Clinical observation on the effect of Chinese medicine-"TCM formula" intervention on recurrence and metastasis of triple negative breast cancer.

OBJECTIVE: This study used a prospective cohort study to observe the effect of triple-negative breast cancer on the 2-year disease-free survival rate with or without "TCM formula". METHODS: From November 1 st, 2016, the first patient was enrolled in the cohort study. A total of 356 patients were enrolled on January 30, 2019. Among them, 154 cases were followed up for 2 years. During the follow-up, there were 6 cases of shedding, so 6 cases were affected. A total of 148 cases were included in the analysis, including 73 in the exposed group and 75 in the non-exposed group. The exposed group was given "TCM formula" on the basis of standardized treatment, and the non-exposed group was treated with simple triple-negative breast cancer. The two groups visited each of the three months. The interview included safety examination (hematology and imaging). The endpoint was the difference in 2-year invasive disease-free survival between the exposed and non-exposed groups and the safety of the "TCM formula". RESULTS: There were 6 cases of shedding during the experiment and the shedding rate was 3.9 %. The 2-year rate of invasive disease-free survival in the exposed team was 88.7 % and the non-exposed group was 82.5 %. Logistic multivariate regression analysis predicted that "TCM formula" could reduce the disease-related recurrence and metastasis rate by 11 % (OR = 0.89, 95 % CI 0.37-0.956, P＜0.05). Through K-M survival analysis, TNBC patients with age ≤35 years and regional lymph node stage N1 may be the benefit group of "TCM formula"(P＜0.05). During the study, the incidence of total adverse events was 8.2 % in the exposed group, mainly manifested as stomach discomfort, diarrhea, and hepatocyte damage. CONCLUSION: 1. In the exposed group, the two-year rate of invasive disease-free survival increased by 6.2 % compared with the non-exposed group(P＞0.05). 2. According to K-M survival analysis, TNBC patients with age ≤35 years and regional lymph node metastasis to N1 may be potential beneficiaries of "TCM formula". 3. "TCM Formula" is safe and tolerable to most patients.

SCD1 activity promotes cell migration via a PLD-mTOR pathway in the MDA-MB-231 triple-negative breast cancer cell line.

BACKGROUND: Breast cancer is the most common cancer in women. Despite high survival rates in Western countries, treatments are less effective in metastatic cases and triple-negative breast cancer (TNBC) patient survival is the shortest across breast cancer subtypes. High expression levels of stearoyl-CoA desaturase-1 (SCD1) have been reported in breast cancer. The SCD1 enzyme catalyzes the formation of oleic acid (OA), a lipid stimulating the migration of metastatic breast cancer cells. Phospholipase activity is also implicated in breast cancer metastasis, notably phospholipase D (PLD). METHODS: Kaplan-Meier survival plots generated from gene expression databases were used to analyze the involvement of SCD1 and PLD in several cancer subtypes. SCD1 enzymatic activity was modulated with a pharmaceutical inhibitor or by OA treatment (to mimic SCD1 over-activity) in three breast cancer cell lines: TNBC-derived MDA-MB-231 cells as well as non-TNBC MCF-7 and T47D cells. Cell morphology and migration properties were characterized by various complementary methods. RESULTS: Our survival analyses suggest that SCD1 and PLD2 expression in the primary tumor are both associated to metastasis-related morbid outcomes in breast cancer patients. We show that modulation of SCD1 activity is associated with the modification of TNBC cell migration properties, including changes in speed, direction and cell morphology. Cell migration properties are regulated by SCD1 activity through a PLD-mTOR/p70S6K signaling pathway. These effects are not observed in non-TNBC cell lines. CONCLUSION: Our results establish a key role for the lipid desaturase SCD1 and delineate an OA-PLD-mTOR/p70S6K signaling pathway in TNBC-derived MDA-MB-231 cell migration.

Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)-positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein). METHODS: A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included. RESULTS: A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4-6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9-14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2-5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents. CONCLUSIONS: Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1-positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.

Hormone Receptor Expression in Multicentric/Multifocal versus Unifocal Breast Cancer: Especially the VDR Determines the Outcome Related to Focality.

The aim of this study was to evaluate the prognostic impact that hormone receptor (HR) expressions have on the two different breast cancer (BC) entities-multifocal versus unifocal BC. As the prognosis determining aspects, we investigated the overall survival (OS) and disease-free survival (DFS) by univariate and multivariate analysis. To underline the study's conclusions, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging. A retrospective analysis was performed on survival-related events in a series of 320 breast cancer patients treated at the Department of Gynecology and Obstetrics at the Ludwig Maximillian University in Munich between 2000 and 2002. All three steroid receptors analyzed by immunohistochemistry, namely, the estrogen receptor (ER), the progesterone receptor (PR), and the vitamin D receptor (VDR), showed a significantly positive influence on the course of the disease, but only for the unifocal breast tumor patients. The prognosis of patients with multifocal breast cancer was either not affected by estrogen and/or progesterone receptor expression or even involved a worse etiopathology for the vitamin D receptor-positive patients. The estrogen receptor in unifocal breast cancer and the vitamin D receptor in multifocal breast cancer were especially identified as an independent prognostic marker for overall survival, when adjusted for age, grading, and staging. Altogether, our results strengthen the need to further investigate the behavior of the hormone receptors in breast cancer and understand why they have different effects on each focality type. Moreover, the studies for an adopted vitamin D supplementation due to breast cancer focality type must be enlarged to fully comprehend the remarkable and interesting role played by the vitamin D receptor.

Anthracycline could be essential for triple-negative breast cancer: A randomised phase II study by the Kanagawa Breast Oncology Group (KBOG) 1101.

BACKGROUND: It is important to determine whether anthracycline-containing regimens or taxane-containing regimens are more effective in individual patients. The present study compared the efficacy of six cycles of docetaxel and cyclophosphamide (TC6) with that of three cycles of 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel (FEC-D) in Japanese patients with hormone receptor (HR)-negative breast cancer (BC) to identify subtypes requiring anthracycline treatment. METHODS: The study included 103 patients with operable HR-negative BC. Of these patients 53 received FEC-D and 50 received TC6. The primary endpoint was pathological complete response (pCR). The secondary endpoints were safety, breast-conserving surgery, disease-free survival (DFS) and overall survival (OS). The predictive factors for each regimen were evaluated. RESULTS: Of the 103 patients, 97 completed the study (FEC-D, 50 patients; TC6, 47 patients). The pCR rate was higher with FEC-D (36%) than with TC6 (25.5%); however, the difference was not significant (P = 0.265). TC6 was safer than FEC-D, as the adverse events with docetaxel in the FEC-D regimen were similar to those with the TC6 regimen. Among patients with basal BC, the pCR rate was significantly higher with FEC-D (42.9%) than with TC6 (13.6%; P = 0.033). Among patients with triple-negative breast cancer (TNBC), the DFS and OS were significantly better with FEC-D than with TC6 (P = 0.016 and P = 0.034, respectively). CONCLUSION: TC6 was not as effective as FEC-D for treating HR-negative BC, as TC6 was not sufficient to treat TNBC, particularly the basal subtype. Our findings suggest that anthracyclines are better treatment options than taxanes for basal BC.

YY1-regulated LINC00152 promotes triple negative breast cancer progression by affecting on stability of PTEN protein.

Thousands of lncRNAs have been identified but few have been functionally characterized in triple negative breast cancer (TNBC). LINC00152 was known as cytoskeleton regulator RNA (CYTOR) and expressed in various cancers including breast cancer. But the underlying molecular mechanism of LINC00152 in pathogenesis of TNBC have not been elucidated. In our study, we identified that LINC00152 expression was dramatically elevated in TNBC tissue and cells. Inhibition or overexpression of LINC00152 obviously increased or suppressed PTEN protein expression but did not affect the mRNA expression level. Our further experiments showed up-regulated LINC00152 in TNBC obviously enhanced NEDD4-1 mediated ubiquitination and degradation of PTEN protein. Finally, we demonstrated that YY1 bound with LINC00152 promotor and mostly inhibited the transcription of LINC00152. Furthermore, analysis of clinical samples resource retrieved from databases suggested high LINC00152 expression was correlated with ER or PR negative expression, late TNM stage and lymphatic invasion, as well as shorter overall survival time in patients. Consequently, this study firstly reveals that up-regulated LINC00152 mediates PTEN protein stability attenuation in TNBC.

Clinical study on postoperative triple-negative breast cancer with Chinese medicine: Study protocol for an observational cohort trial.

BACKGROUND: Breast cancer (BC) poses a tremendous threat to the health of women worldwide, especially triple-negative breast cancers (TNBCs). Currently, the curative effect of traditional Chinese medicine (TCM) has been recognized in more and more people worldwide; however, the specific effect has not been systematically evaluated. The purpose of this cohort study is to evaluate the clinical effects of TCM syndrome differentiation on recurrence and metastasis rate, survival rate, and the quality of life in patients with TNBC. METHODS: This study is a multicenter observational cohort trial taking 2 years. A total of 620 patients will be allocated at a ratio of 1:1 to receive TCM or not. The primary outcomes are progression-free survival (PFS) and overall survival (OS), which are calculated at the end of the trial. Secondary outcomes include TCM symptoms, Karnofsky Performance Status (KPS), ECOG score, European Organization for Research and Treatment of Cancer (EORTC) Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23), as well as clinical indicators including tumor markers, immune function evaluation, chest computed tomography/magnetic resonance imaging, and abdominal B-ultrasound. Assessments will be performed at baseline and 3, 6, 9, 12, 16, and 20 weeks after observation. DISCUSSION: This will be the first clinical trial to evaluate the PFS and OS in TNBC patients receiving TCM, which may be used to assess the feasibility of a larger-scale clinical trial in the future, and formulate a standardized TCM treatment plan. STUDY REGISTRATION: ClinicalTrials.gov (NCT03332368).

The effect of adjuvant chemotherapy on survival in Korean patients with node negative T1c, triple negative breast cancer.

BACKGROUND: The present study investigated the prognostic role of adjuvant systemic chemotherapy in patients with node negative, T1c triple negative breast cancer (TNBC) from a nationwide cohort. In addition, the prognostic effect between 3 different chemotherapy regimens were compared in node-negative T1c TNBC patients by subgroup analysis. METHODS: From the Korean breast cancer registry database, 1,151 T1c node negative TNBC patients were included in this study. Patients were categorized into four treatment groups according to chemotherapy regimen: (1) no chemotherapy, (2) adriamycin plus cyclophosphamide (AC), (3) adriamycin/epirubicin plus cyclophosphamide plus 5-FU (FAC/FEC), and (4) cyclophosphamide plus 5-FU plus methotrexate (CMF). Overall survival (OS) was evaluated between each patient group. RESULTS: Of the 1,151 T1c node negative TNBC patients, 1,006 received adjuvant chemotherapy, while 145 received no chemotherapy. Among the patients receiving adjuvant chemotherapy the distribution of regimens was: 586 AC, 168 FAC/FEC (126 FAC, 42 FEC), and 252 CMF. The mean follow-up time of the full study cohort was 87.98 ± 33.56 months (range = 6-192 months). Patients in the no chemotherapy group showed significantly worse OS compared to each chemotherapy regimen group. However, when OS was compared between each chemotherapy regimen, no significant difference was found. CONCLUSIONS: This study showed that adjuvant systemic chemotherapy improved OS in T1c node negative TNBC patients, regardless of chemotherapy between AC, FAC/FEC, and CMF regimens.

Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer: The Randomized Clinical FinXX Trial.

IMPORTANCE: Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC). OBJECTIVE: To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2). DESIGN, SETTING, AND PARTICIPANTS: This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015. MAIN OUTCOMES AND MEASURES: Recurrence-free survival (RFS). RESULTS: Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively). CONCLUSIONS AND RELEVANCE: Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00114816.

(18)F-FDG-PET/CT for systemic staging of newly diagnosed triple-negative breast cancer.

PURPOSE: National Comprehensive Cancer Network guidelines recommend (18)F-FDG-PET/CT, in addition to standard staging procedures, for systemic staging of newly diagnosed stage III breast cancer patients. However, factors in addition to stage may influence PET/CT utility. As breast cancers that are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (triple-negative breast cancer, or TNBC) are more aggressive and metastasize earlier than other breast cancers, we hypothesized that receptor expression may be one such factor. This study assesses (18)F-FDG-PET/CT for systemic staging of newly diagnosed TNBC. METHODS: In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with TNBC who underwent (18)F-FDG-PET/CT in 2007-2013 prior to systemic or radiation therapy. Initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery, if performed prior to (18)F-FDG-PET/CT. (18)F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases, as well as unsuspected synchronous malignancies. Kaplan Meier survival estimates were calculated for initial stage IIB patients stratified by whether or not stage 4 disease was detected by (18)F-FDG-PET/CT. RESULTS: A total of 232 patients with TNBC met inclusion criteria. (18)F-FDG-PET/CT revealed unsuspected distant metastases in 30 (13 %): 0/23 initial stage I, 4/82 (5 %) stage IIA, 13/87 (15 %) stage IIB, 4/23 (17 %) stage IIIA, 8/14 (57 %) stage IIIB, and 1/3 (33 %) stage IIIC. Twenty-six of 30 patients upstaged to IV by (18)F-FDG-PET/CT were confirmed by pathology, with the remaining four patients confirmed by follow-up imaging. In addition, seven unsuspected synchronous malignancies were identified in six patients. Initial stage 2B patients who were upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival compared to initial stage 2B patients who were not (3-year Kaplan Meier estimate 0.33, 95 % CI 0.13-0.55 versus 0.97, CI 0.76-0.93, p < .0001). CONCLUSION: F-FDG-PET/CT revealed distant metastases in 15 % of patients with stage IIB TNBC. Stage IIB patients upstaged to 4 by (18)F-FDG-PET/CT had significantly shorter survival than those who were not, consistent with (18)F-FDG-PET/CT detecting an increased burden of disease. This study provides further evidence that populations of patients with stage IIB breast cancer, such as TNBC, should be considered for systemic staging with (18)F-FDG-PET/CT at the time of initial diagnosis.

A novel EGR-1 dependent mechanism for YB-1 modulation of paclitaxel response in a triple negative breast cancer cell line.

Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Because a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required. One protein shown to be involved in drug resistance is Y-box binding protein 1 (YB-1). High levels of YB-1 have previously been associated with resistance to PTX in TNBCs. In this study, we aimed to determine mechanisms by which YB-1 confers PTX resistance. We generated isogenic TNBC cell lines that differed by YB-1 levels and treated these with PTX. Using microarray analysis, we identified EGR1 as a potential target of YB-1. We found that low EGR1 mRNA levels are associated with poor breast cancer patient prognosis, and that EGR1 and YBX1 mRNA expression was inversely correlated in a TNBC line and in a proportion of TNBC tumours. Reducing the levels of EGR1 caused TNBC cells to become more resistant to PTX. Given that PTX targets cycling cells, we propose a model whereby high YB-1 levels in some TNBC cells can lead to reduced levels of EGR1, which in turn promotes slow cell cycling and resistance to PTX. Therefore YB-1 and EGR1 levels are biologically linked and may provide a biomarker for TNBC response to PTX.

Modifiable Lifestyle Factors and Triple-negative Breast Cancer Survival: A Population-based Prospective Study.

BACKGROUND: Very little is known about the effect of modifiable lifestyle factors on outcomes of triple-negative breast cancer. We examined this association in a population-based prospective cohort study of patients with triple-negative breast cancer. METHODS: A total of 518 women with confirmed triple-negative breast cancer, recruited by the Shanghai Breast Cancer Survival Study, completed 6-, 18-, 36-, and 60-month postdiagnosis surveys. We applied Cox proportional hazard models to evaluate the associations. RESULTS: The mean age at diagnosis was 53.4 (standard deviation = 10.6) years old. After a median follow-up of 9.1 years (range: 0.6-11.8), 128 deaths and 112 recurrences were documented. Exercise during the first 60 months postdiagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with adjusted hazard ratios (HRs) of 0.67 (95% confidence interval [CI] = 0.46, 0.96) and 0.58 (95% CI = 0.39, 0.86), respectively. Women with higher exercise-metabolic equivalent scores (≥7.6 metabolic equivalent-hours/week) and longer duration of exercise (≥2.5 hours/week) had lower risk of total and recurrence/disease-specific mortality than did nonexercisers. Compared with nontea drinkers, survival was better among women who were regular tea drinkers during the first 60 months for all cause (HR = 0.57, 95% CI = 0.34, 0.93) and recurrence/disease-specific mortality (HR = 0.54, 95% CI = 0.31, 0.96). There was no dose-response pattern for tea consumption. No interactions were observed for body mass index, menopausal status, and comorbidity. CONCLUSIONS: These findings show that postdiagnosis exercise and tea intake were associated with improved survival among women with triple-negative breast cancer.

CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid.

BACKGROUND: Clinical trials designed to test the efficacy of retinoic acid (RA) as an adjuvant for the treatment of solid cancers have been disappointing, primarily due to RA resistance. Estrogen receptor (ER)-negative breast cancer cells are more resistant to RA than ER-positive cells. The expression and subcellular distribution of two RA-binding proteins, FABP5 and CRABP2, has already been shown to play critical roles in breast cancer cell response to RA. CRABP1, a third member of the RA-binding protein family, has not previously been investigated as a possible mediator of RA action in breast cancer. METHODS: CRABP1 and CRABP2 expression in primary breast tumor tissues was analyzed using gene expression and tissue microarrays. CRABP1 levels were manipulated using siRNAs and by transient overexpression. RA-induced subcellular translocation of CRABPs was examined by immunofluorescence microscopy and immunoblotting. RA-induced transactivation of RAR was analyzed using a RA response element (RARE)-driven luciferase reporter system. Effects of CRABP1 expression and RA treatment on downstream gene expression were investigated by semi-quantitative RT-PCR analysis. RESULTS: Compared to normal mammary tissues, CRABP1 expression is significantly down-regulated in ER+ breast tumors, but maintained in triple-negative breast cancers. Elevated CRABP1 levels are associated with poor patient prognosis, high Ki67 immunoreactivity and high tumor grade in breast cancer. The prognostic significance of CRABP1 is attributed to its cytoplasmic localization. We demonstrate that CRABP1 expression attenuates RA-induced cell growth arrest and inhibits RA signalling in breast cancer cells by sequestering RA in the cytoplasm. We also show that CRABP1 affects the expression of genes involved in RA biosynthesis, trafficking and metabolism. CONCLUSIONS: CRABP1 is an adverse factor for clinical outcome in triple-negative breast cancer and a potent inhibitor of RA signalling in breast cancer cells. Our data indicate that CRABP1, in conjunction with previously identified CRABP2 and FABP5, plays a key role in breast cancer cell response to RA. We propose that these three RA-binding proteins can serve as biomarkers for predicting triple-negative breast cancer response to RA, with elevated levels of either cytoplasmic CRABP1 or FABP5 associated with RA resistance, and elevated levels of nuclear CRABP2 associated with sensitivity to RA.

A retrospective analysis of adjuvant CAF, AC-T and TAC regimens in triple negative early stage breast cancer.

PURPOSE: To compare the effectiveness of adjuvant chemotherapy regimens in triple negative breast cancer (TNBC) for which no protocol has been determined to be treatment of choice. METHODS: In this single-center retrospective trial, we analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin, cyclophosphamide followed by docetaxel) regimens were compared in terms of disease free survival (DFS) and overall survival (OS). RESULTS: In terms of both DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When node negative and positive patients were analyzed together, TAC was still significantly superior to AC-T in terms of DFS and OS. There was a trend favoring CAF over AC-T, however, it was only significant in terms of OS when all node negative and positive TNBC patients were incorporated together. CONCLUSION: In the adjuvant setting, especially in node positive patients, TAC should be the treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.

p53 status identifies triple-negative breast cancer patients who do not respond to adjuvant chemotherapy.

Genomic analysis and protein expression assimilate triple-negative breast cancers (TNBC) with basal-like breast tumors. TNBCs, however, have proved to encompass also tumors with normal-like phenotype and known to have favorable prognosis and to respond to chemotherapy. In a recent paper, we have provided evidence that p53 status is able to subdivide TNBCs into two distinct subgroups with different outcome, and consistent with basal- and normal-like phenotypes. Based on this finding, we explored the contribution of p53 status in predicting the response to adjuvant CMF or CMF followed doxorubicin chemotherapy of a group of TNBC patients. Results indicated that TNBC patients with a p53-positive tumor had a shorter relapse-free and overall survival than patients carrying a p53-negative TNBC, corroborating our hypothesis about the relationship between TNBC phenotype (basal-like versus normal-like) and p53 status as predictor of response to anthracycline/CMF-based chemotherapy.

Metronomic capecitabine as extended adjuvant chemotherapy in women with triple negative breast cancer.

PURPOSE: High interest in triple-negative breast cancers is not surprising as this category of patients benefits neither from hormonal therapies nor from anti HER2 treatments. Blockade of angiogenesis by metronomic chemotherapy as well as other antiangiogenics might improve outcomes in this group of patients. This study aims to evaluate the tolerability and efficacy of metronomic capecitabine as extended adjuvant treatment for women with triple-negative breast cancer. METHODS: This is a prospective phase II study that included 41 patients diagnosed with triple-negative breast cancer and who were indicated for adjuvant chemotherapy. They received capecitabine 500mg PO twice daily and continuously for six months after finishing six cycles of adjuvant FEC100±postoperative radiotherapy. RESULTS: Forty-one patients were enrolled in this study between June 2010 and December 2013. Median age was 50years ranging from 27 to 67years. Treatment was well tolerated. Adverse effects were grade 1 palmar-plantar erythrodysesthesia in 13 patients (31.7%); grade 1 diarrhea in five patients (12.2%); and grade 1 vomiting in two patients (4.9%). Estimated median follow-up duration was 34 months. Estimated mean disease-free survival (DFS) was 42.4months (95% CI, 39.02-45.79), while median DFS was not reached. Estimated mean overall survival was 44.34months (95% CI 41.9-46.9). CONCLUSION: Extended adjuvant metronomic capecitabine is well tolerated with patient compliance. These results need to be compared in a study with control arm, larger sample, as well as longer follow-up.