scholarly journals Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?

2013 ◽  
Vol 35 ◽  
pp. 595-605 ◽  
Author(s):  
Danae Pracella ◽  
Serena Bonin ◽  
Renzo Barbazza ◽  
Anna Sapino ◽  
Isabella Castellano ◽  
...  

In this study we investigate the clinical outcomes of 305 breast cancer (BC) patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN−) and 154 lymph node positive (LN+) patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%), while for LN+ patients survival at 20 years (around 40%) was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Xiao-Fang Dong ◽  
Yan Wang ◽  
Bi-Fei Huang ◽  
Gui-Nv Hu ◽  
Jun-Kang Shao ◽  
...  

It is unclear whether the methyltransferase-like 14 (METTL14) protein promotes or suppresses cancer growth. We examined the association between METTL14 expression, cancer progression, and patient prognosis in a total of 398 breast cancer tissue specimens. Significantly fewer cancer tissue specimens compared with normal breast tissue expressed high levels of METTL14 (52.8% vs. 75.0%). METTL14 expression was negatively associated with tumor grade and positively associated with patient age, estrogen, and progesterone receptor status. High METTL14 expression was more common in luminal A and luminal B tissue (75.9% and 60.8%, respectively), compared with human epidermal growth factor receptor 2- (HER2-) enriched and triple-negative breast cancer (TNBC) samples (38.2% and 18.6%, respectively). In multiple logistic regression analysis, independent predictors of METTL14 expression in breast cancer included higher tumor grade ( odds   ratio   OR = 0.494 , 95% confidence interval (CI): 0.289–0.844; P = 0.010 ), TNBC subtype ( OR = 0.109 , 95% CI: 0.054–0.222; P < 0.001 ), and HER2-enriched subtype ( OR = 0.298 , 95% CI: 0.156–0.567; P < 0.001 ). No clear relationship was observed between patient prognosis and METTL14 expression. It appears that downregulated METTL14 expression in breast cancer is associated with tumor grade and molecular classification.


2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Lalnun Puii ◽  
Lalram Sangi ◽  
Hrishi Varayathu ◽  
Samuel Luke Koramati ◽  
Beulah Elsa Thomas ◽  
...  

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]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.


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 ◽  
...  

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.


2020 ◽  
Vol 66 (1) ◽  
pp. 89-94
Author(s):  
T.S. Kalinina ◽  
V.V. Kononchuk ◽  
S.V. Sidorov ◽  
L.F. Gulyaeva

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.


Author(s):  
Chu Nguyen Van

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tatiana S. Kalinina ◽  
Vladislav V. Kononchuk ◽  
Alisa K. Yakovleva ◽  
Efim Y. Alekseenok ◽  
Sergey V. Sidorov ◽  
...  

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3045-3045
Author(s):  
J. Horiguchi ◽  
Y. Koibuchi ◽  
N. Rokutanda ◽  
R. Nagaoka ◽  
M. Kikuchi ◽  
...  

3045 Background: The purpose of this study is to determine the clinical efficacy of neoadjuvant paclitaxel and trastuzumab in women with advanced breast cancer, with or without metastatic disease. Methods: Patients with HER2-positive breast cancer (clinical stage IIB-IV) were included in this study. The patients received trastuzumab 4mg/kg loading dose intravenously then 2mg/kg weekly and concurrently paclitaxel 80mg/m2 (Day 1, 8, 15) weekly for 4 cycles followed by surgery. Results: Preliminary results from 15 patients are reported. Of these, six patients (40%) had a clinical complete response and nine patients (60%) a clinical partial response. Fourteen of 15 patients received surgery; eight breast-conserving surgery and six modified radical mastectomy. Six patients (43%) had pathological complete response. With a median follow-up of 19 months (range, 5–32 months), these 15 patients are alive. Patients with clinical stage IIB-III breast cancer are alive without any distant metastasis. Conclusion: Combined neoadjuvant weekly paclitaxel and trastuzumab had high clinical and pathological response rates for HER2 overexpressing breast cancer. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11599-11599
Author(s):  
Sherry X. Yang ◽  
Eric Polley

11599 Background: It is unclear whether survival varies among breast cancer molecular subtypes without systemic and locoregional therapy. This study aims to evaluate the survival profile by molecular subtypes after surgery. Methods: In total, we evaluated 301 women with invasive breast cancer with stage I, II or III disease. Patients were classified into four major breast cancer subtypes by immunohistochemistry/FISH classifiers: luminal-A (ER+ and/or PR+/HER2-), luminal-B (ER+ and/or PR+/HER2+), HER2-enriched (HER2+/ER-/PR-) or basal-like (ER-/PR-/HER2-; triple-negative). Overall survival (OS) was analyzed by Kaplan-Meier analysis, and log-rank test for differences. Association between clinical outcome and subtype adjusting for breast cancer prognostic factors was assessed by multivariable Cox proportional hazards model. Results: All patients did not receive systemic chemotherapy and hormone therapy as well as radiation therapy. Luminal A was the most common subtype (N = 224), followed by basal-like (N = 43), luminal B (N = 21) and HER2-enriched (N = 13). Median follow-up for OS was 197 months (range: 1 – 273 months). Age at diagnosis was statistically different among the subtypes, with basal-like and luminal B having high proportions less than 50 years (P = 0.047). Patients with basal-like and HER2-enriched had more high grade tumors (P < 0.001). Notably, there was no difference in OS among the four subtypes (log-rank P = 0.983). In multivariable analysis, the adjusted hazard ratio (HR) was 1.1 for luminal A vs. luminal B (P = 0.781), 0.62 in luminal A vs. HER2-enriched (P = 0.273), or 0.67 in luminal A vs. basal-like (P = 0.158). In contrast, the adjusted HR were 2.2 in age less than 50 years (P = 0.0017), and 1.1 for number of positive nodes (P = 0.00074). Conclusions: OS, through long-term clinical follow-up, is not significantly different among molecular subtypes if not controlling for other prognostic factors in patients who only received surgery. Age and number of positive nodes are independent prognostic factors in patients with no systemic and locoregional treatments.


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