Pathological features and prognosis of different molecular subtypes of breast cancer
ABSTRACT To examine the pathological features and prognosis of different molecular subtypes of breast cancer, the clinical data of 892 breast cancer patients were retrospectively analyzed and divided into four subtypes according to hormone receptor expression in breast cancer tissue: Her-2 overexpression, luminal A, luminal B and basal-like subtypes. The pathological data and prognosis of these subtypes were compared. Of the 892 breast cancer patients, there were 46 cases (5.2%) with Her-2 overexpression-type, 698 cases (78.3%) with luminal A-type, 38 cases (4.3%) with luminal B-type and 110 patients (12.2%) with basal-like-type. Immunohistochemistry was used to identify the progesterone and estrogen receptors in the tumor tissues. The χ2 test was used to verify the measurement data. The Cox proportional hazard regression model was used for the univariate and multivariate analyses. Results showed there was no statistical difference for lymphatic metastasis among the various molecular subtypes of breast cancer (P>0.05). The distant metastatic rate of patients with Her-2-type breast cancer was significantly higher compared to patients with the other three subtypes (P<0.05). The difference in local recurrence among molecular subtypes was not significantly significant (P>0.05). Lymph node metastasis, age and different molecular subtypes were found to have an impact on patient overall survival (OS) and disease-free survival (DFS). Her-2 overexpression-type breast cancer patients had the lowest 9-year DFS and 7-year OS compared to the other subtypes (P<0.05). Thus, Her-2-type was associated with the worst prognosis. In conlusion, the molecular typing of breast cancer has important clinical value in prognosis estimation and is expected to affect breast cancer treatment approaches.
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ABSTRACT: Patients with estrogen-independent (ER(neg)) human epidermal growth factor receptor-2 (HER-2)-positive ductal carcinoma in situ (DCIS) treated with lumpectomy alone or lumpectomy and radiation are at increased risk of developing subsequent breast cancer events. Thirty-eight patients with HER-2 expressing DCIS received a HER-2 pulsed autologous dendritic cell (DC1) vaccine administered over 4-6 weeks before surgical resection. HER-2 and estrogen receptor (ER) expression were determined by immunohistochemistry. In 35 patients, CD4(pos) T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8(pos) T-cell responses were identified by ELISA. Clinical and immune responses postvaccination were compared between intermediate-expressing HER-2 (2+) and high-expressing HER-2 (3+) patients, as well as ER(neg) and estrogen-dependent (ER(pos)) patients. There was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ER(neg) and ER(pos) tumors. Complete tumor regression rates were similar in patients with HER-2 (2+) and (3+) DCIS. Overall, clinical response rates were similar in patients with ER(neg) and ER(pos) DCIS, but complete tumor regression was significantly more common in patients with ER(neg) DCIS. Despite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ER(neg) and ER(pos) DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ER(neg) DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ER(neg) DCIS for whom there are currently limited adjuvant options.Annals of Surgical Oncology 07/2013; 20(10). DOI:10.1245/s10434-013-3119-y · 3.94 Impact Factor
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ABSTRACT: The aim of the current study was to investigate the expression of the proliferation antigen, Ki67, in triple-negative breast cancer (TNBC) and its correlation with clinicopathological factors. The expression of Ki67 and other biological indicators in 24 cases of TNBC tissues and 178 cases of non-TNBC tissues were detected using immunohistochemistry. Their correlation with the clinicopathological factors were also analyzed using the χ(2) test. The positive rate of Ki67 expression in TNBC tissues was 83.3%, exhibiting a statistically significant difference when compared with that in non-TNBC tissues (73.0%) (P<0.05). The expression of Ki67 in breast cancer tissue significantly correlated with the tumor size and lymph node metastases; however, no correlation was observed with the age and the clinical stage. Ki67 may be an indicator of poor prognosis in TNBC patients.Oncology letters 01/2015; 9(1):149-152. DOI:10.3892/ol.2014.2618 · 0.99 Impact Factor
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ABSTRACT: A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/10(6), p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-γ(+) (i.e., Th1) - not CD4(+)GATA-3(+)IFN-γ(+) (i.e., Th2) - phenotypes, and not attributable to non-pCR patients' immune incompetence, host-level T-cell anergy, or increased immunosuppressive populations. In recruited non-pCR patients, anti-HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs. 33.9 SFC/10(6), p = 0.014) improved significantly following HER2-pulsed DC1 vaccination. Anti-HER2 CD4(+) Th1 response is a novel immune correlate to pathologic response following neoadjuvant T + C. In non-pCR patients, depressed Th1 responses are not immunologically "fixed" and can be restored with HER2-directed Th1 immune interventions. In such high-risk patients, combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity may improve outcomes and mitigate recurrence.Breast cancer research: BCR 05/2015; 17(1):71. DOI:10.1186/s13058-015-0584-1 · 5.88 Impact Factor