All cancers have one thing in common: They’re an overgrowth of cells that are behaving abnormally because of a genetic change. Genes contain the codes that run how our cells work, and if there’s a mistake in the code, that can lead to problems. In breast cancer specifically, the disease can result from several different genetic alterations, and treating your specific disease effectively requires your doctor to determine which alterations have been involved.
Dr. Jennifer Lehman, a breast surgeon with Lennox Hill Hospital in New York City, says that “when a patient is diagnosed with breast cancer, their breast cancer cells are tested to see what characteristics they express.” Determining this information provides the doctor with critical insight to “how aggressively a cancer grows, what stimulates the cancer and what treatments it will respond to.”
[See: 10 Innovations in Cancer Therapy.]
One of the things the pathologist is looking for is which receptors or proteins are on the surface of the cancer cells. Determining which and how many of these receptors are expressed by the cancer cells will guide your doctor in selecting an appropriate treatment. “The proteins that are routinely checked for are HER-2, estrogen receptors — ER — and progesterone receptors — PR. Cancers are then categorized as being HER-2 positive or negative, ER-positive or negative and PR-positive or negative. If cancers are lacking all three receptors they are then labeled triple negative,” Lehman says.
Estrogen and progesterone are two hormones that regulate the development of female characteristics in the body, and are thus commonly involved in the development of breast cancer. Breastcancer.org reports that roughly 80 percent of breast cancers are ER-positive and about 65 percent of breast cancers are ER- and PR-positive. HER-2, also sometimes called HER-2/neu, refers to human epidermal growth factor receptor 2, a growth hormone that’s integral to the normal development of breast cells that can become overexpressed in breast cancer because of genetic mutations that accumulate over time. Lehman says about one in five breast cancers test positive for HER-2. These categories aren’t mutually exclusive; some tumors can express both HER-2 and ER or PR. About 25 percent of breast cancers do not express any of these receptors and are thus labeled triple negative, Breastcancer.org reports.
In her authoritative tome, “Dr. Susan Love’s Breast Book,” Love, a surgeon, author and breast cancer advocate, explains how HER-2 receptors can influence the growth of breast cancer. “Instead of having only one copy of this [HER-2] gene, the cell makes many — 10 to 60 — copies of the gene. When this happens, the cell has more HER-2/neu receptors than normal, which helps to create more protein and a louder message” for the cells to grow. “This accelerates the growth of any cancer cells in the neighborhood.”
There are several different ways of detecting the presence of HER-2 receptors on your cancer cells. The most common is through immunohistochemistry, a process by which slides of cells collected during a biopsy are stained with antibodies that will bind with and mark the presence of these receptors. Dr. Nimmi Kapoor, breast surgical oncologist at Cedars-Sinai Medical Center in Los Angeles, says these results are graded from zero to +3. “A +3 we would consider positive for that receptor. The zero we consider negative. The +1 and +2 is considered the gray zone,” meaning that some receptors have been detected, but not as many as would be present in a clearly positive +3 grading. This may necessitate further testing to confirm the presence of HER-2, such as fluorescence in-situ hybridization — FISH — testing and dual in-situ hybridization — DISH. Still other types of tests exist to check for the presence of HER-2 “to make sure we’re not missing a potential target for treatment,” Kapoor says.
These days, there are many more options available to patients who’ve been diagnosed with HER-positive breast cancer than there once was, Lehman says. “Cancers that are HER-2 positive may grow more aggressively than some other types of breast cancer. Fortunately, there are incredibly effective unique medications that treat only cancers that overexpress HER-2, and often result in dramatic responses to therapy.”
[See: What Not to Say to a Breast Cancer Patient.]
These treatments include monoclonal antibodies and kinase inhibitors, two types of targeted therapies that block the substances that help cancer cells grow. They are often used in combination with more conventional chemotherapies, hormone therapies, radiation and surgery. “The biology of these tumors is so aggressive that we even treat stage 1 disease with chemotherapy,” Kapoor says. That chemotherapy is often given first and coupled with a targeted monoclonal antibody treatment. A drug called trastuzumab (Herceptin), is often used in this manner. “It’s an antibody to the protein that’s specific to the HER-2 receptor on the cancer cells,” Kapoor explains. “It typically works best when given with chemotherapy and then after the chemotherapy portion is complete, the trastuzumab therapy is given every three weeks for one year.” Other targeted therapies include pertuzumab (Perjeta), lapatinib (Tykerb), neratinib (Nerlynx) and ado-trastuzumab emtansine (Kadcyla, also known as TDM-1).
“In general, we prefer tumors to be estrogen-receptor positive but HER-2 negative, because HER-2-positive tumors are generally thought to be more aggressive,” Kapoor says. “Previously, before we had any targets for HER-2-positive cancer, these were considered just as bad as triple negative tumors. They were aggressive, they were deadly, they were more likely to recur.” However, the development of targeted therapies such as Herceptin means these cancers can be treated more effectively. “There’s still a higher level of recurrence compared to HER-2-negative, estrogen positive breast cancer,” Kapoor says, but the discovery of targeted therapies means prognosis for this type of cancer has improved in recent years.
Giving these drugs prior to surgery could shrink the tumor significantly, resulting in less extensive surgery. “If we can actually downsize the tumors and decrease the number of lymph nodes involved, we can potentially do less surgery if we have a complete response” to systemic therapies like chemotherapy and targeted treatment, Kapoor says. If any ER-positive cancer, for example, is left behind, “that tells you that the tumor is heterogeneous. Sometimes we see that variability, that the HER-2 was treated and killed,” and only ER-positive cancer was left behind, which means the patient will have endocrine therapy next. “That’ll be the next route that’s going to be important to continue this patient’s care. You can learn a lot by doing the treatment up front and then seeing what you have left,” she says. But each patient’s situation will be considered individually. “Which drugs a patient may benefit from, in what combination or sequence and the roles for and timing of surgery and radiation vary on a case-by-case basis,” Lehman says.
[See: A Tour of Mammographic Screenings During Your Life.]
The bottom line is that although HER-positive breast cancers tend to be more aggressive and appear more likely to recur, there are much better treatments available now than there once were, Lehman says “Patients should know that while having HER-2 positive breast cancer has been traditionally considered a worse prognostic factor, we now frequently see dramatic responses to treatment that can save lives,” Lehman says. “We must credit many years of breast cancer research, innovative HER-2 positive specific cancer regimens and the many patients and their physicians who have participated in trials to get to where we are.”
Kapoor encourages patients to investigate clinical trial options for HER-2 positive breast cancer to help continue this advancement. “At Cedars-Sinai, we have many clinical trials available because we have newer targets that might potentially have fewer side effects or potentially be more effective.”
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What Is HER-2-Positive Breast Cancer? originally appeared on usnews.com
