A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade

Nuciforo, Paolo; Pascual, Tomás; Cortés, Javier; Llombart-Cussac, Antonio; Fasani, Roberta; Paré, Laia; Oliveira, Mafalda; Galván, Patricia; Martínez, Noelia; Bermejo, Begoña; Vidal, María; Pernas, Sònia; López, Rafael; Muñoz, M.; Garau, Isabel; Manso, Luís; Alarcón, Jesús; Martínez, E.; Rodrik-Outmezguine, Vanessa; Brase, Jan C.; Villagrasa, Patricia; Prat, Aleix; Holgado, Esther

doi:10.1093/annonc/mdx647

Cited by 91 publications

(66 citation statements)

References 11 publications

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“…Stromal tumor-infiltrating lymphocytes and tumor cellularity at C1D15 were independently associated with pCR. 22 The HER2-enriched intrinsic subtype (defined by PAM50) also was identified as a potential predictor of pCR. 20 In a study that investigated 12 weeks of lapatinib and trastuzumab, TBCRC006 investigators reported that activation of the phosphoinositide 3-kinase pathway is associated with resistance to therapy.…”

Section: Discussionmentioning

confidence: 99%

TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Connolly

Leal

Solnes

et al. 2019

JCO

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PURPOSE Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS Patients with stage II/III, estrogen receptor–negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION Early changes in SULmax predict response to four cycles of PT in estrogen receptor–negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

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Section: Discussionmentioning

confidence: 99%

TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Connolly

Leal

Solnes

et al. 2019

JCO

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“…These results are consistent with previous studies showing that TILs observed in breast cancers were associated with higher rate of pCR or improved overall survival outcomes [5,6]. Moreover, increasing TILs during systemic therapy was reported to be correlated with pCR [39], which suggests that MRI could provide valuable information regarding response during treatment.…”

Section: Luminal Subtypesupporting

confidence: 92%

Imaging features of breast cancer molecular subtypes: state of the art

Cho

2021

J Pathol Transl Med

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Characterization of breast cancer molecular subtypes has been the standard of care for breast cancer management. We aimed to provide a review of imaging features of breast cancer molecular subtypes for the field of precision medicine. We also provide an update on the recent progress in precision medicine for breast cancer, implications for imaging, and recent observations in longitudinal functional imaging with radiomics.

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“…None of the four major categories of change (proliferation, immune, stroma, and ERBB2 signaling) correlated with pCR ( Supplementary Figure 11), and in contrast to previous reports 53,54 as well as protein data from this cohort 52 , on-treatment immune infiltration, whether assessed using immune score or stromal TILs, was no more predictive than pre-treatment immune infiltration ( Supplementary Figure 12). There were also no differences in the changes in signatures by HR status (Supplementary Figure 13).…”

Section: Global Gene Expression Changes After Short-term Her2-targetecontrasting

confidence: 58%

Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)

Hurvitz

Caswell-Jin

McNamara

et al. 2020

Preprint

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In this neoadjuvant trial (TRIO-US B07), participants with early-stage HER2-positive breast cancer (N=128) were randomized to receive trastuzumab (T), lapatinib (L), or both (TL) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. We observed similar pathologic complete response (pCR) rates between T and TL, and a lower pCR rate with L. Higher-level amplification of HER2 and hormone receptor-negative status were associated with a higher pCR rate. Higher pre-treatment immune infiltrate trended toward higher pCR rate in T-treated groups, and greater HR expression correlated with lower immune infiltrate. Large shifts in tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.

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A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade

Abstract: NCT01973660.

Cited by 91 publications

References 11 publications

TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Imaging features of breast cancer molecular subtypes: state of the art

Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)

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