Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer
Zhen ShiJulia WulfkuhleMałgorzata NowickaRosa I. GallagherCristina SauraPaolo NucíforoIsabel CalvoJay AndersenJosé Luís Passos‐CoelhoMiguel Gil‐GilBegoña BermejoDebra A. PrattEva CiruelosPatricia VillagrasaMatthew WongchenkoEmanuel F. PetricoinMafalda OliveiraSteven J. Isakoff
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Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast CancerKeywords:
Triple-negative breast cancer
Neoadjuvant Therapy
Complete response
Triple-negative breast cancer
Neoadjuvant Therapy
Complete response
Minimal Residual Disease
Triple negative
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Background: Neoadjuvant concurrent chemoradiation (CTRT) is not widely practised in breast cancer. We present our experience with the use of neoadjuvant CTRT in patients with locally advanced breast cancers (LABC) treated at our centre. Methods: The study included all consecutive female patients with inoperable stage III LABC treated at our centre from December 2015 to June 2016. Data were collected retrospectively from the patients' case records. The impact of neoadjuvant CTRT on pathological complete response and survival was analysed. All patients received 2 cycles of Paclitaxel 3 weekly (175 mg/m2/dose) with External beam radiotherapy (EBRT) delivered at 46 Gy in 23 fractions given over 5 weeks. Results: The study included 100 patients with a median age of 49 years among whom 9/100 (9%) had IIIA disease, 73/100 (73%) IIIB and 18/100 (18%) had IIIC disease. Hormone receptor-positive disease was observed in 36/100 (36%) patients, triple negative in 24/100 (24%) and Her2 neu positive disease in 40/100 (40%) patients. All patients were operable after completing the planned neoadjuvant treatments. Ninety-one out of 100 (91%) patients underwent modified radical mastectomy whereas 9/100 (9%) did not consent for surgery. pCR was observed in 12/21 (57.1%) patients with triple-negative disease, 11/34 (32.3%) patients with hormone receptor-positive disease and 16/36 (44.4%) patients with Her2 neu positive disease. Most common morbidity observed was grade 3 skin reactions. No grade 4 skin toxicity was observed. The 2-year event-free survival (EFS) and overall survival (OS) for the entire cohort was 88 % and 73.1 % respectively. Conclusions: Neoadjuvant CTRT is well tolerated and is associated with higher pCR rates than what has been reported with neoadjuvant chemotherapy alone. However, further prospective studies with longer follow-up are required to confirm our findings. Legal entity responsible for the study: Cancer Institute, Chennai, India. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Neoadjuvant Therapy
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Triple-negative breast cancer
Carboplatin
Neoadjuvant Therapy
Triple negative
Complete response
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Abstract Background: Triple negative breast cancer (TNBC) refers to breast cancers that don't express ER, PgR and HER-2, and several studies reported poorer clinical outcome than other groups. In spite of their poor outcome, on the basis of limited clinical data, TNBC patients demonstrated higher objective response rate and pathological complete response (pCR) rate than other subgroups with neoadjuvant chemotherapy. In this study, we evaluated the response to neoadjuvant chemotherapy of TNBC, reported the outcome of TNBC and other subgroups after neoadjuvant chemotherapy.Method: We analyzed the outcome and characteristics of patients treated with neoadjuvant chemotherapy using anthracycline and/or taxanes. Breast cancer subtypes are defined the following: Luminal A (ER+ and/or PgR+, HER2-), Luminal B (ER+ and/or PgR+, HER2+), HER2 (ER-, PgR-, HER2+), TN (ER-, PgR-, HER2-), Luminal A/B and HER2 subtypes were regarded as non-TNBC in this study.Result: Between 2000 and 2007, 639 breast cancer patients were treated with neoadjuvant chemotherapy at Cancer Institute Hospital. Clinical and immunohistochemical data was available on 596 patients. Median observation period was 1085 days (84-3382). In these cases, 111cases (18.6%) were defined as TNBC, and 485 cases (81.4%) were classified as non-TNBC. In each group, 28 and 138 cases (25.2% vs 28.5%), 35 and 132 cases (31.5% vs 27.2%), 48 and 215 cases (43.2% vs 44.3%) were treated with anthracycline (A), taxane (T), both A and T, respectively. Clinical complete response (cCR) rate and response rate (RR: CR + partial response (PR)) of TNBC were higher than of non-TNBC (cCR: 10.8% vs 2.7%, p=.0006) (RR: 66.7% vs 64.5%, p<.0001), respectively. Despite the better cCR rates of TNBC, the clinical progressive disease (cPD) rate was higher than non-TNBC (15.3% vs 3.9%)(p<.0001). With using only A or T regimen and the same treatment period, there was no difference in the cCR rate of TNBC between A and T (7.1% vs 2.9%)(p=.4274), but there was a difference in the cPD rate (0% vs 31.4%)(p=.0009). The pCR rate of TNBC and non TNBC was 9.0% and 2.5%, respectively (p=.001). The 3-yr disease free survival (DFS) rate was 78.4% with TNBC cases, and 84.7% with non-TNBC cases (p=.1027). However there was not difference in the 3-yr DFS between pCR and non-pCR groups of both TNBC (80.0% vs 78.2%, p=.8776) and non TNBC (91.7% vs 84.6%, p=.4994), respectively.Conclusions: With neoadjuvant chemotherapy, cCR and pCR rate of TNBC were higher than non-TNBC, but their cPD rate was also high. As for chemotherapy regimen, T might be less effective in treating TNBC. In this study, the total numbers of pCR cases were few, therefore pCR subsets might not contribute to good DFS. Despite standard neoadjuvant regimen usually including both A and T, half of the patients in this study underwent the chemotherapy with only A or T, due to our institutional previous study. TNBC tends to have worse prognosis, therefore more effective treatment would be required. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1102.
Triple-negative breast cancer
Taxane
Neoadjuvant Therapy
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The use of neoadjuvant chemotherapy in treating breast cancer has shown efficacy in downstaging primary tumors, and allows breast conservative surgery to be performed instead of mastectomy. This study aims to evaluate patterns of clinical and pathological response after two cycles of neoadjuvant chemotherapy in patients with locally advanced breast cancer.This is a prospective study. Ninety-eight patients who presented from April 2009 through May 2011 with locally advanced breast cancer and treated with neoadjuvant chemotherapy were included.The clinical response rate was 83%; 11 patients (11.2%) had a complete clinical remission (cCR); 71 had a partial remission (72.4%); 13 had stable disease (13.3%), and 3 had progressive disease (3.1%). Seven patients had complete pathological response.Neoadjuvant chemotherapy can achieve a high objective response rate in patients with locally advanced breast cancer even after two cycles. We recommend further research to find predictors for response.
Neoadjuvant Therapy
Complete response
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Triple-negative breast cancer
Neoadjuvant Therapy
Complete response
Triple negative
Clinical Practice
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Neoadjuvant Therapy
Complete response
Axillary lymph nodes
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Abstract Neoadjuvant chemotherapy is the current standard of care for large, advanced, and/or inoperable tumors, including triple‐negative breast cancer. Although the clinical benefits of neoadjuvant chemotherapy have been illustrated through numerous clinical trials, more than half of the patients do not experience therapeutic benefit and needlessly suffer from side effects. Currently, no clinically applicable biomarkers are available for predicting neoadjuvant chemotherapy response in triple‐negative breast cancer; the discovery of such a predictive biomarker or marker profile is an unmet need. In this study, we introduce a generic computational framework to calculate a response‐probability score (RPS), based on patient transcriptomic profiles, to predict their response to neoadjuvant chemotherapy. We first validated this framework in ER‐positive breast cancer patients and showed that it predicted neoadjuvant chemotherapy response with equal performance to several clinically used gene signatures, including Oncotype DX and MammaPrint. Then, we applied this framework to triple‐negative breast cancer data and, for each patient, we calculated a response probability score (TNBC‐RPS). Our results indicate that the TNBC‐RPS achieved the highest accuracy for predicting neoadjuvant chemotherapy response compared to previously proposed 143 gene signatures. When combined with additional clinical factors, the TNBC‐RPS achieved a high prediction accuracy for triple‐negative breast cancer patients, which was comparable to the prediction accuracy of Oncotype DX and MammaPrint in ER‐positive patients. In conclusion, the TNBC‐RPS accurately predicts neoadjuvant chemotherapy response in triple‐negative breast cancer patients and has the potential to be clinically used to aid physicians in stratifying patients for more effective neoadjuvant chemotherapy.
Triple-negative breast cancer
Signature (topology)
Gene signature
Neoadjuvant Therapy
Complete response
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CA: A Cancer Journal for Clinicians publishes information about the prevention, early detection, and treatment of cancer, as well as nutrition, palliative care, survivorship, and additional topics of interest related to cancer care.
Triple-negative breast cancer
Complete response
Neoadjuvant Therapy
Triple negative
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[Purpose] To investigate the expression of ER and HER-2 in breast cancer tissue and its clinical significance. [Methods] Expressions of ER, HER-2 in 100 cases patients with breast cancer were detected by immunohistochemistry before and after neoadjuvant chemotherapy. The relationship of ER and HER-2 with response of neoadjuvant chemotherapy was analyzed. [Results] The overall response rate of neoadjuvant chemotherapy was 79%. Response rate in patients with negative expression of ER was higher than that with positive expression of ER(P0.05). There was no significant relation between the response and HER-2 expression(P0.05). Expression of ER and HER-2 did not change significantly after neoadjuvant chemotherapy (P0.05). [Conclusion] Neoadjuvant chemotherapy did not significantly influence on status of ER and HER-2. ER may be used to predict the therapeutic response of neoadjuvant chemotherapy in breast cancer.
Clinical Significance
Neoadjuvant Therapy
Complete response
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