. The uncertainty derives from a lack of data on long-term ovarian function and pregnancies, as well as safety concerns regarding potential negative interactions between endocrine therapy and chemotherapy.
Thus, Lucia Del Mastro, MD, of the National Institute for Cancer Research in Genova, Italy, and colleagues conducted a randomized, open-label phase 3 superiority trial to observe the long-term effects of LHRHa–induced ovarian suppression during chemotherapy for breast cancer.
Between October 2003 and January 2008, the researchers enrolled 281 women (median age, 39 years; range, 24-45) with stage I to stage III HR-positive or HR-negative breast cancer from 16 treatment centers in Italy. Researchers randomly assigned women neoadjuvant or adjuvant chemotherapy alone (n = 133) or with triptorelin pamoate (n = 148).
The incidence of chemotherapy-induced early menopause served as the primary endpoint. Long-term ovarian function, pregnancies and DFS served as post hoc endpoints.
Median follow-up was 7.3 years (interquartile range, 6.3-8.2).
Overall, 72.6% of women assigned triptorelin pamoate achieved menstrual resumption at 5 years compared with 64% of women assigned chemotherapy alone (HR = 1.28; 95% CI, 0.98-1.68; age-adjusted HR = 1.48; 95% CI, 1.12-1.95).
Eight pregnancies occurred in the triptorelin pamoate arm (5-year cumulative incidence estimate, 2.1%; 95% CI, 0.7-6.3) vs. three in the chemotherapy monotherapy arm (5-year cumulative incidence estimate, 1.6%; 95% CI, 0.4-6.2). However, this difference did not reach statistical significance (HR = 2.56; 95% CI, 0.68-9.6; age-adjusted HR = 2.4; 95% CI, 0.62-9.22).
Five-year DFS rate also appeared comparable in the triptorelin pamoate arm (80.5%) and chemotherapy monotherapy arm (83.7%; HR = 1.17; 95% CI, 0.72-1.92).
Among women with hormone receptor-positive disease, 5-year DFS rates were 85.1% in the triptorelin pamoate arm and 85.2% in the chemotherapy arm. Among patients with hormone receptor-negative disease, 5-year DFS rates were 62.1% in the triptorelin pamoate arm and 76.2% in the chemotherapy monotherapy arm. When researchers adjusted for baseline disease stage and hormone receptor status, there was no statistically significant difference in DFS between the arms (HR = 1.1; 95% CI, 0.67-1.79).
The researchers acknowledged the inclusions of these endpoint analyses after the initial study protocol as a limitation to these results.
Further, the researchers noted that these results differed from those of the POEMS-SWOG S0230 study, which showed improved rates of 4-year DFS in the LHRHa arm (89% vs. 78%; HR = 0.49; P = .04).
“The discordance between our finding and that of the POEMS-SWOG S0230 trial, and the potential for breast cancer recurrence beyond 5 years, underscores the importantce of obtaining data on long-term recurrence and mortality by hormone receptor status for all participants in trials evaluating preservation of fertility,” Del Mastro and colleagues wrote.
Ann H. Partridge
“Our results, together with the findings from the POEMS-SWOG S0230 study, indicate that, in addition to fertility preservation strategies such as embryo and oocyte cryopreservation, temporary ovarian suppression with LHRHa is an option to preserve ovarian function in premenopausal women with early-stage breast cancer receiving adjuvant chemotherapy,” they added.
These data add to the evidence base in this area, Ann H. Partridge, MD, MPH, founder and director of the Program for Young Women and breast cancer director of the Adult Survivorship Program at Dana-Farber Cancer Institute, as well as associate professor of medicine at Harvard Medical School, wrote in an accompanying editorial.
“Although the findings suggest modest benefits regarding the potential prevention of treatment-associated infertility, collectively these studies reflect the emerging importance of understanding and improving such critical quality-of-life issues, offering patients new treatment and supportive care options, and ultimately providing hope regarding an issue that is highly valued by many young patients diagnosed with cancer,” Partridge wrote. – by Cameron Kelsall
Disclosure: Del Mastro reports honoraria from Takeda and personal fees from Ipsen and Takeda. Please see the full study for a list of all other researchers’ relevant financial disclosures. Partridge reports an advisory role with Pfizer.