Subgroup of women with HER-2-positive breast cancer highly sensitive to treatments, study finds

A UNC Lineberger-led study published in the Journal of Clinical Oncology identified a group of women with HER2 positive breast cancer who could benefit from less intensive targeted treatment

Subgroup of women with HER-2-positive breast cancer highly sensitive to treatments, study finds click to enlarge “This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer,” said Carey. “To take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments & have a good prognosis.”

Using molecular profiling of patients’ breast cancer tumors, a National Cancer Institute-sponsored study led by UNC Lineberger Comprehensive Cancer Center researchers has identified a group of women with HER2-positive breast cancer who may benefit from less intensive treatment at the outset.

The results of the trial, which was performed by a national cooperative group, the Alliance for Clinical Trials in Oncology, were published in the Journal of Clinical Oncology. Researchers say the findings could spare unnecessary treatment for those patients and help save health care dollars.

“This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer, and may allow us to take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments and to have a good prognosis,” said the study’s lead author Lisa Carey, MD, a UNC Lineberger member, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at the University of North Carolina School of Medicine and the physician-in-chief of the N.C. Cancer Hospital.

HER2-positive breast cancer is a type of breast cancer that tests positive for a protein called human epidermal growth factor. The protein helps to promote cancer cell growth, but can be targeted with anti-HER-2 drugs. Treatments that target HER2 have improved the outlook for women with this type of breast cancer – with one HER2 targeted treatment called trastuzumab cutting death rates for stage I to III cancers by 37 percent when combined with postoperative chemotherapy.

The study examined whether combining two anti-HER2 drugs with chemotherapy would improve response to the treatment compared with a single anti-HER2 drug with chemotherapy.

The study found a relatively small difference in responses for women in those two groups. The pathologic complete response rate, which is a measure of response to treatment, was 56 percent for women taking both HER-2 treatments, compared to a pathologic complete response rate of 46 percent for women taking the single targeted treatment and chemotherapy. However, this was an unusual study in that all participating patients agreed to have biopsies taken of their tumors before starting therapy.  By examining the biology of those tumors, the investigators found a group of women who, based on the molecular profile of their tumors, were highly sensitive to the treatment regardless of whether one or two anti-HER2 drugs were given.

Previous comprehensive analyses of breast cancer tumors have identified subtypes of breast cancer based on the molecular or genomic characteristics of their tumors. And one of those molecular subtypes – called HER2-enriched – was highly sensitive to all of the HER2 treatments used in this study. The researchers found that women with the HER2-enriched subtype had a 70 percent complete pathologic response rate, about double the response rates to the treatments for women with luminal A or luminal B molecular subtypes, who had pathologic complete response rates of 34 and 36 percent.

“These are important findings because we treat all of these tumors the same -- with multiple chemotherapy drugs and now often 2 anti-HER2 drugs at a cost of more than one hundred thousand dollars,” Carey said.  “These findings suggest that we may be able to be more sophisticated in determining up front which tumors need more aggressive treatment and which will do well with a less aggressive therapy.”

The study was supported by the National Cancer Institute (NCI), National Institutes of Health, under Awards No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology, as well as NCI Grants No. 1U10CA180838, 1U10CA180867, 1U10CA180801, and 1U10CA180791, and in part by grants from the Breast Cancer Research Foundation (Alliance, L.A.C., C.M.P.), Susan G. Komen (L.A.C.), Glaxo- SmithKline, and the University of North Carolina Specialized Program of Research Excellence in Breast Cancer (NCI Grant No. P50-CA58223). Alliance/Cancer and Leukemia Group B is supported by NCI Grant No. CA31946 and Alliance Statistics and Data Center by NCI Grant No. CA33601.

In addition to Carey, other authors included David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou of the University of North Carolina Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.