Abstract 2835: Voruciclib, a clinical stage oral CDK inhibitor, sensitizes triple negative breast cancer xenografts to proteasome inhibition

e12117 Background: Triple-negative breast cancer (TNBC) remains a poor prognosis subtype of breast cancer (BC). We are lacking of definitive effective combinations in this tumor. So, it is warranted to explore new combinations. Neo-adjuvant setting is one of the most effective scenarios to explore a treatment efficacy. We aimed to evaluate efficacy of Nab-paclitaxel plus Carboplatin followed byanthracycline regimen by pathologic complete response (pCR: no disease in breast and axilla) in women with TNBC. Secondary endpoints were toxicity profile and breast conserving surgery. Methods: Women with stage II or III disease were included. Hormone receptors and HER2 negativity was confirmed by immunohistochemistry and/or FISH. Patients received Nab-paclitaxel 125 mg/m2 plus Carboplatin AUC 2 intravenously on days 1, 8 every 21 for four cycles followed by Epirubicin 90 mg/m2 and Cyclophosphamide 600 mg/m2 intravenously every 2 weeks for 4 cycles and subsequent surgery. Breast Magnetic Resonance was done in all cases at diagnosis and before surgery. We obtained informed consent from all patients. Results: Thirty-two patients with confirmed clinical stage II (56.3%) or III (43.7%) TNBC were treatedbetween January 2015 and February 2019. The median age of the patients was 53.1 years (30.3-77.6 years). The average of received chemotherapy was 12 doses (7-14). The mean dose of nab-paclitaxel plus carboplatin was 8 doses. All patients received surgery with or without radiotherapy. There was only one case (3.1%) of progression during neoadjuvant treatment. The rate of pCR was 50% (16) in breast and axilla, partial response 43.8% (14) and stable disease 3.1% (1). Conservative surgery was performed in 50% of patients (16). The 3/4 grade toxicities were asthenia 3.1% (1), nausea/vomiting 6.3% (2), thrombocytopenia 6.3% (2), leukopenia 6.3% (2), neutropenia 40.6% (13), febrile neutropenia 6.3% (2), diarrhea 3.1% (1), allergy 3.1% (1), peripheral neurotoxicity 3.1% (1). After a median follow-up of 18.3 months (5.0–41.9) 93.8% (30) of patients are alive. Two patients (6.3%) had early local relapse and distant relapse, respectively, and are deceased due to progression disease. Conclusions: Nab-paclitaxel plus carboplatin followed by anthracycline regimencombination as neoadjuvant treatment in TNBC achieved an encouraging rate of pCR, allowing conservative surgery in half of our patients. Toxicities were not severe in most patients and hematologic toxicity was manageable with G-CSF.

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Pathogenic variants inBRCA1/2genes among patientswith triple-negative breast cancer: a case series

Mastology ◽

10.29289/2594539420210032 ◽

2021 ◽

Vol 31 ◽

Author(s):

Rafael Everton Assunção Ribeiro da Costa ◽

Fergus Tomás Rocha de Oliveira ◽

Ana Lúcia Nascimento Araújo ◽

Sabas Carlos Vieira

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Residual Disease ◽

Molecular Subtype ◽

Clinical Stage ◽

Case Series ◽

Neoplastic Disease ◽

Ki 67 ◽

Pathogenic Variants

Triple-negative breast cancer (TNBC) is an uncommon molecular subtype (representing 15%–20% of breast cancers) characterized by the non-expression of estrogen receptor, progesterone receptor, and human epidermal growth receptor factor 2. More aggressive and lethal, TNBC is often associated with pathogenic variants in BRCA1/2 genes. This study aimed to describe a series of seven cases of patients with TNBC and pathogenic variants in BRCA1/2 genes. All patients were female and under 50 years of age at diagnosis. Four of them presented a family history of breast cancer and/or other neoplasms. The predominant clinical stage was IIB, and the main anatomopathological stage was pT2pN0M0. The mean tumor size in the series was 2.5 cm (1.0 to 3.2 cm). Ki-67 was > 30% in all patients. Three cases (43%) had pathological complete response, and only one presented extensive residual disease after neoadjuvant chemotherapy. Six patients showed pathogenic variants in BRCA1 (86%) and one in BRCA2+ (14%). After a mean follow-up of 38 months (19 to 68 months), five patients were alive and without neoplastic disease, and two progressed to metastasis.

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Differential pathologic complete response rates after neoadjuvant chemotherapy among molecular subtypes of triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1005 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1005-1005 ◽

Cited By ~ 4

Author(s):

Hiroko Masuda ◽

Keith A. Baggerly ◽

Ying Wang ◽

Ya Zhang ◽

Ana M. Gonzalez-Angulo ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Clinical Stage ◽

Pathologic Complete Response ◽

Gene Profiling ◽

Intrinsic Subtypes ◽

Subtype Classification ◽

Tnbc Subtype

1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported that triple-negative breast cancer (TNBC) can be classified into 6 clusters—basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR)—plus an unstable (UNS) cluster. While it is clear that patients with TNBC differently respond to chemotherapy, the clinical relevance of these molecular TNBC subtypes is unknown. Methods: We qualitatively reproduced the Lehmann et al. experiments using Affymetrix CEL files from the public datasets. We identified 130 TNBC gene expression microarrays obtained from 03/00 to 03/10. All patients had received neoadjuvant chemotherapy containing sequential taxane and anthracycline-based regimens and had evaluable pathological tumor response data. Median follow-up was 68.1 months. (5.1-147.5). We classified TNBC samples using Lehmann’s gene signatures, then performed Fisher's exact test to correlate TNBC subtype and pCR status. To assess the independent utility of TNBC subtype for predicting pCR status, we fit a logistic regression model to our data and used age, clinical stage, treatment regimens, and nuclear grade as potential explanatory factors. We also performed comparison of the subtypes with the PAM50 intrinsic subtypes and RCB index. Results: The BL1 subtype had the highest pCR rate (52%); BL2 and LAR the lowest (0% and 10%, respectively). TNBC subtype and pCR status were significantly associated (p = 0.044). TNBC subtype was an independent predictor of pCR status (p = 0.022) by a likelihood ratio test.The Lehmann’s subtype classification better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like). Conclusions: Dividing TNBC into 7 subtypes predicts high vs. low pCR rate. The 7-subtype classification may lead to innovative personalized medicine strategies for patients with TNBC. There is a need for prospective validation of the hypothesis that pCR rates associated with the seven TNBC subtypes will predict long-term patient outcome.

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Clinical outcomes in HER2-positive and triple-negative breast cancer: Assessing racial disparities.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18624 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18624-e18624

Author(s):

Maithreyi Sarma ◽

Ashwini Ronghe ◽

Samar Nasir ◽

Ankita Kapoor ◽

Kristopher Attwood ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcomes ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Clinical Stage ◽

Dose Intensity ◽

Comprehensive Cancer Center ◽

Her2 Positive ◽

Significant Difference ◽

Grade 3

e18624 Background: Triple negative breast cancer (TNBC) & HER2 positive breast cancer (Her2BC), are aggressive breast cancer subtypes. Both are associated with higher mortality in Non-Hispanic Black (NHB) compared to Non-Hispanic White women (NHW). Factors attributed to this racial disparity include socioeconomic status, insurance status, diagnosis(dx)/ treatment delays & comorbidities. We examined the association between race & clinical outcomes (pathological complete response, pCR; recurrence free survival, RFS & overall survival, OS) in patients (pts) dxed with TNBC/Her2BC treated with neoadjuvant chemotherapy (NAC) at Roswell Park Comprehensive Cancer Center. Methods: Pts dxed with Stage I-III TNBC/Her2BC who received NAC from 2000-2018 were included. pCR was defined as absence of residual invasive cancer in the breast & lymph nodes after NAC. Association of race with pCR & survival outcomes was evaluated using logistic & Cox regression models, respectively. Multivariate (MV) models were used to evaluate the association between race & pCR or survival while controlling for relevant confounders including age, BMI, insurance, comorbidities, clinical stage, grade & time from dx to chemotherapy(chemo)/surgery. Analysis was conducted using SAS v9.4 at a significance level of 0.05. Results: 174 TNBC (49 NHB, 125 NHW) & 80 Her2BC (13 NHB, 67 NHW) pts were analyzed. Among TNBC pts, NHB pts had higher baseline BMI(34.3 vs 28.6 kg/m2; p<0.001), higher incidence of hypertension (HTN) (45% vs. 24%; p<0.01), diabetes mellitus (20% vs 8%; p<0.05) & higher Medicare/Medicaid use (M/M) (55% vs. 28%; p<0.01). Among Her2BC pts, NHB pts had higher incidence of HTN (54% vs 25%; p<0.05). There was no statistically significant difference in mean chemo relative dose intensity by race. Among TNBC pts, those with pCR were younger (47 vs 53 yrs; p=0.002) & had more grade 3 tumors (96% vs 80.5%; p<0.05) at dx compared to pts without pCR. Similarly, among Her2BC pts, those with pCR had more grade 3 tumors (64% vs 36%; p<0.05) at dx compared to pts without pCR. Among TNBC pts, advanced age, higher clinical stage & longer time from dx to surgery were associated with worse RFS & OS (p<0.05). Among Her2BC pts, M/M use & advanced clinical stage were associated with worse RFS & OS (p<0.05). There were no significant associations between race & pCR/RFS/OS on MV analysis (table below). Conclusions: Similar outcomes were noted between races for TNBC/Her2BC pts treated at a single academic center in Buffalo, NY. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography & clinical outcomes are warranted.[Table: see text]

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