Breast cancer polygenic risk score predicts invasive disease development, study shows

A polygenetic risk score can predict which women with preinvasive breast cancer lesions will go onto develop further breast disease, potentially guiding clinical decisions, a UK-led study finds.

It was important to identify which women with ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) were at high risk of further breast disease to personalise treatment, researchers wrote in the journal Cancer Epidemiology, Biomarkers & Prevention.

Using data from more than 2,000 women diagnosed with DCIS (n=2,169) or LCIS (n=185), researchers led by King’s College London, UK, examined whether the 313-SNP breast cancer polygenic risk score (PRS₃₁₃) could predict the likelihood of patients going onto develop ipsilateral or contralateral breast cancer.

Most cases analysed in the study were women aged 50 years and older at diagnosis who were postmenopausal and followed up for a median of 11 years.

Of the DCIS cases where the grade was available, 63% were high grade and 78% were oestrogen-receptor positive.

In addition, 65% of DCIS cases had breast conserving surgery, 33% had a mastectomy, and 34% received radiotherapy following breast conserving surgery.

In contrast, LCIS cases generally did not undergo mastectomy or radiotherapy, the researchers noted, adding that while oestrogen receptor status was generally not assessed, studies have shown the majority were oestrogen-receptor positive.

Value of polygenic risk scores in clinical practice

Cox regression analysis demonstrated a significant association between increasing continuous PRS₃₁₃ and the risk of contralateral disease following DCIS (HR: 1.30) and a link between PRS₃₁₃ and ipsilateral disease after LCIS (HR = 2.16).

‘We have shown for the first time that PRS₃₁₃ is associated with outcomes following in situ breast cancer,’ the researchers concluded.

‘In clinical practice, PRS₃₁₃ could be valuable in identifying patients at higher risk for second primaries in either breast following in situ disease.’

Higher risk individuals might benefit from risk-reduction therapies such as tamoxifen or an aromatase inhibitor, as most lesions express oestrogen receptors, they added, noting that PRS₃₁₃ could also help determine the optimal duration for annual surveillance.

Currently women in the UK with DCIS are recommended to undergo yearly mammograms for five years after diagnosis, after which women older than 50 years are typically transitioned to mammograms every three years.

‘However, our data show that only about 40% of contralateral disease occurrences happen within the first five years after primary in situ disease,’ the researchers wrote.

‘Consequently, individuals in the highest PRS₃₁₃ quartile may benefit from extended annual screening to 10 years.’

Avoiding unnecessary invasive treatments

Senior author Professor Elinor Sawyer, consultant clinical oncologist at Guy's and St Thomas’ NHS Foundation Trust and King’s College London, noted that until now treatment decisions had mostly been based on how cells appeared under a microscope.

‘Our research shows that a genetic risk score can also help predict which women are more likely to develop invasive breast cancer,’ she said.

‘By looking at the full picture, we can give women more accurate information about their personal risk of recurrence. This helps them make more informed choices about their treatment options and what’s right for them.’

Study first author Jasmine Timbres, clinical information analyst at King’s College London, UK, said predicting who was most likely to develop invasive breast cancer using PRS₃₁₃ was vital to offering the best possible treatment options for women, as not all with DCIS or LCIS would go onto develop invasive cancer.

‘The results of this study show that the genetic risk score could be useful in this prediction, meaning that treatments could be more personalised, rather than giving everyone the same treatment approach,’ she said.

‘In some cases, this could avoid unnecessary invasive treatments altogether, which can take a toll on patients both physically and emotionally. Focusing more on individual risk could improve overall wellbeing and help reduce the stress that comes with being overtreated.’