Breast Cancer Reseach

Health & research

Jan 25

Who: Haukeland University Hospital

What: Hormone sensitive breast cancer

Where: Bergen

Project period: 2020

Web: Haukeland University Hospital

The aim of this study was to select patients with hormone sensitive breast cancer to the best possible treatment, while reducing the use of chemotherapy.

Primary therapy, with the use of chemotherapy or hormonal therapy, is today stanadard-of-care to shrink large breast cancers before breast cancer surgery. With good response, more patients can have breast-conserving therapy instead of mastectomy (the whole breast taken away), reduced surgery in the axilla, thereby avoiding complications such as arm edema (lymphedema) and reduced shoulder mobility. Primary therapy also makes it possible to monitor prospectively whether the actual cancer therapy is effective and allows us to change therapy if not.

In our hospital we have broad experience using primary therapy, with a large proportion of patients included in our own, investigator-initiated clinical trials. Last year about 35% of new breast cancer patients were given primary therapy before surgery, which is in accordance with common practise in international breast cancer centers.

Traditionally, chemotherapy and not hormone therapy, has been used as primary therapy to all patients, even though it is known that many patients with hormone sensitive cancer have less effect of this treatment. Also, chemotherapy is associated with harsh side effects and frequent late effects, reducing quality-of-life for many patients for years afterwards.

In our last study, PETREMAC, selected patients with hormone sensitive cancer got hormonal treatment instead of chemotherapy as primary therapy. This selection was based on genetic analyses of the tumour tissue taken before commencing cancer treatment.

63% in this group had good response to hormonal therapy and did not need chemotherapy. These patients had substantially less side effects than patients given chemotherapy.

Identifying gene mutations

In this project supported by Grieg Foundation, whole genome analysis of the tumour tissue was done to identify specific gene mutations which could predict response or lack of response to hormonal treatment already before starting therapy. We also wanted to identify biomarkers pinpointing tumours responding so well that we could safely reduce the extent of mutilating surgery; i.e. breast conserving therapy and minimal surgery in the axilla.

88 patients in the PETREMAC study had hormone sensitive cancer. We selected five patients with good response to the hormone therapy; these did not need any chemotherapy. Also, we seleceted five patients with no effect of hormone therapy; these patients had to switch to chemotherapy. Based on the support from Grieg Foundation we could perform whole genome sequencing of the cancer genome from these tumours before and after treatment; two tumour samples for each patient, altogether 20 tissue samples and analyses.

Results

Patients with hormone sensitive breast cancer and good response to hormonal therapy before surgery have a better chance to get breast-conserving therapy and reduced, less mutilating surgery in the axilla.
Patients getting hormonal therapy have less late effects compared to patients treated with chemotherapy.
So far, it seems that one specific gene mutation is overrepresented in tumours with good response to hormonal therapy, and it seems that this mutation can help us to select patients who can safely be treated without chemotherapy. Still, our analyses is so far limited to 5+5 patients, and needs to be extended, further analyzing the complete trial population of 88 patients. Also, we have initiated a collaboration with a well-known study group at Royal Marsden Hospital, London, UK. They will perform the same analyses as we have in a larger number of their patients, to see if our results can be verified.

Based on the funding from Grieg Foundation we have performed whole genome sequencing of the ten most interesting tumours among patients with hormone sensitive cancer. Results from these analyses have given us a complete overview of mutations predicting response or not to hormonal therapy. However, we will still need more time to analyse and interpret the data.