Breast cancer may begin in the breast as the name implies, but as it progresses, it can spread its damage to other parts of the body and establish new strongholds in other organs. Breastcancer.org reports that “cancer cells can break away from the original tumor in the breast and travel to other parts of the body through the bloodstream or the lymphatic system, which is a large network of nodes and vessels that works to remove bacteria, viruses, and cellular waste products.” When this happens, the disease has reached stage 4 and is called metastatic breast cancer.
For many patients in the past, being diagnosed with metastatic breast cancer meant they had very little time left. But lately, survival rates have improved. According to a study in Cancer Epidemiology, Biomarkers & Prevention in May 2017, the five-year relative survival rate for patients with metastatic breast cancer doubled between 1992 to 1994 and 2005 to 2012, rising from 18 percent to 36 percent. Survival rates were highest among women diagnosed at younger ages. That same study also found that more than 11 percent of women who were diagnosed between the years 2000 and 2004 and were younger than 64 years old survived 10 years or more.
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Doctors attribute these improved survival rates largely to new treatments and approaches to managing metastatic disease. Although treatment approaches to late-stage breast cancer still fall into the three general categories of chemotherapy, radiation therapy and surgery, their application is often different than in earlier stages. For example, for some early stage breast cancer patients, surgery may be the first order of business, but that may not be an option with stage 4 breast cancer. “If a woman has metastatic breast cancer, surgery can be used to remove metastatic tumors — for example, a metastatic liver lesion that is hormone-receptor positive and has responded to chemotherapy before surgery and did not grow in the time between the metastatic diagnosis and the surgery,” says Dr. Constance Chen, clinical assistant professor of surgery (plastic surgery) at Weill Cornell Medical College in New York and a board-certified plastic surgeon with special expertise in breast reconstruction related to breast cancer. “In general, however, surgery to remove metastatic breast cancer is not common, and it would be done on a case-by-case basis.”
Drug Therapies
Because metastatic breast cancer is a systemic disease, drug therapies are typically the first choice in controlling the disease. But there aren’t as many drugs available to treat later stage disease as there are for earlier stage disease and the focus of these treatments shifts from cure to management.
“The fundamental issue is that once the patient has been diagnosed with metastatic breast cancer, they’re out of the curable range, so physicians are trying to choose therapies that will improve survival of those patients but also strike the right balance between side effects, quality of life, etc.,” says Dr. Levi Garraway, senior vice president of global development and medical affairs with Lilly Oncology. Although stage 4 is not usually curable, it is treatable, and some newer drugs, such as Eli Lilly’s new drug Verzenio (abemaciclib), have been shown to help some patients live longer. Garraway says Verzenio can be used alone in certain patients but is usually administered with a chemotherapy drug called Faslodex (fluvestrant). These two drugs work in combination to disrupt the pathway by which estrogen-receptor positive breast cancers signal themselves to divide and grow. (About two-thirds of all breast cancers are ER-positive, and it’s the most common form of metastatic breast cancer.)
“It turns out there can be a lot of sophisticated cellular machinery that decides which exact proteins are used to cause a different cell to divide, and Verzenio targets a particular mechanism that we know to be relevant,” Garraway says. Unlike some drugs that block the estrogen receptors on the cancer cells, this form of targeted therapy uses a different mechanism to stop or slow the growth of cancer cells and can be used to manage the disease. “The median time that women were on this combination and were able to have the disease stay under control is 17 months,” Garraway says. For some patients with metastatic disease, that year and a half is considered a long time to keep the disease at bay.
However, Garraway notes that “not all breast cancers are created equally. There are different subtypes of breast cancer that will require different types of treatment. And even within the subtypes, the clinical behavior of the cancer [how quickly it progresses] can vary widely.” Some metastatic breast cancer patients have forms of cancer that grow slowly, and these patients may have “years of very decent quality of life ahead, whereas others, when they’re diagnosed, are already quite far along and their cancers grow very rapidly.” This variability and the difficulty in predicting how a particular cancer is going to progress makes managing the disease challenging.
[See: Breast Pain? Stop Worrying About Cancer.]
Liquid Biopsy
One potential solution to this prognosis problem could come in the form of a simple blood test, according to a recent study conducted by Dr. Daniel Stover, a breast medical oncologist, translational scientist and member of the Translational Therapeutics Program at the Ohio State University Comprehensive Cancer Center. In the study, Stover and his team analyzed blood samples from 164 women with metastatic triple-negative breast cancer. TNBC is a particularly aggressive form of breast cancer that’s not fed by hormones and has “the poorest prognosis” of the various types of breast cancer, Stover says.
“Historically, we’ve analyzed tumor genomes by getting a piece of tissue,” as would be collected during a surgical biopsy. This tissue is then carefully analyzed, and that information is used to develop a diagnosis, prognosis and treatment protocol. But “for patients with metastatic breast cancer, often [the biopsy site] is in difficult-to-reach or potentially dangerous places, such as a spot on the liver or the lungs.” But if the physician could use a blood test, also called a liquid biopsy, to get this information instead, that would make things easier. But how can you see a solid tumor in a blood sample?
“There’s growing evidence that normal cells and tumor cells shed DNA” into the bloodstream, Stover says. These microscopic bits of tumor cells are genetically different from other types of cells in the body. By looking for certain genetic markers in DNA extracted from patients with metastatic triple negative breast cancer, Stover says doctors may soon be able to easily derive a lot more information about how a patient is doing, which could lead to better tracking of the disease as it progresses and the application of more targeted treatment options.
Although this current test has only been tried on metastatic patients with triple negative breast cancer, Stover says work continues to expand our knowledge and the potential application of this sort of approach to other cancers and disease stages. “The progress that’s been made in liquid biopsy in just five years has been remarkable. It feels like every month, there’s a new advance or approach or application and I think that speed is really a positive thing because we’re working on getting tests to patients quicker.”
Radiation Advances
Although drug therapies are usually top-of-mind in discussions of managing metastatic breast cancer, new applications of radiation therapy could also provide relief in some cases. “The traditional role of radiation in metastatic disease has been palliation,” or to lessen the symptoms of the disease rather than to cure it outright, says Dr. Reshma Jagsi, professor and deputy chair in the department of radiation oncology at Michigan Medicine. “It’s very important to deal with symptoms — we should never understate the importance of doing that. It’s the bedrock of our contribution [to treating cancer] to date. But more recently, there’s been quite a bit of interest in harnessing radiation therapy to either prolong life or potentially even cure” metastatic breast cancer in some patients through the use of two new approaches, she says.
[See: 7 Innovations in Cancer Therapy.]
The first of these radiation therapies is used “in the setting of oligometastatic disease, where there’s only a few metastases,” or distant cancer tumors. She says a randomized clinical trial is currently investigating whether radiation treatments can ablate, or kill off, these metastases where they are.
“The other area that’s very exciting is combining radiation therapy with immunotherapies,” such as immune checkpoint inhibitor drugs, she says. This approach capitalizes on an observed reaction some patients have had to radiation in the past. “On occasion, we see an abscopal effect — where radiation applied to one spot leads to regression at other spots. We always thought that had to do with the immune system, but only in recent years have scholars begun to elucidate those pathways,” by which one tumor’s radiation treatment causes another tumor somewhere else in the body to shrink. She says researchers are now trying to “prime that immune response. So by causing damage [with radiation], we may actually be able to turn on certain signaling pathways that actually turn the tumor into an in-situ vaccine.” In other words, the radiation and drug combo can trigger the body to treat the tumor as an invader and kill it with its own defense mechanisms.
It’s believed that when we know a little more about how these processes work and which doses, frequencies and combinations best stoke this immune response, that could turn radiation — which has until now largely been a pinpointed form of therapy — into a more systemic treatment.
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The Future of Treatment for Metastatic Breast Cancer originally appeared on usnews.com
