By Richard C. Frank, MD
Breast cancer begins in the breast, where it can be detected by imaging tests, such as mammography and MRI or when a lump is felt by the affected woman or her physician. The cancerous tumor in the breast is referred to as the primary tumor.
Metastatic breast cancer is diagnosed when breast cancer spreads to distant sites in the body, most commonly the bones, liver, lungs or brain. The cancerous tumors in distant locations are referred to as metastatic tumors (or metastases). Metastatic breast cancer can occur at the same time that the primary cancer is detected in a small percentage of cases; most commonly, it occurs years after the primary cancer has been treated.
Traditionally, oncologists have not always performed a biopsy of metastatic tumors because it has been assumed that their treatment can be based on the properties of the primary tumor. But new research, that I discuss below, suggests that performing such a biopsy may be a good idea.
The main properties of a breast cancer that determine how it will be treated include the presence or absence of the estrogen receptor (ER) and Her2 protein. If a primary breast cancer contains the ER, it is assumed that the metastatic tumors also contain the ER and should respond to drugs that block the ER, such as tamoxifen, letrozole (Femara) and fulvestrant (Faslodex). Similarly, if the primary is Her2 positive, it is assumed that the metastases are also Her2 positive and will respond to anti-Her2 therapies, such as trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb) and T-DM1 (pending FDA approval).
But what if the properties of a breast cancer primary and its metastases are not the same?
For example, what if the primary cancer was ER positive but the metastases were ER negative? In such a situation, hormone therapies, such as those listed above, would not be expected to work very well to control the cancer. The same could be said for Her2 directed therapies: if the primary is Her2 positive but the metastases are not, then administering anti-Her2 therapies might not be worth it. The term used to describe a different pattern of ER and Her2 between primary and metastatic tumors is “discordance.”
Reports last year in the Journal of Clinical Oncology estimate that discordance occurs in approximately 25% of cases of metastatic breast cancer. The most common finding was loss of the ER or Her2 proteins by the metastases. This means that although some patients may have been treated with hormonal and/or anti-Her2 therapies after their breast cancer was removed, as adjuvant therapy, the same therapies would not be effective in treating discordant metastatic disease. On the other hand, it is much less common for metastases to acquire the ER or Her2 proteins when the corresponding primary did not contain them. The MD Anderson Cancer Center found that women whose metastatic cancer was discordant for Her2 (the primary contained it, but the metastases did not) lived for a shorter period of time than those in whom Her2 expression was maintained. Overall, performing a biopsy on a metastasis resulted in a change in therapy in 14% of the affected women.
According to Dr. Richard Zelkowitz, a breast cancer oncologist at Norwalk Hospital,
“We always try to perform a biopsy when a woman is diagnosed with metastatic breast cancer. First, we want to prove it’s cancer and second, we want to make sure that we target our treatments appropriately. But sometimes the location makes it too difficult to obtain a biopsy. And if a biopsy is performed on a bone metastasis, then testing for ER and Her2 is more technically challenging. It is not always so straightforward.
Cancer can grow in strange and unpredictable ways. When deciding on how best to treat metastatic breast cancer, performing a biopsy on a metastatic tumor is now recommended by most breast cancer specialists.