Irish research on breast cancer

Women who take vitamin D after being diagnosed with breast cancer may have an increased chance of survival, new research supported by the Irish Cancer Society has shown.

Researchers from the Irish Cancer Society cancer research centre BREAST-PREDICT analysed data from almost 5,500 breast cancer patients and found that taking vitamin D supplements after diagnosis was associated with an increased relative survival of 20 per cent compared to those who did not.

For the research, recently published in the journal Breast Cancer Research and Treatment, anonymised data on the pharmacy claims of women with a record of invasive breast cancer aged 50-80 years between 2000 and 2011 (n = 5417) was provided by the National Cancer Registry of Ireland.

Initiation of de novo vitamin D post-diagnosis was identified from linked national prescription data (n = 2581, 49 per cent). Multivariate Cox proportional hazards models were used to estimate adjusted HRs (95 per cent CIs) for breast cancer-specific mortality.

There was a 20 per cent reduction in breast cancer-specific mortality in de novo vitamin D users (modelled as a time-varying variable) compared to non-users (HR 0.80; 95 per cent CI 0.64–0.99, p = 0.048) and the reduction was greater at 49 per cent (HR 0.51; 95 per cent CI 0.34–0.74, p < 0.001), if vitamin D was initiated soon after the breast cancer diagnosis (within six months).

Vitamin D, therefore, has the potential as a non-toxic and inexpensive agent to improve survival in breast cancer patients, the study authors concluded, adding there is a need for RCTs exploring the effect of vitamin D supplementation on breast cancer survival.

This research was led by RCSI researcher Dr Jamie Madden, under the supervision of Prof Kathleen Bennett, Associate Professor in Pharmacoepidemiology at RCSI Dublin.

“Previous studies have found that higher blood levels of vitamin D, which can come from our diet, sunlight or supplements, is associated with increased breast cancer survival. Our study suggests that vitamin D supplementation might be useful for women diagnosed with breast cancer. Large clinical trials are already underway overseas to look into this further,” Prof Bennett said.

While the findings are significant, the researchers did not have access to information on other measures from the women that could possibly impact their likelihood of better outcome. For example, increasingly studies are showing that moderate physical activity and maintaining a healthy diet can benefit a patient undergoing cancer treatment but this was not collected in this study.

The research also found vitamin D users to be younger on average, be less likely to smoke and have lower tumour stage and tumour grade progression compared to non-users, all factors more likely to be associated with better survival.

Dr O’Connor added: “Before rushing out to buy vitamin D supplements, we urge women with breast cancer to first talk to their medical team. Vitamin D use can cause health issues and each woman’s cancer is unique and will require personalised treatment.

“While this is an important preliminary study, the findings only shows an association, and not causal link. We will only know if vitamin D supplementation should be recommended to improve breast cancer treatment outcome in the coming years when the results of clinical trials emerge.”

A separate study carried out by BREAST-PREDICT researchers is focusing on the development of a personalised therapeutic strategy for HER2-positive breast cancer patients with ERBB gene mutations.

At least one-in-five HER2-positive breast cancer patients have cancers that are resistant or become resistant to the latest targeted therapies.

This study used tumour samples from 227 Irish HER2-positive breast cancer patients and found that 7 per cent of patients had mutations in these genes. Mutations were most common in the ERBB4 gene. The researchers then tested cell lines with and without these mutations with different anti-cancer drugs to see if the mutations would make the cells grow more aggressively or make them less likely to respond to the drugs.

One of the mutations that was tested (ERBB4-V721I) made the cells grow more aggressively. Cells with this mutation were less likely to respond to afatinib, an EGFR tyrosine kinase inhibitor, which targets the ERBB family. However, the cells were more likely to respond to the newer phosphoinositide 3-kinase (PI3K) inhibitor copanlisib.

According to study co-author Dr Sinead Toomey, “Although our findings need to be confirmed in a larger study, it is possible that these mutations may be able to tell us which patients will respond or not respond to certain therapies, and ultimately we hope to be able to use this information to personalise treatment so as to increase the percentage of women with HER2-positive breast cancer who we are able to treat effectively.”

Commenting on BREAST-PREDICT’s work to date, Head of Research at the Irish Cancer Society, Dr Robert O’Connor, said: “Since the Irish Cancer Society established BREAST-PREDICT five years ago, we’ve funded the work of over 50 breast cancer researchers across the country. That’s meant a €7.5 million investment that’s only been possible through the public’s generous donations.

Cancer Trials Ireland is currently involved in a number of breast cancer trials, at various stages of initiation and completion. See tinted panel below for information on its trials that are investigating overcoming HER2-therapy resistance in breast cancer.