When a woman is diagnosed with metastatic breast cancer, she rarely undergoes a new biopsy, despite the knowledge in the scientific community that most cancers undergo molecular changes over the course of the disease. Treatment decisions are based on the results of the original biopsy of the primary tumor. However, this course of action may now change in light of a recent study published in the Annals of Oncology on March 18, 2009.

The study, performed by a group in Toronto headed by M. J. Clemons, compared biopsies from suspected metastatic tumors with biopsies from the original tumors. They found that in 10 out of 29 cases examined, the metastatic tumor was different from the primary tumor. In an additional 4 cases, the suspected metastatic tumor was actually found to be benign. The results of the new biopsies caused 6 out of the 29 patients (20%) to change their course of treatment.

The study examined changes in estrogen receptor (ER) status, progesterone receptor (PgR) status, and Her2 expression. In all cases in which a change was observed, it resulted in either a loss of ER or PgR or a gain of Her2. A loss of ER or PgR was observed in 10 out of 25 cases (40%); a gain of Her2 was observed in 2 cases (8%). To ensure that the discrepancies in the biopsy findings were not due to errors stemming from variability among the laboratories where the biopsies were analyzed or the scientists performing the biopsy analysis, in each case tissues from the primary tumors were reexamined at the same time as tissues from the suspected metastatic tumor by the same scientist (who was blinded to the identities of the tumors).

Those patients for whom the biopsy showed the suspected metastases to be benign were clearly able to completely alter their course of treatment, since their prognosis had changed dramatically. Those patients whose tumors exhibited a gain of Her2 were able to qualify for treatment with Herceptin, a molecular targeted therapy that is available only for patients with Her2-positive tumors.

The causes of the molecular tumor changes are unknown. The authors hypothesize that hormone treatment, which selectively kills ER- and PgR-positive cancer cells, could allow rare ER- or PgR-negative cells to survive and eventually grow into a new tumor. Additional molecular changes could also account for the loss of ER or PgR or the gain of Her2.

The authors also note that physicians often do not recommend a new biopsy in the treatment of metastatic cancer because they do not believe that the information gained is worth the potential anxiety and discomfort for the patient. However, the data reported in this study suggest that the amount of discomfort is low and that the information gained is worth the inconvenience and extra expense.

In light of the results of this study, repeat biopsies of suspected metastatic breast cancer lesions are likely to become more common or even standard. Furthermore, the frequency of molecular changes observed in these tumors warrants the retesting of tumors prior to enrollment in clinical trials for molecular targeted drugs to verify that the targets are still present.

Reference:
Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, Clemons MJ. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol. 2009 Mar 18. [Epub ahead of print]. PMID: 19299408. Abstract.