Two simple biomarkers could differentiate which young women with ER+ breast cancer need chemotherapy

New research from Yale Cancer Center identified that two simple biomarkers, immune cells and estrogen receptor levels, could differentiate which young women with ER+ breast cancer need chemotherapy to improve their survival, and which only need a monthly injection to suppress ovarian function.

The findings were recently published in npjBreast, Nature Partner Journals.

Age is not only a risk factor for cancer, but it also interacts with adjuvant chemotherapy benefit in hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) breast cancers."

Lajos Pusztai, MD, DPhil, Professor of Medicine (Medical Oncology) and senior author on the study

Two large clinical trials, the RxPONDER and TAILORx, demonstrated the value of postoperative chemotherapy in premenopausal women to reduce risk of recurrence compared to endocrine therapy alone, whereas in postmenopausal women there was no benefit from chemotherapy if the recurrence score (a commonly used genomic prognostic test) was less than 25. Why age/menopausal status influenced chemotherapy efficacy was not clear; until now.

"We examined molecular differences between HR+/HER2- breast cancers from younger and older patients in genomic data from over 4,500 cancers. What we found is that cancers in younger women are more molecularly heterogeneous than in older patients," said Tao Qing, PhD, a postdoctoral researcher at Yale and lead author on the study. "Some young women have ER+ cancers that are very rich in immune cells, and we know that immune cells augment the anti-cancer effect of chemotherapy drugs, and this subset of patients likely benefit from chemotherapy because of its direct effect on the cancer."

"However," Dr. Pusztai noted, "Another group of young women have cancers that do not have many immune cells, similar to what we see in older patients, and these cancers often also have low ER levels, unlike the older patients who have high levels of ER in the cancer. We think that young women with the immune low and ER low cancers benefit from chemotherapy not so much because the chemotherapy kills cancer cells, but because the chemotherapy causes ovarian suppression and early menopause and functions as a form of intense hormonal therapy."

This finding is substantial because it means that a subset of younger patients may not need adjuvant chemotherapy, but rather an intensified endocrine therapy with ovarian suppression (that could be accomplished with a monthly injection), while other young women have more chemotherapy sensitive cancers and they will have better outcome with chemotherapy. The study team is working on translating these observations into clinically applicable tests that measure immune presence and estrogen signaling and validate these in the already completed clinical trials.

Funding for the study was provided by grants from the Susan Komen Foundation Leadership Award (SAC160076) and Breast Cancer Research Foundation Investigator Award (BCRF-21-133), and H.W. & J. Hector-Stiftung, Mannheim, Germany (M82).

Additional Yale authors include Mariya Rozenblit, Michal Marczyk, Naing Lin Shan, and Kim Blenman.