Gut Microbiota May Influence pCR in Early-Stage Breast Cancer

A study out of Scotland, to be presented at this year’s virtual European Breast Cancer Conference in October, has linked levels of 2 short-chain fatty acids (SCFAs) in female patients with early-stage breast cancer to pathological complete response (pCR) to neoadjuvant chemotherapy (NACT), according to the abstract released today.

The 2 SCFAs are propionate and butyrate, and they were shown to be lower in the gut bacteria of patients achieving pCR compared with those not achieving pCR after surgery.

“In this study we have started to look at whether the function of the gut microbiome could be one factor that influences the effectiveness of chemotherapy,” said Kirsty Ross, MBChB, MSc, a specialist registrar in medical oncology at the Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.

Ross and her fellow authors also noted that the 2 SCFAs they investigated are known to “dampen down the immune system’s ability to target cancer cells,” but they haven’t been looked at in the present study’s setting. To determine the levels of propionate and butyrate, the investigators examined the study group’s stool samples using gas chromatography at 3 time points: before first NACT (T1), at NACT mid point (T2), and after the final NACT cycle (T3). The healthy group was sampled just once. pCR was evaluated through tissue samples following surgery.

The study population comprised 2 cohorts. The 21 patients in the study group had early-stage breast cancer and were being treated at Beatson West of Scotland Cancer Centre. Their median age and BMI were 56 (range, 33-72) years and 28.6 kg/m² (range, 19.6-55.6 kg/m²), respectively. In the healthy control group, there were 24 women, with a median age of 46 (range, 31-61) years and BMI of 25.9 mg/m² (range, 18.0-42.4 kg/m²).

Overall, pCR was seen in 25% of evaluable patients, and there were no significant differences in SCFA levels for the health controls and study patients at T1.

However, significantly lower mean concentrations (μmol/g) were seen at T3 for propionate and butyrate between the patients who achieved pCR and those who did not:

• Propionate:
  • T1: 14.5 vs 25.3 (P = .036)
  • T3: 6.6 vs 23.7 (P = .027)
• Butyrate:
  • T1: 13.2 vs 28.2 (P = .027)
  • T3: 7.8 vs 20.5 (P = .024)

Results were available for 20 participants in each cohort. In the study group, 42.9% had human epidermal growth factor receptor 2 (HER2)-positive disease, 38.1% had triple-negative disease, and 19% had estrogen receptor-positive, HER2-negative disease. Their treatments consisted of FEC-T (42.9%), FEC-TH (28.6%), and other (28.6%).

“We speculate that lower proprionate and butyrate concentrations may result in a relatively lower peripheral Treg proportion, which in turn supports development of a more immune-stimulatory tumour microenvironment and improved pCR,” the investigators concluded. “Further investigation is warranted including immunophenotyping of patients peripheral blood and tumour-infiltrating lymphocytes.”

They hope their results lead to additional investigations of how to increase chemotherapy’s effectiveness, and they are planning larger studies on the influence of gut microbiota in breast cancer subtypes and on anticancer immune responses.

Reference

Ross K. Gut microbial short chain fatty acids are associated with pathological complete response (pCR) after neoadjuvant chemotherapy for breast cancer. Presented at: 12th European Breast Cancer Conference; October 2-3, 2020. Abstract 105.