Those of us living with metastatic breast cancer know that testing has now become an unpleasant routine. Finding out how the cancer is responding to treatment and which therapy options we have depends on continuous surveillance. Some tests tell us whether our tumor pathology has changed and point to alternative treatments, while other tests determine how our tumors are responding to therapy, whether they are stable, shrank, grew or disappeared. Test results are not always clear, however, because while some tumors have grown, others have gone away, which sends a mixed message.
A recent workshop given by Dr. Ruth Oratz at Living Beyond Breast Cancer's annual conference for those living with metastatic breast cancer offered information on how oncologists use tests to determine the best course of action to treat metastatic breast cancer. Dr. Oratz is a clinical professor and firm chief of the Department of Medicine at NYU Langone Medical Center in New York City.
In this workshop, Dr. Oratz discussed genetic and genomic testing and clinical, pathological, and radiographic staging. She also spoke briefly about how our environment affects our bodies, from the food we eat to the air we breathe and the medicines we take as children and adults. The animals or plants we eat, she said, have been exposed to fertilizers, pesticides and antibiotics, which affect our health and our body's ability to fight off disease.
Genetics and Genomics
Genetic testing involves testing our genes for mutations, while genomic testing refers to testing breast cancer tumors for mutations, as Dr. Oratz explained.
Genetics is the study of genes, which we inherit from both of our parents—half from our mother and half from our father. Our genes determine our genotype and influence our phenotype, or our gene expression, Dr. Oratz said. Our phenotype accounts for whether we have red hair or brown eyes. Malignant cells also express a phenotype, such as whether they are ductal or lobular in nature.
Genetic testing tells us about the status of our BRCA 1 and 2 genes, which repair DNA. These genes normally help to protect us from getting breast cancer, but when mutated they lose the repair function, which increases exponentially our chances of developing cancer and allows it to grow unchecked. These mutations are passed down in families through both our father's and mother's lineages. BRCA mutations account for 5%-10% of breast cancers.
Genomic assays (tests) that are not involved in a research effort are relatively new in treating metastatic breast cancer. Dr. Oratz noted that certain labs do genomic tests but large cancer hospitals do their own testing. In any case, she said it's important to know what we intend to do with the genomic information that we obtain from a test.
For example, an oncologist may order a genomic test to look for potential treatment options when progression occurs after several lines of therapy. The test may discover DNA mutations in a signaling pathway that scientists understand, and a targeted drug or clinical trial may be available. One of Dr. Oratz's patients had a mutation common in lung cancer, and the patient was able to take a drug which targeted that mutation and delayed progression.
Genomic testing requires a fair amount of tumor tissue, and sometimes a metastatic tumor is difficult to biopsy if it is situated in a spot that is hard to reach or in the bones. Dr. Oratz said that patient comfort and safety are paramount, and bone biopsies "hurt." Further, the chemical used to decalcify a bone biopsy for processing often disturbs the tumor cells, such that the test result may not be entirely accurate. In addition, she noted that systemic treatments could affect our biopsy results because they alter our cancer.
Biopsies can tell us whether our pathology has changed from our early stage diagnosis of breast cancer or whether our metastatic status has altered, she said. They tell us the molecular subtype of our breast cancer, which is the hormone receptor and HER2 status of the cancer cells. This information affects our treatment options. Biopsies include a fine needle aspiration, core biopsy or surgery.
In regard to liquid biopsies, which measure the circulating tumor cells (CTCs) or cell-free DNA (cfDNA) in our blood, Dr. Oratz noted that enthusiasm was initially high because the test would allow patients to skip an invasive biopsy such as a core biopsy or surgery. Scientists know that cancer cells circulate in the blood and were banking on a correlation between the number of cells circulating and the extent of disease present. But the tests are not reliable, she said. Sampling error may be part of the problem because our blood is always circulating and it is not clear whether the sample is truly representative of the cancer at the time of the test. Unfortunately the technique is not currently reliable enough to follow a patient's response to treatment, in Dr. Oratz's view.
Metastatic breast cancer staging
Staging is important for following the course of cancer and includes clinical, pathological and radiographic procedures. In general, Dr. Oratz does not find the concept of breast cancer staging very useful because stage IV cancers are not all alike. The tumor's biology and its interaction with the microenvironment surrounding our cancer cells are much more important in understanding the "natural history of metastatic breast cancer," she said.
Clinical staging involves taking a history, such as noting whether we have a lump on our neck, a persistent pain or cough, or frequent indigestion, among other symptoms. Such symptoms can give our oncologist a heads-up about whether he or she should look further into their source.
Blood work such as a complete blood count (CBC), complete metabolic panel (CMP), serum (tumor) markers, and biopsies help oncologists determine the pathological status of our cancer. However, tumor markers do not work for everyone, Dr. Oratz pointed out. Sometimes a tumor marker rises but a scan does not show any lesions, or metastatic lesions are visible on a scan but the markers are not out of normal range. Such tests for breast cancer include CEA, CA 15-3, CA 27-29 and CA 125.
An immunohistochemistry (IHC) blood test lets us know the molecular subtype of our cancer, or its hormone receptor and HER2 status. In the case of the HER protein, if a score is not 3+ but rather 2+, the test is inconclusive and the tissue would be tested further by a florescence in situ hybridization (FISH) test. The FISH test counts the number of genes within the cell that code for the protein on the surface. The slides Dr. Oratz presented showed that when the tumor tissue sample is stained for a FISH test, the normal cells glow green and the abnormal cells glow pink under a microscope. If the ratio is greater than 2:1 in favor of pink, then the number of copies would be sufficient to show amplification and the sample is therefore HER2 positive.
Guidelines on using scans to monitor patients with metastatic breast cancer are hard to write, according to Dr. Oratz, because an oncologist's decision on radiographic staging often depends on the symptoms presented, as well as on the molecular subtype of the cancer. Tumor cells that are very estrogen positive and HER2 negative have a strong tendency to move to the bone marrow, while HER2 positive cells gravitate toward the central nervous system and the brain. This information helps an oncologist know which sites of the body need additional attention.
Following up on a complaint of persistent bone pain involves x-rays and scans. If a patient has early stage breast cancer and presents with pain, Dr. Oratz will begin with an x-ray. If the plain film does not show a lesion, she will then use a bone scan, which is a very sensitive roadmap of the whole skeleton. A bone scan is also a tool that can be repeated to find out how a patient being treated for metastatic breast cancer is responding to treatment.
Radiographic tests such as a computed tomography (CT) scan, magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT provide more detail than a bone scan. Those scans can be used with or without intravenous contrast, but contrast provides a better image, Dr. Oratz said. Which scan an oncologist chooses often depends on which part of the body to be scanned. She noted that an MRI is good for scanning the brain and spine, while a CT scan is better for imaging the lungs and liver.
A PET/CT is a fused image, in which the anatomic roadmap of the CT scan and the uptake of contrast from the PET scan improve interpretation. PET contrast is a nuclear isotope that malignant cells preferentially take up or absorb in the organs and bones, which allows radiologists to measure metabolic activity. Cancer cells are more metabolically active than benign cells, and the more the cells take up the contrast and "light up" the more likely they are cancerous, Dr. Oratz explained. The standard uptake value, or SUV, can be measured and provides information about the presence of malignant cells. An SUV of 3 and above raises a red flag about a potential malignancy. Dr. Oratz noted that the uptake of the contrast medium can vary from scan to scan and is therefore indicative of how well we are responding to treatment.
Joan is a helpline volunteer, member of SHARE Leaders, and a consumer reviewer at the Department of Defense Breast Cancer Research Program. She also facilitates SHARE's metastatic breast cancer support group, Living with Uncertainty.