Vaginal estrogen therapy safe for some breast cancer patients, but may pose risk for others

Vaginal estrogen therapy may be safely used to treat genitourinary symptoms in early-stage breast cancer patients with HR-negative tumours and in those concurrently treated with tamoxifen, according to the results of a target trial emulation. However, its use may be detrimental to disease-free survival (DFS) outcomes in patients receiving aromatase inhibitors.

Analysis of nationwide data from French insurance claims showed that vaginal estrogen therapy initiation had a long-term effect on DFS in specific subgroups, with DFS at 5 years decreasing by 2.1 percentage points (95 percent confidence interval [CI], –4.8 to 0.1) among patients with HR-positive tumours and by 3.0 percentage points (95 percent CI, –6.5 to –0.3) among those who were concurrently receiving aromatase inhibitors, reported Dr Elise Dumas from the Institut Curie Hospital in Paris, France.

Looking at the individual effect of the two compounds of vaginal estrogen therapy in the subgroup of aromatase inhibitor users, Dumas noted that estriol was associated with earlier recurrences or deaths, with a decrease in DFS of –4.2 percentage points (95 percent CI, –8.7 to –0.1) at 3 years relative to promestriene (1.0 percentage points, 95 percent CI, –0.9 to 2.9). [ESMO Breast Cancer 2024, abstract 268MO]

There was no decrease in DFS seen following vaginal estrogen therapy initiation in patients with HR-negative tumours or in tamoxifen-treated patients. 

“Breast cancer survivors frequently experience genitourinary symptoms, especially vaginal dryness, due to declining estrogen levels,” Dumas said.

Vaginal estrogen therapies, including compounds like estriol and promestriene, can relieve genitourinary symptoms and are recommended in healthy women, she added. However, in women with a history of breast cancer, there are concerns about the use of such therapies because of its potential effect on disease growth and relapse.

In light of the findings, Dumas advised that vaginal estrogen therapy should be avoided in breast cancer patients currently treated with aromatase inhibitors. “In the absence or after failure of nonhormonal alternatives, promestriene should be preferred over estriol in this subgroup of patients.”

Study discussant Dr Matteo Lambertini from the IRCCS Ospedale Policlinico San Martino in Genova, Italy echoed Dumas and pointed out that the present data on the use of vaginal estrogen therapies in the management of vulvovaginal symptoms in breast cancer reinforce the idea that, if needed, clinicians can use such therapies with some caution and consider them as the last resort if all the other options are not effective.

“We really need to partner with gynaecologists, particularly those focusing on the field of fertility preservation in patients, when managing vulvovaginal symptoms in patients with breast cancer,” Lambertini said.

“I think this network with gynaecologists will not only be important in terms of offering fertility preservation treatments in a timely manner but also to counteract all the gynaecological issues that our patients face, including vulvovaginal symptoms,” he added.

The target trial emulation included 134,942 women with a history of early breast cancer who had undergone surgery plus systemic treatment. These women were under 70 years of age and had not used vaginal estrogen therapies for at least 2 years.

Of the patients, 1,739 initiated vaginal estrogen therapy, specifically promestriene in 55.5 percent, estriol in 34.6 percent, or both in 9.9 percent. The DFS analysis covered 368,597 patient-years of follow-up.