Recommendations for screening mammography have been a heated topic of debate among clinicians, scientists and patient advocates since the US Preventive Services Taskforce revised its breast cancer screening guidelines in 2009 and updated them in 2015. With US screening guidelines currently ranging from annually starting at age 40 (endorsed by many clinicians, advocacy groups and BCRF) to annually starting at age 45 (American Cancer Society) and biannually starting at age 50 (USPSF guidelines), it may be difficult for a woman or her physician to know what is best.
Part of the debate centers on the risk vs. benefit of screening before age 50, particularly as it concerns over-treatment of pre-malignant breast lesions called DCIS, non-invasive lesions frequently detected by mammography. It is widely acknowledged that most DCIS will not progress to invasive cancer, but there is no way to know which will, and which will not. Currently most women with DCIS are treated with both local therapy (surgery and possibly radiation) and systemic therapy (chemo or endocrine therapies), just as invasive cancer is.
Using the MammaPrint 70-gene panel assay, Drs. Laura Esserman and Laura van ‘t Veer identified in preliminary research that some women with early stage breast cancer have what they called an “ultra-low” risk of their disease recurring after treatment. Based on these findings, the UCSF group has initiated a trial that they hope will identify markers of risk in women with DCIS that will provide new information for the development of a more personalized approach to the clinical management of DCIS.
Dr. Kornelia Polyak described work in her lab that showed a change in the immune microenvironment in the breast as DCIS progressed to invasive breast cancer. Her studies showed that the presence of T-cells, specialize cancer killing cells, decreased as the cancer progressed. This marked disappearance of T-cells could also be used as a marker of risk for invasive disease or to alert the physician that aggressive therapy is warranted.
Another part of the screening debate is that delaying or increasing intervals of breast cancer screening (from every year to every other year, for instance) will put some women at risk. Current risk assessment models that guide the decisions of when and how often a woman should be screened are imprecise and don’t often leverage new information on genetic risk factors that is emerging. For many women, biannual breast cancer screening starting at age 50 is appropriate and sufficient, but for others, it will be too little, too late.
Just as precision medicine is built on the precept of treating disease in the context of the individual, rather than a one-size-fits-all approach, it is becoming increasingly obvious that screening guidelines should also be based on individual risk. Identifying the women in each group is the basis of risk-adjusted screening.
Identifying biological and genetic markers of risk in the general population is difficult in an otherwise healthy population, but efforts are ongoing to tackle some of these challenges.
New information on validated genetic variants of risk are beginning to be incorporated into some screening models, but these are still in the research phase and not used in the general population. Dr. Jack Cuzick recently convened a meeting co-sponsored by BCRF and the American Cancer Society to address the challenges of risk adjusted and precision breast cancer screening. The meeting included BCFRF investigators Mark Robson and Mary Beth Terry as well as screening and prevention experts from US and Europe.
Other screening and prevention experts funded by BCRF include: Wendie Berg, Ira Bleiweiss, and Hedvig Hricak. Contributions to this area of research also come from experts in hereditary breast cancer discussed here.