scholarly journals Results of organ-preserving treatment of breast cancer using intraoperative radial therapy

2021 ◽  
Vol 17 (3) ◽  
pp. 16-23
Author(s):  
I. S. Chumachenko ◽  
R. A. Murashko ◽  
A. A. Keshabyan ◽  
P. V. Krivorotko ◽  
S. N. Novikov
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Luminal B ◽  
End Of Treatment ◽  
Cosmetic Effect ◽  
The Mean ◽  
Biological Subtype

Objective: to compare the immediate and long-term outcomes of patients with early breast cancer treated with intraoperative radial therapy depending on the biological subtype of breast cancer.Materials and methods. We prospectively evaluated number of recurrences, cosmetic effect and early treatment results of 104 patients with early breast cancer aged 66.72 ± 0.68 years old. The mean follow-up period was 36 months. The mean dose on the surface of applicator was 17.8 Gy, on the depth 0.5 cm – 8.8 Gy, on the depth 1.0 cm – 5 Gy. The mean time of radiation was 22.15 min ± 28.09 sec.Results. The local recurrence was in 3 patients. The first patient had triple negative breast cancer subtype, the second patient had luminal B HER2+, and the third one had luminal B HER2– subtype. Relapses occurred in 7, 14 and 20 months after the end of treatment respectively. The recurrence rate in patients with luminal B biological subtype was 10.71 %; in patients with triple negative subtype was 20 %. All recurrences were found in the area of the postoperative scar.Conclusion. The obtained results question the rationale for the use of the demonstrated method in patients with luminal B and triple negative molecular subtypes of tumors.

Epigenetic aspects of triple-negative in patients with breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1041-1041
Author(s):  
Joaquina Martínez-Galan ◽  
Sandra Rios ◽  
Juan Ramon Delgado ◽  
Blanca Torres-Torres ◽  
Jesus Lopez-Peñalver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Regulation Of Gene Expression ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p>0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

Response-Guided Neoadjuvant Chemotherapy for Breast Cancer

2013 ◽  
Vol 31 (29) ◽  
pp. 3623-3630 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Jens Uwe Blohmer ◽  
Serban Dan Costa ◽  
Carsten Denkert ◽  
Holger Eidtmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Exploratory Analysis ◽  
Her2 Positive ◽  
Luminal B ◽  
Hormone Receptor Positive

Purpose We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. Patients and Methods We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery. Results DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor–negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74). Conclusion This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor–positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.

scholarly journals Prognostic role of clinical and biological factors and parameters of hormonal profile in patients with primary inoperable HER2-negative breast cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 82-87
Author(s):  
Natalia I. Samaneva ◽  
Liubov I. Vladimirova ◽  
Irina V. Kolyadina ◽  
Elena M. Frantsiyants ◽  
Anna E. Storozhakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Surgical Treatment ◽  
Disease Progression ◽  
Triple Negative ◽  
Biological Factors ◽  
Hormonal Profile ◽  
Luminal B ◽  
Group 2 ◽  
Biological Subtype ◽  
Group 1

Relevance. Breast cancer (BC) is among the most common cancers and the leading causes of cancer death in women worldwide. Much attention is paid to the problem of its hormoneresistance; however, the issues of using prognostic markers and predictors in routine cancer clinical practice remain unresolved. Aim. Study and analysis of prognostic significance of clinical and biological factors and parameters of the hormonal profile in patients with primary inoperable HER2-negative breast cancer receiving neoadjuvant chemotherapy. Materials and methods. The study included 162 patients with locally advanced primary inoperable HER2-negative breast cancer. Patients were divided into 2 groups. Group 1 included 58 patients with early disease progression within 6 to 12 months after radical surgical treatment. Group 2 included 104 patients with no disease progression within 2 years after radical surgical treatment. In all cases, diagnosis was verified histologically and immunohistochemically. Levels of prolactine, progesterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone, testosterone and cortisol were measured by RIA. The blood plasma values in 20 healthy donors were used as reference one. The data were processed using the Statistica 7.0 and MedCalc (version 9.3.5.0) programs. All patients received combination antitumor treatment according to clinical guidance. Results. An analysis of the overall (OS) and event-free (EFS) survival in group 1 showed that the median EFS in patients with luminal B BC was 9 months, with triple-negative BC (TNBC) 8 months. 6-month EFS in luminal B subtype was 87.5%, in TNBC 79.4%, p=0.37985. 1-year EFS was 1.721.7% regardless of the biological subtype. The median OS in luminal B BC was 25 months, in TNBC 26 months. 1-year OS in luminal B BC 100%, in TNBC 93.9%, p=0.138. 2-year OS in luminal B BC 54.2%, in TNBC 55.9%, p=0.697. 3-year survival in luminal B BC 37.5%, in TNBC 41.2%, p=0.639. An analysis of OS and EFS in group 2 showed that the median EFS was not reached for all biological subtypes. 3-year survival in the group was 100% regardless of the biological subtype. The median OS was not reached for all biological subtypes. 3-year OS in the group was 100%. An analysis of the hormonal profile in the treatment dynamics showed decreased levels of estradiol in all groups of patients (by 1.6 times). In group 1, progesterone was decreased by 2.1 times, testosterone by 2.4 times and LH by 2.1 times in all BC subtypes (p0.05). Patients of group 2 showed 2 times reduced cortisol and 3 times reduced prolactin in all BC subtypes, while LH levels were elevated by 1.6 times in luminal A and B BC. Conclusion. Aggressive course was observed similarly in triple-negative cancer as well as in luminal cancer with primary hormone resistance. Studying of pituitary and sex hormones and cortisol have a great clinical significance in patients with all biological subtypes of BC. This should be taken into account when predicting the course of the disease and developing further treatment options.

Distant disease-free survival (DDFS) discrimination capacity of various pathologic complete response (pCR) definitions according to breast cancer subtypes.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 162-162
Author(s):  
Masaya Hattori ◽  
Keitaro Matsuo ◽  
Mari Ichikawa ◽  
Takashi Fujita ◽  
Masataka Sawaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Roc Curves ◽  
Luminal A ◽  
Distant Disease ◽  
Free Survival ◽  
Cancer Subtypes ◽  
Luminal B

162 Background: pCR has been postulated to be correlated with long-term clinical benefits in some subtypes of breast cancer. Here, we analyzed the discriminatory ability and the predictive power of various pCR definitions for distant disease-free survival (DDFS) according to breast cancer subtypes. Methods: We analyzed 326 (114 Luminal A: ER+/PR+/HER2-, 44 Luminal B/HER2-: ER+/PR-/HER2-, 51 Luminal B/HER2+: ER+/PR+ and/or -/HER2+, 51 HER2: ER-/PR-/HER2+, and 66 Triple negative: ER-/PR-/HER2-) non-metastatic breast cancer patients (pts) who had received neoadjuvant chemotherapy at our institution between January 2003 and June 2012. Four pCR definitions were used: ypT0ypN0, ypT0/isypN0, ypT0/isypN0/+, ypT<1micypN0/+. DDFS was estimated by Kaplan-Meier method, and analyzed by log-rank test and Cox proportional hazard model. The receiver operating characteristic (ROC) curves analysis was used for comparing DDFS prediction models with and without various pCR definitions in addition to other covariates (tumor stage, nodal status, BMI, tumor grade, use of trastuzumab) as variables. Results: The pCR rate was comparatively low in Luminal A and high in HER2. 94.1% of HER2 and 74.5% of Luminal B/HER2+ received total 1 year of trastuzumab therapy. In multivariate analysis, no pCR definitions were associated with improved DDFS significantly in Luminal A, Luminal B/HER2-, Luminal B/HER2+ and HER2, whereas each pCR definition was associated with improved DDFS in Triple negative (ypT0ypN0: HR0.12, p=0.043, ypT0/isypN0: HR0.06, p=0.007, ypT0/isypN0/+: HR0.107, p=0.004, ypT<1micypN0/+: HR0.104, p=0.003). In the ROC curves analysis of triple-negative, a DDFS prediction model including pCR defined as ypT0/isypN0 showed the highest accuracy, but low statistical significance (AUC: 0.834 vs.0.749 p=0.076). Conclusions: pCR could discriminate good and poor prognosis groups only in Triple negative and pCR defined as ypT0/isypN0 has the potential to provide better discrimination in this subtype. The predictive power of pCR for long term clinical benefit in other subtypes may not be obvious due to the influence of effective adjuvant therapies.

No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 564-564
Author(s):  
Jose Ales-Martinez ◽  
Raquel Tur ◽  
Juan Parra ◽  
Jaime Ceballos ◽  
Elena Filipovich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Axillary Lymph ◽  
Her2 Positive ◽  
Luminal B ◽  
Tumor Load

564 Background: The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes a complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. Methods: Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2017 at our center. Results: A total of 321 patients underwent SNB assessed by OSNA with an average follow-up of 56 months. 320 were female and 1 male. Age range 27-89 years (mean 58.9). 85 % were ductal, 10 % lobular and 5 % other. 53.5% were luminal A, 28.66% luminal B, 7.78%, triple negative, 4.3%, Her2 positive and 4.3%. luminal B-Her2 positive.TTL was equal to 0 in 183 cases and greater than zero in 138 cases.71 cases showed a TTL higher than 15,000 copies. Only 21 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse and 8 metastatic disease. 12 have died, only two from metastatic breast cancer. Conclusions: Using Z0011 criteria, we have adequate clinical outcomes with a low rate of ALND; If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 3.3 (from 21 to 71); We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes; Work is in progress to increase our sample size.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

scholarly journals The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stijn Moens ◽  
Peihua Zhao ◽  
Maria Francesca Baietti ◽  
Oliviero Marinelli ◽  
Delphi Van Haver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Mitotic Checkpoint ◽  
Breast Cancers ◽  
Checkpoint Kinases ◽  
Xenograft Models ◽  
Potential Strategy ◽  
Shrna Screen ◽  
Resistant Cells

AbstractTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking effective therapy. Many TNBCs show remarkable response to carboplatin-based chemotherapy, but often develop resistance over time. With increasing use of carboplatin in the clinic, there is a pressing need to identify vulnerabilities of carboplatin-resistant tumors. In this study, we generated carboplatin-resistant TNBC MDA-MB-468 cell line and patient derived TNBC xenograft models. Mass spectrometry-based proteome profiling demonstrated that carboplatin resistance in TNBC is linked to drastic metabolism rewiring and upregulation of anti-oxidative response that supports cell replication by maintaining low levels of DNA damage in the presence of carboplatin. Carboplatin-resistant cells also exhibited dysregulation of the mitotic checkpoint. A kinome shRNA screen revealed that carboplatin-resistant cells are vulnerable to the depletion of the mitotic checkpoint regulators, whereas the checkpoint kinases CHEK1 and WEE1 are indispensable for the survival of carboplatin-resistant cells in the presence of carboplatin. We confirmed that pharmacological inhibition of CHEK1 by prexasertib in the presence of carboplatin is well tolerated by mice and suppresses the growth of carboplatin-resistant TNBC xenografts. Thus, abrogation of the mitotic checkpoint by CHEK1 inhibition re-sensitizes carboplatin-resistant TNBCs to carboplatin and represents a potential strategy for the treatment of carboplatin-resistant TNBCs.

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