Adding to the Bigger Picture of an
Effective Breast Cancer Treatment

Drug therapy is an unfolding story: it takes time to understand impact on disease, recurrence, side effects and long-term impact.

Research published by the Oxford-based Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) has added a new chapter to the story of some of the most effective drug treatments available to patients with estrogen receptor-positive breast cancer. In doing so, it suggests alternative treatment options to reduce the chance of disease recurring.

The paper, published in Lancet Oncology, is a meta-analysis of four clinical trials involving 7030 premenopausal women who were treated with drugs that attack cancer by blocking the manufacture of estrogen or its uptake in cells.

Professor Prue Francis chairs the International Steering Committee for the SOFT and TEXT clinical trials, that investigated the impact of treatment combinations in premenopausal women and part of the meta-analysis data set. She explains that when estrogen-targeted treatment first emerged several decades ago, tamoxifen was recommended for postmenopausal women no longer producing estrogen in their ovaries.

Clinicians feared that, for premenopausal women, tamoxifen might increase estrogen production in their ovaries and be unhelpful. It took time and research to build the clinical case for tamoxifen’s effectiveness in treating younger patients.

“It became clear from later analyses that it was useful,” says Professor Francis. “And then it became a standard of care to give five years of tamoxifen for women under 50.”

Another common therapy for women with this type of cancer is an aromatase inhibitor (AI), which halts production of estrogen in body fat. It is a treatment option for post-menopausal women with estrogen receptor-positive breast cancer. But could it also be a useful therapy for premenopausal patients if used with ovarian suppression?

Professor Francis says that the new meta-analysis answers that question, finding that for premenopausal women with early-stage estrogen receptor-positive cancer, AI with ovarian suppression is more effective than tamoxifen with ovarian suppression at reducing the risk of breast cancer recurrence.

More work needs to be done over time to understand treatment implications on patient mortality and Professor Francis says that while the new meta-analysis is essential to the long-term story, implications for patients receiving ovarian suppression are nuanced.

“Clinicians may look at this result in different ways,” says Professor Francis. “Some might feel that this gives them greater reassurance given that distant recurrence is reduced by using AIs.”

“Others might say that, if my patients haven’t got a proven survival advantage at this stage, I don’t want to put them through what we know as clinicians are difficult side effects of the combination of the aromatase inhibitor and the ovarian suppression.”

Publication

Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Early Breast Cancer Trialists’ Collaborative Group. The Lancet Oncology. 2 2022 epub 03 February 2022. Doi: 10.1016/S1470-2045(21)00758-0.