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  • 1
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    Abstract P3-03-01: Functional tumor volume at 3 and 6-week MRI as an indicator of patients with inferior outcome after neoadjuvant chemotherapy
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-03-01-P3-03-01
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-03-01-P3-03-01
    Abstract: Purpose. Functional tumor volume (FTV) is a quantitative measure of tumor burden derived from dynamic contrast-enhanced breast MRI1, 2. In the I-SPY 2 TRIAL, FTV is measured during neoadjuvant chemotherapy (NAC) at pre-treatment (T0), 3 weeks (T1), 12 weeks (T2), and pre-surgery (T3) time points. In I-SPY2 protocol amendment 18, activated in Dec 2017, an optional MRI at 6 weeks (T1a) recommended at clinician’s discretion was added for patients with low response at T1. Patients are treated with standard NAC with or without addition of experimental agents. A treatment escalation option being planned for future I-SPY2 implementation will give patients with suboptimal response the opportunity to pursue more aggressive therapy. T1 and T1a MRI may be helpful to select candidates for this option. We retrospectively investigated the ability of FTV reduction at 3 and 6 weeks to detect non-responders. Methods. We included 104 patients who underwent T1a MRI between Jan 2018 and Mar 2021. FTV was measured using in-house software developed in IDL (Exelis Visual Information Solutions, Boulder, CO). FTV reduction at 3 and 6 weeks was dichotomized to under and over with a cutoff of 20% reduction from T0 to T1 and 65% reduction (the 3D equivalent of size-based partial response criteria by RECIST) from T0 to T1a, respectively. Treatment outcome was evaluated based on residual cancer burden (RCB) on surgical pathology, an established surrogate for survival outcome3. Patients with RCB 0/I were considered as responders and those with RCB II/III as non-responders. Fisher’s exact test was used to examine the association between FTV reduction and treatment outcome, with P & lt;0.05 considered statistically significant. Ability of FTV reduction to detect non-responders was assessed by positive predictive value (PPV) and sensitivity, where non-responder was defined as “positive”. Results. Of the 104 patients, 49 patients (31 HR+HER2–;16 HR–HER2–; 2 HR+HER2+) who had both RCB and analyzable FTVs were included. Other patients were excluded because of missing RCB or FTV data (n = 18) or not having completed the assigned therapy (n = 37).FTV reduction at T1 and T1a was associated with outcome (P = 0.022 and & lt;0.001, respectively) (Table 1). FTV reduction at T1a was also associated with outcome in 26 patients with & lt;20% reduction at T1 (P = 0.047). The combined criteria of & lt;20 % reduction at T1 and & lt;65 % reduction at T1a detected non-responders with PPV of 82% and sensitivity of 95%, which outperformed the T1 only or T1a only criterion (Table 2†).Ability of combined criteria was experimentally tested using 20% cutoff for T1 and various cutoffs for T1a (Table 2). Criteria of & lt;20 % reduction at T1 and & lt;50 % reduction at T1a detected non-responders with PPV of 89% and sensitivity of 89%(Table 2‡). Conclusion. In this early small study, combined criteria using FTV reduction at 3 and 6 weeks of NAC showed high PPV and high sensitivity in early detection of non-responders as candidates for the treatment escalation option. Reference. 1. Radiology 263:663–672, 2012. 2. Radiology 279:44–55, 2016. 3. J Clin Oncol. 2007 Oct 01; 25(28) 4414-4422 Table 1.Association between FTV Reduction and Treatment ResponseCriteria based on FTV reduction at T1Total n = 49 & lt;20% reduction at T1 (n = 26) & gt;20% reductionat T1 (n = 23)P-valueNon-responder (RCB II or III)281990.022*Responder (RCB 0 or I)21714Criteria based on FTV reduction at T1aTotal n = 49 & lt;65% reduction at T1a (n = 30) & gt;65% reduction at T1a (n = 19)P-valueNon-responder (RCB II or III)28244 & lt; 0.001*Responder (RCB 0 or I)21615Combined criteria based on FTV reduction at T1 and T1aTotal n = 26 & lt;20% reduction at T1 & & lt;65% reduction at T1a (n = 22) & lt;20% reduction at T1 & & gt;65% reduction at T1a (n = 4)P-valueNon-responder (RCB II or III)191810.047*Responder (RCB 0 or I)743 Table 2.Performance of FTV Reduction-based CriteriaCriteria to detect non-respondersPPVNPVSensitivitySpecificityTrue positiveFalse negativeFalse positiveTrue negativeTotalT1 & lt;20% reduction†73%61%68%67%19971449T1a & lt;65% reduction†80%79%86%71%24461549T1 & lt;20% reduction & T1a & lt;40% reduction88%56%79%71%1542526T1 & lt;20% reduction & T1a & lt;45% reduction89%62%84%71%1632526T1 & lt;20% reduction & T1a & lt;50% reduction ‡89%71%89%71%1722526T1 & lt;20% reduction & T1a & lt;55% reduction86%80%95%57%1813426T1 & lt;20% reduction & T1a & lt;60% reduction86%80%95%57%1813426T1 & lt;20% reduction & T1a & lt;65% reduction †82%75%95%43%1814326T1 & lt;20% reduction & T1a & lt;70% reduction78%67%95%29%1815226T1 & lt;20% reduction & T1a & lt;75% decrease75%50%95%14%1816126Note: Unless otherwise specified, data represent the number of patients Citation Format: Natsuko Onishi, Jessica E Gibbs, Wen Li, David C Newitt, Elissa R Price, Barbara LeStage, William F Symmans, Angela M DeMichele, Christina Yau, the I-SPY 2 TRIAL Imaging Working Group, the I-SPY 2 TRIAL Consortium, Laura J Esserman, Nola M Hylton. Functional tumor volume at 3 and 6-week MRI as an indicator of patients with inferior outcome after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P3-03-01
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
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    Abstract P3-02-01: Initial experience of FES-dedicated breast PET imaging of early-stage ER+ invasive lobular carcinoma
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-02-01-P3-02-01
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-02-01-P3-02-01
    Abstract: BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, representing 15% of all invasive breast cancers. Most ILC tumors are estrogen receptor-positive (ER+) and may respond to endocrine therapy. However, tumor biologic factors such as ER functionality, cell proliferation, and molecular traits may influence endocrine treatment response and long-term recurrence risk, thus necessitating a comprehensive approach to characterize the primary breast tumor. [18F]fluoroestradiol (FES) is a radiotracer developed for positron emission tomography (PET) imaging of ER status. For this work, we studied the utility of imaging FES uptake in early-stage primary ER+ ILC lesions, using high-resolution dedicated breast PET (dbPET) to assess the relationship between FES uptake and tumor characteristics. METHODS: With institutional review board approval, patients with biopsy-proven ER+/HER2- ILC were prospectively imaged using dbPET with 5 mCi of FES before treatment. FES uptake (SUVmax, SUVmean, and SUVpeak), tumor uptake volume (TUV), and background parenchymal uptake (BPU) values were calculated. Background values (SUVbkg) were obtained from the normal region of the ipsilateral breast. Lesions with background-corrected SUVmax 2 times higher than SUVbkg were considered FES-avid. Tumor grade, Ki 67 cell proliferation index, and ER expression were obtained from core biopsies before treatment. Ki67 was dichotomized to low and high using a 20% cutoff1. Tumor size (longest diameter) was measured by magnetic resonance imaging (MRI). Spearman rank correlation was used to assess the relationship between FES uptake and tumor size. Differences between FES uptake at high and low Ki67 were compared using a Wilcoxon rank-sum test. RESULTS: 13 treatment-naïve ILC patients aged 32-82 years were included in this analysis (Table 1). Despite all lesions exhibiting strongly positive ER expression & gt;90% by immunohistochemistry (IHC), we observed varying FES avidity with 9 FES avid and 4 FES non-avid ILC lesions. SUVmax, TUV, and TBR had substantial median differences between Ki67 high and low lesions (5.9, 4.3, and 9.6, respectively), but the difference did not achieve statistical significance. FES tumor uptake also correlated with tumor size, with the highest correlation observed for SUVpeak (ρ = 0.71 (95% CI: 0.22, 0.91), p=0.010) (Table 2). CONCLUSION: We found that not all highly ER expressing ILC by IHC were FES-avid. As FES-dbPET captures information from the entire tumor, it provides a more comprehensive assessment of functional ER status than IHC of a limited tumor sample. FES uptake in ILC also relates to tumor size and Ki67. This is an ongoing study; additional data may help to guide endocrine therapy decisions. Future studies with a larger cohort are planned to assess the relationship between FES uptake and tumor grade and molecular risk profiles. 1. Acs, B. et al. Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagn Pathol 12, 20, doi:10.1186/s13000-017-0608-5 (2017). Patient and tumor characteristicsCharacteristicsNumber of patients (Total N=13)Age (median (range))56.0 (32-80)Pre-menopausal3Post-menopausal10MRI tumor size (median (interquartile range)4.1 (2.4-6.8)Tumor grade132931Ki6712Low/High3/9FES13Avid/Non-avid9/4 Summary of FES uptake values and correlation coefficients.FES avidity (N=13)Ki67 (N=12)MRI tumor size (N=12)Avid vs Non-avidHigh vs LowSpearman rank correlationMedian Difference (95% CI)P-valueMedian Difference (95% CI)P-valueSpearman ρ (95% CI)P-valueSUVmax8.68 (2.86, 12)0.0075.9 (-19.5, 11.6)0.140.67 (0.16, 0.9)0.017SUVmean2.56 (1.43, 4.86)0.0071.34 (-4.14, 3.1)0.200.6 (0.042, 0.87)0.039SUVpeak2.86 (1.14, 4.59)0.0112.15 (-14.4, 3.72)0.190.71 (0.22, 0.91)0.01BPU-0.31 (-1.89, 1.02)0.82-0.73 (-2.34, 0.28)0.0960.01 (-0.57, 0.58)0.98TUV (cm3)5.45 (1.04, 10)0.014.3 (-185, 10)0.190.70 (0.21, 0.91)0.011TBR3.61 (2.2, 13)0.0079.57 (-19.6, 12.4)0.0640.66 (0.13, 0.89)0.02 Citation Format: Ella F Jones, Deep K Hathi, Natalia Konovalova, Julissa Molina-Vega, David C Newitt, Courtney Lawhn-Heath, Kimberly M Ray, Bonnie N Joe, Diane Heditsian, Susie Brain, I-SPY 2 TRIAL Imaging Working Group, I-SPY 2 TRIAL Consortium, A. Jo Chien, Laura J Esserman, Nola M Hylton, Rita A Mukhtar. Initial experience of FES-dedicated breast PET imaging of early-stage ER+ invasive lobular carcinoma [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P3-02-01
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 3
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    Abstract P3-03-02: Diffusion-weighted MRI for prediction of pathologic complete response in HER2- breast cancer treated with pembrolizumab plus neoadjuvant chemotherapy
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-03-02-P3-03-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-03-02-P3-03-02
    Abstract: Background: Checkpoint blockade pembrolizumab has demonstrated great potential to improve pathologic outcome for HER2- breast cancer. The apparent diffusion coefficient (ADC) is a non-contrast MRI-derived biomarker that is sensitive to changes in tumor cellularity. Clinical trial ACRIN 6698, a sub-study of I-SPY 2, demonstrated that ADC can predict pathologic complete response (pCR). This study compares the utility of ADC for early prediction of pCR in patients with HER2- breast cancer randomized to pembrolizumab versus standard neoadjuvant chemotherapy (NACT) in I-SPY 2. Methods: A retrospective analysis of imaging and clinical data was performed on a cohort of 249 women diagnosed with high-risk, stage II/III breast cancer. All patients were randomized to the standard NACT (paclitaxel) or pembrolizumab plus paclitaxel for 12 weeks, followed by doxorubicin plus cyclophosphamide. MRI exams performed at pretreatment (T0) and 3 weeks after the treatment started (T1) were analyzed. Tumor ADC was calculated within manually delineated region-of-interests on diffusion-weighted MRI. The percent change of ADC from T0 to T1 was evaluated in the prediction of pCR after NACT. Statistical analysis included Wilcoxon rank sum test and the area under the ROC curve (AUC). A p-value & lt;0.05 was considered statistically significant. Results: A subcohort of 103 patients with analyzable diffusion-weighted MRI exams and known pCR (n=30)/non-pCR (n=73) outcome were included in this analysis. Among 103 patients, 62 had HR+/HER2- and 41 had triple negative breast cancer. Twenty-eight patients (17 HR+/HER2- and 11 triple negative) were randomized to receive pembrolizumab and 75 (45 HR+/HER2- and 30 triple negative) to standard NACT. Tumor ADC increased at 3 weeks in both standard and pembrolizumab cohorts with median ADC change of 11.5% (interquartile range [IQR]: 4.6, 16.2)% and 14.4% (IQR: 0.2, 19.9)%, respectively. In the pembrolizumab cohort, the difference in ADC change between non-pCR and pCR groups was estimated as -9.7% (95% confidence interval [CI] : -22.4, -0.9), with ADC increasing more in the pCR group. The AUC of predicting pCR in the pembrolizumab cohort was estimated as 0.73 (95%CI: 0.52, 0.93), while it was estimated as 0.63 (95% CI: 0.43, 0.83) in the standard NACT cohort. In comparison, the AUCs using functional tumor volume (FTV) to predict pCR were 0.61 (95%CI: 0.39, 0.83) and 0.66 (95% CI: 0.47, 0.85) in the corresponding cohorts (Table 1). The results suggest that ADC had higher association with pCR than FTV in the pembrolizumab cohort and FTV had higher association than ADC in the standard cohort. Conclusions: Tumor ADC, measured using diffusion-weighted MRI, demonstrates potential as a biomarker for assessing early response to immunotherapy in the neoadjuvant setting for high risk HER2- breast cancer. This study is limited by sample size. Future analysis with larger cohorts is warranted. Table 1.Association between MRI variables and pCRN (pCR rate)Difference between non-pCR and pCR groups (95% CI)AUC (95% CI)pDiffusion weighted MRI (percent change of ADC)Pembrolizumab28 (54%)-9.7 (-22.4, -0.9)0.73 (0.52, 0.93)0.041Standard75 (20%)-5.6 (-13.9, 2.1)0.63 (0.43, 0.83)0.13DCE-MRI (percent change of FTV)Pembrolizumab28 (54%)10.6 (-18.3, 43.9)0.61 (0.39, 0.83)0.34Standard74 (20%)25.3 (-0.6, 49)0.66 (0.47, 0.85)0.056 Citation Format: Wen Li, Nu N Le, Natsuko Onishi, David C Newitt, Jessica E Gibbs, Lisa J Wilmes, John Kornak, Savannah C Partridge, Barbara LeStage, Elissa R Price, Bonnie N Joe, I-SPY 2 TRIAL Imaging Working Group, I-SPY 2 TRIAL Consortium, Laura J Esserman, Nola M Hylton. Diffusion-weighted MRI for prediction of pathologic complete response in HER2- breast cancer treated with pembrolizumab plus neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-03-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P3-03-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 4
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    Abstract P3-02-02: FES-dedicated breast PET uptake in early-stage ER+ breast cancers
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-02-02-P3-02-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P3-02-02-P3-02-02
    Abstract: BACKGROUND: Patients with ER+ breast cancer may have a recurrence risk of aggressive disease. While clinical evidence suggests that ER+ tumors are responsive to endocrine therapy, up to one-third of patients with early-stage ER+ disease may not respond to endocrine therapy. Tumor biologic factors such as ER functionality, cell proliferation, and molecular traits may influence endocrine treatment responsiveness and long-term recurrence risk. More comprehensive tools are needed to depict the primary breast tumor. [18F]fluoroestradiol (FES) is a radiotracer developed for positron emission tomography (PET) imaging of ER status. We used FES with a high-resolution dedicated breast PET (dbPET) to quantify ER expression in primary ER+ tumors and assessed the relationship between FES uptake and tumor characteristics. METHODS: With IRB approval, patients with biopsy-proven ER+/HER2- breast cancer were imaged using dbPET with 5 mCi of FES before treatment. FES uptake (SUVmax, SUVmean, and SUVpeak), background parenchymal uptake (BPU), tumor uptake volume (TUV), and tumor to background ratio (TBR) were calculated. Background values (SUVbkg) were obtained from the normal region of the ipsilateral breast. Lesions with background-corrected SUVmax 2 times higher than SUVbkg were considered FES avid. Tumor size (longest diameter) was measured by MRI. The histologic subtype, ER expression, tumor grade, and Ki67 were obtained from core biopsies before treatment. Ki67 was dichotomized to low and high using a 20% cutoff. Spearman’s rank correlation was used to assess the correlation between FES uptake and tumor size. Differences between FES uptake, histologic subtype, and Ki67 were compared using a Wilcoxon rank-sum test. RESULTS: 19 treatment-naïve patients were included in this analysis as part of an ongoing study. Patient and tumor characteristics are listed in Table 1. While all patients had ER positivity & gt;90% by immunohistochemistry (IHC), we observed varying FES avidity in ER+ breast cancers, with 14 FES avid and 5 non-FES avid lesions. There was a statistically significant difference between FES avid vs. non-avid lesions measured by all uptake metrics except BPU. FES uptake in invasive ductal carcinoma was similar to invasive lobular carcinoma. FES uptake correlated with tumor size, with the highest correlation ρ = 0.58, 95% CI (0.17, 0.84), p=0.012, detected in TUV. FES uptake was associated with Ki67, with all uptake metrics except BPU showing a statistically significant difference between high and low Ki67 expression (Table 2). CONCLUSION: We found that not all lesions that were highly ER+ by IHC were FES avid. FES-dbPET captures information from the entire tumor, providing a more comprehensive assessment of functional ER status than IHC of a limited tumor sample. Moreover, FES uptake correlates with tumor size and cell proliferation. This is an ongoing study; additional data may help to guide endocrine therapy decisions. Future studies with a larger cohort are planned to assess the relationship between FES uptake and tumor grade and molecular risk profiles. Table 1.Patient and tumor characteristicsCharacteristicsNo. of patientsTotal N=19Age (median (IQR))56.0 (21.5)Pre-menopausal7Post-menopausal12Histologic subtypeInvasive ductal carcinoma (IDC)6Invasive lobular carcinoma (ILC)13Tumor size (N=18) (MRI LD (cm), median (IQR))3.2 (4.1)Tumor grade1421332Ki67Low12High6Unknown1FESNon-avid5Avid14 Table 2.Summary of baseline FES uptake valuesTumor Size (cm)FES AvidityHistologic SubtypeKi67Spearman CorrelationAvid vs. Non-avidILC vs. IDCHigh vs. Lowρ (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-valueMedian Diff (95%CI)P-valueSUVmax0.51 (0.054, 0.79)0.0318.02 (3.55, 11.9)0.0010.187 (-8.04, 6.32)0.976.38 (2.36, 11.6)0.017SUVmean0.31 (-0.18, 0.68)0.2042.42 (1.47, 3.49)0.001-0.477 (-1.96, 1.37)0.571.61 (0.81, 2.77)0.028SUVpeak0.46 (-0.0053, 0.76)0.0533.16 (1.42, 5.2)0.003-0.583 (-3.76, 2.61)0.633.16 (1.32, 4.66)0.013BPU-0.09 (-0.53, 0.39)0.723-0.33 (-1.25, 0.46)0.3790.226 (-0.58, 1.19)0.40-0.49 (-1.49, 0.28)0.122TUV (cm3)0.58 (0.15, 0.82)0.0125.45 (1.09, 12.5)0.005-2.82 (-12.5, 4.06)0.405.9 (0.98, 12.66)0.021TBR0.5 (0.047, 0.79)0.0333.48 (2.2, 13.5)0.001-0.295 (-11.9, 7.42)0.9010.2 (1.47, 13.49)0.028 Citation Format: Ella F. Jones, Deep K. Hathi, Julissa Molina-Vega, David C. Newitt, Courtney Lawhn-Heath, Kimberly M. Ray, Bonnie N. Joe, Diane Heditsian, Susie Brain, Rita A. Mukhtar, A. Jo Chien, Hope S. Rugo, I-SPY 2 TRIAL Consortium, I-SPY 2 TRIAL Imaging Working Group, Laura J. Esserman, Nola M. Hylton. FES-dedicated breast PET uptake in early-stage ER+ breast cancers [abstract] . In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-02.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P3-02-02
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 5
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    Abstract PS4-10: Serial MRI and pathology combined to select candidates for therapy de-escalation in the I-SPY 2 TRIAL
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS4-10-PS4-10
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS4-10-PS4-10
    Abstract: Background: The I-SPY 2 TRIAL, open to patients with locally advanced, molecular high-risk breast cancer, aims to bring each patient to pathologic complete response (pCR) with a minimum of toxicity. Here we test the hypothesis that imaging (MR volume predictors) combined with core biopsy may be used to accurately select candidates who show early response and provide an option of treatment de-escalation at mid-therapy (12 weeks). Methods: Of 100 I-SPY 2 patients with pathologist-assessed core biopsies at the inter-regimen time point (~12 weeks through treatment) and pCR data, 87 also had serial MR images and were considered in this study. Eleven I-SPY 2 TRIAL pathologists independently provided a digital assessment of the presence or absence of residual invasive cancer from H & E stained, and any requested ancillary IHC, images from imaging-guided core biopsies. Pathology predicts pCR if there is a consensus of no invasive residual disease. We generated predictions for all (55) unique pairs over the 11 pathologists, where pCR is predicted if both pathologists find no invasive cells. MRI pCR prediction models were previously developed on an independent dataset of ~990 I-SPY 2 patients, and applied to this cohort. Volume-based prediction models were previously optimized within each subtype and predicted probability thresholds were selected over a range of positive predictive value (PPV). In this study, MR predicts pCR (positive test) if the predicted probability is above a threshold that yields a given PPV value. For each pathologist pair, we combined pathology-based and MR-based predictors into a predictive-RCB (pre-RCB); and pre-RCB predicts a patient as pCR (RCB0) if both MR and pathology predicts pCR. Predictive performance is assessed by calculating the mean and range of PPV and sensitivity.Results: 39% (34/87) of the patients in this study achieved pCR. Over all pairs of pathologists, on average 80% of pathology-only predicted pCRs were true pCRs (mean PPV = 80% [range: 69-92%]), and 74% of patients who achieved pCR were predicted pCR by pathology alone (mean sensitivity = 74% [65-82%] ). We assessed combinations with MR probability thresholds at PPV levels 50%-70%; and observed the best balance of PPV and sensitivity for the pre-RCB when MR thresholds were set at 50% PPV level. At this threshold setting, the pre-RCB achieved a PPV = 92% [83-100%], meaning on average 92% of predicted pCRs were true pCRs, and this improvement in positive predictive performance over pathology alone is achieved with a lower but still-reasonable 53% sensitivity [33-62%] . Conclusion: Pre-RCB, which predicts a patient as pCR if both MR and inter-regimen pathology predicts pCR, provides clinically actionable accuracy for treatment de-escalation for early responders (PPV & gt;90%). Adding a final MR review at the time of early surgery may further improve performance. Resulting from data presented in this abstract, the pre-RCB algorithm, including the final MR review, has been operationalized and will be used prospectively to identify patients who are highly likely to have already achieved pCR by the inter-regimen timepoint. Citation Format: Sara J Venters, Wen Li, Denise M Wolf, Jodi M Carter, Molly E Klein, Kamaljeet Singh, Kimmie Rabe, I Tolgay Ocal, David Newitt, Christina Yau, Natsuko Onishi, Jessica Gibbs, Sunati Sahoo, Shuko Harada, Laila Khazai, Malini Harigopal, Alexander D Borowsky, Gregor Krings, Ronald Balassanian, Yunn-Yi Chen, Kimberley Cole, Sonal Shad, Barbara LeStage, Amy Delson, Sandra Finestone, Lamorna Brown-Swigart, I-SPY 2 Imaging Working Group, I-SPY 2 TRIAL Consortium, Laura Esserman, Laura van ‘t Veer, W Fraser Symmans, Nola M Hylton. Serial MRI and pathology combined to select candidates for therapy de-escalation in the I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-10.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS4-10
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    Abstract P2-07-03: Refining neoadjuvant predictors of three year distant metastasis free survival: Integrating volume change as measured by MRI with residual cancer burden
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 4_Supplement ( 2019-02-15), p. P2-07-03-P2-07-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 4_Supplement ( 2019-02-15), p. P2-07-03-P2-07-03
    Abstract: Background: Patients achieving a pathologic complete response (pCR) following neoadjuvant therapy have significantly improved event-free survival relative to those who do not; and pCR is an FDA-accepted endpoint to support accelerated approval of novel agents/combinations in the neoadjuvant treatment of high risk early stage breast cancer. Previous studies have shown that recurrence risk increased with increasing burden of residual disease (as assessed by the RCB index). As well, these studies suggest that patients with minimum residual disease (RCB-I class) also have favorable outcomes (comparable to those achieving a pCR) within high risk tumor subtypes. In this study, we assess whether integrating RCB with MRI functional tumor volume (FTV), which in itself is prognostic, can improve prediction of distant recurrence free survival (DRFS); and identify a subset of patients with minimal residual disease with comparable DRFS as those who achieved a pCR. Imaging tools can then be used to identify the subset that will do well early and guide the timing of surgical therapy. Method: We performed a pooled analysis of 596 patients from the I-SPY2 TRIAL with RCB, pre-surgical MRI FTV data and known follow-up (median 2.5 years). We first assessed whether FTV predicts residual disease (pCR or pCR/RCB-I) using ROC analysis. We applied a power transformation to normalize the pre-surgical FTV distribution; and assessed its association with DRFS using a bi-variate Cox proportional hazard model adjusting for HR/HER2 subtype. We also fitted a bivariate Cox model of RCB index adjusting for subtype; and assessed whether adding pre-surgical FTV to this model further improves association with DRFS using a likelihood ratio (LR) test. For the Cox modeling, penalized splines approximation of the transformed FTV and RCB index with 2 degrees of freedom was used to allow for non-linear effects of FTV and RCB on DRFS. Result: Pre-surgical MRI FTV is significantly associated with DRFS (Wald p & lt;0.00001), and more effective at predicting pCR/RCB-I than predicting pCR alone (AUC: 0.72 vs. 0.65). Larger pre-surgical FTV remains associated with worse DRFS adjusting for subtype (Wald p & lt;0.00001). The RCB index is also significantly associated with DRFS adjusting for subtype (Wald p & lt;0.00001). Adding FTV to a model containing RCB and subtype further improves association with DRFS (LR p=0.0007). RCB-I patients have excellent DRFS (94% at 3 years compared to 95% in the pCR group). Efforts are underway to identify an optimal threshold for dichotomizing pre-surgical FTV and FTV change measures for use in combination with pCR/RCB-I class to generate integrated RCB (iRCB) groups as a composite predictor of DRFS. Conclusion: Pre-surgical MRI FTV is effective at predicting minimal residual disease (RCB0/I) in the I-SPY 2 TRIAL. Despite the association between FTV and RCB, FTV appears to provide independent added prognostic value (to RCB and subtype), suggesting that integrating MRI volume measures and RCB into a composite predictor may improve DRFS prediction. Citation Format: Hylton NM, Symmans WF, Yau C, Li W, Hatzis C, Isaacs C, Albain KS, Chen Y-Y, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal I, Tawfik O, Grasso LeBeau L, Sahoo S, Vinh T, Yang S, Adams A, Chien AJ, Ferero-Torres A, Stringer-Reasor E, Wallace A, Boughey JC, Ellis ED, Elias AD, Lang JE, Lu J, Han HS, Clark AS, Korde L, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Wood WC, Park JW, Liu MC, Olopade O, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, Haugen PK, van't Veer LJ, Perlmutter J, Melisko ME, Wilson A, Peterson G, Asare AL, Buxton MB, Paoloni M, Clennell JL, Hirst GL, Singhrao R, Steeg K, Matthews JB, Sanil A, Berry SM, Abe H, Wolverton D, Crane EP, Ward KA, Nelson M, Niell BL, Oh K, Brandt KR, Bang DH, Ojeda-Fournier H, Eghtedari M, Sheth PA, Bernreuter WK, Umphrey H, Rosen MA, Dogan B, Yang W, Joe B, I-SPY 2 TRIAL Consortium, Yee D, Pusztai L, DeMichele A, Asare SM, Berry DA, Esserman LJ. Refining neoadjuvant predictors of three year distant metastasis free survival: Integrating volume change as measured by MRI with residual cancer burden [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS18-P2-07-03
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    Abstract PS4-09: Pathologic features of the inter-regimen biopsy predict response to neoadjuvant therapy in the I-SPY 2 TRIAL
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS4-09-PS4-09
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS4-09-PS4-09
    Abstract: Background: I-SPY 2 is a neoadjuvant platform trial open to patients with locally advanced, molecular high-risk breast cancer. In a concerted pursuit of mid-therapy response biomarkers, we evaluated inter-regimen biopsies, to identify patients who may be candidates for treatment de-escalation. In a pilot study, we observed that absence of carcinoma in an inter-regimen biopsy may predict pathologic complete response (pCR). In this expanded study of 100 participants, we sought to confirm that finding and assess pathologic features of the inter-regimen biopsy as predictors of tumor response to neoadjuvant therapy. Methods: Digital H & E images of 100 inter-regimen (12 week) image-guided breast biopsies +/- ancillary immunohistochemistry (p63 and/or cytokeratin) were reviewed by 9 I-SPY affiliated pathologists to record 1) tumor bed and 2) presence/absence of residual invasive carcinoma (IC) (with tumor cellularity scored as 0-100%). The data set included 393 cores (mean 3.9 (2-4) cores/biopsy). Fisher’s exact t-test was used for association of presence/absence of IC with pCR, and tumoral hormone receptor (HR) and HER2 status. Association between biopsy tumor cellularity and residual cancer burden (RCB) indices used Pearson’s correlation. Results: In the biopsy set, 84 (84%) had ≥80% inter-observer diagnostic agreement on both 1) presence of tumor bed and 2) presence/absence of IC (53 IC+ /31 IC-). IC+/IC- biopsies had equal numbers of evaluable tissue cores. The primary tumors were 63% HR+/37% HR-. The presence of IC in the biopsy correlated with tumoral HR/HER2 status (p=0.0014: 74%: HR+HER2-; 62%: TN; 60%: HR+HER2+; 10%: HR-HER2+). Of 31 patients with IC- biopsies, 25 (80%) went on to pCR, whereas only 7/53 (13%) of patients with IC+ biopsies had pCR, conferring an odds ratio for pCR of 26, Fisher p=7.5E-10. Overall, IC- biopsies had a positive predictive value (PPV) for pCR of 81%, with a PPV for HR- tumors of 94% vs. 67% for HR+ tumors (Table 1). In the 6 IC- biopsies from patients with non-pCR (“false-negatives”), most were HR+ (5/6, Table 1), and tumor bed size in the resection specimen was smaller than for IC+ biopsies with non-pCR: 276 mm2 (0.4-1000 mm2) vs. 1166 mm2 (1-11960 mm2). In contrast, the 46/53 IC+ biopsies in patients with non-pCR had a PPV for predicting non-pCR of 86%, (PPV for HR+ tumors: 94% vs. PPV for HR- tumors: 66%. Tumor cellularity in the biopsy (mean 37%, [2.5-93%]) did not correlate with RCB index (p=0.57) or RCB breast-only index (p = 0.17) at resection. Conclusion: In this 100 biopsy set from the I-SPY2 trial, the absence of residual carcinoma in inter-regimen biopsies was highly predictive of pCR, particularly for HR- tumors. The “false-negative” biopsies (IC-/non-pCR) were predominantly HR+ tumors with small residual tumor beds at resection. Conversely, the presence of carcinoma in inter-regimen biopsies was highly predictive of non-pCR, particularly for HR+ tumors. These data demonstrate the utility, and the limitations, of the inter-regimen biopsy as one tool to identify patients who may benefit from therapeutic de-escalation. Table 1: PPV for pCR/non-PCR by Inter-regimen Biopsy StatusInter-regimen biopsy with or without Invasive carcinoma (IC+/-)pCRnon-pCRPPV (Sensitivity) for pCR(IC- Biopsies)PPV (Sensitivity) for non-pCR(IC+ biopsies)IC- biopsiesAll25681% (78%)-HR+10567% (83%)-HR-15194% (75%)-IC+ biopsiesAll746-86% (88%)HR+236-94% (88%)HR-510-66% (91%) Citation Format: Jodi M Carter, Molly E Klein, Sara J Venters, Kimmie Rabe, I Tolgay Ocal, Kamaljeet Singh, Denise M Wolf, Sunati Sahoo, Shuko Harada, Laila Khazai, Malini Harigopal, Alexander D Borowsky, Gregor Krings, Ronald Balassanian, Yunn-Yi Chen, Kimberley Cole, Sonal Shad, Amy Delson, Lamorna Brown-Swigart, I-SPY 2 TRIAL Consortium, Laura Esserman, Laura van ‘t Veer, W Fraser Symmans. Pathologic features of the inter-regimen biopsy predict response to neoadjuvant therapy in the I-SPY 2 TRIAL [abstract] . In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-09.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS4-09
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    Adaptively randomized trial of neoadjuvant chemotherapy with or without the Akt inhibitor MK-2206: Graduation results from the I-SPY 2 Trial.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. 524-524
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. 524-524
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.524
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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    Abstract GS5-01: Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. GS5-01-GS5-01
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. GS5-01-GS5-01
    Abstract: Background: Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer (BC) to better inform on patient outcomes. Also, a pooled subject-level analysis allows more detailed analyses of generalizability of the prognostic meaning of RCB assessments in a broader experience of practice settings. Method: Subject-level RCB results, with relevant clinical and pathologic stage, tumor subtype and grade, demographic, treatment and follow-up data from 11 institutes/trials are being collected for combined analysis. The association between the continuous RCB index and event-free survival (EFS), and distant recurrence free survival (DRFS) were assessed using mixed effect Cox models with the incorporation of random RCB coefficients to account for between-study heterogeneity. We will also allow for differences in baseline hazard across biological BC subtypes and, if needed, across studies as well. In addition to this stratified mixed effect model, a multivariate analysis adjusting for age, T-category, nodal status and grade was performed within each subtype. In addition, mixed effect Cox models will be employed to evaluate association between RCB index with EFS and DRFS within each HR/HER2 subtype. Kaplan Meier estimates of EFS and DRFS at 5 and 10 years were computed for each RCB class within subtype. Results: We analyzed subject-level data from 9 institutes/trials representing 4077 patients currently available from an anticipated final total of 4,800 patients (to be presented at the meeting). There were 950 EFS and 876 DRFS events during follow up (median 65 months, IQR: 70 months). RCB index (continuous) was independently prognostic within each subtype: HR+/HER2- (EFS HR (per unit increase in RCB index) =1.64, 95%CI 1.48-1.82; DRFS HR=1.68, 1.51-1.87), HR+/HER2+ (EFS HR=1.80, 1.57-2.05; DRFS HR=1.93, 1.67-2.24), HR-/HER2+ (EFS HR=2.15, 1.76-2.62; DRFS HR=2.10, 1.77-2.50), and HR-/HER2- (EFS HR=2.05, 1.89-2.22; DRFS HR=2.16, 1.90-2.46); and remained prognostic in multivariate models adjusting for age, grade, and clinical T and N stage at diagnosis. Table 1 contains the response rate and estimated EFS at 5 years and 10 years for each RCB class within each HR/HER2 phenotype (DRFS results were similar). Conclusions: Long-term prognosis after pCR was similarly excellent in all phenotypic subtypes. RCB index and classification was independently and strongly prognostic in all subtypes, and generalizable to multiple practice settings. Prognostic differences by RCB class occurred within 5 years in HR- BC, but extended to 10 years in HR+ BC. RCB-I had slightly worse EFS than pCR in HR- BC and HR+/HER2+ BC (after 5 years), but the same EFS as pCR in HR+/HER2- BC. Complete analysis of all subjects, including neoadjuvant treatments, will be presented at the meeting. PhenotypeOutcomepCRRCB-IRCB-IIRCB-IIIHR+/HER2-Frequency (%)11%10%52%27%(N=1467)5 yr EFS (95% CI)91% (86-96)93% (89-98)82% (79-85)70% (65-75)10 yr EFS (95% CI)84% (75-93)88% (82-95)71% (67-75)52% (46-58)HR+/HER2+Frequency (%)38%18%35%9%(N=762)5 yr EFS (95% CI)94% (91-97)93% (88-98)78% (73-84)49% (37-65)10 yr EFS (95% CI)91% (86-96)79% (70-90)65% (59-73)42% (29-60)HR-/HER2+Frequency (%)66%11%18%5%(N=550)5 yr EFS (95% CI)93% (90-96)88% (79-97)60% (50-71)45% (30-69)10 yr EFS (95% CI)90% (86-94)84% (74-95)56% (46-68)45% (30-69)HR-/HER2-Frequency (%)41%13%33%13%(N=1293)5 yr EFS (95% CI)92% (90-94)85% (79-91)68% (63-72)28% (21-36)10 yr EFS (95% CI)87% (82-91)80% (72-88)63% (58-68)24% (18-33) Citation Format: Christina Yau, Marieke van der Noordaa, Jane Wei, Marie Osdoit, Fabien Reyal, Anne-Sophie Hamy, Marick Lae, Miguel Martin, Maria del Monte, I-SPY 2 TRIAL Consortium, Judy C Boughey, Rebekah Gould, Jelle Wesseling, Tessa Steenbruggen, Maartje van Seijen, Gabe Sonke, Stephen Edge, Stephen-John Sammut, Elena Provenzano, Jean Abraham, Peter Hall, Ashley Graham, Lorna Mackintosh, David Cameron, Alice Wang, Priyanka Sharma, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura van ‘t Veer, Laura Esserman, W. Fraser Symmans. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-GS5-01
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 10
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    Abstract PS6-05: Impact of body mass index on pathological complete response after neoadjuvant chemotherapy: Results from the I-SPY 2 trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS6-05-PS6-05
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS6-05-PS6-05
    Abstract: Purpose: Increased body mass index (BMI) is a risk factor for breast cancer and has been associated with poor outcomes in both premenopausal and postmenopausal breast cancer patients. Several retrospective studies have demonstrated higher BMI to be associated with inferior pathological complete response (pCR) to neoadjuvant chemotherapy, yet it remains unclear if this difference is related to chemotherapy underdosing among obese breast cancer patients. We evaluated the association between BMI and response to neoadjuvant chemotherapy (defined by pCR) in the I-SPY 2 trial, an adaptive clinical trial platform enrolling biologically high-risk breast cancer patients (triple negative, human epidermal growth factor receptor 2 (HER2) positive and MammaPrint high-risk) that utilizes standard neoadjuvant therapy regimens with treatment based on actual body weight. Patients and Methods: From 3/2010 to 11/2016, 989 patients were enrolled in the I-SPY 2 trial, 978 had a recorded baseline BMI prior to treatment and were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI & gt;=30 kg/m2), overweight (25= & lt;BMI & lt;30 kg/m2), and normal or underweight ( & lt;25 kg/m2) based on World Health Organization criteria. pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR, and we reported odds ratios (OR) and 95% confidence intervals (CI). Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. Results: The median age in our study population was 49 years. 35% of patients were normal/underweight, 32% overweight, and 33% obese. Black patients were more likely to be obese (P & lt;0.0001). pCR rates differed significantly by tumor subtype (P & lt;=0.0001) and tumor stage (P=0.0009). pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariate analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR to neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR=1.1, 95%CI: 0.68-1.63, p=0.83), and for overweight compared with normal/underweight (OR=1, 95%CI: 0.64-1.47, p=0.88). We tested for potential interaction between BMI and breast cancer subtype, however, the interaction was not significant in the multivariate model (P=0.09) (Table 1). Multivariate Cox regression showed there was no difference in EFS (p=0.81) or OS (p=0.52) between obese, overweight and normal/underweight breast cancer patients with a median follow-up time of 4.0 years. Conclusions: There was no difference in pCR rates by BMI with actual body weight based neoadjuvant chemotherapy in this biologically high-risk breast cancer population. In contrast, breast cancer subtype and stage showed predictive value for pCR in this high-risk operable breast cancer population receiving neoadjuvant chemotherapy in the I-SPY 2 clinical trial. Table 1: pCR rate of different BMI categories by breast cancer subtypes.Breast Cancer SubtypepCRNormal/underweight Frequency (%)OverweightFrequency (%)ObeseFrequency (%)P-valueHR+/HER2+No39 (61.9)27 (61.4)32 (66.7)0.83Yes24 (38.1)17 (38.6)16 (33.3)HR+/HER2-No105 (80.8)116 (89.2)93 (78.8)0.06Yes25 (19.2)14 (10.8)25 (21.2)HR-/HER2+No7 (25.0)11 (35.5)15 (51.7)0.11Yes21 (75.0)20 (64.5)14 (48.3)HR-/HER2-No83 (65.4)58 (55.8)76 (60.8)0.33Yes44 (34.7)46 (44.2)49 (39.2)(HR: hormone receptor, HER2: human epidermal growth factor receptor 2) Citation Format: Haiyun Wang, Douglas Yee, David Potter, Patricia Jewett, Christina Yau, Heather Beckwith, Allison Watson, Nicholas G O'Grady, Amy Wilson, Susie Brain, I-SPY 2 TRIAL Consortium, Anne Blaes. Impact of body mass index on pathological complete response after neoadjuvant chemotherapy: Results from the I-SPY 2 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-05.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS6-05
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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