Herceptin Before Surgery Offers Same Long-Term Benefits When Given At Same Time or After Chemotherapy

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Long-term results show that women with HER2-positive breast cancer who were treated with Herceptin and chemotherapy before surgery had similar survival rates whether they received Herceptin at the same time or after chemotherapy.

HER2-positive breast cancers have too many copies of the HER2/neu gene, which make too much of the HER2 protein. HER2-positive breast cancers tend to be aggressive, so doctors may recommend treatment with chemotherapy and/or Herceptin (chemical name: trastuzumab) before surgery. Herceptin works by attaching itself to the HER2 receptors on the surface of HER2-positive breast cancer cells and blocking the cells’ ability to receive growth signals.

An anthracycline chemotherapy medicine is typically part of the combination used to treat HER2-positive disease. Adriamycin (chemical name: doxorubicin) and Ellence (chemical name: epirubicin) are anthracyclines.

Treatments given before breast cancer surgery are called neoadjuvant treatments.

When Herceptin is given as a neoadjuvant treatment with chemotherapy, Herceptin can be given:

  • at the same time as chemotherapy -- called concurrent treatment
  • after chemotherapy -- called sequential treatment

Herceptin and anthracyclines can damage the heart

Both Herceptin and anthracycline chemotherapy medicines can have toxic effects on the heart, including heart muscle damage and heart failure. Concurrent treatment can increase the risk of heart damage. Women who will be treated with anthracycline chemotherapy and/or Herceptin should have their heart function tested before treatment starts and should be monitored for any developing heart problems during treatment.

Still, researchers wanted to make sure there were no differences in outcomes between sequential and concurrent treatment with  Herceptin. Early study results with 2 years of follow-up suggested that concurrent treatment offered no additional benefits.

Long-term results with 5 years of follow-up confirm no difference in disease-free survival or overall survival in women treated with concurrent Herceptin and chemotherapy compared to women treated with sequential Herceptin and chemotherapy for HER2-positive breast cancer.

The research was published online on Sept. 6, 2018, by the journal JAMA Oncology. Read the abstract of “Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial.”

Disease-free survival is how long the women lived without the cancer growing or coming back. Overall survival is how long the women lived regardless of whether the cancer grew.

The study was done at 36 facilities in the continental United States and Puerto Rico. It included 280 women age 28 to 76 diagnosed with HER2-positive breast cancer between September 2007 and December 2011:

  • 82.9% of the women were white
  • 10.3% were black
  • 2.9% were Asian
  • 1.4% were Native American/Alaskan Native
  • 2.5% didn’t report race/ethnicity

All the women were scheduled to be treated with chemotherapy and Herceptin before breast cancer surgery.

Five years of follow-up found no difference in outcome for concurrent vs. sequential treatment

The women were randomly split into two groups. One group received concurrent chemotherapy and Herceptin before surgery. The other group received sequential chemotherapy and Herceptin before surgery.

  • The sequential group (138 women) was treated with fluorouracil, Ellence (chemical name: epirubicin), and cyclophosphamide (brand name: Cytoxan) every 3 weeks for 12 weeks, followed by the combination of Taxol (chemical name: paclitaxel) and Herceptin every week for 12 weeks. Within 6 weeks after completing the 12 weeks of Taxol and Herceptin, the women had surgery.
  • The concurrent group (142 women) was treated with Taxol and Herceptin every week for 12 weeks, followed by fluorouracil, Ellence, and cyclophosphamide every 3 weeks, along with weekly Herceptin, for 12 weeks. Within 6 weeks after completing the 12 weeks of fluorouracil, Ellence, cyclophosphamide, and Herceptin, the women had surgery.

Women diagnosed with hormone-receptor-positive, HER2-positive disease also were treated with hormonal therapy.

After about 5 years of follow-up:

  • 22 women in the sequential group had the cancer grow/come back during follow-up
  • 27 women in the concurrent group had the cancer grow/come back during follow-up

Disease-free survival and overall survival were the same for both treatment groups.

If you’ve been diagnosed with HER2-positive breast cancer and will be treated with anthracycline chemotherapy and Herceptin before surgery, this study offers reassuring results. Giving Herceptin after anthracycline chemotherapy offers the same benefits as giving the medicines at the same time and may reduce the risk of heart damage.

If Herceptin and chemotherapy are part of your treatment plan, it’s a good idea to ask your doctor about your risk of treatment-related heart problems and how your heart function will be monitored during treatment. You also may want to ask if visiting a cardiologist before treatment starts is a good idea for you, especially if you have any risk factors for heart disease, such as high blood pressure or diabetes. The cardiologist can evaluate your heart function and decide if you’re at high risk for developing heart disease or heart failure from breast cancer treatment.

Together, you and your healthcare team can decide on the best treatment plan for your unique situation.

If you've been diagnosed with HER2-positive breast cancer and would like to discuss treatment options with others, join the Breastcancer.org Discussion Board forum HER2+ (Positive) Breast Cancer.


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