Benefit of Adding Neoadjuvant Bevacizumab for TNBC Varies With Subtype

For women with triple-negative breast cancer (TNBC), adding bevacizumab (Avastin) to standard neoadjuvant chemotherapy was more beneficial for those diagnosed with basal-like tumors compared to those with nonbasal-like tumors. This data was presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), being held Dec. 9-13, 2014 in San Antonio.

"We found that adding bevacizumab to standard preoperative, or neoadjuvant, chemotherapy increased pathologic complete response (pCR) rates for women with basal-like cancers-that is, it increased the proportion of women who had no residual cancer detected at surgery-but decreased pathologic complete response rates for women with nonbasal-like cancers," said William M. Sikov, MD, associate director of clinical research for the Program in Women's Oncology at Women and Infants Hospital, and associate professor of medicine at the Alpert Medical School of Brown University in Providence, Rhode Island.

For those TNBC patients with basal-like disease, adding bevacizumab to standard neoadjuvant chemotherapy increased pCR from 45% to 64%. Interestingly, for those patients with nonbasal-like disease, the pCR actually decreased from 60% to 43%. Sikov notes that adding carboplatin to standard neoadjuvant chemotherapy treatment increased pCR equally for women with basal-like and nonbasal-like TNBC.

“We don’t understand the reasons for the difference in benefit from bevacizumab experienced by patients with basal-like and nonbasal-like disease," said Sikov. “With low numbers of triple-negative breast cancer patients with nonbasal-like disease it will be hard to study this.”

Last year, Sikov and colleagues reported on the CALGB 40603 (Alliance) trial which examined whether or not the addition of bevacizumab or carboplatin to standard neoadjuvant chemotherapy was beneficial at achieving pCR in stage II or III TNBC patients. While the addition of carboplatin or bevacizumab increased pCR rates, the ability to achieve relapse-free or improve overall survival is currently unknown.

Further analysis of data from this clinical trial, in which 443 patients with operable stage II or III TNBC patients were enrolled, was performed.

Pretreatment tumor samples from 360 patients for whom pCR information was available were classified as basal-like or nonbasal-like following mRNA sequencing analysis and comparison of gene expression patterns to a standard panel from The Cancer Genome Atlas. Three hundred and thirteen were classified as basal-like, while the other 47 were a mix of subtypes--which included 25 normal-like tumors.

"Of particular interest is the observation that gene signatures indicating high proliferation rates and low estrogen-receptor signaling, which are both considered characteristics of more aggressive disease, were associated with higher pathologic complete response rates overall and with increased benefit from adding bevacizumab," said Sikov. Further studies are now being done using existing tissue and blood samples from the TNBC patients treated in this particular study.

As basal-like breast cancer cells make up the majority of the triple-negative subtype, additional studies are warranted here.

For further information, take a look at this video from the 2014 SABCS, with Dr. William Sikov discussing the benefit of bevacizumab when treating TNBC patients with basal-like disease.

References:

American Association for Cancer Research.  (2014). Impact of Adding Bevacizumab to Presurgery Chemo for Triple-negative Breast Cancer Varies With Subtype. 2014 San Antonio Breast Cancer Symposium.