scholarly journals Glycans unique to the relapse-prone subset within triple-negative breast cancer as revealed by lectin array-based analysis of surgical specimens

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250747
Author(s):  
Madoka Sakata-Matsuzawa ◽  
Kaori Denda-Nagai ◽  
Haruhiko Fujihira ◽  
Miki Noji ◽  
Katrin Beate Ishii-Schrade ◽  
...  

Introduction Molecular and cellular characteristics of the relapse-prone subset within triple-negative breast cancer (TNBC) remain unclear. Aberrant glycosylation is involved in the malignant behavior of cancer cells. In the present study, we aimed to reveal glycan profiles unique to relapsed TNBC patients. Methods Thirty TNBC patients who did not undergo neoadjuvant chemotherapy but postoperative standard adjuvant therapy from 2009 through 2016 at Juntendo Hospital were investigated. TNBC cells were resected from primary breast cancer sections of formalin-fixed surgical specimens using laser-assisted microdissection. The binding intensities of the extracted glycoproteins to 45 lectins were quantified using lectin microarray and compared between relapsed and non-relapsed patients. Immunohistochemical staining with TJA-II lectin in specimen sections was performed. Results Five patients relapsed during the follow-up (range 37–123 months). Lectin microarray analysis revealed that 7 out of 45 lectins showed significant differences in binding intensity between the relapsed and the non-relapsed group. TJA-II, ACA, WFA, and BPL showed stronger binding in the relapsed group. PNGase F treatment of TNBC cell lysates suggested that TJA-II and ACA bind O-glycans. TJA-II staining of tissue sections revealed strong binding to cell surface membranes and to the cytoplasm of TNBC cells, but not to other types of cells. Significantly more TNBC cells were stained in tissue sections from relapsed than non-relapsed patients. Conclusions TNBC cells from relapsed patients showed a unique lectin reactivity, with higher levels of TJA-II (also WFA and BPL) binding than in non-relapsed patients. The results are potentially useful to develop new prognostic and therapeutic tools.

2021 ◽  
pp. 767-781
Author(s):  
Manikandan Dhanushkodi ◽  
Velusamy Sridevi ◽  
Viswanathan Shanta ◽  
Ranganathan Rama ◽  
Rajaraman Swaminathan ◽  
...  

PURPOSE There are sparse data on the outcome of patients with locally advanced breast cancer (LABC). This report is on the prognostic factors and long-term outcome from Cancer Institute, Chennai. METHODS This is an analysis of untreated patients with LABC (stages IIIA-C) who were treated from January 2006 to December 2013. RESULTS Of the 4,577 patients with breast cancer who were treated, 2,137 patients (47%) with LABC were included for analysis. The median follow-up was 75 months (range, 1-170 months), and 2.3% (n = 49) were lost to follow-up at 5 years. The initial treatment was neoadjuvant concurrent chemoradiation (NACR) (77%), neoadjuvant chemotherapy (15%), or others (8%). Patients with triple-negative breast cancer had a pathologic complete response (PCR) of 41%. The 10-year overall survival was for stage IIIA (65.1%), stage IIIB (41.2%), and stage IIIC (26.7%). Recurrence of cancer was observed in 27% of patients (local 13% and distant 87%). Multivariate analysis showed that patients with a tumor size > 10 cm (hazard ratio [HR], 2.19; 95% CI, 1.62 to 2.98; P = .001), hormone receptor negativity (HR, 1.45; 95% CI, 1.22 to 1.72; P = .001), treatment modality (neoadjuvant chemotherapy, HR, 0.56; 95% CI, 0.43 to 0.73; P = .001), lack of PCR (HR, 2.36; 95% CI, 1.85 to 3.02; P = .001), and the presence of lymphovascular invasion (HR, 1.97; 95% CI, 1.60 to 2.44; P = .001) had decreased overall survival. CONCLUSION NACR was feasible in inoperable LABC and gave satisfactory long-term survival. PCR was significantly higher in patients with triple-negative breast cancer. The tumor size > 10 cm was significantly associated with inferior survival. However, this report acknowledges the limitations inherent in experience of management of LABC from a single center.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22214-e22214
Author(s):  
M. Dioca ◽  
M. Savignano ◽  
L. Gimenez ◽  
L. Marino ◽  
C. Delfino ◽  
...  

e22214 Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 140-140
Author(s):  
Anna Kaminsky

140 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple-negative and neoadjuvant chemotherapy (NAC) is often used in triple-negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive [H score of 10 or less] and HER2 negative or indeterminate [HER2 1+ or 2+ without amplification by FISH]), were identified. Nine of these TNBCs had metaplastic subtype and two groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Average follow-up in MBC group was 43 months and no patients were lost to follow-up. Average tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow-up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%). Follow-up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple-negative paradox is likely not applicable to MBC.


Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Ana Luiza de Freitas Magalhães Gomes ◽  
Marina Paixão de Madrid Whyte ◽  
Wagner Antonio Paz ◽  
Kerstin Kapp Rangel ◽  
Paulo Guilherme de Oliveira Salles

Introduction: Triple-negative breast cancer (TNBC) does not express estrogen and progesterone receptors, and does not overexpress the human epidermal growth factor 2. It represents 15%‒20% of breast cancers and have worse prognosis, with scarce available therapies and overall survival (OS) of 18 months. For these particularities, research on TNBC is important for its greater understanding. Objectives: To describe the clinical-epidemiological profile of patients with TNBC at Instituto Mário Penna (IMP). To compare findings with data from the literature. Methods: Consultation of breast immunohistochemistry (IHC) performed at IMP between July/2012 and June/2017. TNBC were selected. Data were collected from patients in electronic medical records. Maximum follow-up until December/2018. Database and statistical analysis using the SPSS program. Bibliographic review used the key phrase: “triple-negative breast cancer”. Results: 1,343 breast IHC performed at IMP in the studied period, 168 were TNBC (12.5%). Mean age of 53.4 years. Mean follow-up of 41.7 months. Neoadjuvant chemotherapy (CT) performed in 46.4%, with 12.8% of complete pathological response. Mean SG of 23.6 months, 20.2% progressed before the end of the treatment. Tumor mean size of 4.04 cm. Mortality of 22%, with 31.5% without information on death in the medical record, and about 17% on average with missing information. Table 1 shows the frequency distribution of the variables evaluated. Discussion: TNBC is a heterogeneous group of diseases, more commonly found in people aged under 40 years, of African descent, diagnosed at an advanced stage and with a high histological grade. Earlier metastasis, preferably visceral. More sensitive to CT, but with worse OS compared to other subtypes. Use of platinum, capecitabine and recent studies with immunotherapy are promising, in the search for better outcomes. Conclusion: The profile of patients with TNBC in IMP is compatible with that described in the literature. This study is a hypothesis generator and the basis for more complex research. High rates of missing information are a limiting factor.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1038-1038 ◽  
Author(s):  
Anna Kaminsky ◽  
Rohit Bhargava ◽  
Kandace P McGuire ◽  
Shannon Puhalla

1038 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple negative and neoadjuvant chemotherapy (NAC) is often used in triple negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive (H score of 10 or less) and HER2 negative or indeterminate (HER2 1+ or 2+ without amplification by FISH)), were identified. Nine of these TNBCs had metaplastic subtype and 2 groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Mean follow up in MBC group was 43 months and no patients were lost to follow up. Mean tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple negative paradox is likely not applicable to MBC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11543-e11543
Author(s):  
Jose Ignacio Chacon ◽  
Ana Rosa Rubio Salvador(2) ◽  
Nazaret Cordero Franco(1) ◽  
Begona Martinez Carrasco (1) ◽  
Sonia Alonso Soler(1) ◽  
...  

e11543 Background: Triple negative breast cancer (TNBC) is an anthracycline resistant subtype, for which there is no standard chemotherapy. Taxanes, platinum-derived drugs and bevacizumab all seem to be active drugs in this setting, but definitive data are still lacking. Our purpose is to report our experience with the combination Docetaxel-Carboplatin-Bevacizumab (TCV) in TNBC. Methods: We retrospectively analysed our database using medical claims for patients diagnosed with TNBC and treated with TCV in neoadjuvant (NAJ) or metastasic( MD), between July 1, 2009, and December 31, 2011. Informed consent was obtained from all patients. Results: 13 pts have received 86 TCV cycles, 8 in NAJ and 5 for MD. NAJ: Median age: 48(28-60) y. T3-T4 tumors: 62,5% . N+: 62.5%. All pts received 6 TCV cycles, except 1 pt, still on therapy. 5 (62.5%) pts received quadrantectomy, 2(25%) mastectomy as surgical treatment after TCV. One pt has not received surgery yet. Sentinel lymph node biopsy was done in 5/8 (62.5%) pts, the other 3 received axillary dissection for clinically N+ metastasis. After surgery, pathologic complete response (pCR) in breast in 6/7 pts (85.7%); in axillary nodes, pCR in 5/7 pts (71,4%). One has not been surgically evaluated yet. Median follow-up: 10 months (2-18). Only one pt has relapsed with cerebral metastasis. MD: Median age: 54.4 (40-71) y. 4 pts received TCV as first line, one as third line therapy. 3 pts obtained complete response, 2 partial responses, but both progressed in three months. Median follow-up: 14.4 months. Only one of these pts has died. Toxicity: Was mild, without any grade 3 or 4 toxic effect. Only one pt showed grade 2 hypertension after bevacizumab infusion. Neutropenia was not evaluable for use of G-CSF per protocol. Conclusions: Although this is a short series, it suggests that TCV may be a highly active combination in TNBC with a good tolerability profile. These data warrant continuing testing of this combination in TNBC.


2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 28-28 ◽  
Author(s):  
Damien Mikael Hansra ◽  
Rebecca Rollins ◽  
Karen Rados ◽  
Anita Johnson ◽  
Johnathan Ramey ◽  
...  

28 Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) with unique clinical-pathological & prognostic characteristics. Studies have shown obesity to be risk factor for TNBC. Furthermore, patients (pts) with BC and overweight/obesity have a worse prognosis. Here we investigate body mass index (BMI) & weight trends among BC survivors. Methods: A retrospective review BC pts at Cancer Treatment Centers of America Atlanta from 2012-10/27/17. Definition of a survivor: pts who have completed definitive therapy with no evidence of disease. Survivor BMI & weight gain (kg) calculated from chart review. Weight gain in kg was recorded post chemotherapy, at 3, 6, 9, 12 month follow up. Inclusion: Pts with ER-PR-HER2- (TNBC), adults > 18 yo, pts who completed chemo (neoadjuvant or adjuvant) & surgery +/- radiation. Exclusion: Pts who died, had relapsed local disease or metastatic disease; missing BMI data; currently on chemotherapy; who did not receive chemotherapy; missing continuous BMI data or pathology report; lost to follow up. Results: 1756 BC pts with stage IA-IIIC identified, 300 pts identified as TNBC. A total of 134 patients met full inclusion/exclusion survivorship criteria. Average age of survivors = 52 (range 25-76). Stage: I = 38%; II = 50%, III = 12%. BMI categories: 0% underweight (BMI < 18.5 kg/m2), 15% normal weight (BMI 18.5 to < 25 kg/m2), 18% overweight (BMI 25 to < 30 kg/m2), 55% obese (BMI ≤30 kg/m2), 12% morbid obesity (BMI ≤ 40 kg/m2). Average BMI for all survivors = 32.23 +/-0.59 kg/m2 (range 19-52 kg/m2); post chemotherapy weight change = 0.53 +/-0.41 kg; at 3 month follow up = -0.16 +/-0.51 kg; at 6 month = -0.02 +/-0.54 kg; at 9 month follow up 1.20 +/-0.59 kg; at 12 month follow up = 2.25 +/-0.61 kg. BMI by stage: I = 32.81 +/- 1.00 kg/m2; II = 32.12 +/- 0.91 kg/m2; III = 32.44 +/- 1.27 kg/m2. Conclusions: In our study, female survivors with TNBC present with obesity and gain weight after chemotherapy. Also, weight gain continues at 9 & 12 months post definitive treatment. Survivors with TNBC should be treated with intensive weight loss interventions given that overweight/obesity is a risk factor for recurrence, worse prognosis, & cardiovascular events.


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