Even if your provider expects your current treatment to work well, it’s a good idea to understand the next possible phase. “Planning ahead and knowing what to expect next makes patients better prepared and less anxious,” says Adriana Kahn, MD, a medical oncologist at Smilow Cancer Hospital and breast cancer researcher for Yale Cancer Center.
“When patients are in need of treatment change, the selection of treatment depends on how well patients may have responded to their first-line treatment,” says Ali. “If patients remain on endocrine therapy with CDK4/6 inhibitors for at least 12 months or longer, treating oncologists may feel that cancer may still benefit from additional endocrine therapy–like treatments.”
If your first treatment regimen doesn’t work or stops working, your oncologist may recommend another type of hormone therapy with different medications, depending on a few factors, such as genetic mutations.
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Breast cancer can develop from different genetic mutations, and about 28 percent of people with HR+/HER2- MBC have a mutation in the PIK3CA gene.
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Sometimes mutations can arise during treatment with aromatase inhibitor therapy, which can affect not only PIK3CA, but also the estrogen receptor gene (ESR1).
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As soon as your treatment has stopped working or the cancer has progressed, the American Society of Clinical Oncology recommends testing for ESR1 mutations.
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Your oncologist may order molecular profiling tests to look for ESR1 or PIK3CA gene mutations.
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This testing can be done through a tissue biopsy or by looking for this DNA in your blood (liquid biopsy).
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If your initial therapy included aromatase inhibitors like letrozole (Femara) or anastrozole (Arimidex), your oncologist may recommend one of the following therapies that block estrogen receptors:
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- Another AI called exemestane (Aromasin), paired with a targeted drug like everolimus (Afinitor)
- A selective estrogen receptor degrader (SERD) like elacestrant (Orserdu), imlunestrant (Inluriyo), or fulvestrant (Faslodex)
- A different aromatase inhibitor with a CDK4/6 inhibitor
When you develop a PIK3CA gene mutation during treatment, your provider may suggest fulvestrant (Faslodex) with a PI3K inhibitor like alpelisib (Piqray) or inavolisib (Itovebi). For other gene mutations like AKT1 or PTEN, fulvestrant (Faslodex) with capivasertib (Truqap) may work better.
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For cancer that has stopped responding to hormone treatment completely, you may need to try another option, such as chemotherapy, immunotherapy, or PARP inhibitors, which prevent cancer cells from repairing themselves.
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All these options can feel overwhelming, but your provider can help you decide on the best path forward. To better understand your future HR+/HER2- MBC treatment options, you can ask these questions:
- What tests will I need to decide on my next treatment (such as molecular profiling or liquid biopsy to look for ESR1 or PIK3CA mutations)?
- How will this treatment work?
- What are its benefits and risks?
- How long is the course of this treatment?
- When, where, and how often will treatments take place?
- What kind of prognosis can I expect with this treatment?
- What follow-up tests or monitoring will I need?
- What happens if it doesn’t work?
