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STILs may predict RFS, therapy benefit in HER-2–positive breast cancer
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The presence of stromal tumor-infiltrating lymphocytes appeared associated with RFS in patients with HER-2–positive early-stage breast cancer treated with chemotherapy alone, according to study results publishing in JAMA Oncology.
However, the association did not persist among patients treated with chemotherapy and trastuzumab (Herceptin, Genentech), and high levels of stromal tumor-infiltrating lymphocytes (STILs) appeared associated with a lack of trastuzumab therapy benefit.
The presence of tumor-infiltrating lymphocytes at diagnosis is believed to be prognostic in triple-negative breast cancer, according to study background.
Edith A. Perez
Thus, Edith A. Perez, MD, vice president and head of Bio-Oncology and U.S. Medical Affairs at Genentech/Roche, and colleagues sought to evaluate the association of STILs with RFS in women with HER-2–positive early-stage breast cancer.
Perez and colleagues collected tumor slides from 945 women enrolled in two arms of the N9831 trial (arm A, n = 489; arm C, n = 456), which studied the safety and efficacy of chemotherapy or chemotherapy plus trastuzumab.
Treatments used in the trial included standard chemotherapy (doxorubicin and cyclophosphamide) followed by weekly paclitaxel (arm A) or doxorubicin and cyclophosphamide, followed by weekly paclitaxel and trastuzumab, then trastuzumab alone (arm C).
The association between STILs and RFS served as the primary endpoint.
Median follow-up was 4.4 years (range, 0-13.6).
Researchers classified most of the samples as having between 0% and 19% STILS. Ninety-four samples were classified as lymphocyte-predominant breast cancer (LPBC) — or as having at least 60% STILs — and these samples were balanced between arm A (9.8%) and arm C (10.1%).
Perez and colleagues found that women in arm A who had LPBC had a 10-year RFS estimate of 90.9%, compared with 64.5% among women with low STIL levels (HR = 0.23; 95% CI, 0.07-0.73).
Among women in arm C, patients with LPBC and low STIL levels had similar 10-year RFS estimates (80% vs. 80.1%; HR = 1.26; 95% CI, 0.5-3.17).
The researchers observed a statistically significant interaction between STIL status and trastuzumab treatment (P = .03). Patients with LPBC tumors did not benefit from the addition of trastuzumab (HR = 2.43; 95% CI, 0.58-10.22), whereas patients with non-LPBC tumors did (HR = 0.49; 95% CI, 0.35-0.69).
Results of a multivariable analysis indicated STIL status remained significantly associated with RFS in arm A and statistically insignificant for arm C (HR = 1.01; 95% CI, 0.89-1.15).
Perez and colleagues acknowledged limitations of their study. They noted that their analysis was not pre-specified in the N9831 trial protocol. Further, they acknowledged that their analysis only included a small subset of patients enrolled in the trial (total trial enrollment, n = 3,505).
“These data have implications with respect to cancer pathogenesis and metastasis,” Perez and colleagues wrote. “For more than 75 years, STILs have been a known prognostic factor, and we have confirmed this finding in patients with HER-2–positive breast cancer treated with chemotherapy without trastuzumab in the adjuvant setting.”
Continued research of STILs may guide future treatment of HER-2–positive early-stage breast cancer, Sylvia Adams, MD, MS, associate professor of medicine at NYU Langone Medical Center, wrote in an accompanying editorial.
“Further study of tumor-infiltrating lymphocytes as a predictive biomarker for HER-2–positive breast cancer is required, ideally stratified by hormone receptor subset,” Adams wrote. “This information will be essential to develop biology-driven trials and ultimately answer the question of if and how tumor-infiltrating lymphocytes can provide useful information about which patients with breast cancer benefit from immunotherapies, including T-cell checkpoint inhibitors.” – by Cameron Kelsall
Disclosure: Perez reports an employment role with and stock ownership in Genentech/Roche, which began following the conduct of this study. Two other study researchers report employment roles with and stock ownership in Genomic Health. The other researchers report no relevant financial disclosures. Adams reports membership on the global steering committee for the phase 3 IMpassion-130 trial and a principal investigator role on the phase 2 Keynote-086 trial.
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