tbuckley/cabot-search huggingface dataset:
Prognostic value of response assessed by RECIST and WHO criteria to neoadjuvant chemotherapy in locally advanced gastric cancer patients
Authors: S. R. Park, J. S. Lee, Y. W. Kim, I. J. Choi, K. W. Ryu, J. H. Lee, J. Y. Lee, Y. L. Park, S. Y. Park, Y. I. Park, N. K. Kim
Journal: Journal of Clinical Oncology (2009)

e15647 Background: In metastatic gastric cancer, the response to chemotherapy is assessed by RECIST or WHO criteria according to the change of tumor size. There are no data, however, on the usefulness of those criteria in evaluating tumor response in the setting of neoadjuvant chemotherapy. The aim of this study was to evaluate the relationship between tumor response to neoadjuvant chemotherapy-as assessed by RECIST and WHO criteria-and clinical outcome in locally advanced gastric cancer (LAGC) patients. Methods: This study recruited LAGC patients who, from January 2003 through November 2005, entered the neoadjuvant arm of prospective randomized phase II trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy. LAGC was defined as stage III or IV (M0) disease based on computed tomography (CT) according to the Japanese Classification of Gastric Carcinoma. Patients with measurable lesions received 3 cycles of neoadjuvant chemotherapy consisting of docetaxel (36 mg/m 2 ) and cisplatin (40 mg/m 2 ) on days 1 and 8 every 3 weeks, followed by surgery. Results: After chemotherapy, 40 (95%) patients underwent surgery and the remaining 2 patients showed new distant metastasis on CT scan. Thirty-five (83%) patients had curative R0 resection. Twenty-eight (67%) patients had a clinical response to neoadjuvant chemotherapy according to RECIST/WHO criteria. Although R0 resection rate (93% vs 64%, P = 0.03), median relapse-free survival (RFS) (43.2 vs 7.5 months, P = 0.14), and overall survival (OS) (not reached vs 27.0 months, P = 0.10) were better in responders than non-responders, they did not differ significantly in the subgroup that subsequently underwent surgery. When we redefined the decrease in tumor size judged as a response by RECIST (≥60% rather than ≥30%) and WHO (≥75% rather than ≥50%) criteria, response correlated significantly with both RFS (P = 0.03) and OS (P = 0.02). Conclusions: In the neoadjuvant setting, which frequently involves smaller measurable lesions than the metastatic setting, larger changes in tumor size than those specified by RECIST and WHO criteria are needed to predict postoperative outcome. No significant financial relationships to disclose.
만성 간질환에서 혈청 retinol binding protein 4의 임상적 의의
Authors: 권정현 ( Jung Hyun Kwon ), 박성태 ( Seong Tae Park ), 김기대 ( Gi Dae Kim ), 유찬란 ( Chan Ran You ), 김진동 ( Jin Dong Kim ), 우현영 ( Hyun Young Woo ), 장정원 ( Jeong Won Jang ), 김창욱 ( Chang Wook Kim ), 배시현 ( Si Hyun Bae ), 최종영 ( Jong Young Choi ), 윤승규 ( Seung Kew)
Journal: Clinical and Molecular Hepatology (2009)

목적: 혈청 retinol binding protein 4(RBP4)는 레티놀의 특이적인 운반단백질로 알려져 있었으나 최근 인슐린 저항성과의 연관성이 보고되었다. 혈청 hyaluronic acid(HA)는 간섬유화의 지표로 알려져 있다. 이번 연구는 만성 간질환 환자에서 혈청 RBP4의 간질환의 진행 정도를 반영하는 혈청 표지자로서의 역할을 알아보고자 하였다. 대상과 방법: 강남성모병원 소화기내과를 방문하여 혈청 RBP4와 HA를 검사한 573명(만성 간염 환자 235명, Child-Pugh A등급 간경변증 환자 230명, Child-Pugh B와 C등급 간경변증 환자 108명)의 만성 간질환 환자와 정상 대조군 40명의 결과를 분석하였다. 결과: 대상 환자의 평균 나이는 53.1세였고, 남녀 비율은 410:203이었다. 원인별로는 B형간염바이러스에 의한 간질환이 61.9%로 가장 많았고, C형간염바이러스와 알코올에 의한 간질환이 각각 9.8%와 9.0%, 비알코올지방간 질환이 3.8%였다. 혈청 RBP4치는 정상 대조군에서 진행성 간경변증으로 진행할수록 유의하게 감소하였고, 반대로 혈청 HA치는 간질환이 진행할수록 증가하였다(정상 대조군, 만성 간염, Child-Pugh A등급 간경변증, Child-Pugh B와 C등급에서 각각 RBP4는 4.3±0.1, 3.6±0.1, 2.6±0.1, 1.6±0.1 mg/ dL, HA는 25.3±28.1, 75.5±7.8, 184.4±14.5, 656.5±86.7 ng/mL, P<0.001). 사후분석에서 혈청 RBP4는 만성 간염환자군과 Child-Pugh A등급 간경변증 환자군 간에도 차이를 보여 조기에 만성 간질환을 구분할 수 있었다. 혈청 RBP4와 HA는 간조직검사의 섬유화 정도와 상관관계를 보였고(n=80, P<0.05), 다른 혈청 간기능 지표들과도 관련성을 보였다. 항바이러스치료 전후로 혈청 RBP4와 HA를 측정하였던 45명에서(관찰기간의 중앙값 1,205일), 치료 후 혈청 RBP4치와 혈청 알부민치, ALT치, HBV DNA 수치는 유의하게 호전되었으나 HA 수치는 차이를 보이지 않았다. 결론: 혈청 RBP4는 만성 간질환 환자에서 간질환의 진행 정도에 따라 감소하여 질환의 진행 정도를 평가할 수 있는 새로운 지표로 의미가 있으며, 항바이러스치료 후 간질환의 호전을 관찰할 수 있는 지표로 고려할 수 있겠다.
Effects of bortezomib (PS-341) on NF-κB activation in peripheral blood mononuclear cells (PBMCs) of advanced non-small lung cancer (NSCLC) patients: A phase II/pharmacodynamic trial
Authors: J. P. Stevenson, C. W. Nho, S. W. Johnson, T. L. Evans, K. A. Algazy, M. Gallagher, I. A. Vasilevskaya, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2004)

7145 Background: The proteasome inhibitor PS-341 disrupts multiple pathways involved in malignant cell growth and survival including antiapoptotic signaling by the transcription factor NF-κB. Inihibition of proteasomal degradation of ubiquitinated IκB prevents activation of NF-κB and phosphorylation of its p65 (RelA) subunit. Previous human studies showed proteasome inhibition in whole blood to occur within 1 hour after PS-341 dose and return to near-baseline levels in 24 hours. Methods: 23 patients with advanced NSCLC (≤ 1 prior regimen) received 1.3–1.5 mg/m2 PS-341 as an IV bolus on days 1,4,8,11 every 21 days. PBMCs were collected on day 1 of cycle 1 pre-treatment and 0.5, 1, 4, 8, and 24 h post-treatment. Expression of p65 and phosphorylated-p65 (pp65) was examined by western blot analysis in a group of patients (n=12) with and without gr 3 toxicity. Results: There was 1 PR and 9 SD (lasting > 4 cycles in 5 pts) in 22 evaluable pts. Grade 3 toxicities included N/V (3 pts), sensory neuropathy (1 pt), constipation (2 pts), rash (1 pt), and thrombocytopenia (3 pts). Total p65 did not change in the toxicity cohort. The ratio of pp65/p65 was similarly unaffected across the entire group, but in patients who experienced gr 3 toxicity a significant decrease in pp65/p65 was noted beginning at 30 min, with nadir at 4 h and recovering at 24 h. The mean decrease was to 79±21% of control. Patients without gr 3 toxicity had no decrease in pp65/p65 ratio. The expression of NF-κB-regulated genes and the relationship of NF-κB effects in PBMCs to outcome is being studied. Conclusions: 1) Single-agent PS-341 was tolerable and displayed antitumor activity in pts with minimally-pretreated advanced NSCLC. 2) The effects of PS-341 on NF-κB in PBMCs showed a decrease in antiapoptotic signaling in the 24 h after dose, maximal at 4 h, only in pts who experienced gr 3 toxicity. 3) The time-course of signaling effects may have implications for the scheduling of PS-341 in combination with cytotoxic chemotherapy. No significant financial relationships to disclose.
A phase I study of 17-AAG in relapsed/refractory pediatric patients with solid tumors: A Children’s Oncology Groups study
Authors: B. Weigel, S. Blaney, J. Kersey, R. Bagatell, S. P. Ivy, L. Whitesell, M. Krailo, J. Reid, M. Ames, P. Adamson
Journal: Journal of Clinical Oncology (2006)

9018 Background: A pediatric phase I study of 17-allylaminogeldanamycin (17-AAG), an Hsp90 inhibitor, was conducted to determine the dose limiting toxicities (DLTs), the recommended phase II dose, the pharmacokinetics (PK), and to evaluate a surrogate marker for Hsp90 inhibition in peripheral blood mononuclear cells (PBMCs). Methods: Cohorts of 3–6 pts were enrolled at dose levels of 150, 200, 270 and 360 mg/m 2 /dose, administered as a 60 min infusion, on days 1, 4, 8 and 11 of a 21-day cycle. PK and PBMC evaluations were done during the first course of therapy. Results: 17 pts (7 male), median 7 yrs of age (range 1–19), were enrolled. 5 pts who developed PD prior to completing a full cycle of therapy were not considered evaluable for toxicity. No DLTs occurred. Non-DLTs included elevated transaminases (n=6), anemia (n=3), and vomiting (n=3). Based on the adult recommended dose and challenges posed by infusing the large volumes of DMSO, dose escalation was stopped at dose level 4. No CRs or PRs were observed; 3 patients remain on therapy at 6, 7 and 9 months with SD. One patient with hepatoblastoma had a reduction in AFP and SD over 3 cycles. PK data is available from the initial 3 dose levels. Drug exposure increases in proportion to dose for both17-AAG and its metabolite 17-AG. At 270 mg/m 2 /dose the Cmax and AUC of 17-AAG were 5,303 ± 1,591 ng/ml and 13,150 ± 5,086 ng/ml*hr, respectively, similar to the exposure in adults. The mean terminal half-life for 17-AAG was 3.0 ± 0.5 hrs. Induction of Hsp72, a surrogate marker for inhibition of Hsp90 was detected at all dose levels. Conclusions: The recommended phase II dose of 17AAG is 360mg/m 2 /day. Non-DMSO formulations may allow for further dose escalation in children and should be studied. No significant financial relationships to disclose.
Phase I study of amonafide + cytosine arabinoside (AraC) in patients with poor risk acute myeloid leukemia (AML)
Authors: S. L. Allen, J. E. Kolitz, A. Lundberg, M. Champagne, S. Devost, R. Dubon, M. Drouin, M. A. Boss, C. K. Grieshaber, D. R. Budman
Journal: Journal of Clinical Oncology (2005)

6602 Background: Amonafide (Am) is an ATP independent topoisomerase 2 inhibitor that in prior clinical studies demonstrated activity in breast cancer (18–25% response rate (RR)) and prostate cancer (12% RR) with the dose limiting AE being myelosuppression. Prior studies evaluated single agent Am in AML; in one study a complete response (CR) rate of 24% (4/17) was observed. This cohort dose-escalation study was designed to evaluate Am in combination with conventional dose AraC in patients (pts) with poor risk AML. Methods: 26 pts with relapsed AML (n=8), 2° AML (n=15) or CML in blast crisis (BC) (n=3) were treated with AraC 200 mg/m2/day CIV x 7 days plus a fixed dose of Am IV over 2 hrs daily x 5 days. Pts were treated at Am doses of 600 mg/m2/d (n=6), 800 mg/m2/d (n=5) and 700 mg/m2/d (n=15). Median patient age was 67 years (range 30–82). Results: All 26 pts were evaluable for safety. The dose limiting toxicity (DLT) was painful mucositis and erythematous rash in 3/5 pts at 800 mg/m2/d. The MTD of Am when given together with AraC in this regimen was 700 mg/m2/d. 5 early deaths occurred on study; 1 additional pt was discontinued for worsening clinical condition. Among all pts the CR rate was 10/26 (38%). 2 additional pts with AML secondary to MDS were noted to have partial remissions. Of the 10 pts with CR, 3 were diagnosed with 2° AML from MDS, 2 with 2° AML from previous radiotherapy and/or chemotherapy, 4 with relapsed AML, and 1 with CML BC. The CRs occurred in 5/15 pts with 2° AML, 4/8 pts with relapsed AML, and 1/3 pts with CML BC. The median CR duration following Am + AraC therapy (and consolidation therapy for some pts) was 5 months; 2 pts remained disease free for >2 years. Conclusions: The combination of Am + AraC demonstrated antileukemic activity in poor risk AML pts with an acceptable safety profile. The MTD of Am is 700 mg/m2/d x 5 days when combined with conventional dose AraC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xanthus Life Sciences Xanthus Life Sciences
Low dose mitomycin c, capecitabine &amp; radiation for HIV patients with anal squamous cell carcinoma
Authors: R. Wadleigh, K. Dinh, J. Manning, A. Kuntz, R. Dorn
Journal: Journal of Clinical Oncology (2006)

14148 Background: Chemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal squamous cell carcinoma (ASCC). Optimal chemotherapy regimen for ASCC in HIV positive patients is not yet defined. The addition of mitomycin C to 5-FU and radiotherapy in the past improves local control, colostomy-free, and even disease-free survival in large tumors. The concern is hematologic toxicity if use in HIV positive patients. We report 2 cases safely using low dose mitomycin C, capecitabine and concurrent XRT. One of these patients has ESRD, which the use of cisplatin is not an option. Methods: 2 HIV positive patients, (CD4 range 106–113, at diagnosis of ASCC) were treated with low dose of mitomycin C on day 1 for 2 cycles (5mg flat dose), day 1–7 capecitabine titrated up to 1.5 gm/m 2 divided b.i.d, and concurrent XRT (total dose 5040 cGy). Prior to treatment, 1 patient was diagnosed with squamous cell carcinoma in-situ and the other with stage 1 squamous cell carcinoma. 1 patient has end stage renal disease with SCr between 10 and 12 mg/dl at the time of treatment. Results: Both patients completed treatment. No grade 3 or 4 hematologic or gastrointestinal toxicities were noted. No hand-foot syndrome was observed probably due to low dose of capecitabine. Both patients are still alive and remain in remission (16–18 months post treatment). Conclusions: Our 2 cases suggest that the use of low dose mitomycin C in addition to capecitabine and XRT is well tolerated and is efficacious in HIV-positive patients with ASCC. No significant financial relationships to disclose.
Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.
Authors: S Kaul, L N Igwemezie, D J Stewart, S Z Fields, M Kosty, N Levithan, R Bukowski, D Gandara, G Goss, P O'Dwyer
Journal: Journal of Clinical Oncology (1995)

PURPOSE To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.
Patient preferences for adjuvant treatment of early-stage breast cancer
Authors: T. Fama, M. Wood, H. Muss
Journal: Journal of Clinical Oncology (2005)

733 Introduction: Several recent studies show that women would choose adjuvant therapy for a small improvement in survival. This study examines patient preferences for chemotherapy and hormonal therapy in women with breast cancer prior to surgery. Methods: Patients with a clinically negative lymph node exam and invasive or non-invasive (DCIS) breast cancer based on fine-needle aspirate or core biopsy. Prior to breast cancer surgery, patients answered questions on demographics, cancer beliefs, and psychological distress. They reviewed three clinical scenarios, with low, moderate, or high risk for breast cancer recurrence. They chose one of four treatments: standard chemotherapy; hormonal therapy; combined therapy; or no adjuvant therapy. Statistical methods were based on contingency table approaches and the calculation of p-values using Fisher's Exact Tests as implemented with SAS. Results: Between 2/02 and 11/04, 70 women were enrolled. The mean age of participants was 55.8 years, with 24% age 65 or older. Regardless of recurrence risk, 5% of women would choose chemotherapy alone, 19% hormonal therapy alone, 70% combined therapy, and 6% no adjuvant therapy. Overall in the univariate analyses, age, education, level of psychological distress, and whether or not the patient saw a medical oncologist prior to surgery were not correlated with treatment preference. However, in the low risk scenario subgroup, women with higher educational attainment were more likely to choose no adjuvant therapy (p=0.03) compared with women with lower educational attainment, 26% versus 6%, respectively. The results from the hypothetical scenarios, however, were dramatically different from the actual post-surgical adjuvant treatment chosen by women. In particular, 12% of women chose chemotherapy alone, 38% chose hormonal therapy alone, 18% combined therapy, and 32% no adjuvant therapy. Conclusion: Preliminary analysis suggests that there is a high pre-surgical preference for combined therapy regardless of recurrence risk. However, women's actual choices tended to favor hormonal therapy alone or no adjuvant treatment. Level of education may contribute to a patient's ability to weigh risks and benefits of treatment. No significant financial relationships to disclose.
Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients
Authors: B. Coiffier, P. Feugier, N. Mounier, P. Franchi-Rezgui, E. Van Den Neste, M. Macro, C. Haioun, C. Sebban, D. Bordessoule, H. Tilly
Journal: Journal of Clinical Oncology (2007)

8009 Background: The prospective randomized study LNH-98.5 was first reported in the N Engl J Med and J Clin Oncol with a median follow-up of 2 and 5 years. Here, we present the 7-year follow-up of the 399 patients included in the study. Methods: Patients had untreated diffuse large B-cell lymphoma and were 60 to 80 years old with a median age at diagnosis of 69 years. 60% had a poor risk lymphoma as defined by the aaIPI risk score of 2 or 3. 197 patients were randomized in CHOP arm and 202 in R-CHOP arm. Treatment consisted of 8 cycles of CHOP every 3 weeks with rituximab the same day in R-CHOP. Results: With a median follow-up of 7.1 years, 76% of the patients had an event in CHOP compared to 58% in R-CHOP, p=0.0002 ( Table ). 65% of patients died in CHOP arm compared to 47% in R-CHOP arm: 80% and 71% of them from lymphoma or treatment toxicity, 5% and 5% from another cancer, and 15% and 22% in CR from other causes, respectively. Survival curves show the same difference as reported before with a large difference in favour of R-CHOP ( Table ). Patients not expressing bcl-2 protein treated with R-CHOP have a statistically longer PFS but only a trend for OS because they responded better to salvage treatment. No statistically significant difference was observed for patients &lt;70, 70–74, or ≥75 years old. Patients treated with R-CHOP have good survival even with poor risk parameters: 43% are alive for age ≥75 years, 38% for PS=2, 54% for B symptoms, 47% for stage IV, 45% for high LDH level, 54% for Hb ≤10 g/dl, and 42% for high aaIPI score. Death in CR was associated with high risk aaIPI score and presence of other diseases before lymphoma diagnosis. Conclusions: This analysis confirms the long term benefit associated with the combination of rituximab and CHOP and shows that older patients must be treated as younger patients even in presence of high risk characteristics or concomitant diseases. [Table: see text] [Table: see text]
Plant proteinase inhibitor from enterolobium contortisiliquum (EcTI) attenuates elastase-induced pulmonary inflammatory and remodeling alterations in mice
Authors: Osmar A. Theodoro, Rafael Almeida-Reis, Leandro V. Oliva, Bruno T. Martins-Oliveira, Daniel S.S. Mello, Fernanda D.T.Q.S. Lopes, Carla M. Prado, Patrícia M.G. Paiva, Edna A. Leick, Marlon V. Brito, Milton M. Martins, Maria L.V. Oliva, Iolanda F.L.C. Tibério
Journal: European Respiratory Journal (2011)

Aims: To evaluate if a plant Kunitz proteinase inhibitor EcTI contributes to inactivation of elastase-induced mechanical, inflammatory and extracellular matrix remodelling alterations.

Methods: C57Bl6 mice received elastase (50ml/animal- IN-E group). Control group received saline (Ve group). Mice were treated with EcTI (2mg/kg) at days 1, 7, 14, 21, 28 and 35 after elastase instillation (I-E group). At day 40, mice were anesthetized, mechanically ventilated and we analyzed respiratory system resistance and elastance, tissue elastance, tissue damping, and airway resistance. Afterwards, BAL was performed and lungs were removed. By morphometry, we quantified the mean linear intercept (Lm), collagen and elastic fibers in distal lung.

Results: There were no differences in pulmonary mechanics comparing all groups. In E-group, there was an increase in BAL-total cells, BAL-lymphocytes, BAL-neutrophils, collagen, elastic fibers and LM compared to control (p<0.05). In I-E group, EcTi attenuated the increase in BAL-total cells (65.2±3.3×104 cells/mL) and BAL-neutrophils (1.3±0.7×104 cells/mL) compared to E-group (respectively: 110.7±9.7×104cells/mL and 8.0±1.4×104 cells/mL, p<0.05). There was a decrease in the collagen content in I-E group (43.2±4.3%) compared to E-group (59%±2.5, p<0.05).

Conclusions: This proteinase inhibitor ( EcTI ) reduced elastase-induced pulmonary inflammatory and extracellular matrix remodeling alterations induced by elastase. Although more studies need to be performed, this inhibitor may contribute as potential therapeutic tool for COPD management.

Financial support: FAPESP, CNPq, LIM-20 HCFMUSP.
Prognostic value of residual cancer burden after neoadjuvant taxane-anthracycline chemotherapy in phenotypic subsets of breast cancer
Authors: R. Hubbard, F. Peintinger, C. Liedtke, C. Hatzis, H. M. Kuerer, V. Valero, A. U. Buzdar, G. N. Hortobagyi, L. Pusztai, W. F. Symmans
Journal: Journal of Clinical Oncology (2008)

544 Background: The aim of this study was to evaluate the prognostic strength of residual cancer burden (RCB) measurements according to tumor phenotype in patients who were uniformly treated with neoadjuvant chemotherapy. Methods: We studied 559 patients who received paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC) as neoadjuvant chemotherapy, including 241 previously reported and 318 new cases. No patients received any trastuzumab therapy. RCB index was determined from retrospective pathologic review of the surgical resection specimen (www.mdanderson.org/breastcancer_RCB). Tumor phenotype was determined by standard tests for HER2 status, then estrogen receptor (ER) status, and categorized as: HER2+, ER+/HER2-, or ER-/HER2-. Association of RCB with distant relapse-free survival (DRFS) was evaluated using Kaplan-Meier (log-rank test) and Cox regression analyses. Results: RCB was significantly associated with DRFS in both the original and new cohorts (median follow-up 79 months and 31 months, respectively), and in each phenotypic group (Table). DRFS was identical for RCB-0 and RCB-I. RCB was significantly prognostic (HR 2.08, 95% CI 1.74–2.52, P<0.0001) in multivariate analysis after adjusting for phenotype (P=0.0004), age dichotomized at 50 (P=0.03), clinical Stage at diagnosis (P=0.11), and use of adjuvant hormone therapy (P=0.08). Conclusions: Residual cancer burden after neoadjuvant T/FAC chemotherapy is strongly prognostic in all phenotypic subsets of breast cancer. Number RCB Index (continuous) RCB Classes (0-III) HR (95% CI) P value Log-rank test (P value) Original cohort 241 1.82 (1.42–2.39) < 0.0001 < 0.0001 New cohort 318 1.74 (1.40–2.19) < 0.0001 < 0.0001 HER2+ 142 (25%) 1.86 (1.45–2.41) < 0.0001 < 0.0001 ER+/HER2- 256 (46%) 1.80 (1.26–2.66) 0.0009 0.002 ER-/HER2- 161 (29%) 2.35 (1.80–3.14) < 0.0001 < 0.0001 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Nuvera Biosciences, Inc. Nuvera Biosciences, Inc. Nuvera Biosciences, Inc.