THE BENEFITS OF DIFFERENCE: HOW TARGETING SUBTYPES OF A DEADLY CANCER COULD IMPROVE PATIENT OUTCOMES

Triple negative breast cancer (TNBC) represents about 15% of early stage diagnoses and has the worst prognosis of any type of breast cancer.

Recent developments in treatment strategies have improved outcomes, but it remains an aggressive disease. Patients with early stage TNBC are more likely to experience recurrence and die of their cancer, and those with metastatic disease to have a shorter survival.

Researchers have reviewed the results of a phase III clinical trial, conducted between 2000 and 2012, to explore the potential for lowdose chemotherapy to benefit patients with particular subtypes of TNBC in its early stage.

The IBCSG 22-00 trial examined the effects of continuous low-dose chemotherapy, using cyclophosphamide and methotrexate, for about 1000 patients with ER-negative cancer. Unfortunately, its findings showed no significant benefits in the disease-free survival rates of trial participants.

Dr Nick Zdenkowski, chair of the Scientific Advisory Committee for Breast Cancer Trials, says that while there is more understanding of the disease and new approaches to trial design since IBCSG 22-00 was completed, its rich data and tissue samples have enduring value.

Researchers have re-examined IBCSG 22-00, applying an updated perspective and revealing new information about how subtypes of the disease responded to the treatment.

TNBC is defined by what it lacks: estrogen, progesterone and HER2 markers. But as Dr Zdenkowski explains, this type of cancer isn’t homogenous. This new study focuses on the impact of low-dose chemotherapy on three specific subtypes.

“Researchers found that two of the three subtypes were more immune activated,” says Dr Zdenkowski. “There was a statistically significant benefit in those subgroups from this chemotherapy regimen.”

The new study has reinforced the need to further explore heterogeneity of TNBC and establish subtypes’ responses to both existing therapies and emerging strategies like immunotherapy.

“If we can find subtypes of triple-negative breast cancer that respond well to cyclophosphamide and methotrexate and then potentially add in some immunotherapy, that could be a very effective,” he says.

While not yet able to influence changes in patient care, the new data will benefit planning of next-generation trials and the development of new therapies.

“Having tissue specimens from trials [like IBCSG] in biobanks is hugely valuable,” says Dr Zdenkowski. “We can analyse specimens from patients who have volunteered their time and their bodies, and they are valuable for years and potentially decades to come. If the biobank is used wisely, then we can design our current trials based on that information.”

Publication:
Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22-00. Clin Cancer Res. 2023 Dec 1;29(23):4908-4919. doi: 10.1158/1078-0432.CCR-23-1267. PMID: 37733800. Joaquin Garcia A, Rediti M, Venet D, Majjaj S, Kammler R, Munzone E, Gianni L, Thürlimann B, Laáng I, Colleoni M, Loi S, Viale G, Regan MM, Buisseret L, Rothé F, Sotiriou C.