Estrogen receptor in HER2-positive early breast cancer: Two different diseases?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Eva Maria Ciruelos Gil ◽  
Ismael Ghanem ◽  
Luis Manso ◽  
Sergio Hoyos ◽  
Carlos Castañeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Study Groups ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Ki 67 ◽  
Luminal B ◽  
Her2 Breast Cancer ◽  
Group A ◽  
Long Term Prognosis ◽  
Group B

642 Background: HER2+ breast cancer (BC) is a well characterized subtype of BC, due to the predictive value of HER2 overexpression for anti-HER2 targeted therapies. Nevertheless, around 50% of HER2+ BC are ER+ and clasiffied as luminal B/HER2+, but their biological and clinical behaviour may be different from HER2+/ER- tumors. Methods: We retrospectively reviewed 347 HER2+ (Herceptest +++ or FISH+) early BC patients (see Table) diagnosed at our institution in 1997-2007, and were divided into two study groups: HER2+/ER+ (group A) and HER2+/ER- (group B). ER+ was defined if expressed in > 10% tumor cells. Results: See table below. Mean age: 54.7 y (44.6 – 65). Mean Ki 67 was higher in B (37,2 vs 22,4%, p<0.0001). At the current FU, n¼ of events were insufficient to reach median DFS/OS. Mean DFS was 6.9 y (3.5 – 10.2); recurrent disease was higher (p 0.003) for B (54 pts, 43%) vs A (62 pts, 28%). 5-year DFS estimates: 78.4 % (95% CI 72.3 – 83.3) and 62.3 % (95% CI 53 – 70.27) for A and B, and 10-year DFS was 73.4% (95% CI 66.6 – 79) and 52.5% (95% CI 42.4 – 61.6) for A and B, respectively (p 0.0006). Most common recurrent sites were local (18) and bone (9) for HER2+/ER+ and liver (8) and lung (8) for HER2+/ER-. Mean OS was 8.03y (5.4 – 10.8); 28 (12,6%) pts died in A, vs 26 (21%) in B (p 0.043). 5-year OS estimates: 93.9 % (95% CI 89.7 – 96.4) and 87.6 % (95% CI 80.3 – 92.3) for A and B, and 10-year DFS was 84.2% (95% CI 77.5 – 89.0) and 74.1% (95% CI 63.4 – 82.2) for A and B, respectively (p 0.01). Conclusions: ER expression in HER2+ early BC defines two clinically distinct diseases with different long-term prognosis. These data may help to better individualize adjuvant therapies and future clinical trial designs. [Table: see text]

Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Ki67 Index ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Ki 67 ◽  
Luminal B ◽  
Therapeutic Implications ◽  
Significant Difference

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

Should liver metastases of breast cancer be biopsied to improve treatment choice?

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA1008-CRA1008 ◽  
Author(s):  
M. A. Locatelli ◽  
G. Curigliano ◽  
L. Fumagalli ◽  
V. Bagnardi ◽  
G. Aurilio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Treatment Choice ◽  
Her2 Status ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Er Positive ◽  
Group A ◽  
Group B

CRA1008 Background: Decision making on systemic treatment of women with metastatic breast cancer is based on features like estrogen receptor (ER), progesterone receptor (PgR), and HER2 status assessed on the primary tumor. We evaluated the concordance of receptor status between primary tumor and liver metastases (mts) and its impact on treatment choice. Methods: We retrospectively analyzed a database including ultrasound guided liver biopsies performed from 1995 to 2008. All tissue samples, both from primary tumor and liver mts, were analyzed for ER, PgR and HER2 status. Clinical and biological data were obtained from medical charts. Differences between proportions were evaluated using the Pearson chi-square test. Results: We identified 255 consecutive patients (pts) with matched primary and liver tissue samples. Median time from primary diagnosis to liver biopsy was 3.4 years (range 0-18.3 years). Changes in ER status were observed in 41/255 pts (16.0%). 16/58 pts (27.6%) changed from ER-negative to ER-positive and 25/197 pts (12.7%) changed from ER-positive to ER-negative (p=0.0066). Changes in PgR status were observed in 76/255 pts (29.8%). 18/91 pts (19.8%) changed from PgR-negative to -positive and 58/164 pts (64.6%) from PgR-positive to PgR-negative (p <0.0001). 12/52 pts (23.1%) changed from ER- and PgR-negative to ER- or PgR-positive (group A) and 27/203 pts (13.3%) changed from ER- or PgR-positive to ER- and PgR-negative (group B) (p=0.087). In the group A the treatment of 4/12 pts (33.3%) was changed after biopsy: 2/4 started endocrine treatment (HT) and 2/4 stopped it. In group B the treatment of 18/27 pts (66.6%) was changed after biopsy: 17/18 stopped HT. Changes in HER2 status were observed in 22/167 pts (13.1%): 6/116 pts (5.1%) changed from HER2-negative to HER2-positive and 16/51 pts (31.4%) changed from HER2-positive to negative (p≤0.0001). In this group pts started and/or stopped a trastuzumab containing treatment after biopsy. Conclusions: There was a discordance in receptor status between primary tumor and liver mts, which led to change in therapy for 48/255 of pts (18.8%). Biopsy of metastases for reassessment of biological features should be considered in all pts when safe and easy to perform, since it is likely to impact treatment choice. No significant financial relationships to disclose.

scholarly journals The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Charity Ameh-Mensah ◽  
Babatunde Moses Duduyemi ◽  
Kweku Bedu-Addo ◽  
Elijah Atta Manu ◽  
Francis Opoku ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Histological Grade ◽  
Her2 Overexpression ◽  
Luminal A ◽  
Ki 67 ◽  
Cross Sectional ◽  
Luminal B ◽  
Protein P53

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.

scholarly journals Modelling hypersensitivity to trastuzumab defines biomarkers of response in HER2 positive breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Laura Díaz-Gil ◽  
Fara Brasó-Maristany ◽  
Claudriana Locatelli ◽  
Ariana Centa ◽  
Balász Győrffy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Surface ◽  
Therapeutic Option ◽  
Cell Counting ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Cellular Models ◽  
Her2 Breast Cancer

Abstract Background Trastuzumab-based therapies are the therapeutic option for HER2 positive (HER2+) breast cancer. HER2 amplification is the only biomarker validated for trastuzumab-based therapies. However, a proportion of tumors become refractory during treatment course. For this reason, the finding of new biomarkers beyond HER2 overexpression to identify patients who would benefit most from trastuzumab regimens is of outstanding importance. Methods Models of trastuzumab-resistant or hypersensitive cells were generated by exposure to trastuzumab. Cell surface, total HER2, and analyses of proteins involved in cell cycle or apoptosis were analyzed by western blotting. Cell proliferation was analyzed by cell counting, cell cycle and apoptosis was evaluated by FACS. Transcriptomic characterization of the cellular models was performed using bioinformatic online tools, and clinico-genomic analyses were performed using the PAMELA clinical trial data. Results Besides differing in sensitivities to trastuzumab, the different cellular models also showed distinct response to other anti-HER2 drugs (lapatinib, neratinib, pertuzumab and T-DM1) used in the clinic. That differential effect was not due to changes in cell surface, total or activated HER2. Trastuzumab caused important induction of cell death in hypersensitive cells but not in parental or resistant cells. Transcriptomic analyses of these cellular models together with querying of online databases allowed the identification of individual genes and gene signatures that predicted prognosis and trastuzumab response in HER2+ breast cancer patients. Conclusion The identification of trastuzumab response biomarkers may be used to select patients particularly sensitive to facilitate the use of trastuzumab-based therapies and refine follow-up guidelines in patients with HER2+ tumors.

scholarly journals Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer

Breast Care ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. 391-394 ◽  
Author(s):  
Giulia Galli ◽  
Giacomo Bregni ◽  
Stefano Cavalieri ◽  
Luca Porcu ◽  
Paolo Baili ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptors ◽  
Residual Disease ◽  
Luminal A ◽  
Her2 Positive ◽  
Ki 67 ◽  
Surgical Specimen ◽  
Luminal B ◽  
Basal Phenotype

Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. Results: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. Conclusions: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.

scholarly journals Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: analysis from the ALTTO (BIG 2-06) trial

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e000979
Author(s):  
Matteo Lambertini ◽  
Dominique Agbor-Tarh ◽  
Otto Metzger-Filho ◽  
Noam F Ponde ◽  
Francesca Poggio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
First Line ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Distant Disease ◽  
Free Interval ◽  
Group A ◽  
Group B ◽  
Disease Free

BackgroundIn HER2-positive breast cancer, time elapsed between completion of (neo)adjuvant trastuzumab and diagnosis of metastatic disease (‘trastuzumab-free interval’, TFI) is crucial to choose the optimal first-line treatment. Nevertheless, there is no clear evidence to support its possible prognostic role.MethodsIn the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial, patients with HER2-positive early breast cancer were randomised to 1 year of either trastuzumab alone, lapatinib alone, their sequence or their combination. This exploratory analysis included only patients in the trastuzumab alone or trastuzumab plus lapatinib arms who developed a distant disease-free survival (DDFS) event. Overall survival (OS) was defined as time between date of DDFS event and death; age at diagnosis, tumour size and hormone receptor status were the variables included in the multivariate models.ResultsOut of 8381 patients included in ALTTO, 404 patients in the trastuzumab alone and trastuzumab plus lapatinib arms developed a DDFS event, of which 201 occurred <12 months (group A) and 203 >12 months (group B) after completion of adjuvant trastuzumab. No significant difference in location of first DDFS event was observed (p=0.073); a numerically higher number of patients in group A than in group B developed brain metastasis (26% vs 15%). Choice of first-line therapy differed between the two groups (p=0.022): in group A, more patients received lapatinib (25% vs 11%) and less pertuzumab (8% vs 17%). Median OS was 29.3 and 18.4 months in groups B and A, respectively (adjusted HR 0.69; 95% CI 0.54–0.89; p=0.004). The longer OS for patients in group B was observed across the analysed subgroups without interaction according to hormone receptor status (p=0.814) nor type of administered adjuvant anti-HER2 treatment (p=0.233).ConclusionsTFI has prognostic value in patients with HER2-positive early breast cancer treated with adjuvant trastuzumab-based therapy. TFI is a valid tool to better individualise clinical recommendations and to design future first-line treatment trials for metastatic patients.

scholarly journals Stage iv breast cancer surgery. Case serie

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
María Liz Bareiro Paniagua
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
De Novo ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Luminal B ◽  
Group A ◽  
Her 2 ◽  
Group B

Introduction: Distant site tumor implantation implies a severe condition, stimulated by an additional genome evolution that compromises the survival (6 months in the visceral metastasis). The literature is still controversial, and the guidelines recommend surgery only as palliative care. New results are conflicting, however, the initial modern systemic therapy, followed by the resection of the primary tumor, seems to improve the global survival (GS). “De Novo Metastasis (MT)” is that found in the diagnostic investigation. Objective: To assess the results of the primary metastatic breast cancer (BC) surgery. Method: retrospective review of medical records in a cohort of patients with metastatic BC treated between 2011 and 2018 in the state of Rio de Janeiro. Result: Eleven patients were included. (Group A= 6 patients with De Novo MT, and Group B= 5 patients with MT in the follow-up). In both cases, invasive ductal carcinoma was prevalent, frequently of grade 3 and with high Ki-67, Luminal B and Her-2. There was a mutation (BRCA2), and the PET CT was correlated to the complete pathological response. In group A, the patients were younger (50% <40 years old), 5/6 initiated neoadjuvant chemotherapy (NACT), all underwent mastectomy (multicentricity or size), 33% presented with imaging and pathological complete response (pCR). Of the MT, 50% were in the bone; 1/6 had negative and operated liver and pulmonary MT (HER-2), with disease-free survival (DFS) superior to 12 months. In group B, all MTs came after local recurrence (LR) (between 3 and 11 months); 40% had high initial axillary compromise (pN= mean of 25), and Luminal B, being treated according to the guidelines. In 2/5 (40%) of visceral MT, 18 months of DFS were observed after pCR and primary tumor resection. Finally, in the follow-up (mean of 42 months), there were two casualties (TN) in group A, and 4/6 presented DFS between 17 and 72 months. In group B, 3/5 presented DFS between 12 and 24 months. Conclusion: In this sample, the pathological complete response suggested better prognosis before surgery. There was benefit in the survival of visceral MT (including multiple ones) with pCR and breast surgery in comparison to the literature; further studies are required, considering the limitations of this analysis.

Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12550-e12550
Author(s):  
Aimaz Afrough ◽  
Heather Lin ◽  
Angelica M. Gutierrez-Barrera ◽  
Jennifer Keating Litton ◽  
Vicente Valero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Brca Mutations ◽  
Her2 Breast Cancer

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.

Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer: Results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Jonas C. S. Bergh ◽  
Anne Andersson ◽  
Judith Bjohle ◽  
Ana Bosch ◽  
Lena Carlsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Preoperative Treatment ◽  
Severe Toxicity ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Group A ◽  
Group B ◽  
Positive Breast Cancer

501 Background: Neoadjuvant therapy produces high rates of pathological complete response (pCR) and is the standard of care in HER2 positive breast cancer; however, the optimal treatment regimen remains to be established. Methods: In this randomized phase II study patients ≥18 years with HER2 positive breast cancer > 20mm or verified lymph node metastases were randomized to 6 courses of docetaxel, trastuzumab and pertuzumab (DTP, group A) or trastuzumab emtansine (T-DM1, group B), q 21 days. The protocol allowed switch to the competing treatment upon lack of response or drug-related severe toxicity. Patients received postoperative epirubicin+cyclophosphamide, trastuzumab for a total of one year and endocrine therapy. Accrual was completed in October 2018 after randomization of 202 patients, data on pCR were available for 190 at the time for this abstract submission. Median age, 52 years (26-74), menopausal status, histological type and grade were well balanced between the treatment groups. 62.6% of the tumors were hormone receptor (HR) positive. Results: Primary endpoint was pathological objective response. 190 patients completed the protocol-specified preoperative treatment. pCR was achieved in 45.3% of patients, 46.4% in patients treated with DTP and 44.1% with T-DM1 (chi-sq., p = 0.75). In HR-positive tumors, pCR was obtained in 35.3% of patients, 35.9% in group A vs. 34.6% in group B (p = 0.87); in HR-negative tumors, the overall pCR rate was 62.0%, 66.7% in group A vs. 57.9% in group B (p = 0.45). Severe (grade 3/4) toxicity was reported at 68 occasions related to DTP, compared with 16 related to T-DM1, 26 vs. 3 caused by febrile neutropenia. Significantly better quality of life was reported by patients treated with T-DM1. Conclusions: Our data on TDM-1 demonstrates similar efficacy and less toxicity, in particular for patients with HER2 and HR positive cancers, being a potential new standard for neoadjuvant therapy. Clinical trial information: NCT02568839.

Prognostic value of Tfh-like cells in breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14285-e14285
Author(s):  
Linxiaoxi Ma ◽  
Liang Guo ◽  
Shyamal Goswami ◽  
Xiaoming Zhang ◽  
Jiong Wu
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Cell Subpopulation ◽  
Her2 Overexpression ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Tfh Cells ◽  
Er Expression

e14285 Background: The treatment of breast cancer, one of the most common malignant tumors for female, focuses on the combined treatments based on subtypes including Luminal A, Luminal B, HER2 overexpression and triple negative. Given that none of those subtypes takes into consideration of immunological parameters, it is valuable to explore the biological characteristics and prognostic value of immune cells in breast caner. T follicular helper cells (Tfh cells) have been identified in different types of tumors with rare datas in breast cancer. One of them indicated the positive prognostic value of 8-gene Tfh signature. Exploration of Tfh cells may provide new clues to the potential immunotherapies in breast cancer. Methods: Freshly resected invasive breast cancer tissue from Fudan University Shanghai Cancer Center were collected during 06/2015 to 05/2017. Patients were divided into Luminal A (N = 61), Luminal B (HER2-) (N = 138), Luminal B (HER2+) (N = 72), HER2+ (non-luminal) (N = 57) and triple negative (N = 58) based on St Gallen International Expert Consensus. Results: A subpopulation of PD1hiCD4+ T cells in the tumor tissues of breast cancer was identified as Tfh-like cells, with the specific expression of Bcl-6 and CXCL13, confirmed by IHC. Phenotypes of those cells were checked by flow cytometry. Tfh-like cells were of a high level of ICOS but negative for CXCR5, suggesting that they were atypical Tfh cells. Data showed that high grade (N = 166; mean±SEM, 17.62±0.87) compared with low grade (N = 220; mean±SEM, 12.41±0.46) or high Ki-67 level (N = 300; mean±SEM, 15.38±0.58) with low Ki-67 level (N = 86; mean±SEM, 12.10±0.67), and negative ER expression (N = 115; mean±SEM, 17.47±1.05) compared with positive ER expression (N = 271; mean±SEM, 13.46±0.50) or negative PR expression (N = 177; mean±SEM, 16.87±0.83) compared with positive PR expression (N = 209; mean±SEM, 12.77±0.50) was associated with higher frequency of Tfh-like cells (P < 0.01 to all). Patients with triple negative had higher frequency of Tfh-like cells than those with Luminal A (difference, 6.83; P = 0.0006) and Luminal B (HER2-) (difference, 4.61; P = 0.0124). Patients with HER2+ (non-luminal) had higher frequency of Tfh-like cells than those with Luminal A (difference, 5.34; P = 0.0146). These results indicate that higher frequency of Tfh-like cells could have negative prognostic influence. Conclusions: Our study defined a PD1hiBcl6+CXCL13+CD4+ T cell subpopulation, which specifically secretes cytokine IL-21 as Tfh-like cells. Higher frequency of Tfh-like cells is more likely to be seen in patients with poor prognosis.

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