Biomarker analyses improve survival outcome for high risk breast cancer

Health & research

Jan 28

Biomarker analysis can reduce chemotherapy for patients with high-risk breast cancers and improve survival outcome.

Breast cancer is the most frequent type of cancer among women in Norway, and approximately 90% are cured with today´s standard of care. Women with larger breast tumors are at higher risk of dying from breast cancer. They need improved therapy. Currently, in Norway, most high-risk breast cancers are treated with the same type of chemotherapy, regardless of cancer biology. Some patients respond well, but others do not.

Clinical Trial

In the PETREMAC clinical trial, 200 patients with high-risk breast cancer from all regions of Norway received breast cancer therapy designed to fit each individual tumor. Out of 200 patients, 88 patients had hormone sensitive breast cancer and received hormone blocking therapy instead of chemotherapy before curative surgery.

In 70% of the patients their breast cancers responded well to hormone sensitive therapy, and chemotherapy was not needed to shrink the tumors before surgery. These patients experienced fewer side effects from the endocrine therapy than what is usually observed with chemotherapy. On the other hand, 30% of the patients needed chemotherapy prior to surgery.

With funding from Grieg Foundation, whole genome analysis of the tumor tissue from a selected group of patients in the PETREMAC trial was performed to identify specific gene mutations which could predict response or lack of response to anti-hormonal treatment already before starting therapy. They also wanted to identify biomarkers pinpointing tumors responding so well that we could safely reduce the extent of mutilating surgery; i.e. breast conserving therapy and minimal surgery in the arm pit (axilla).

Shrink the tumor

More patients can have breast-conserving therapy instead of mastectomy (the whole breast taken away) and minimal 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 in 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 got primary therapy before surgery, which is in accordance with common practice in international breast cancer centers.

Chemotherapy is not necessary for all patients

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

Anti-hormonal therapy instead of chemotherapy

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

This project is based on 30 years of close collaboration between the Department of Surgery, Section of breast & endocrine surgery and the Department of Oncology, Haukeland University Hospital, where clinical trials in breast cancer have been conducted on a continous basis to improve the outcome for this disease. Former head surgeon Turid Aas and national principal investigator/breast cancer oncologist Hans Petter Eikesdal, together with Professors Per Eystein Lønning and Stian Knappskog, initiated the PETREMAC trial, and are going to lead the scientific analyses funded by the Grieg Foundation in the current project.”

Main findings

Patients with hormone sensitive breast cancer and good response to anti-hormonal therapy before surgery, have a better chance to get breast-conserving therapy and less mutilating surgery.
Patients getting anti-hormonal therapy have less late effects compared to patients treated with chemotherapy.

Results from these analyses have given us a complete overview of mutations predicting response or not to hormonal therapy.

These results will likely benefit a large proportion of our breast cancer patients, as they will help us personalize treatment and avoid chemotherapy to patients that do not benefit from such treatment.