A Cambridge-led study investigating a new type of breast cancer treatment, targeted at women after the menopause, reports promising early trial results in stopping tumour growth.
Early trial results suggest that for this specific group of breast cancer patients, taking a high or low dose of the hormone drug megestrol combined with the standard hormone therapy letrozole, could be more effective, compared to just taking letrozole alone. These results will need to be confirmed in larger trials before they are routinely available.
Personalised and precise cancer treatments underpins the focus of care at the future Cambridge Cancer Research Hospital, which will bring together researchers from the University of Cambridge and its Cancer Research UK Cambridge Centre and clinicians from Addenbrooke’s Hospital, under one roof in a new 'world-class' facility.
The PIONEER trial was made up of nearly 200 post-menopausal women, including over a hundred patients from Addenbrooke’s Hospital in Cambridge, diagnosed with early-stage ER positive breast cancer. The patients compared giving a mimic of the hormone progesterone, called megestrol acetate, in combination with standard hormone therapy, called letrozole, with standard hormone therapy alone.
Megestrol is a readily available treatment taken as a daily tablet, and at low dose has also already been shown to reduce side effects of standard hormone therapy such as severe hot flushes and sweats.
Dr Rebecca Burrell, the lead oncology trainee for PIONEER, presented the first results of the trial at the San Antonio Breast Cancer Conference, the largest global gathering of breast cancer researchers and clinicians.
Chief Investigator for the trial, Dr Richard Baird, from the Department of Oncology at the University of Cambridge and consultant oncologist at CUH said: “ We are excited that the PIONEER trial results suggest that adding low-cost megestrol to standard hormone therapy could stop tumour growth and also help with side effects. This result will need to be confirmed in larger trials before becoming a routinely available treatment."
Dr Adrienne Morgan is a breast cancer patient advocate and chair of trustees for the organisation Independent Cancer Patient’s voice. She was involved in trial design as a patient representative on the Trial Steering Committee .
“The PIONEER trial is very good news for breast cancer patients. Not only is megestrol safe and can reduce hot flushes, but it also had an anti-cancer effect."Dr Adrienne Morgan, patient
The idea for the trial originated from lab research led by Professor Jason Carroll, who co-leads the Precision Breast Cancer Institute at the CRUK Cambridge Centre, to understand why breast cancer patients whose tumours express high levels of oestrogen receptor plus progesterone receptor – respond well to treatment.
When breast cancer cells have high levels of the molecule known as oestrogen receptor (ER), it means that the hormone oestrogen fuels the cancer cells to keep growing and dividing. This type of cancer is called ER positive breast cancer.
EP positive breast cancer
About 75% of breast cancer cases are ER positive and patients treated with an anti-oestrogen hormone therapy, such as letrozole, can help prevent the cancer cells responding to oestrogen, thereby slowing tumour growth.
Some breast cancer patients also have high levels of another molecule known as progesterone receptor (PR) and this group of patients also respond better to the anti-oestrogen hormone therapy.
In order to find out why, Professor Carroll’s team at the CRUK Cambridge Institute conducted experiments on cancer cells and discovered that the hormone progesterone stops ER positive cancer cells dividing, by indirectly blocking ER, resulting in slower growth of the tumour. And when mice treated with anti-oestrogen hormone therapy were also given progesterone, the tumours grew even more slowly.
Dr Baird and Professor Carroll went about testing whether the results seen in the lab, published in Nature in 2015, could be replicated in the clinic with breast cancer patients.
Together with Dr Sanjeev Kumar, a clinical PhD student, they devised the PIONEER trial to look at whether giving progesterone to post-menopausal women with early-stage ER positive breast cancer, in addition to standard hormone therapy, effectively slows the growth of their tumour, more than the standard hormone therapy alone. It was a ‘Window of opportunity’ trial which means that patients received the trial treatment in the ‘window’ of time – usually 2–3 weeks – between their diagnosis and surgery to remove their tumour.
With funding from the Anticancer Fund and support from the NIHR Cambridge Biomedical Research Centre, the trial opened in 2017 and continued to recruit during the COVID pandemic, completing recruitment in October 2022.
More than 200 participants completed the trial treatment, including over one hundred patients at Addenbrooke’s Hospital, and many participants from Belfast City Hospital, Ninewells Hospital Dundee, Aberdeen Royal Infirmary and The Royal Cornwall Hospital Truro.
Although this conference presentation is the first time the PIONEER results have been shared with the breast cancer research community, a full paper is being submitted to a peer-reviewed journal and will be published in early 2024.
It is hoped these findings will pave the way for further studies leading to a potential new strategy for improving and personalising treatment for some ER positive breast cancer patients.
The Precision Breast Cancer Institute will move into the Cambridge Cancer Research Hospital when the new specialist hospital for the East of England opens on the Cambridge Biomedical Campus.
The specialist facility will combine clinical expertise from Addenbrooke's Hospital with cutting-edge research from the Cancer Research UK Cambridge Centre and the University of Cambridge. It will change the story of cancer, breaking down barriers between laboratory and clinic, and enabling patients to benefit from the latest innovations in cancer science.