RESEARCH RESULTS

A study published in JAMA Oncology in 2024 found a way to identify which premenopausal women were most likely to benefit from ovarian-function suppression as part of their cancer treatment, and who was unlikely to benefit and should avoid that treatment.

Researchers used tumour samples from 1,687 premenopausal people with breast cancer, which were collected as part of the original Suppression of Ovarian Function Trial (SOFT), and applied a genetic test called the Breast Cancer Index (BCI) that looked at the activity levels of 11 genes known to play important roles in hormone-sensitive breast cancer.

Their theory was that those women with a cancer that exhibited a high score on this test would be more likely to benefit from the addition of hormone-suppressing therapy than to the standard treatment options of either tamoxifen or exemestane.

Surprisingly, they found the opposite: those with a lower score on the genetics test were the ones who benefited the most in terms of freedom from breast cancer recurrence during the 12 years of follow-up.

“It may be that those patients with a BCI low score have more sensitivity to the maximum endocrine blockade, and therefore that high endocrine sensitivity leads to them getting more of a benefit from getting rid of all of the estrogen,” said Dr Nicholas Zdenkowski, a medical advisor with Breast Cancer Trials and medical oncologist at Hunter Valley Oncology.

The difference was significant. Participants with a low BCI score who were treated with ovarian suppression and exemestane had about half the risk of their breast cancer returning, and those given ovarian suppression and tamoxifen had a 31% lower risk, compared to those treated with tamoxifen alone.

In contrast, those in the trial with a high BCI score had no benefits from the additional ovarian-suppressing treatment.

The original SOFT trial, which demonstrated the additional benefit of ovarian suppression, was practice-changing, as it led to the standard use of ovarian suppression in premenopausal women with hormone-sensitive breast cancer, and saw those drugs listed on the Pharmaceutical Benefits Scheme in Australia.

While the BCI test isn’t routinely available, Dr Zdenkowski said it could also have an impact on clinical practice if it becomes more widely used.

“If we had access to this test, then we could use it to help refine our decision-making about who specifically might get most benefit from ovarian suppression,” he said.

Publication

O’Regan RM, Zhang Y, Fleming GF, Francis PA, Kammler R, Viale G, Dell’Orto P, Lang I, Bellet M, Bonnefoi HR, Tondini C, Villa F, Bernardo A, Ciruelos EM, Neven P, Karlsson P, Muller B, Jochm W, Zaman K, Marino S, Geyer CE, Jerzak KJ, Davidson NE, Coleman RI, Ingle JN, van Mackelenbergh MR, Loi S, Colleoni M, Schnabel CA. Breast cancer index in premenopausal women with early-stage hormone receptor-positive breast cancer. JAMA Oncology. 2024; epub 15 August 2024; doi:10.1001/jamaoncol.2024.3044