Chemotherapy, Rather Than Hormonal Therapy, Plus Targeted Therapy Seem Best Pre-Surgery for Hormone Receptor-Positive, HER2-Positive Breast Cancer
Weekly Taxol (chemical name: paclitaxel) plus the anti-HER2 medicines Herceptin (chemical name: trastuzumab) and Perjeta (chemical name: pertuzumab) before surgery resulted in better pCR rates than daily hormonal therapy plus Herceptin and Perjeta for early-stage, hormone receptor-positive, HER2-positive breast cancer, according to a study.
The research was published online on May 11, 2023, by the journal JAMA Oncology. Read the abstract of “Efficacy of Endocrine Therapy Plus Trastuzumab and Pertuzumab vs De-escalated Chemotherapy in Patients with Hormone Receptor-Positive/ERBB2-Positive Early Breast Cancer: The Neoadjuvant WSG-TP-II Randomized Clinical Trial.”
Doctors call treatments given before surgery neoadjuvant treatments.
The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene, so you may see it referred to by that name in some studies, including this one.
What is pCR?
One way doctors judge the effectiveness of neoadjuvant treatments is by looking for any actively growing cancer cells in tissue removed during surgery. If there aren’t any cancer cells in the tissue, doctors call it a pathologic complete response or pCR. If there are cancer cells in the tissue, doctors call it residual cancer.
Many studies show that people who have pCR after neoadjuvant treatments usually need fewer treatments after surgery and, importantly, have better outcomes, including survival.
What is de-escalated treatment?
De-escalated breast cancer treatment aims to reduce side effects and improve quality of life while still effectively treating the cancer.
For hormone receptor-positive breast cancer, hormonal therapy is considered to cause fewer and less severe side effects than chemotherapy.
Research has also shown that receiving Taxol weekly instead of every three weeks causes less severe side effects. The weekly dose is about half of what the every-three-week dose is.
When treating early-stage breast cancers that are both hormone receptor-positive and HER2-positive, studies have shown that neoadjuvant chemotherapy plus Herceptin and Perjeta offer pCR rates of up to about 40%.
Other studies have suggested that neoadjuvant hormonal therapy plus Herceptin and Perjeta may offer similar pCR rates.
Still, until this study, no research had directly compared neoadjuvant chemotherapy plus Herceptin and Perjeta with neoadjuvant hormonal therapy plus Herceptin and Perjeta.
About the study
The study included 207 women diagnosed with early-stage, hormone receptor-positive, HER2-positive breast cancer. The women were between the ages of 25 and 83. Just over half of the women were diagnosed with stage II or stage III breast cancer. Nearly 75% of the cancers were node-negative.
The researchers randomly assigned the women to one of two treatment groups:
100 women took hormonal therapy (either tamoxifen or an aromatase inhibitor) each day and received Herceptin and Perjeta every three weeks for 12 weeks before surgery
107 women received Taxol weekly and Herceptin and Perjeta every three weeks for 12 weeks before surgery
All the women continued receiving Herceptin and Perjeta after surgery so they received the medicines for a total of one year.
Overall, 22 women decided to not start treatment or stopped treatment during the study. Of the remaining women:
93 women completed hormonal therapy plus Herceptin and Perjeta treatment
92 women completed Taxol plus Herceptin and Perjeta treatment
About 70% of the women had lumpectomy and 14% had mastectomy.
After surgery, pCR rates were:
23.7% in women who took hormonal therapy and received Herceptin and Perjeta
56.4% in women who received Taxol, plus Herceptin and Perjeta
Rates of serious side effects were similar in the two treatment groups:
10 women in the hormonal therapy plus Herceptin and Perjeta group had a serious side effect
13 women in the Taxol plus Herceptin and Perjeta group had a serious side effect
The women completed surveys about their quality of life before and after the 12 weeks of neoadjuvant treatment. The results showed that women receiving Taxol before surgery had a decrease in quality of life that was statistically significant. This means that it was likely due to the treatment and not just because of chance. Women who took hormonal therapy before surgery had the same quality of life scores before and after neoadjuvant treatment.
The researchers noted that while the pCR rate in the hormonal therapy group was lower than the pCR rate in the chemotherapy group, the near pCR rate was 36.1%.
“The present trial indicates that a small but substantial proportion of patients with ERBB2-positive [early-stage breast cancer] could have an exceptionally good prognosis already after an effective short-term anti-ERBB2 treatment even without any systemic chemotherapy, in line with hypothesis-generating results from other trials,” the researchers wrote.
Still, more research is needed to figure out exactly which people diagnosed with early-stage, hormone receptor-positive, HER2-positive breast cancer can take hormonal therapy, rather than receive chemotherapy, along with Herceptin and Perjeta before surgery.
“The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing two neoadjuvant de-escalation treatments in hormone receptor-positive/ERBB2-positive [early-stage breast cancer] and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after [estrogen therapy] plus trastuzumab and pertuzumab,” the researchers concluded.
What this means for you
If you’ve been diagnosed with early-stage, hormone receptor-positive, HER2-positive breast cancer, this study offers you and your doctor interesting information on possible treatments.
It is very important to remember that this study only looked at pCR, not recurrence-free survival or overall survival.
Recurrence-free survival is how long a person lives without the cancer coming back. Overall survival is how long a person lives, whether or not the cancer comes back.
So although pCR is linked to better outcomes, pCR does not automatically mean better survival. The researchers plan to continue following the women in the study to collect overall survival information. Those findings can help doctors determine the best neoadjuvant treatment approach for early-stage, hormone receptor-positive, HER2-positive breast cancer.
Learn more about chemotherapy for breast cancer.
Learn more about hormonal therapy for breast cancer.
Learn more about targeted therapy for breast cancer.
— Last updated on June 20, 2023 at 3:13 PM