The Real Impact of Target Therapy in Breast Cancer Patients: Between Hope and Reality

Over the last 15 years, we have seen a huge expansion of the development of drugs directed against biomolecular targets within breast cancer cells. The over-expression of certain receptors (ER, PgR, HER-2, VEGF-R), as well as alteration of several intracellular signal transduction pathways (the PI3K-AKT-mTOR pathway, MEK-MAPK pathway, loss of PTEN, etc ...) has a great impact on the likelihood of recurrence and progression of the disease, influencing the natural history of breast cancer. The recent biomolecular classification of breast cancer (Luminal A / B, HER2- driven, Basal Like) allowed finally to identify specific treatments against molecular target to associate or not to traditional chemotherapy, and to use in relation to the prognosis of the disease. In the following paragraphs, we will set out the major targeted drug that have received indications in breast cancer, both in the localized and in advanced disease, referring to the specific target (hormonal receptors, HER2, VEGF, m-TOR, PARP etc ...).

Download Full-text

Molecular classification of breast cancer. Treatment and prognosis implications.

Cirugía Andaluza ◽

10.37351/2021322.9 ◽

2021 ◽

Vol 32 (2) ◽

pp. 155-159

Author(s):

M Alcaide Lucena ◽

CJ Rodríguez González ◽

S de Reyes Lartategui ◽

R Gallart Aragón ◽

MT Sánchez Barrón ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Molecular Classification ◽

Breast Cancer Treatment ◽

Cáncer De Mama ◽

Luminal A ◽

Luminal B ◽

Her 2

Resumen Los avances recientes en el campo de la biología molecular y la secuenciación del genoma se han traducido en una nueva clasificación del cáncer de mama, que busca mayor precisión y se correlaciona mejor con el riesgo de recaída de la enfermedad y la respuesta al tratamiento. Establece cuatro subtipos de cáncer de mama: luminal A, luminal B, HER 2 positivo y triple negativo, siendo el subtipo luminal A el de mejor pronóstico, y el triple negativo, el de peor pronóstico. Si combinamos la clasificación clásica histológica con la nueva molecular, nos permite encuadrar a estas pacientes de una forma más precisa en función del riesgo, definiendo así un manejo terapéutico adaptado.

Download Full-text

Áp dụng hóa bảng phân loại của ST GALLEN 2013 trong phân nhóm phân tử ung thư vú biểu mô tuyến vú

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2020.65.16 ◽

2020 ◽

Author(s):

Chu Nguyen Van

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Molecular Classification ◽

Breast Cancer Patients ◽

Luminal A ◽

Prognostic Information ◽

Patient Groups

Molecular classification of breast cancer is target to category patient groups who need to treat by the appropriate adjuvant therapy and provide more exact prognostic information. Purpose: Determining the proportion of molecular types and commenting on some association with clinicpathological characteristics of breast cancer. Methods: 521 operated breast cancer patients were stained by immunohistochemistry with markes such as: ER, PR, HER2, and Ki67 for classifying into 5 molecular categories and follow up assessment. Results: Type LUMBH- accounted for the highest proportion of 26.5%, followed by luminal A (22.5%). Typically, LUMA was the highest rate in good NPI (35.0%), whereas in poor NPI group, HER2 type was the highest rate (36.4%) (p<0.001). The LUMBH - group has the OS rate during the 5-year follow-up of 94.6% and LUMA is 93.5%; In contrast, the HER2 group showed the lowest OS ratio (72.6%) (p<0.05). Conclusion: Molecular classification of breast cancer according to St Gallen 2013 classification can provide the important information for treatment and prognosis.

Download Full-text

Effects of different chemotherapy regimens and tamoxifen for HER2 over-expressed breast cancer adjuvant therapy

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.11048 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 11048-11048

Author(s):

J. Zhang ◽

Y. Liu ◽

X. Hao ◽

Z. Fang ◽

L. Ning

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Subgroup Analysis ◽

Negative Group ◽

Breast Cancer Patients ◽

Node Negative ◽

Over Expression ◽

Node Positive ◽

Her 2

11048 Background: To evaluate effects of different adjuvant chemotherapy regimens and TAM in HER-2-overexpressed breast cancer patients. Methods: To study 1625 primary breast cancer cases after operation from 2002.7 to 2005.11 given adjuvant chemotherapy ,600 cases given CMF, 600 cases given CEF, and 425 cases given T-regimen (anthracyclines follow taxanes),1090 HR+ cases given tamoxifen. HER-2 expression were measured by immunohistochemistry (IHC). Median follow-up time is 42 months. Results: (1)3yr DFS of HER-2 over-expression is inferior to HER-2 negative ones in CMF group(p<0.05), no difference between HER-2- overexpressed and HER-2-negative group treated with either CEF or taxanes-based regimen (p>0.05). Subgroup analysis suggested: patients treated with CMF, 3yr DFS of HER-2 over-expression is inferior to HER-2-negative ones in node-positive subgroup, but no difference in node-negative ones; HER-2 expression has no influence on effects of CEF or T-regimen in node-positive or node-negative subgroup. (2) 425 HER-2 over-expressed patients(183 cases given CMF , 121 cases given CEF , and 121 cases given T-regimen): compared to CMF, anthracyclines and taxanes are more effective, but no difference between anthracyclines and T-regimen. (3) 235 patients with HER-2 over- expression and node-postive (72 cases given CMF , 68 cases given CEF, and 95 cases given T-regimen):, anthracyclines and taxanes are more effective than CMF, but no difference between anthracyclines and T-regimen. (4)3yr DFS is 91.23% in HER-2 over-expressed group and 93.42% in HER-2-negative group (p=0.04) with TAM. HER-2 over-expressed patients are resistant to TAM. (5) Subgroup analysis suggested that: 3yr DFS is 88.67% with HER-2 over-expression and 92.20% with HER-2-negative in postmenopausal node-positive subgroup(p=0.0069), postmenopausal patients with HER-2 over-expression and node-positve are resistant to TAM; no difference in either premenopausal or postmenopausal node-negative subgroup (p>0.05). Conclusions: No difference between Anthracyclines based and T-regimens for HER2 over-expressed patients with node-positive for 3yr DFS.Postmenopausal ER+/PR+ patients with HER2 over- expression are resistant to Tamoxifen endocrine therapy. No significant financial relationships to disclose.

Download Full-text

Is HER-2 over expression associated with brain metastases in Chinese breast cancer patients?

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)70729-8 ◽

2008 ◽

Vol 6 (7) ◽

pp. 173-174

Author(s):

D. Suen ◽

A. Lee ◽

A. Kwong

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Over Expression ◽

Her 2

Download Full-text

Prognostic significance of HER-2/neu over-expression on the incidence of brain metastasis in newly diagnosed breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.649 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 649-649 ◽

Cited By ~ 1

Author(s):

B. S. Abdulkarim ◽

Z. Gabos ◽

R. Sinha ◽

J. Hanson ◽

N. Chauhan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Size ◽

Univariate Analysis ◽

Prognostic Significance ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Over Expression ◽

Increased Risk ◽

Her 2

649 Background: As systemic therapy improves, brain metastases (BM) from breast cancer are becoming increasingly evident. An increased risk of BM in HER-2/neu over-expressing metastatic breast cancer patients has been suggested. However, the relationship between HER-2/neu over-expression and the risk of BM in newly diagnosed breast cancer patients is unknown. Methods: To determine incidence of BM in HER-2/neu over-expressing breast cancer patients, a cohort of patients between 01/1998 and 12/2003 with uniform HER-2/neu testing were identified from a cancer registry. A total of 460 patients with HER-2/neu over-expression and 500 patients with HER-2/neu negative disease were reviewed. Patients were excluded if there was breast cancer diagnosed before 01/1998 or others cancer. A total of 301 HER-2/neu over-expressing and 363 HER-2/neu negative patients were included for this analysis. The association between histological features and the occurrence of BM were evaluated with univariate and multivariate analyses. Results: BM were identified in 8% (24 patients) of HER-2/neu over-expressing breast cancer patients compared to only 1.7% (6 patients) in the HER-2/neu negative patients (hazard ratio 5.15 [2.079–12.78], p=0.0001). In patients with recurrent disease, the proportion of BM for HER-2/neu over-expressing patients was 24% compared to 10% in HER-2/neu negative patients. HER-2/neu over-expression, tumor size >2cm, ≥ 4 nodes positive and grade 2/3 were predictors of BM in univariate analysis. In multivariate analysis, HER-2/neu over-expression and tumor size>2cm were an independent prognostic factors for the development of BM, while hormone receptors expressions was protective (p=0.02). Conclusions: Our population based study show that newly diagnosed HER-2/neu over-expressing breast cancer patients are at significantly increased risk for BM. As most BM occur in HER-2/neu over-expressing patients with systemic metastatic disease, these findings could prompt consideration of brain prophylaxis strategies and/or serial radiologic screening to detect asymptomatic BM. No significant financial relationships to disclose.

Download Full-text

Molecular Subtypes of Breast Cancer Patients According to St Gallen Classification

Chattagram Maa-O-Shishu Hospital Medical College Journal ◽

10.3329/cmoshmcj.v19i1.48805 ◽

2020 ◽

Vol 19 (1) ◽

pp. 55-58

Author(s):

Shafatujjahan ◽

Ifatujjahan ◽

Rajat Sanker Roy Biswas

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Molecular Subtypes ◽

Hormonal Treatment ◽

Left Breast ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

Her 2

Introduction: Breast cancer is a common malignancy among female in Bangladesh.But its molecular subtypes are not evaluated due to lack of expert investigationsupport. So objectives of the present study are to evaluate the molecular subtypesof breast cancer patients according to St Gallen classification in our contest. Materials and methods: It is retrospective study done among histopathologicallyproved 40 breast cancer patients visiting Medical Oncology and Radiotherapydepartment of Chattogram Maa-O-Shishu Hospital. Molecular subtypes wasevaluated by immunohistochemistry according to St Gallen Classification. Results: In this study a total of 40 cases of invasive female breast cancers wereincluded. Age of the patients ranged from 31-62 years, with a mean age of 41 ±13.5 years. ER expression was seen in 60% and PR in 55% of cases and Her-2/neupositivity in 16%. Majority (52.5%) of the tumors were located in the left breast. Thepercentage of ER but not PR positivity increased with age, though this differencewas not statistically significant. Majority of the cases were diagnosed at stage IIwith a percentage of 42.5%. Stage II tumors showed more ER and PR positivity.Among all 57.9% of ER positive and 49.5% of PR positive tumors were present while72.2% of tumors were negative for Her-2/neu. The triple-negative breast tumorswere more commonly found at grade 2. Regarding luminal status 14(35%) wasLuminal A, 5(12.5%) was Luminal B, 9(22.5%) was TNBC and 12(30%) was HER 2positive. Conclusion: In this study luminal A was the commonest molecular subtypes. LuminalA subtypes tumors had a long term risk of distant matastatic disease which can bereduced by hormonal treatment. Chatt Maa Shi Hosp Med Coll J; Vol.19 (1); January 2020; Page 55-58

Download Full-text

The AMAZONA Project: Retrospective Cohort Study Describing Breast Cancer Patients' Characteristics and Survival in Brazil

Journal of Global Oncology ◽

10.1200/jgo.18.88600 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 219s-219s

Author(s):

M. Caleffi ◽

S. Simon ◽

J. Bines ◽

G. Werutsky ◽

J. Soares Nunes ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Retrospective Cohort ◽

Triple Negative ◽

Molecular Subtypes ◽

The United States ◽

Breast Cancer Patients ◽

Luminal A ◽

Pathologic Stage ◽

Her 2

Background: Breast cancer is the most common cancer in women in Brazil and worldwide. There is large variation in survival among patients and molecular subtypes are important prognostic factors. However, most of the data comes from developed countries such as the United States and in Europe. Aim: Our goal was to describe breast cancer patients' demographic and pathologic characteristics, as well as their survival according to estimated molecular subtypes, assessed by common immunohistochemistry stains. Methods: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer diagnosed in the period between 1 January 2001 and 31 December 2001 and between 1 January 2006 and 31 December. Estimated molecular subtypes by local immunohistochemical stains were luminal A, luminal B, HER-2 positive and triple-negative. Data were obtained from medical records and public databases. Kaplan-Meier method was used for data description and log-rank test for comparison between the subgroups. Results: 2296 patients were included in this analysis. Mean age was 54 years. Most subjects included came from hospitals located in the southeast region of the country, treated in the public health system and had stage II invasive ductal carcinoma of breast. Regarding subtype, 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. Overall survival (OS) was significantly different among molecular subtypes and was independent of pathologic stage for stages II and III patients. For stage III patients 5-years OS for luminal A subtype was 75.8% and for triple-negative was 56.1% ( P .0002). Conclusion: Classification of breast cancer patients in predicted molecular subtypes using immunohistochemistry is currently available in most underdeveloped countries and is a useful prognostic tool that goes beyond clinical or pathologic stage.

Download Full-text

The role of Ki-67 in molecular breast cancer classification.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.583 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 583-583

Author(s):

George Stathopoulos ◽

Nikolaos Malamos ◽

Christos Markopoulos ◽

Athanasios Polychronis ◽

Sotirios Rigatos ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Progesterone Receptors ◽

Molecular Classification ◽

Breast Cancer Patients ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Her 2

583 Background: The Ki-67 antigen was identified the involvement in early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that the protein has an important function in cell division, its exact role is still obscure and there is little published work on its overall function. The aim of the present study is to evaluate the contribution of Ki-67 level in respect of tumor recurrence in molecular classified groups of breast cancer patients. Methods: Breast cancer tumor samples were examined for histological confirmation and for estrogen and progesterone receptors, c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided in percentage levels, up to 20 and higher than 20%. Immunohistochemistry and Fluorescence in situ hybridization is described for the results of ER, PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were paraffin wax embedded and processed for paraffin sections. The primary antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation, Carpinteria, CA) for the detection of ER, the monoclonal anti-PR antibody 636 was used. For the detection of Ki-67 we used monoclonal mouse anti-human Ki-67 MIB-1. The patients molecular classification was Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative). Results: 847 breast cancer patients were recruited. 291 were group as Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative. Follow-up was from 3 years to 15 years since diagnosis. It was found that in Luminal A patients, none had Ki-67 higher than 20% and the recurrence was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of the patients and recurrence 23.68%. In Her-2 subtype >20% Ki-67 was 78.94%, recurrence 17.19%. In triple negative > 20% Ki-67 was in 68.75% and recurrence in 29.90% of the patients. Conclusions: The data presented here indicate that Ki-67 level may be considered as one of valuable biomarkers in breast cancer patients process and recurrence.

Download Full-text