After you’re diagnosed with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer, your doctor’s goal is to build a treatment plan that gives you the best chance of controlling your cancer while maintaining your quality of life.
Breast cancer treatments have improved by leaps and bounds in recent years, and as a result, doctors have been able to move away from a one-size-fits-all approach to more precise care.
“Treatment for breast cancer is becoming more and more nuanced now,” says Helen Chew, MD, vice chief of hematology and oncology and director of the clinical breast cancer program at UC Davis Health.
“We used to say if you have HR-positive, HER2-negative metastatic breast cancer, you start with hormone-blocking therapy and then go to chemotherapy. But the number of drugs we have for HR-positive, HER2-negative metastatic breast cancer is increasing.”
The decisions about which drugs to use, when to use them, and how to combine them all depend on multiple factors, including where the cancer has spread, your overall health, and how your cancer behaves at a genetic level.
Understanding Your Cancer
To better understand how doctors approach your treatment, it’s important to know what it means for your breast cancer to be HR+/HER-negative and metastatic.
Metastatic breast cancer is cancer that started in breast cells but has now spread beyond your breast and nearby lymph nodes to other parts of your body. No matter where the cancer is, your doctor will still treat it as breast cancer, since that’s the type of cell it started in.
When your cancer is metastatic, the focus of treatment shifts from local therapy such as surgery or radiation to a larger scale approach, says Adriana Kahn, MD, medical oncologist at Yale Cancer Center.
“Our intention in treatment is to treat the disease as a whole because we want our medicines to reach all of the little cancer cells, not just a few of them,” Kahn says.
HR+/HER2-negative breast cancer is the most common subtype, and many people live for years with effective, well-tolerated treatments. Hormone receptor-positive (HR+) means your cancer cells have receptors for the hormones estrogen and/or progesterone, which help the cancer grow.
HER2-negative means the cancer doesn’t have too much of a protein called HER2 (human epidermal growth factor receptor 2), another common growth driver. Together, these results tell your doctor that your cancer relies more on hormones than on HER2 to grow. This is important for crafting your treatment plan.
Hormone therapy and targeted drugs
Your cancer’s hormone status tells your doctor that treatments should focus on blocking hormones or lowering estrogen levels, typically with drugs called endocrine (hormone) therapies. In some cases, your doctor combines hormone therapy with targeted medicines that make hormone therapy work even better.
“If you know that these cancers are eager to eat hormones like food, we know we need to stop that hormonal availability,” Kahn says.
Today, doctors often combine hormone therapy with a CDK4/6 inhibitor. This targeted treatment you take as a pill stops cancer cells from dividing.
Genetic Testing
One of the first steps your doctor may take after diagnosis is to do genetic testing on your tumor. This is called next-generation sequencing (NGS). This helps your care team look for specific mutations (changes) that may influence which targeted drugs could help you.
“We try really hard to get a biopsy and send the tumor for next-generation sequencing, testing for what we call somatic mutations, as opposed to germline mutations, which are inherited,” Chew says.
About 40% of people with HR+/HER2-negative mBC have one of these additional tumor mutations — most often in the ESR1 or PIK3CA genes. There are now FDA-approved drugs that target both.
“For example, if a cancer has a PIK3CA mutation and it recurs while someone was on adjuvant endocrine therapy, typically we’ll change to a different endocrine therapy, a CDK4/6 inhibitor, and a PIK3CA-targeted drug — what we call triplet therapy,” Chew says.
Your doctor may also retest the cancer later since mutations can change over time.
“We try to repeat next-generation sequencing at each progression,” Chew says. “Sometimes we can get that from circulating tumor DNA in the blood with a simple blood draw.”
Factors Doctors Consider When Choosing Treatment
Beyond your cancer’s hormone status and genetic testing, there are other factors that help shape the best treatment for you. These include:
Where the cancer has spread. Metastatic breast cancer can show up in different places. Most commonly, it moves into bones, liver, or lungs. This information helps guide treatment decisions. Bone-only disease often responds well to hormone therapy and targeted drugs. Liver or lung involvement may sometimes require stronger, faster-acting treatments, such as chemotherapy or newer antibody-drug conjugates (ADCs).
Your age and overall health. Older adults or those who have other health issues may not tolerate certain drugs as well, Chew says. And some targeted drugs can cause higher blood sugar levels, heart rhythm changes, or liver inflammation. “For anybody who has underlying lung problems or cardiac history, we might be more hesitant to use some of the antibody-drug conjugates because of how they can affect the heart or lungs.”
Tumor resistance. Over time, some tumors become resistant to hormone therapy, which means the treatment stops working as well. If that happens, your doctor might test again to look for new mutations or consider switching to chemotherapy or a targeted drug that attacks the cancer in a different way.
Personal preference. Your lifestyle, schedule, and comfort level with potential side effects are also key. “It’s really not a cake recipe that you just give out to everyone,” Chew says. “We need to look at who’s who and measure who needs how much.” You may prefer the convenience of pills, or you may not mind coming in for infusions if it means a better response.
Talking With Your Doctor: Questions to Ask Early On
When you first meet with your oncologist, you’ll have a lot of information to take in. Asking the right questions can help you feel more in control and confident about your next steps.
Kahn adds that it’s important to share your own goals and values. Think about what matters most to you before treatment begins.
“For some people, time with quality is important versus time period,” she says. “You might decide you want to live well for less time instead of living longer with miserable side effects.”
The Role of Lifestyle During Treatment
During your initial visits, your care team may also discuss whether there are lifestyle changes that could help you tolerate treatment or feel better day-to-day.
This may include:
Nutrition. Eating a balanced diet to maintain strength and support your immune system.
Exercise. Light physical activity — such as walking or stretching — can help manage fatigue and improve mood.
Managing side effects. Keeping track of symptoms, like hot flashes or fatigue, and sharing them with your team can help your doctor adjust your medications.
Mental and social support. As Kahn says, “Social history is a part of the medical exam that is often disregarded, but it matters. Tell your doctor what your life is like — your support system, your work schedule, your goals.”
Above all, it’s important you have a voice in your care. Asking questions, sharing your priorities, and staying open to discussion can help your care team tailor treatment that fits not only your medical needs but also your life.
“Share your needs, even if it’s something the doctors didn’t ask,” Chew says. “It might be important for decision-making.”
Show Sources
Photo Credit: E+/Getty Images
SOURCES:
Helen Chew, MD, vice chief, hematology & oncology, director, clinical breast cancer program, UC Davis Health.
Adriana Kahn, MD, medical oncologist, Yale Cancer Center.
National Breast Cancer Foundation: “Metastatic Breast Cancer.”
National Cancer Institute: “Hormone Therapy for Breast Cancer,” “Cabozantinib in Treating Patients with Hormone Receptor-Positive Metastatic Breast Cancer with Bone Involvement.”
American Cancer Society: “Breast Cancer HER2 Status,” “Treatment of Stage IV (Metastatic) Breast Cancer.”
Histopathology: “Next‐generation sequencing in breast pathology: real impact on routine practice over a decade since its introduction.”
FDA: “FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer,” “FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer.”
Nature: “Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer.”
iLIVER: “Research advances in treatment strategies for breast cancer liver metastases: A comprehensive review.”
Moffitt Cancer Center: “7 Healthy Lifestyle Tips for Breast Cancer Patients.”
