Complete Pathologic Responses Associated with Prognosis in Triple-Negative Breast Cancer

Posted on March 24th, 2016 by

A complete pathologic response (no cancer cells detected through microscopic evaluation) appears to be the most accurate indicator of long-term prognosis for women with triple-negative breast cancer. These results were recently presented at the 2015 annual meeting of the San Antonio Breast Cancer Symposium (SABCS).

Approximately 10-20% of breast cancers are referred to as triple-negative breast cancer (TNBC). These types of cancers are both hormone-negative and HER2-negative.

Hormone-negative breast cancer refers to a type of breast cancer that is both estrogen- and progesterone-receptor negative. This means that this type of cancer is not stimulated to grow from exposure to the female hormones estrogen and/or progesterone. Only about one-third or fewer breast cancers are hormone-negative.

Approximately 25-30% of breast cancers are referred to as human epidermal growth factor receptor (HER)2-positive, in which the cancer cells have a gene mutation that causes extra HER2 receptors to be present on the cell surface. Since the HER2 pathway is involved in cellular growth and replication, excessive HER2 receptors result in uncontrolled replication and spread of the HER2-positive cancer cells. HER2-negative breast cancer refers to cancer that does not have a mutated HER2 pathway, and therefore, is not stimulated to replicate and spread through the activity of excessive HER2 receptors.

Many treatments are available specifically for hormone-positive breast cancers, as well as HER2-breast cancers. Since these treatments are ineffective in TNBC, research efforts are underway to find new treatment options or optimal combinations of agents for this type of breast cancer.

Standard treatment for TNBC typically consists of surgery, chemotherapy, and/or radiation therapy. However, optimal chemotherapy regimens for TNBC continue to be explored.

Researchers continue to explore which measures of response to treatment are most accurately associated with a patient’s long-term prognosis. Some patients might achieve what appears to be a complete disappearance of cancer upon scans; however, cancer cells might still be present when tissue and/or biopsy samples are closely scrutinized under a microscope.

The determination of a pathologic complete response (pCR) refers to the absence of cancer cells upon microscopic evaluation from the breast, as well as the lymph nodes in the armpit (axilla) – a common initial site of cancer spread from the breast.  No other sites of cancer within the body are detectable through standard methods.

The understanding of which measures of response to therapy are most accurately associated with long-term outcomes helps to refine treatment strategies based on these results for each patient.

Researchers affiliated with the CALBG 40603/Alliance study evaluated responses to therapy and associated outcomes among 443 women with stages 2 and 3 operable TNBC.

All patients were treated with neoadjuvant therapy (treatment used prior to surgery). The 4 different neoadjuvant therapeutic regimens are as follows:

  • Standard neoadjuvant chemotherapy (paclitaxel, doxorubicin, cyclophosphamide)
  • Standard neoadjuvant chemotherapy plus the chemotherapy agent carboplatin
  • Standard neoadjuvant chemotherapy plus the vascular endothelial growth factor (VEGF) inhibitor Avastin® (bevacizumab)
  • Standard neoadjuvant chemotherapy plus both carboplatin and bevacizumab

Women underwent surgery 4-8 weeks after the completion of their therapy. The median follow-up was 39 months.

  • Overall survival was 93% among women who achieved a pCR, compared with only 73% who did not achieve a pCR.
  • 9% of patients who achieved a pCR developed a recurrence of cancer at a distant site in the body, compared with 27% of women who did not achieve a pCR.
  • Neither the addition of carboplatin, nor bevacizumab, resulted in improved outcomes for patients in this trial.

The researchers concluded that women with operable TNBC who achieve a pCR with neoadjuvant therapy have a good long-term prognosis. They caution that although carboplatin and bevacizumab did not demonstrate a benefit for women in this trial, further study evaluating these agents for treatment of TNBC is warranted as different trials have produced conflicting results.

Several clinical trials comparing different treatment regimens for operable TNBC are currently ongoing to further clarify optimal strategies for patients with this disease.

Reference: Sikov W, Berry D, Perou D, et al. 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). Proceedings from the 2015 annual San Antonio Breast Cancer Symposium. Abstract S2-05.

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Tags: Breast Cancer, complete pathologic response, HER2-negativeresearch, long-term prognosis, News, pCR, tnbc, Triple Negative Breast Cancer

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