Luminal and basal subtyping of prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Felix Yi-Chung Feng ◽  
Shuang Zhao ◽  
Seiwon Laura Chang ◽  
Nicholas Erho ◽  
Jonathan Lehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Biology ◽  
Microarray Platform ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Luminal B ◽  
Clinical Tools ◽  
Prostate Cancers

3 Background: There is a clear need to develop a clinically relevant molecular subtyping approach for prostate cancer. We hypothesized that prostate cancer can be subtyped based on luminal versus basal lineage. Methods: We applied the PAM50 classifier, which is used clinically to identify luminal and basal cancers in breast cancer, to subtype a total of 3,782 prostate cancer samples using a high-density microarray platform run in a CLIA-certified laboratory. We examined the associations of these subtypes and clinical outcomes. Results: We demonstrate that PAM50 segregates prostate cancer into three reproducible subtypes in both retrospective cohorts and on prospective validation: luminal A (33.3%-34.3%), luminal B (28.5%-32.6%), and basal (34.1%-37.1%). Luminal B prostate cancers exhibited the worst clinical prognoses, followed by basal and luminal A subtypes (10-year biochemical recurrence-free survival: 29/39/41%; distant metastasis-free survival: 53/73/73%; prostate cancer-specific survival: 78/86/89%; overall survival: 69/80/82% respectively) on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors. Known luminal lineage markers, such as NKX3.1 and KRT18, and the basal lineage CD49f signature, were enriched in luminal- and basal-like cancers respectively, demonstrating the connection between these subtypes and established prostate cancer biology. While both luminal-like subtypes were associated with increased AR expression and signaling, only luminal B prostate cancers were significantly associated with post-operative response to androgen deprivation therapy (ADT) in a subset analysis matching patients based on clinicopathologic variables (interaction p = 0.006, luminal B 10-year metastasis: 33% (treated) vs. 55% (untreated), non-luminal B: 37% (treated) vs. 21% (untreated)). Conclusions: These findings contribute novel insight into the biology of prostate cancer, and provide translatable clinical tools for personalizing post-operative ADT for patients with prostate cancer. Similar to breast cancer, these findings suggest that luminal/basal subtyping may be useful in treatment selection in prostate cancer.

scholarly journals Prognostic Significance of Low Claudin3 Expression in Luminal Breast Cancers

2017 ◽  
Vol 11 ◽  
pp. 117822341774585
Author(s):  
Lakmini Mudduwa ◽  
Harshini Peiris ◽  
Shania Gunasekara ◽  
Deepthika Abeysiriwardhana ◽  
Thusharie Liyanage
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Molecular Classification ◽  
Rank Test ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Luminal B

Aim: To study the prognostic value of immunohistochemically detected low Claudin3 expression in breast cancers. Methods: This retrospective study included patients with breast cancer who were investigated at our unit from 2006 to 2015. Tissue microarrays were constructed, and immunohistochemical staining was done to assess the Claudin3 expression and to classify breast cancers according to the immunohistochemical surrogates for molecular classification. Kaplan-Meier model and log-rank test were used for recurrence-free survival and breast cancer–specific survival analysis. Results: Of the 853 patients, overall low expression of Claudin3 was seen in 18.4%. Recurrence-free survival of patients with overall low Claudin3 breast cancers was poor in luminal A ( P = .006) and luminal B (Her2−) ( P = .009) subtypes compared with those who had Claudin3 expression in each group. Conclusions: Assessment of Claudin3 expression by immunohistochemistry is suggested for luminal A and luminal B (Her2−) subtypes to identify patients with poor prognosis.

Luminal B subtype as a predictive biomarker of docetaxel benefit for newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A correlative study of E3805 CHAARTED.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 162-162 ◽  
Author(s):  
Anis Hamid ◽  
Xin Victoria Wang ◽  
Yu-Hui Chen ◽  
Felix Y Feng ◽  
Robert Benjamin Den ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
De Novo ◽  
Local Therapy ◽  
Microarray Platform ◽  
High Volume ◽  
Predictive Biomarker ◽  
Luminal A ◽  
Luminal B ◽  
Basal Subtype

162 Background: Through gene expression profiling (GEP), the PAM50 classifier demonstrates prognostic value in localized prostate cancer (PCa). Pre-clinical drug response models predict increased taxane sensitivity in luminal subtypes compared to basal subtype. Men with mHSPC and high-risk features have greatest benefit from androgen deprivation therapy (ADT) plus docetaxel (D) vs ADT alone. We therefore sought to test the prognostic and predictive value of PAM50 in pre-ADT specimens from E3805 CHAARTED. Methods: Whole transcriptomic profiling of formalin-fixed, paraffin-embedded primary PCa biopsies from pts enrolled in the E3805 CHAARTED trial of ADT vs ADT+D was performed using the Human Exon 1.0 ST microarray platform (Decipher Biosciences). Normalized gene expression was used to classify subjects as luminal A, luminal B or basal subtype. Multivariable analyses (MVA) adjusted for ECOG status, de novo metastasis vs prior local therapy and volume of disease. The primary endpoint was overall survival (OS). Secondary endpoint was time to castration resistant PCa (TTCRPC). Results: Successful GEP was completed in 160 of 198 pts with available specimens. Eighty (50%), 77 (48%) and 3 (2%) pts were classified as luminal B, basal and luminal A, respectively. High volume disease was similarly present in luminal B (79%) and basal (78%) subtypes. In the ADT arm, luminal B subtype was associated with shorter OS vs basal (HR 1.75, p=0.05); consistent in MVA. Pts with luminal B subtype treated with ADT+D showed significant improvement in TTCRPC and OS (Table). By contrast, basal subtype showed no OS benefit from ADT+D even in pts with high volume disease. Conclusions: We demonstrate that GEP identifies tumor subtypes associated with differential benefit from chemohormonal therapy for mHSPC. Luminal B subtype is associated with poorer OS with ADT alone and benefits from addition of D. Basal subtype shows a lack of OS benefit from upfront ADT+D. We plan to validate these findings in independent trial cohorts.[Table: see text]

scholarly journals Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1304 ◽  
Author(s):  
Nancy Y. Yu ◽  
Adina Iftimi ◽  
Christina Yau ◽  
Nicholas P. Tobin ◽  
Laura van ’t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Recurrence ◽  
Tamoxifen Therapy ◽  
Recurrence Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B

scholarly journals Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors

2015 ◽  
Vol 33 (20) ◽  
pp. 2254-2261 ◽  
Author(s):  
Erica T. Warner ◽  
Rulla M. Tamimi ◽  
Melissa E. Hughes ◽  
Rebecca A. Ottesen ◽  
Yu-Ning Wong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Cancer Survival ◽  
Growth Factor Receptor ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Luminal B ◽  
Estrogen Receptor Positive ◽  
Epidermal Growth

Purpose To evaluate the relationship between race/ethnicity and breast cancer–specific survival according to subtype and explore mediating factors. Patients and Methods Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer–specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. Results In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer–specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor–positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A–like and luminal B–like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2–type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Conclusion Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor–positive tumors.

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.

New molecular breast cancer classification with adjuvant therapy in our population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11624-e11624
Author(s):  
E. Richardet ◽  
B Mascheroni ◽  
I Magri ◽  
L Perelli ◽  
M Cortés
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Type A ◽  
Molecular Classification ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

e11624 Background: The molecular classification (Perou) helped to identify new groups of patients with different biological behaviors. A retrospective, descriptive, comparative trial with adjuvant chemotherapy treatment was conducted. Objectives: Analyze the natural history of the subgroups of patients, frequency, site of relapse and Disease-free survival (DFS). Materials and Methods: 200 Medical charts of patients with breast cancer were analyzed from 1997 to 2007, who had received adjuvant treatment without Trastuzumab. The 92, 5 % of Luminal A, 91 % of Luminal B y C, the 75.9 % of Her2 (+) and the 69.2 % of Triple Negative (TN) had received adjuvant therapy with FAC, while 30% of the last two groups were treated with taxanes and anthracyclines. We evaluated the site of the first relapse after adjuvant treatment in relation to the new molecular classification. Log-rank test was used to compare the rates of Disease-free survival (DFS). Results: Frequency: Luminal A (86, 42%) Luminal B y C (65, 33%) Her2 + (33, 17%) TN: (16, 8%) The locoregional relapse in the TN group was 36.4% (P = 0.003), the average of bone relapses were 64.5% on the four groups without statically significance compared to other groups. The CNS had a greater trend in TN groups (16.7%) and Her2+ (13.6%), compared to Luminal Type A-B (0 % y 8.3 %). Disease-free survival (DFS): Luminal A 65.0 ± 5.0 months Luminal B y C 50.3 ± 4.3 months HER2 42.9 ± 5.5 months TN 31.1 ± 7.3 months In the analysis of type A luminal subgroup, a prolonged disease free time was showed when compared with the others subgroups, of major statistical significance Log rank (p = 0.002). Conclusions: Her2 negative and TN tumors have less DFS and a higher locoregional and CNS relapse. No significant financial relationships to disclose.

Molecular pattern of breast cancer among a series of Egyptian patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11614-e11614
Author(s):  
Salah Eldeen Elmesidy ◽  
Wessam Elsherief ◽  
Mohamed Abdelshafy ◽  
Walid Hammam
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B ◽  
Platinum Based Chemotherapy ◽  
Egyptian Patients ◽  
Platinum Chemotherapy ◽  
Disease Free

e11614 Background: Triple negative (TN) breast cancer has a bad prognosis. It is associated with a poor progression-free and overall survivals. Accordingly, we explored the outcome of different molecular subtypes among a series of Egyptian breast cancer patients. Methods: A total of 661 non-metastatic breast cancer patients' files with were reviewed from Kasr Al-Aini Center of Clinical Oncology and Nuclear Medicine of Cairo University between January 2005 and December 2010. Data were analyzed for age; menopausal status, tumour size, nodal status, pathological type, grade; estrogen status, progesterone status, and human epidermal growth factor receptor 2 (HER2) status. Disease free survival (DFS) was the primary end point. Results: The median age was 50 years. 50.4% of patients were premenopausal, 93.1% had invasive duct carcinoma, 93.3% had grade II tumours, 79.4% had early tumours (T1&T2), 70.4% had positive lymph nodes, 51.7% had luminal A subtype, 21.3% had luminal B, 10.2% had HER2-enriched and 16.6% had TN. Disease free survival after 3 years for each subtype was 87.8% for luminal A, 86% for luminal B, 69% for TN and 66% for HER2 (p= .008). The 3-year disease-free survival was significantly better for postmenopausal patients 92.1% as compared with premenopausal patients 80.1% (P= <0.001), with early tumours (T1&T2) 92.1% & 87.3% respectively as compared with advanced tumours (T3+T4) 80.1% (p= <0.001), LN negative (N0) 98.1% as compared with LN positive (N1+N2) 85.2% and (N3) 68% (p= <0.001), (ER) positive 90.2% as compared with (ER) negative 78.2% (p= <0.001), (PR) positive 90% as compared with (PR) negative 80.2% (p= 0.003), non TNBC 89.8% as compared with TN 72.1% (p= 0.012). The 3-year disease-free survival for TN patients who received adjuvant platinum-based chemotherapy was 46% and for those who received adjuvant non-platinum chemotherapy was 78% (p= 0.135). Conclusions: In our series of Egyptian patients luminal breast cancer subtypes (A and B) had the highest 3-year disease-free survival followed by TN then HER2-enriched type. Adjuvant platinum based chemotherapy had no impact on the 3-year disease-free survival when compared with non-platinum chemotherapy in TN patients.

Outcome Evaluation in Pre-Trastuzumab Era between Different Breast Cancer Phenotypes: A Population-Based Study on Italian Women

2012 ◽  
Vol 98 (6) ◽  
pp. 743-750 ◽  
Author(s):  
Laura Cortesi ◽  
Elisabetta De Matteis ◽  
Claudia Cirilli ◽  
Luigi Marcheselli ◽  
Manuela Proietto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B ◽  
Italian Women ◽  
Disease Free ◽  
Over Time

Aims and background Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2–, Ki67 <14%), luminal B (ER and/or PgR/HER2–, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2–), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women. Methods and study design We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated. Results A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups. Conclusions In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.

Use of microarray analysis of differentially expressed genes in luminal B subtype of breast cancers to evaluate NHERF1 as a marker of endocrine resistance

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11015-11015
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
E. Ruckhaeberle ◽  
L. Hanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Biology ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

11015 Background: In vitro and in vivo data demonstrate that the expression of estrogen receptor (ER) in breast cancer is mainly associated with low proliferation. Gene expression profiling has recently been used to identify a group of high proliferating estrogen receptor positive breast cancers (the luminal B subtype), which are associated with a prognosis that is even worse than that of high proliferating estrogen receptor negative tumors. The analysis of those tumors might provide valuable information about breast cancer biology and could be helpful for adjuvant or neoadjuvant treatment decisions.Methods and Results: We analyzed microarray data from breast cancer specimens to gain insight into genes which play a role in estrogen receptor signalling. Genes were identified showing strong expression in high proliferating ER-positive tumors but no expression in either Ki67-/ER+ or Ki67+/ER- samples. Among these genes the Na+/H+ exchanger regulatory factor NHERF1 was found. We assessed the clinical relevance of NHERF1 transcript levels using a total of 2469 breast cancers. Analysis indicates that enhanced NHERF1 expression is associated with metastatic progression and poor prognosis of breast cancer patients. We found no correlation between NHERF1 and the nodal status as well as age, but positive correlations for tumor size (P<0.001), grade (P<0.001) and erbb2 (P=0.033). Weak NHERF1 expression correlated with longer disease free survival (DFS) in grade 1 and 2 tumors, but not in grade 3 breast cancers. Since NHERF1 expression is strongly linked to the presence of ER, the predictive value for endocrine treatment was analyzed. For samples with weak or none NHERF1 expression a treatment benefit was observed (P=0.007). While untreated patients display a 10 yr DFS rate of 67.2 ± 3.8%, endocrine treatment resulted in 80.1 ± 4.0%. In contrast no differences in disease free survival were found for corresponding NHERF1 expressing breast cancers. Conclusions: Our data indicate that expression of NHERF1 defines a state of differentiation, where breast cancer cells are refractory to endocrine treatment. No significant financial relationships to disclose.

Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

2020 ◽  
Vol 20 (9) ◽  
pp. 681-688
Author(s):  
Nikolai V. Litviakov ◽  
Marina K. Ibragimova ◽  
Matvey M. Tsyganov ◽  
Artem V. Doroshenko ◽  
Eugeniy Y. Garbukov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal B ◽  
Cell Clones ◽  
Genetic Landscape ◽  
Intelligent Approach

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

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