Triple-Negative Disease May Have New Treatment Option

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Triple-negative breast cancer is:

  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative

About 15% to 20% of breast cancers are triple-negative. Triple-negative cancers usually are more aggressive, harder to treat, and more likely to come back than cancers that are hormone-receptor-positive and/or HER2-positive. Hormonal therapy and the targeted therapies Herceptin (chemical name: trastuzumab), Tykerb (chemical name: lapatinib), and Perjeta (chemical name: pertuzumab) don't work on triple-negative breast cancer.

Because triple-negative breast cancer is aggressive and there are a limited number of treatment choices, doctors are looking for new ways to treat it, especially early-stage, triple-negative disease.

Two studies presented Dec. 9, 2015 at the 2015 San Antonio Breast Cancer Symposium suggest that adding carboplatin to the standard chemotherapy regimen before surgery may improve outcomes for women diagnosed with triple-negative disease.

The studies are:

  • “Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC +/- carboplatin and/or bevacizumab in triple-negative breast cancer: Outcomes from CALGB 40603 (Alliance)” (Abstract S2-05)
  • “Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto)” (Abstract S2-04)

Treatment given before surgery to weaken or shrink the cancer is called neoadjuvant treatment. Neoadjuvant treatment often is recommended when the breast cancer is large, aggressive, and/or has spread beyond the breast to surrounding tissue.

Carboplatin is the only platinum-based chemotherapy medicine approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer. Platinum-based chemotherapy weakens or destroys breast cancer cells by damaging the genetic material in the cells and making it hard for cells to repair any genetic damage.

In the CALGB 40603 study, researchers randomly assigned 443 women diagnosed with operable stage II or stage III triple-negative breast cancer to one of four chemotherapy regimens before surgery:

  • standard chemotherapy -- weekly Taxol for 12 weeks, then Adriamycin (chemical name: doxorubicin) and Cytoxan (chemical name: cyclophosphamide) every 2 weeks for 8 weeks
  • standard chemotherapy plus carboplatin
  • standard chemotherapy plus Avastin (chemical name: bevacizumab)
  • standard chemotherapy plus carboplatin and Avastin

The women had breast cancer surgery 4 to 8 weeks after chemotherapy was completed. A pathologist examined the tissue that was removed to see if there were signs of cancer cell activity. 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 this study found that adding carboplatin or Avastin to standard neoadjuvant chemotherapy for triple-negative breast cancer increased the number of women who had a pathologic complete response.

After 3 years of follow-up, the researchers have now found that women who had a pathologic complete response to chemotherapy before surgery had better outcomes than women who didn’t have a pathologic complete response.

Women who had a pathologic complete response were 70% less likely to have the cancer come back (recurrence) and 80% more likely to be alive than women who didn’t have a pathologic complete response.

“Our new data show that patients on any arm of this study who had a pCR had far superior outcomes compared with those who did not have a pCR,” said William Sikov, M.D., associate director of clinical research in the Program in Women’s Oncology at Women and Infants Hospital of Rhode Island and associate professor of medicine and obstetrics and gynecology at the Warren Alpert Medical School of Brown University. “After three years of follow-up, only 9% of patients who had a pCR had developed a distant recurrence [cancer coming back in a part of the body away from the breast] and only 6% had died, compared to 27% and 25%, respectively, of patients who did not have a pCR.”

Dr. Sikov also said that while it would be important to know, this study just wasn’t large enough to tell if adding carboplatin or Avastin to standard neoadjuvant chemotherapy for triple-negative breast cancer improved pathologic complete response rates or offered other benefits.

However, the second study, called the GeparSixto study suggests that adding carboplatin to standard neoadjuvant chemotherapy for triple-negative breast cancer improves disease-free survival.

Disease-free survival is how long a woman lives before the cancer comes back.

In the GeparSixto study, 315 women diagnosed with triple-negative breast cancer were randomly assigned to receive either:

  • standard neoadjuvant chemotherapy
  • standard neoadjuvant chemotherapy plus carboplatin

Earlier results from the GeparSixto study found that adding carboplatin to the standard neoadjuvant chemotherapy for triple-negative disease improves pathologic complete response rates.

After about 3 years of follow-up, disease-free survival rates were:

  • 85.5% for women treated with standard neoadjuvant chemotherapy plus carboplatin
  • 76.1% for women treated with standard neoadjuvant chemotherapy alone

This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.

“Here we show that the improved pCR rates translated into improved disease-free survival,” said Gunter von Minckwitz, president of the German Breast Group and professor of gynecology at the University of Frankfurt. “Patients with [triple-negative breast cancer] who received carboplatin as part of their neoadjuvant chemotherapy regimen were almost half as likely to have had disease relapse at 3 years after starting treatment compared with those who did not receive carboplatin, and it was those patients who had a pCR who were least likely to have disease relapse.”

If you’ve been diagnosed with triple-negative breast cancer, the results are very encouraging. It’s important to know that not having a pathologic complete response to chemotherapy before surgery doesn’t mean you won’t do well. Most women don’t have a pathologic complete response to neoadjuvant chemotherapy.

It’s also important to know that while these two studies by themselves won’t change the standard chemotherapy regimen before surgery for triple-negative breast cancer, they do strongly suggest that changes will be coming as larger studies are done.

If you’ve been diagnosed with triple-negative breast cancer, you and your doctor will develop a treatment plan that will likely include chemotherapy and possibly targeted therapy medicines. No matter which treatments are recommended for you, you may want to talk to your doctor about:

  • why each treatment is recommended (including any combinations)
  • treatment timing and sequence
  • the expected benefits, risks, and side effects of each treatment

If you’ll be getting neoadjuvant treatment and carboplatin isn’t part of the regimen, you may want to talk to your doctor about clinical trials with carboplatin that make sense for your unique situation.

For more information, visit the Breastcancer.org pages on Triple-Negative Breast Cancer.

Read more Research News from the 2015 San Antonio Breast Cancer Symposium:



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