New research has found that a rare form of triple-negative breast cancer has a generally favourable long-term prognosis and may not require the same treatment approach as more common triple-negative breast cancers.
The study, led by scientists at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, characterised the features, treatment patterns and long-term outcomes of adenoid cystic carcinoma (ACC) of the breast by analysing patient data over a 20-year period. The research provides detailed long-term outcome data for an exceptionally rare form of breast cancer, for which evidence to guide treatment decisions and opportunities to conduct clinical trials are limited.
The study, published in the journal Oncology Research, was supported by NHS funding to the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR) – which is both a research institute and a charity.
A distinct type of triple-negative breast cancer
Breast ACC is extremely rare, accounting for fewer than one in every 1,000 breast cancer cases. Breast ACC is usually classified as triple-negative because the tumour cells lack oestrogen and progesterone receptors and HER2 expression. More common forms of triple-negative breast cancer are often associated with aggressive disease and higher risk of recurrence. However, despite sharing the triple-negative classification, breast ACC behaves very differently. This distinction is important as applying standard TNBC treatment approaches to ACC could potentially result in overtreatment – which has a number of implications for patients.
To better understand breast ACC, the researchers analysed clinical, pathological and long-term outcome data from 24 patients diagnosed with breast ACC between 2000 and 2020 at The Royal Marsden.
All patients had TNBC, but despite this, outcomes were generally favourable. Only two patients in the study had cancer detected in their lymph nodes, while chemotherapy was used in just two patients specifically for their breast ACC, with most patients treated with surgery and radiotherapy. The estimated five-year and 10-year disease-specific survival was 93.3 per cent, with only two patients passing away from breast ACC during the study period.
Reassuring findings with an important caveat
Although the overall outlook was favourable, five patients experienced a relapse. Importantly, recurrence was not always confined to the first few years after diagnosis. Two patients experienced a relapse more than a decade after their initial diagnosis, one after more than 11 years and another after 14 years.
The findings suggest that patients with breast ACC can generally be reassured by the long-term outlook associated with the disease. At the same time, the occurrence of late relapses highlights that longer-term follow-up may be appropriate.
The researchers also observed that relapses appeared more frequent among patients with a rare subtype of breast ACC, known as solid-basaloid ACC, compared with classic ACC. However, the numbers were small and studies with larger cohorts are required to confirm this finding.
There is an important opportunity to integrate clinical outcomes with molecular profiling. Understanding the molecular biology underlying the behaviour of breast ACC compared with more common forms of TNBC could help refine risk stratification and potentially identify therapeutic opportunities for the small number of patients who develop advanced disease.
Challenging assumptions
The study reinforces the importance of recognising breast ACC as a distinct disease rather than treating it in the same way as more common forms of TNBC. It also suggests that treatment decisions should be guided not only by whether a tumour is triple-negative, but also by its underlying clinical pathology and behaviour.
Lead author Dr Iseult Browne, Post-CCT Clinical Research Fellow at The Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden Hospital, in collaboration with The Toby Robins Breast Cancer Now Research Centre at the ICR, said: “Breast ACC is exceptionally rare, which makes conducting the large prospective clinical trials that guide management of more common breast cancers extremely challenging. Carefully characterised datasets with long-term follow-up are therefore particularly valuable. By studying patients treated at The Royal Marsden over a 20-year period, we were able to provide detailed long-term outcome data for a disease where evidence to guide treatment remains limited.
“We hope our findings will contribute to a better understanding of this rare form of breast cancer and help clinicians make more informed and personalised treatment decisions for patients.”
