Are Metastatic Breast Cancer Patients Getting the Right Treatment?

As many as one in seven women with metastatic breast cancer could be receiving the wrong treatment because of a change in the cancer’s biology when it metastasizes, according to new research.

When breast cancer spreads to another part of the body, a HER2-positive cancer could become HER2-negative. Or estrogen receptor-negative cancer could switch to estrogen receptor-positive. Despite different treatment strategies for each, most oncologists rely on what they know about the primary breast tumor to fight the metastasis, says Giuseppe Curigliano, MD, PhD, co-director of the division of medical oncology at the European Institute of Oncology in Milan, Italy. But researchers now believe inhibiting one cancer growth pathway with treatment may activate signaling of a new pathway that allows it to survive and spread.

Although it’s not routine to biopsy metastatic lesions, pathologist Andrea Richardson, MD, PhD, says it has become more of the norm at Brigham and Women’s Hospital in Boston, where she works. “Our oncologists are much more likely to rebiopsy these if it’s not too risky for the patient. But that’s certainly not the case in small community hospitals and not worldwide either,” says Richardson, who also serves as an assistant professor of pathology at Harvard Medical School.

In a study presented this summer at the annual meeting of the American Society of Clinical Oncology, researchers compared biopsy data from 255 women with breast cancer that had spread to the liver after a median time of about three and a half years since the primary diagnosis. The question was, did the cancer’s estrogen, progesterone, and HER2 receptor status—factors that helped determine the correct course of treatment—remain the same? The cancer switched from estrogen receptor-negative to estrogen receptor-positive—or vice versa—in 37 patients (14.5 percent). When changes in HER2 status and progesterone status were also determined, a total of 31 patients (12.1 percent) changed treatment to match the cancer’s new biology.

“When safe and easy to perform, a biopsy of the metastatic lesion should be considered in all patients … since it is likely to impact treatment choice,” says Curigliano, who served as a co-investigator on the study.

You have to compare possibly being one of those people whose treatment would change versus the risk of doing the procedure.

In another study presented at the same meeting, researchers took tissue from 271 patients whose breast cancer had spread to locations such as the lymph node, liver, or skin. A median time of about six and a half years had passed between the primary cancer diagnosis and the metastatic recurrence biopsy. Forty-one women (15.1 percent) switched treatment after the features of the metastatic lesion didn’t match the primary tumor.

Richardson, who provided the analysis of the research after the two studies were presented, says the differences between primary and metastatic tumors may be related to the method used to test the tissue or how much of the tumor was sampled. But she admits the consistency of the discordant results in the studies suggests it’s a true biologic change.

Experts suspect that because tumors are made up of different kinds of cancer cells, a small fraction of cells may have a different receptor status. If those cells are more resistant to cancer therapy, the resistant cells may outgrow the rest over time. At the time of recurrence or progression, the overall tumor will have subsequently appeared to have “switched.”

Identifying the biologic characteristics of a tumor has become particularly important with the expanding number of targeted cancer drugs now on the market. Herceptin (trastuzumab) and Tykerb (lapatinib), for example, only work on breast cancer cells that overexpress the HER2 gene, while tamoxifen and aromatase inhibitors inflict damage only on estrogen-fueled breast cancers.

A couple decades ago, biopsy of a metastatic lesion wouldn’t have changed the choice of treatment, says Richardson. “The results weren’t going to change what you did. Oncologists gave chemotherapy for metastatic disease—period.” But with the current and upcoming generation of targeted drugs for breast cancer, “you kind of need to know what targets the metastatic tumor is now expressing,” she says.

Richardson and Curigliano agree doctors must consider the safety of rebiopsy. Metastatic lesions in the brain, for example, cannot be safely biopsied, and biopsy of the liver may cause hemorrhage. “You have to compare possibly being one of those people whose treatment would change versus the risk of doing the procedure,” Richardson says. “I think for breast cancer, it’s essential to biopsy anything that can be biopsied safely.”