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Phyllodes tumors are unusual tumors that begin their growth in the connective tissue of the breast. These tumors occur most often in females who are 30 to 40 years of age, although they might be found in women who are older or younger. This form of tumor accounts for less than 1% of all breast tumors.
In about 10% of cases, these tumors can be cancerous. There is also an approximate 25% chance that phyllodes tumors of the breast, when cancerous, will be metastatic. In these instances, a patient essentially has a fatal diagnosis. Long-term survival is rare, and the growth of this tumor cannot always be predicted.
A 2014 study from University of Michigan scientists at the university’s Comprehensive Cancer Center analyzed the genetics of phyllodes tumors. The research was among the first to characterize the molecular state of these tumors. Next generation sequencing (NGS) was applied by investigators to facilitate the identification of any gene alterations that may have occurred.
These unusual fibroepithelial tumors do not exhibit specific, predictable behavior – in fact, researchers have little information on how they begin growth and progress. Many are not cancerous, but can become cancerous over time. It is difficult to determine the type of tumor that may spread or reoccur after an initial treatment has been administered. Moreover, the success of treatment is rare once these tumors have become cancerous.
The University of Michigan effort highlights the genomics involved, and, the role of genomic evolution in how these tumors grow and proceed. The study suggests there are potential molecular correlates to histological grade. The study also led to the expansion of the number of human tumors with frequent recurrent MED12 mutations identified. It also identified the insulin-like growth factor 1 receptor and the epidermal growth factor receptor as possible therapeutic targets in cancerous cases.
In the University of Michigan study, scientists examined 15 phyllodes tumors specimens, pulled from archived samples, which had been equally divided based on their categorization. Five tumors were benign, five were borderline, and five were cancerous. Even such a small sampling allows scientists to obtain genetic biological information.
NGS was applied to find cellular changes in formalin fixed paraffin embedded samples from the patients. The scientists found mutations across more than two-thirds of cases involving the three histological grades. Additionally, certain loss-of-function and deleterious mutations appeared exclusively in cancerous tumors. Therapies have already been developed and tested in other cancers. Data from this research support evaluating the efficacy of treatments that have been developed against the epidermal growth factor receptor and insulin-like growth factor 1 receptor proteins in phyllodes tumors.
Meanwhile, in the UK, a study is underway in which investigators are gathering tumor and blood specimens from those who have a phyllodes tumor. These specimens will help the scientists:
The trial has recruited about 500 people who have phyllodes tumor in the breast. The researchers are asking some to have an operation to remove their tumor. They also are writing to those who have had treatments in the past, asking them to partake in the study.
Investigators are looking for DNA, RNA, and information regarding any genetic changes that might be present. They plan on growing tumor cells in the laboratory from the participants to examine cellular behavior.
In one unusual instance, a phyllodes tumor of the breast converted to fibrosarcoma of the breast, which are tumors that may reoccur after they are surgically removed. Unusually, they may become a breast fibrosarcoma.
A woman in her mid-30s was examined a month-and-a-half after a third surgery for recurrent left breast tumors over six years. The histopathological diagnosis revealed fibrosarcoma of the breast, but the histopathological examination of earlier operative specimens favored a phyllodes tumor. Fortunately, a combination of surgery, chemotherapy and radiotherapy brought a successful health outcome. It is possible that such an approach might be a successful treatment regimen even though fibrosarcoma of the breast currently has poor health outcomes.