The Future of Metastatic Breast Cancer Treatment Is Bright
Sometimes, despite treatment, breast cancer spreads and becomes metastatic, which doctors refer to as “stage IV.” According to the American Society of Clinical Oncology (ASCO), the five-year survival rate for metastatic breast cancer (MBC) is just 27%, leaving many women with this diagnosis fearful for their futures. But groundbreaking research into new treatment options for MBC is moving fast, instilling new hope in patients and doctors alike. Here, the experts share the latest on these advances to learn how they may soon help women with MBC live longer, better lives.
New Treatments Target Three Main Types of MBC
Metastatic breast cancer is not just one disease. “It’s actually a collection of diseases that are designated based on tumor testing results,” explains Erica L. Mayer, M.D., a breast oncologist and senior physician at the Dana-Farber Cancer Institute in Boston. Much of the latest treatment research focuses on three main subtypes—triple-negative, hormone receptor-positive, and HER2-positive cancer. “In each category we’ve seen new drug approvals with exciting agents that attempt to target the specific kind of cancer and open the door for future therapies.” Let’s take a look at these developments now.
Treating Type 1: Triple-Negative Metastatic Breast Cancer
Immunotherapy is a hot topic in the cancer world: “These medicines are designed to awaken the immune system to target it against the cancer,” Dr. Mayer explains. But while they’ve proven effective for other cancer types, there’s been less data to support their use in breast cancer, she says. That said, the U.S. Food and Drug Administration (FDA) has approved use of the immunotherapy drug Tecentriq (atezolizumab) plus chemotherapy for those with a certain type of advanced triple-negative breast cancer. Why? A 2019 clinical trial found the combo may help women live a median of seven months longer than with chemo alone.
Other Immunotherapies Bring Hope for Triple-Negative MBC, Too
Tecentriq (atezolizumab) isn’t the only immunotherapy drug bringing hope to those with triple-negative MBC—especially good news since this subtype has limited treatment options, according to the American Cancer Society. A similar drug, Keytruda (pembrolizumab), has also performed well in several clinical trials for MBC, and more therapies targeting the immune system are currently being studied. “We hope the selection of available immunotherapy drugs and number of patients who can benefit from them will expand,” says Dr. Mayer.
Treating Type 2: Hormone Receptor-Positive Metastatic Breast Cancer
Other new research focuses on treating hormone receptive-positive breast cancers, which express receptors for the hormones estrogen and/or progesterone, explains Dr. Mayer. “We can now examine the genetic code of these cancers and look for any alterations that might help us better understand best treatments,” she says. One group of targeted drugs—called CDK4/6 inhibitors, including Ibrance (palbociclib) and Verzenio (abemaciclib)—is already FDA-approved. Unlike traditional chemo, these medications come in pill form and help slow cell growth.
PI3K Inhibitors With Hormone Therapy May Extend Survival Rates
PI3K inhibitors, which target certain ezymes that can cause cancer cells to die, hold real promise for some women who’ve been diagnosed with hormone-positive breast cancer, Dr. Mayer says. A 2019 clinical trial found a new drug called PIQRAY (alpelisib) was helpful when used in combination with another drug that blocks estrogen's effect on cells. The combo extended progression-free survival a median of 5.3 months longer than when the hormone therapy was used alone, leading to FDA approval in May 2019. “We hope this is the first of many drugs that will be developed that can be selected based on the results of tumor profiling,” Dr. Mayer adds.
Treating Type 3: HER2-Positive Metastatic Breast Cancer
For the last main subtype, HER2-positive MBC, there have been at least two new drug approvals in the past year—impressive, considering the pandemic led to concerns about slowdowns in cancer research, says Dr. Mayer. One of those is Enhertu (trastuzumab deruxtecan), which we'll explore in just a moment; the other is Tukysa (tucatinib). “Tucatinib is designed to be very potent against HER2-positive breast cancer but minimize side effects that have been seen with similar types of medicine in the past,” she explains. “We’re delighted to have these two new approaches available for patients with HER2-positive breast cancer.”
Antibody-Drug Conjugates Show Promise for HER2-Positive Metastatic Breast Cancer
Another new treatment may benefit patients across MBC subtypes, says Bora Lim, M.D., breast medical oncologist at MD Anderson Cancer Center in Houston. Enter the antibody-drug conjugate (ADC). This medicine combines a cancer-specific antibody with a potent chemotherapy drug into one: “When the head of the antibody binds to the receptor (on the cancer cell), the cell creates a pocket that swallows the antibody,” explains Dr. Lim. “Then the tail part of the antibody, which contains the chemotherapy drug, will release into the cell like a highly targeted bomb.”
More Antibody-Drug Conjugates Are On the Way
Now back to Enhertu (trastuzumab deruxtecan), one of the most successful ADCs that was FDA-approved in 2019. This drug targets HER2-positive MBC: “Compared with older-generation ADCs, it uses improved technology so it can bind better, release the tail better, and even kill neighboring cells,” Dr. Lim explains. While some ADCs are already in use for triple-negative disease—another is Todelvy (sacituzumab govitecan)—they’re not widely available, partially because they’re complicated to create, she says. However, the National Cancer Institute has plans for new trials specifically to test ADCs, she adds. “I think it’s going to help a lot of our patients.”
A New Test Could Help Catch All Types of Metastatic Breast Cancer Sooner
One reason why MBC is so insidious? It often goes undetected for too long. This is a big problem researchers are looking to address—especially for patients at high risk of recurrence, Dr. Lim says. “None of the current approaches [for detecting recurrence] are really effective, because by the time you have symptoms, it’s too late or too widespread, and imaging technology isn’t sensitive enough,” she explains. But new technology may provide a solution to this problem, she says: the liquid biopsy. This blood test detects circulating tumor DNA—basically, evidence that cancer may recur and spread.
Liquid Biopsy May Improve Treatment for Metastatic Breast Cancer
So while imaging methods aren’t always effective at catching MBC recurrence right now, Dr. Lim hopes liquid biopsy will provide a better method in the near future. Plus, liquid biopsy may provide doctors with information that can improve treatment of metastatic breast cancer, she adds. “Circulating tumor DNA may be able to tell you whether you’re responding to your treatment, or that you’re not going to respond and therefore we need to find a better treatment,” she explains. “Another aspect that [may emerge] is whether you can actually select treatment based on the circulating tumor DNA.”
It's a Hopeful Time for Metastatic Breast Cancer Research
While no one wants to receive the news that their breast cancer has spread, there is hope: Treatments are better than ever and improving fast. “Looking at the progress we’ve made over the past 20 years with metastatic breast cancer, there has been a dramatic shift from older treatment modalities that were mostly chemotherapy-based to our current modalities, which interrogate the specific cancer to understand what is making it grow and target that cause.” Dr. Mayer says. “I hope our continued efforts to pursue research will translate into many new therapies and strategies to help benefit patients with metastatic disease.”
- Alpelisib and Hormone Therapy Clinical Trial: The New England Journal of Medicine. (2019). “Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer.” nejm.org/doi/full/10.1056/nejmoa1813904
- Antibody-Drug Conjugates for Breast Cancer: (2020). The ASCO Post. “More Antibody-Drug Conjugates on the Horizon for Breast Cancer.” ascopost.com/issues/april-25-2020/more-antibody-drug-conjugates-on-the-horizon-for-breast-cancer/
- Atezolizumab and Chemo Clinical Trial: Lancet Oncology. (2019). “Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.” pubmed.ncbi.nlm.nih.gov/31786121/
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- FDA Approval of Enhertu for Metatastic Breast Cancer: The U.S. Food and Drug Administration. (2019). “FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies.” fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available
- FDA Approval of Ibrance: U.S. Food and Drug Administration. (2017). “Palbociclib (IBRANCE).” fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance
- FDA Approval of Scituzumab Govitecan: U.S. Food and Drug Administration. (2020). “FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer.” fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer
- Pembrolizumab and Chemo Study: Journal of Clinical Oncology. (2020). “KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.” meetinglibrary.asco.org/record/184800/abstract
- Metastatic Breast Cancer Statistics: American Society of Clinical Oncology. (2020). “Breast Cancer - Metastatic: Statistics.” cancer.net/cancer-types/breast-cancer-metastatic/statistics
- Triple-Negative Breast Cancer Treatment: American Cancer Society. (2020). “Treatment of Triple-negative Breast Cancer.” cancer.org/cancer/breast-cancer/treatment/treatment-of-triple-negative.html
- PI3K and Cancer Review: Molecular Cancer. (2019). “Targeting PI3k in cancer: mechanisms and advances in clinical trials.” doi.org/10.1186/s12943-019-0954-x