If you’ve received a diagnosis of breast cancer, you may face the prospect of chemotherapy to treat the disease. It can be a scary word to hear, because most are well aware of the potential side effects these drugs can cause: nausea, hair loss, fatigue and a range of other unpleasant changes.
In common parlance, the word chemotherapy tends to conjure up a very specific mental image related to intravenously administered medications to treat cancer, yet the term “chemotherapy” can refer to any systemic medication. By this definition, virtually any drug treatment for cancer can be considered chemotherapy, as it’s using chemicals (chemo) to provide treatment (therapy). The National Cancer Institute defines chemotherapy as “treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection or infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy.”
[See: 7 Innovations in Cancer Therapy.]
Dr. Robert Wesolowski, assistant professor of medicine at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, says that for breast cancer, chemotherapy can be broadly separated into four categories: endocrine therapies, cytotoxins, targeted therapies, and antibody-drug conjugates.
Endocrine or Hormonal Therapies
The American Cancer Society reports that “about 2 out of 3 breast cancers are hormone receptor-positive.” This means that the cancer cells have receptors (proteins on the cell surface) that attach to estrogen and/or progesterone, two hormones in the body. The cancer cells use these hormones to grow, so reducing the amount of these available hormones can starve the cancers of their food supply and kill them. That’s the concept behind endocrine therapies to treat breast cancer.
“These are medications that target estrogen signaling,” Wesolowski says, “and there are two big categories within that group. One would be called selective estrogen receptor modulators or SERMS. The most popular and most well-known SERM would be tamoxifen.”
The second group of agents that fall under the endocrine header are aromatase inhibitors, “which inhibit estrogen production in peripheral tissues. So unlike tamoxifen, which blocks estrogen receptors in the breast tissue, aromatase inhibitors work by decreasing production of estrogen in postmenopausal women,” Wesolowski says.
These two classes of endocrine treatments are used in different subsets of patients, says Dr. Joseph Vadakara, an oncologist and hematologist with Geisinger Health System in Danville, Pennsylvania. “In younger, premenopausal women, we tend to use tamoxifen. For women who are postmenopausal or those who’ve had their ovaries taken out during surgery, we usually use the aromatase inhibitors,” he says.
These drugs are very common in treating breast cancer patients at various stages of the disease both because hormone-positive breast cancers are the most common type and because “studies again and again have shown that use of these agents have led to an almost 50 percent reduction in the recurrence rate of breast cancer,” Wesolowski says. Patients will typically be prescribed these treatments immediately following surgery for breast cancer and many patients stay on SERMs or aromatase inhibitors for five to 10 years, depending on age, the stage of the breast cancer and other factors specific to each individual. Most of these drugs are administered orally as pills taken once per day.
[See: What Not to Say to a Breast Cancer Patient.]
Cytotoxins
The second group of drugs used for breast cancer are “traditional chemotherapy drugs,” Vadakara says. “These drugs kill rapidly dividing cells but are not specific for cancer cells.” These are the drugs that we usually think of when someone says chemotherapy and are often delivered intravenously. They can cause the familiar side effects of nausea, fatigue and hair loss, but may be “used in patients with both advanced breast cancer and in early stage breast cancer,” Vadakara says.
Wesolowski says these cytotoxic agents can be grouped into a few different sub-categories including anthracyclines, taxenes and alkylating agents. “The most common anthracycline is doxorubicin. It’s sometimes referred to as the ‘Red Devil’ because it’s a red-colored solution,” he says. Vadakara notes this drug is also called Adriamycin and isn’t specific just to breast cancer, but may also be used to treat sarcoma, lymphoma and leukemia. Wesolowki says the most commonly used taxenes — paclitaxel and docetaxel — were originally “derived from the Pacific yew tree and then later synthesized in the lab.” Cytoxan, also called cyclophosphamide, is a common alkylating agent used in breast cancer.
Cytotoxins are effective against cancer because they indiscriminately kill rapidly dividing cells. Wesolowski likens their effect to “carpet bombing” in war. But this can also mean serious side effects for some patients. “These drugs don’t discriminate whether it’s a normal cell that’s supposed to be rapidly dividing or whether it’s a malignant cell that’s dividing rapidly inappropriately. All of the side effects from this therapy are due to the fact that normal cells that are supposed to divide rapidly also get killed by chemotherapy.” These unlucky cells include those in the bone marrow, gastrointestinal tract and hair follicles. These drugs may also kill the quickly dividing cells in the ovaries, causing some women to go into early menopause. With these drugs, side effects can be intense, but most of them usually disappear once treatment is concluded.
Targeted Therapies
Wesolowski says there are “several classes of targeted agents, and the most well-known class is one that targets HER2 receptors.” HER2 receptors are proteins on the cancer cells that signal the cell to grow. “We used to have only one drug that targeted HER2 receptors, and that’s Herceptin,” he says. Herceptin, also called trastuzumab, binds to HER2 receptors and “interferes with signaling to the HER2 receptor. And through some other unknown mechanism, it leads to cancer cell death.” Herceptin and other drugs in its class may be used alongside cytotoxins or endocrine therapy, Wesolowski says.
Also under the heading of targeted therapies are recently developed treatments for metastatic breast cancer that inhibit CDK4 and CDK6, enzymes involved in cellular division. Examples of these drugs are Ibrance (palbociclib), Kisqali (ribociclib) and Verzenio (abemaciclib). The side effects of these treatments may be fewer or better tolerated because these treatments are more targeted, but “there is a small risk of lowering heart function with these agents,” Wesolowski says. Still, he says they’re an exciting development that’s also being studied for potential use in early stage breast cancers in the future.
Antibody-drug Conjugates
Lastly, in some cases of HER2-positive metastatic breast cancer, a combination therapy may be prescribed. In this approach, one component acts as a vehicle for the other, targeting a specific point on the cell and delivering the chemotherapy right there. Wesolowski refers to antibody conjugates as “precision-guided weapons that make it more likely the payload will hit the target.”
[See: A Tour of Mammographic Screenings During Your Life.]
Kadcyla (ado-trastuzumab emtansine) is an antibody-drug conjugate used for breast cancer. Basically, the idea behind the drug is to use Herceptin and chemically add chemotherapy drugs to it. “The idea is that the Herceptin will then bind to the HER2 cells preferentially, and the chemotherapy will be more targeted to breast cancer cells than normal cells,” Wesolowski says.
This new Trojan Horse approach may improve survival rates. “One study that looked at this drug and compared it to a prior standard of care shows that overall survival improved from 25 to 39 percent,” Wesolowski says. Although those numbers may still seem small, “we’re making these incremental improvements in breast cancer. When you compare it to what we had in the 1980s and ’90s, the survival of breast cancer patients is now dramatically improved,” he says.
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Which Chemotherapy Treatments Are Most Commonly Used for Breast Cancer? originally appeared on usnews.com
