Longer hormone treatment before breast cancer surgery has greater impact on tumor growth

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Treating some women with higher-risk breast cancer with longer hormone therapy before surgery led to more changes in the genetic makeup of their tumors, some of which were associated with better survival outcomes.

Researchers have found that treating postmenopausal women with estrogen receptor-positive breast cancer with drugs called aromatase inhibitors – which suppress estrogen levels – for at least two weeks before surgery resulted in changes in the characteristics of their tumour.

The study is the first to directly compare the effects of treating patients with short- and long-term treatments of aromatase inhibitors on the genetic makeup of the tumor before undergoing surgery to remove their tumor.

Led by scientists from the Institute of Cancer Research in London, the study found greater changes were seen in the genetic makeup of a patient’s tumors in those who were treated with aromatase inhibitors for a month or more before surgery compared to two weeks of treatment.

Reduction in tumor growth rate

Researchers found that longer treatment led to reduced expression of genes responsible for the rate of growth of patients’ tumors, which may warrant treatment of women with estrogen receptor positive breast cancer at higher risk with longer treatment of aromatase inhibitors before surgery. .

The study is published in the journal Clinical cancer research, and was largely funded by the Institute for Cancer Research (ICR), which is both a charity and a research institute.

The study compared the genetic fingerprints of two groups of breast cancer patients before and after treatment with aromatase inhibitors for two weeks, or more than a month, before surgery.

Breast cancer can be classified into five major intrinsic subtypes, based on the genes that are expressed by a patient’s tumor. Each intrinsic subtype has a different prognosis and is associated with a different response to treatment.

Switch to a low-risk subtype

Researchers from ICR and Royal Marsden NHS Foundation Trust, ICR’s partner hospital, have played an important role in the clinical development of aromatase inhibitors – and have conducted recent studies that have helped to establish the benefits of new breast cancer treatments such as palbociclib, a “first-in-class” drug that targets CDK4 and CDK6 proteins in advanced metastatic breast cancer.

Dr. Maggie Cheang and her colleagues at the ICR are currently seeking commercial partners to pursue the development of a breast cancer genetic signature that can predict resistance or susceptibility to aromatase and CDK4/6 inhibitors.

In this study, which used tumor samples from the Cancer Research UK-funded POETIC trial, ICR researchers found that treating patients with aromatase inhibitors before surgery led to a clear change in the subtype of their cancer in the majority of cases. Changes to a low-risk subtype were associated with a better prognosis whether patients were treated for two weeks or more than a month before surgery.

Reassure doctors

In the current landscape where there is still a backlog of patients awaiting surgery due to the disruptions caused by the Covid-19 pandemic, these results provide reassurance that physicians can effectively treat some patients with hormone therapy while they wait for their surgery.

Next, the researchers plan to validate the results in a larger clinical trial.

First author Dr Milana Bergamino, Clinical Research Fellow in Integrative Genomic Analysis of Clinical Trials at the Institute of Cancer Research, London, said:

“In this study, we found that treatment with aromatase inhibitors before patients underwent surgery to remove breast tumors made female cancers identifiable as low-risk subtypes and was associated to better outcomes and a better response to treatment.

“We also observed that giving longer treatment with aromatase inhibitors led to more changes in the genetic makeup of patients’ tumors, leading to a reduction in their cancer growth. Longer treatment before surgery may be a good option in some patients with aggressive tumors.

“Usually the first line of treatment after diagnosis of estrogen receptor positive breast cancer is surgery. During the Covid-19 pandemic, when wait times for surgery are still long, this study may provide reassurance that doctors can give aromatase inhibitors as a first-line treatment, and know that this treatment helps to reduce the size of patients’ tumors and change their molecular characteristics towards a lower-risk tumor while they wait a surgical intervention.

Maximize patient benefits

Study leader Dr Maggie Cheang, team leader in genomic analysis (clinical trials) at the Institute of Cancer Research, London, said:

“The current standard of care for postmenopausal women with estrogen receptor-positive breast cancer includes treatment with aromatase inhibitors for five to ten years after surgery. Our study showed that the addition of relatively short treatment with aromatase inhibitors prior to surgery could have a significant positive effect on the patient’s treatment outcome.

“This is an important example of a way to maximize the benefit patients derive from existing treatments and quickly identify those who may be resistant to aromatase inhibitors and need further treatment. .”

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