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Chemotherapy Before Surgery for Early-Stage HER2-Positive Breast Cancer Doesn’t Have to Include Anthracycline

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When given with two anti-HER2 medicines before surgery for early-stage HER2-positive breast cancer, a chemotherapy regimen that didn’t include an anthracycline was just as effective as a regimen that included an anthracycline and caused fewer heart problems, according to a study.

The research is part of the virtual program for the 2020 American Society of Clinical Oncology Annual Meeting. Read the abstract of “Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial.”

Doctors call treatments given before surgery neoadjuvant treatments.

About anthracycline chemotherapy medicines

Anthracycline chemotherapy medicines are:

  • Adriamycin (chemical name: doxorubicin)
  • Ellence (chemical name: epirubicin)
  • Doxil (chemical name: liposomal doxorubicin)
  • daunorubicin (brand names: Cerubidine, DaunoXome)
  • mitoxantrone (brand name: Novantrone)

Anthracyclines work by damaging cancer cells’ genes and interfering with their reproduction.

Like all chemotherapy medicines, anthracyclines may cause serious side effects, including heart damage, which can lead to heart failure. Doctors also are concerned about a higher risk of leukemia in women who have been treated with an anthracycline. Because of these concerns, doctors have been wondering if they could safely avoid using anthracycline medicines without affecting treatment outcomes.

About the study

This Dutch study, called the TRAIN-2 study, included 438 people diagnosed with stage II to stage III HER2-positive breast cancer.

Before surgery to remove the cancer, the people were divided into two treatment groups:

  • The anthracycline treatment group: 219 people treated with three cycles of 5-fluoruoracil, Ellence, and Cytoxan (chemical name: cyclophosphamide), followed by six cycles of Taxol (chemical name: paclitaxel) and carboplatin, along with the anti-HER2 medicines Herceptin (chemical name: trastuzumab) and Perjeta (chemical name: pertuzumab)
  • The no anthracycline group: 219 people treated with nine cycles of Taxol and carboplatin, along with Herceptin and Perjeta

After completing neoadjuvant chemotherapy, the people completed 1 year of Herceptin, radiation therapy, and hormonal therapy if the breast cancer also was hormone-receptor-positive.

All the people in the study then had surgery to remove any cancer that was still there after neoadjuvant treatment.

One way doctors judge the effectiveness of treatment given before surgery is to look at the tissue removed during surgery to see if any cancer cells are present. If no cancer cells are there, doctors call it a “pathologic complete response.” This is abbreviated as pCR. Many doctors believe that a pathologic complete response to neoadjuvant treatment means the cancer is less likely to come back.

Earlier results from the TRAIN-2 study published in 2017 showed that both treatment groups had high pCR rates:

  • pCR was 68% for people treated without an anthracycline
  • pCR was 67% for people treated with an anthracycline

For this new analysis, the researchers looked at rates of event-free survival and overall survival.

For this study, event-free survival meant that the person had none of the following events:

  • disease progression (the cancer grew) that could not be removed with surgery
  • recurrence (the breast cancer came back)
  • diagnosis of a second primary breast cancer
  • death

Overall survival is how long a person lives, whether or not the cancer grows or comes back.

After about 4 years of follow-up, estimated rates of 3-year event-free survival were:

  • 92.7% for people treated with an anthracycline
  • 93.6% for people treated without an anthracycline

Three-year overall survival estimates were:

  • 97.7% for people treated with an anthracycline
  • 98.2% for people treated without an anthracycline

These results were the same, whether the breast cancer was hormone-receptor-positive or not and whether the cancer had spread to the lymph nodes or not.

These results strongly suggest that neoadjuvant chemotherapy for early-stage HER2-positive disease does not have to include an anthracycline.

Heart problems were more common in people treated with an anthracycline:

  • 8.6% of people treated with an anthracycline had heart problems related to treatment
  • 3.2% of people treated without an anthracycline had heart problems related to treatment

Two people in the anthracycline treatment group developed leukemia.

“The 3-year follow-up of the TRAIN-2 study confirms the results of the primary outcome that anthracyclines do not improve efficacy and are associated with clinically relevant toxicity,” the researchers wrote. “A neoadjuvant carboplatin-taxane based regimen with dual HER2-blockade can be considered in all stage II-III [HER2-positive] breast cancer patients, regardless of hormone receptor and nodal status.”

What this means for you

Earlier results from the TRAIN-2 study found that pCR rates were about the same whether an anthracycline was included in the treatment plan or not.

These new results from TRAIN-2 continue to show that adding an anthracycline to neoadjuvant chemotherapy for early-stage HER2-positive disease doesn’t offer any additional benefits and can increase the risk of heart problems.

If you’ve been diagnosed with early-stage HER2-positive breast cancer and will have chemotherapy before surgery to remove the cancer, it’s a good idea to talk to your doctor about this study.

If your doctor suggests including an anthracycline in your neoadjuvant chemotherapy treatment regimen, you may want to ask why, and also ask about the risks and benefits of including an anthracycline in the regimen.

Together, you and your doctor can make the best decision for you and your unique situation.

For more information, visit the Chemotherapy pages.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser

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