TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor(HR)-negative breast cancer or in those with HR-positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR-negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR-positive tumors (−2.1 percentage-point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR-negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease free survival (−4.2 percentage-point after 3 years) compared with initiating promestriene (1.0 percentage-point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy. 

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients. 

SOURCE:

The research (abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024. 

LIMITATIONS:

No limitations were discussed in the presentation. 

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.