HER2-positive and triple-negative breast cancer are among the most aggressive forms of breast cancer and traditionally have had lower survival rates than other types of the disease. However, early detection with routine screening has contributed to improved survival for both in recent years. Further, treatment advances—all available at Regional Cancer Care Associates (RCCA), one of the nation’s largest networks of cancer specialists with locations in New Jersey, Maryland, and Connecticut—also have helped improve outcomes in HER2-positive cancer. Meanwhile, intensive research and emerging therapeutic strategies are offering new hope for women with triple-negative breast cancer.
Four RCCA medical oncologists recently explained what drives the development of these breast cancers, how they are treated, and how women can play an important – and potentially life-saving – role in identifying the cancers in their earliest stages, when they can be treated most effectively.
Aileen Chen, MD, a board-certified medical oncologist practicing with RCCA in Freehold and Holmdel, NJ says, “It’s an exciting time in the fight against breast cancer. Next-generation sequencing technology is detecting genetic mutations that we can treat with targeted therapies in many forms of the disease. This has enhanced our ability to practice ‘personalized medicine’ by customizing a patient’s treatment based on her molecular and genetic profiles.”
Mohammad Pazooki, MD, a board-certified medical oncologist who practices in RCCA’s Hartford and Manchester, CT office adds, “There are many potential treatments for triple-negative breast cancer in the drug-development pipeline,” while researchers also are investigating new combination therapies that target breast cancer cells that have spread throughout the body or metastasized.
What is HER2-positive breast cancer?
Women diagnosed with HER2-positive breast cancer have cancer driven by the overproduction of a protein called human epidermal growth factor receptor 2, or HER2. Some HER2-positive cancers are hormone receptor (HR)-positive, meaning estrogen, progesterone, or both fuels their growth. Others are HR-negative, meaning they are not driven by those hormones. HR-negative cancers are more common in premenopausal women and tend to spread faster than HR-positive types.
HER2-positive cancer accounts for about 15% to 20% of breast cancers. It’s considered aggressive because of how quickly the tumor grows compared with other types of breast cancers.
Women diagnosed with HER2-positive breast cancer more than two decades ago faced extremely poor outlooks, says Maurice Cairoli, MD, a board-certified medical oncologist at RCCA’s Moorestown, NJ office. “That changed in 2000 with the advent of trastuzumab,” he says, referring to a drug that targets the HER2 protein. Thanks to trastuzumab and other treatment advances, the disease is no longer nearly as deadly as it once was, he explains.
The overall 5-year survival rate for HER2-positive cancer is 90%, according to SEER (the Surveillance, Epidemiology, and End Results program of the National Cancer Institute). Rates can be further broken down depending on how far it has spread. If caught early and it hasn’t spread beyond the breast, the 5-year survival rate is 98%. If the cancer has spread into surrounding regions or nearby lymph nodes, the survival rate is 86%. Women whose cancer has spread to more distant areas have an average 5-year survival rate of 41%. However, RCCA cancer specialists add, those rates reflect overall outcomes for a large group of patients. Each woman’s experience will vary based on factors such as her overall health, age, and the treatments she receives. Further, by the time cancer survival statistics are collected, analyzed, and published, they typically are a year or two old. Given the rapid pace of advances in cancer care, the current outlook often is somewhat better, the doctors note.
What is triple-negative breast cancer?
In triple-negative breast cancer, which accounts for 15% of breast cancers according to the American Cancer Society (ACS), the cancer cells have no receptors that attract the HER2 protein or the hormones estrogen and progesterone, it doesn’t need them to fuel its growth. Most often diagnosed in premenopausal women younger than age 40, it is more common in African American women than in white women. Other risk factors include being obese and having a breast cancer susceptibility gene (BRCA) mutation. Up to 20% of women with triple-negative breast cancer have a BRCA1 or BRCA2 gene mutation. As a result, women ages 60 years and younger who are diagnosed with triple-negative cancer should undergo genetic testing, which can help shape treatment decisions.
Compared to women with other forms of breast cancer, women with triple-negative breast cancer have a greater risk of dying, and of having treated cancer re-occur within the first three years after diagnosis. However, after five years have passed without recurrence, triple-negative breast cancer is less likely than other breast cancers to return.
Says Dr. Cairoli, “We talk about these being aggressive tumors, but if these tumors don’t relapse within the first two to three years of diagnosis, it’s unlikely they’re going to relapse.” He adds, “With hormone-receptor-positive breast cancers, we can never say to our patients that they are cured. There’s always a risk of occurrence that’s ongoing for 10 to 20 years after diagnosis. That’s not true of triple-negative cancer. You can tell patients that if three years have gone by and they haven’t relapsed, they probably aren’t going to. But we have to get folks through those first two or three years.”
According to SEER, the overall 5-year survival rate for triple-negative breast cancer is 77%. If it is caught early and hasn’t spread beyond the breast, that survival rate is 91%. If it has spread into surrounding regions or nearby lymph nodes, the survival rate is 65%. However, if cancer has spread to more distant areas, the 5-year survival rate drops to 12%.
Treating aggressive breast cancers
Women diagnosed with breast cancer undergo testing to determine the form of the disease and what’s driving its growth. This information is key to developing an individualized treatment strategy. Choice of treatment also depends on how extensive the cancer is within the breast, whether it has metastasized, and whether the patient is menopausal.
When either HER2-positive or triple-negative breast cancer is diagnosed early, surgery is often performed to remove the tumor and its surrounding tissue (lumpectomy) or the entire breast (mastectomy). Nearby lymph nodes sometimes are removed as well.
Neoadjuvant therapy, a treatment given as a first step before the primary treatment, is standard for both HER2-positive and triple-negative breast cancers if the tumor can be surgically removed. Chemotherapy is often used as a neoadjuvant therapy before surgery to shrink the tumor. The goal is to reduce the area that needs to be removed so the surgery can be less extensive, possibly avoiding a mastectomy. For HER2-positive cancer, chemotherapy may be combined with targeted therapy, medication that acts on the specific cause of the cancer.
After neoadjuvant therapy and surgery, the treatment strategies for HER2 and triple-negative breast cancers differ.
HER2 breast cancer treatment
Targeted therapy is the hallmark of treatment for HER2-positive cancer. The drug used most often is trastuzumab (brand names: Herceptin®, Kanjinti™, Ogivri®, Ontruzant®, and Trazimera™). Trastuzumab interferes with HER2 production and slows or prevents the cancer cells from growing. It is often administered with the chemotherapy agent emtansine (Enhertu®) in a combined drug called T-DM1.
Another medication, pertuzumab (Perjeta®), is sometimes prescribed with trastuzumab when the cancer has spread to other parts of the body or metastasized. Oncologists also may prescribe an aromatase inhibitor, such as lapatinib (Tykerb®) or neratinib (Nerlynx®) to lower estrogen levels.
If the cancer is also HR-positive, oncologists often prescribe endocrine therapy after the completion of targeted therapy. Endocrine or hormone therapy helps prevent cancer from returning by suppressing estrogen production. Tamoxifen is a common form of endocrine therapy used primarily in premenopausal women. It belongs to a class of drugs called selective estrogen receptor modulators (SERMs).
Postmenopausal women have the option instead of taking an aromatase inhibitor (AI), such as anastrozole (Arimidex®), exemestane (Aromasin®), or letrozole (Femara®) to block estrogen production. Postmenopausal women who have completed a tamoxifen regimen may be encouraged to follow up with an AI for added benefit.
Another form of endocrine therapy is ovarian suppression. Women may choose to have their ovaries surgically removed or treated with radiation or chemotherapy to stop hormone production. Ovarian suppression can also be achieved with drugs called gonadotropin-releasing hormone (GnRH) agonists, which temporarily stop estrogen production.
Triple-negative breast cancer treatment
Treatment options for triple-negative breast cancer remain limited, while intensive research is focused on developing new therapies. Unlike HER2-positive cancer, it can’t be controlled with targeted or endocrine therapy, often making it difficult to treat.
RCCA’s Deena Graham, MD, who practices at Hackensack and North Bergen, NJ explains: “The problem with triple-negative breast cancer is that we don’t have a known, specific receptor to target. Triple-negative breast cancers often present with larger tumors and multiple lymph nodes involved and they may be more aggressive. Some triple-negative cancers don’t respond well to treatment, but others do.”
The mainstay of treatment is chemotherapy to destroy cancer cells, either before or after a lumpectomy or mastectomy. Radiation therapy, which uses high-energy X-rays to destroy any remaining cancer cells, is sometimes administered after surgery.
The drug pembrolizumab (Keytruda®), combined with a chemotherapy drug, is used as neoadjuvant therapy to treat early-stage triple-negative breast cancer before surgery is performed. Pembrolizumab is a form of immunotherapy, which helps boost the immune system’s ability to fight breast cancer. The drug can also be used for triple-negative breast cancer that has spread.
Drugs called PARP inhibitors are sometimes combined with chemotherapy to treat women with advanced triple-negative breast cancer and a BRCA gene mutation. PARP refers to poly ADP-ribose polymerase, an enzyme that fixes DNA damage in cells. The drugs inhibit the enzyme’s ability to repair DNA in cancer cells, making it harder for those cells to survive.
Women with triple-negative breast cancer should explore joining a clinical trial, says Dr. Graham, explaining, “I always recommend clinical trials for women who are diagnosed with aggressive forms of breast cancer,” says Dr. Graham, noting that the studies provide women with access to the latest approaches to enhancing care and outcomes.
Too often, she adds, misconceptions make patients reluctant to participate in a study. Dr. Graham explains that people sometimes think that they may be assigned to a placebo group in which they will receive no treatment, just a “sugar pill.” In reality, she adds, when a study has a control group that is used to compare results with the group receiving an investigational treatment, patients in the control group typically receive the current standard treatment, while those in the other group receive the current standard treatment plus the investigational agent. Other patients may think that being urged to join a clinical trial means they’re not doing well on their current treatment. Rather, Dr. Graham says, “It means that we can potentially make your treatment even better.”
Detecting breast cancer with screening and awareness
One of the best ways to improve your chances of surviving breast cancer is to be vigilant about getting routine screenings for the disease. The earlier cancer is found, the better the outlook. According to the ACS, screening reduces breast cancer deaths by 20%. The ACS says that women at average risk for breast cancer should have the option of starting annual screening mammograms between ages 40 to 44 years, while women ages 45 to 54 years should have annual mammograms. Starting at age 55, women should have the option of receiving a mammogram every year or every two years, the ACS says.
Dr. Cairoli points out that younger women who aren’t covered by screening recommendations should not assume they’re not susceptible to breast cancer. “Unfortunately, there’s no such thing as ‘too young.’ Breast cancers can occur in patients even in their 20s.” He recommends that all women, especially those not yet of screening age, perform monthly breast self-examinations.
“Monthly breast self-exams haven’t been shown to improve outcomes for the population at large, but by knowing your body you’ll be able to alert your physician if you notice a change,” Dr. Cairoli says. And if you do find something unusual, he adds, insist on a physical examination or screening even if your doctor tries to tell you you’re too young for breast cancer.
Breast cancer symptoms to be alert for include:
- A lump in the breast or armpit
- A change in the breast’s appearance, such as shape or size
- Breast pain
- An inverted nipple, nipple pain, or nipple discharge
- Thickening or swelling anywhere on the breast or nipple
- Skin redness, flakiness, irritation, or dimpling anywhere on the breast or nipple area
In joining Dr. Cairoli in stressing the importance of breast self-exams, Dr. Pazooki says, “I can’t believe how many times I have seen a patient who had a normal mammogram but then felt a mass or lump in the breast that turned out to be cancer.” He also emphasizes the importance of screening. “We know the cure rate for breast cancer is high when we find it early.”
Drs. Cairoli, Chen, Graham, and Pazooki are among the 80+ cancer specialists who treat patients at more than 20 RCCA care centers in New Jersey, Connecticut, Maryland, and the Washington, DC, area. Those oncologists see more than 22,000 new patients each year and provide care to more than 225,000 established patients, collaborating closely with their patients’ other physicians. They offer patients the latest in cutting-edge treatments, including immunotherapies and targeted therapy, as well as access to a wide range of clinical trials. In addition to serving patients who have solid tumors, blood-based cancers, and benign blood disorders such as anemia, RCCA care centers also provide infusion services to people with many non-oncologic conditions including multiple sclerosis, Crohn’s disease, asthma, and rheumatoid arthritis who take intravenously-administered medications.
To learn more about RCCA, call 844-928-0089 or visit RCCA.com.