This most common breast cancer, 1/4 of patients in a timely change of treatment strategy benefits significantly!

Recently, the Lancet Oncology, a sub-journal of The Lancet, published important findings
.
Identifying a specific mutation in breast cancer patients based on blood testing, the ESR1 mutation, can help clinicians adjust treatment strategies in a timely manner, significantly improving the survival time
of patients.
The authors emphasize that the PADA-1 trial is "the first prospective randomized trial to demonstrate that early targeted therapy for bloodborne ESR1 mutations can bring significant clinical benefits to breast cancer patients.
"

It is worth emphasizing that about a quarter of breast cancer patients in the study had elevated levels of ESR1 mutations in their blood, and early targeted therapy for ESR1 mutations brought significant clinical benefits
.

Screenshot credit: THE LANCET Oncology

The paper notes that the development of aromatase inhibitor resistance is often associated with ESR1 mutations in
cancer cells.
Analysis of cfDNA (i.
e.
, peripheral blood free DNA, a degraded DNA fragment released into plasma) showed that about 40% of patients with ER+/HER2-advanced breast cancer can detect ESR1 mutations in their blood after receiving aromatase inhibitors to treat disease progression
.

ESR1 is responsible for encoding the main subtype of estrogen receptors, the "estrogen receptor α"
.
Previous findings, including preclinical studies and retrospective analysis of clinical data, have shown that mutant estrogen receptor α sensitive
to selective estrogen receptor down-modulators (e.
g.
, flewavirs).

Based on this, in the current multicenter, open-label, randomized controlled Phase 3 clinical trial called PADA-1, the researchers hypothesized that patients with ESR1 mutations detected in the blood under first-line therapy (aromatase inhibitors combined with CDK4/6 inhibitors) could continue to benefit
from fluvixantrans in combination with CDK4/6 inhibitors if the endocrine therapeutics (aromatase inhibitors) were replaced with florviris.

The results of the preliminary analysis of the PADA-1 trial are reported this time
.
The aromatase inhibitors used in patients with advanced breast cancer in the study were letrozole, anastrozole or ezemetall; CDK4/6 inhibitor is pipexil
.

Image source: 123RF

Specifically, between March 22, 2017 and January 31, 2019, a total of 1017 patients with ER+/HER2-advanced breast cancer were enrolled in the study and screened
for blood ESR1 mutations during treatment.
Patients with elevated levels of blood ESR1 mutations during treatment (no simultaneous progression of the disease occurred) were randomly assigned 1:1 to continue receiving the same treatment or to convert to flovistan in combination with CDK4/6 inhibitors
.

The results showed that a total of 279 patients (27%) had elevated levels of blood ESR1 mutations
.
Of these, 172 patients (17%) received a random assignment to receive treatment: 88 patients were converted to florvestrant + CDK4/6 inhibitor therapy; Eighty-four patients continued to receive aromatase inhibitors + CDK4/6 inhibitors
.
As of July 31, 2021, the median follow-up time for patients receiving randomized groups was 35.
3 months (median follow-up time from the date of randomization was 26.
0 months).

After randomization, the median progression-free survival (PFS) was 11.
9 months for patients treated with fluvixaphone + CDK4/6 inhibitor and 5.
7 months for the aromatase inhibitor group + CDK4/6 inhibitor treatment group (stratified HR=0.
61, 0.
43-0.
86; p=0.
0040).

Overall, the results of the current study suggest that it is necessary for patients with ER+/HER2-advanced breast cancer to monitor the occurrence
of relevant resistance mutations (such as blood ESR1 mutations) in the blood during standard first-line therapy (aromatase inhibitors + CDK4/6 inhibitors).

According to the study, for patients with elevated levels of blood ESR1 mutations, the conversion of endocrine therapeutic drugs (such as the conversion of aromatase inhibitors to florvestrane) will improve PFS in patients and will not increase the likelihood
of the occurrence of toxic side effects of treatment.