Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. a single institution survey spanning 1998 to 2010

As far as recent breast cancer molecular subtype classification is concerned, much work has dealt with clinical outcomes for triple negative and Her2 patients. Less is known about the course of patients in the remaining subtypes. Molecular classification based on immunohistochemistry is widely available and correlates well with genetic microarray assessment, but at a lower cost. The aim of our investigation was to correlate immunohistochemical subtypes of breast cancer with clinical characteristics and patient outcomes. Since 1998, 1167 patients operated for 1191 invasive breast tumours were included in our database. Patients were regularly followed up until March 2010. Disease-free survival, overall mortality, and breast cancer-specific mortality at 5 years were calculated for the cohort. 72% of tumours were ER+PR±HER2- group, 13% triple negative (ER-PR-HER2-), 10% ER+PR±HER2+ group, and 5% Her2 (ER-PR-HER2+). Cancer-specific survival was 94.2% for the ER+PR+HER2- subtype, 84.8% for the Her2 subtype, 83.3% for the ER+PR-HER2- subtype, and 78.6% for triple negatives. Distant metastases prevalence ranged from 7% to 22% across subtypes, increasing stepwise from ER+PR+HER2-, ER+PR+HER2+, ER+PR-HER2-, ER+PR-HER2+, ER-PR-HER2+ through triple negative. Small, low-grade tumours with low axillary burden were more likely to belong to the ER+PR±HER2- group. Conversely, larger high-grade tumours with significant axillary burden were more likely to belong to Her2 or triple negative groups. ER+PR±HER2- group patients with negative PR receptors performed more like Her2 or triple negative than like the rest of ER+PR±HER2± groups patients. Molecular classification of breast tumours based only on immunohistochemistry is quite useful on practical clinical grounds, as expected. ER+PR±HER2- group patients with negative PR receptors seem to be at high risk and deserve further consideration.     

Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy

The molecular subtypes of breast cancer based on status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression are associated with markedly different clinical outcomes. We retrospectively analyzed 774 breast cancer patients with four or more positive nodes, who underwent mastectomy between March 1999 and December 2007. Treatment with postmastectomy radiotherapy (PMRT) reduced the rates of locoregional recurrence-free survival (LRFS; 6.7% vs. 26.6%), distant metastasis-free survival (DMFS; 26.9% vs. 50.0%), and mortality (24.4% vs. 45.3%) for luminal-A subtypes (ER+ or PR+, Her2-) and reduced LRFS (12.1% vs. 27.5%) for the luminal-B subtype (ER+ or PR+, Her2+) compared with patients not receiving PMRT. However, PMRT did not affect the endpoints for the Her2-enriched or basal subtypes. Thus, understanding the differences in patterns of relapse between the different subtypes of breast cancer may enable targeted adjuvant therapy and improved surveillance decisions.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Molecular Subtypes of Breast Cancer in South Asian Population by Immunohistochemical Profile and Her2neu Gene Amplification by FISH Technique: Association with other Clinicopathologic Parameters

Molecular breast cancer subtypes were defined by gene expression prolife; however, immunohistochemical (IHC) expression can categorize breast cancers analogous to gene expression profiling. We aimed to evaluate distribution of these molecular breast cancer subtypes in our population and their association with clinocopathologic parameters. We retrospectively analyzed 1,104 cases of primary breast cancers over 3 years duration. ER, PR, Her2neu IHC staining, and subsequent fluorescent in situ hybridization studies (Her2neu gene amplification in cases with 2+ IHC staining) were performed to categorize breast cancer subtypes. Luminal A breast cancers were most frequent (45.8%) followed by triple negative (18.6%), luminal B (17.8%) and Her2neu (17.8%) subtypes. We found a strong association of breast cancer subtypes with tumor grade and Ki67 proliferation index with triple negative cancers being associated with higher grade and proliferation index. Significant association was seen with age groups, luminal A subtype occurring at a slightly older age, whereas triple negative and Her2neu cancers were more frequent in younger age group. We found a higher proportion of triple negative cancers in our set up, and they were found to have high‐tumor grade and proliferation index along with presentation at younger age. As these cancers are associated with BRCA 1 mutations and abnormal BRCA 1 pathways, we suggest that large scale studies should be done to evaluate BRCA 1 mutations and abnormal BRCA 1 pathways in our population to establish risk factors for this highly aggressive tumor subtype.     

Inference of the Basal epithelial phenotype in breast carcinoma from differential marker expression, using tissue microarrays in triple negative breast cancer and women younger than 35

Abstract: Basal‐cell phenotype breast carcinoma has been associated with high‐grade and metaplastic morphology, expression of basal‐type cytokeratins, uniform negativity for ER and HER2, and decreased overall survival. Breast cancers occurring in young women are usually T2 disease at presentation, high‐grade and of poor prognosis. We compared two groups of breast cancers, (a) ER‐, PR‐, HER2‐ (triple negative) [TNBrCa] and (b) non‐triple negative breast cancers (non‐TNBrCa) occurring in women under 35, using tissue microarray technology to characterize expression of the basal/myoepithelial cytokeratins (CK5/6, CK7, and CK14), luminal cytokeratins (CK8, CK18, and CK19), EGFR, p‐cadherin, c‐kit, p63, and p53. We also sought to identify characteristic histomorphologic features indicative of basal‐like phenotype. The triple negative group showed preferential staining versus the age <35 group for CK5/6 (22% versus 4% p = 0.05), CK14 (44% versus 15%, p = 0.013), EGFR (83% versus 24%, p < 0.0001) and c‐kit (19% versus 0% p = 0.026). Conversely, non‐TNBrCa in women younger than 35 demonstrated increased expression of the luminal CK8 (92% versus 60%) compared with the triple negative patients (p = 0.006). The TNBrCa have characteristic histologic features including higher tumor grade, pushing tumor border, geographic necrosis, syncytial growth pattern, brisk mitotic activity, lack of/minimal in situ component, medullary‐like and metaplastic differentiation. Invasive carcinomas in women younger than 35 usually have an associated in situ component, prominent nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple negativity for ER/PR/HER2 coupled with EGFR, c‐kit, and basal/myoepithelial cytokeratins (CK5/6, CK14) expression, and distinctive histomorphologic features predict morphology consistent with basal‐cell phenotype.     

Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation?

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB‐Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND.     

三阴性乳腺癌临床病理特征及预后分析

目的 分析三阴性乳腺癌的临床病理特征及与预后的关系. 方法 回顾性分析2002年1月-2007年2月北京通州妇幼保健院收治的乳腺癌患者196例,进行免疫组织化学法测定Her-2、ER、PR蛋白表达,并分为两组,一组为三阴性(triple-negative)乳腺癌,即Her2(-),ER(-),PR(-),另一组为非三阴性乳腺癌.分析三阴性和非三阴性乳腺癌的临床病理特征,比较三阴性乳腺癌患者术后的3年无瘤生存率. 结果 三阴性乳腺癌在所有患者中所占比例为13.27%(26/196),其肿瘤大小情况、组织学Ⅲ级的比例高于非三阴性乳腺癌(P＜0.05).三阴性乳腺癌和非三阴性乳腺癌3年无瘤生存率分别为84.62%(22/26)和92.94%(158/170). 结论 三阴性乳腺癌较非三阴性乳腺癌易发生局部复发和远处转移,预后差.     

The Relationship of Race,Oncotype DX,and Ki67 in a Population Highly Screened For Breast Cancer

Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi‐Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college‐level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African‐Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African‐Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki‐67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.     

State of art of advanced triple negative breast cancer

Advanced triple negative breast cancer (TNBC) is an aggressive disease (high probability of visceral metastasis) with poor outcome. Triple negative breast cancer is characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor‐2 (HER2), high histologic grade, and high mitotic rate. Chemotherapy remains the primary systemic treatment, with international guidelines supporting the use of single‐agent taxanes (with or without bevacizumab) or anthracyclines as first‐line therapy, with a median overall survival of approximately 18 months or less. Given the suboptimal outcomes with chemotherapy, new targeted therapies for advanced TNBC are urgently needed. This review summarizes the current status of treatment, and future challenges of using new treatment options for advanced TNBC, such as poly‐adenosine‐diphosphate‐ribose‐polymerase inhibitors (olaparib and talazoparib) and immune checkpoint inhibitors (eg atezolizumab) as monotherapy or in combination with chemotherapy.     

Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false‐negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)‐negative (P < .001), progesterone receptor (PR)‐negative (P = .004), HER2‐positive (P = .015), triple‐negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER‐negative, PR‐negative, HER2‐positive, triple‐negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.     

Adjuvant therapy for older women with breast cancer

The major risk factor for breast cancer is increasing age and more than half of all breast cancers in affluent nations occur in women 65 years and older. Co-morbidity is a key consideration in offering systemic adjuvant treatment to older women since significant co-morbidity minimizes the potential value of any adjuvant therapy. Tamoxifen has clearly been shown to significantly decrease the risk of recurrence and improve survival in women of all ages who have estrogen (ER) or progesterone receptor (PR) positive invasive breast cancer, including those 70 years and older. Chemotherapy in older patients can improve survival but adds little to tamoxifen in women with node-negative, ER+ or PR+ tumors: it should be reserved for older women who have reasonable life-expectancy and larger node-negative tumors, or node-positive tumors. Ageism is still a barrier to clinical trials participation and clinical trials focusing on older women are needed.     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

Impact of triple negative phenotype on breast cancer prognosis

Triple negative (TN) [estrogen receptor (ER), progesterone receptor (PgR)] (ER-/PgR-/Her2/neu-) breast cancer (BC) is an aggressive disease without tumor-specific treatment options. Our objective is to evaluate the relative contribution of combined Her2/neu (Her2) and hormone receptor (HR) status to BC progression. A prospective primary BC cohort of 1550 patients at our institution, stage I-IV, from 1998 to 2003 were categorized by HR and Her2 status into ER+/PgR+/Her2- (HR+/Her2-) (n = 1134), ER+/PgR+/Her2+ [triple positive (TP)] (n = 138), ER-/PgR-/Her2- (TN) (n = 183), and ER-/PgR-/Her2+ (HR-/Her2+) (n = 95). Clinical variables were chart abstracted and vital and disease status updated annually. Log-rank tests and Cox regression analyses were used to assess associations with survival. Patient age ranged from 21 to 88 years and average length of follow-up was 4.24 years. Overall survival at 5 years was 94% (HR+/Her2-), 91% (TP), and 81% (TN and HR-/Her2+) (log rank test = 22.22, p < 0.001). Disease-specific survival at 5 years was 98% (HR+/Her2-), 93% (TP), 88% (TN), and 86% (HR-/Her2+) (log rank test = 25.85, p < 0.001) and 5-year relapse-free survival was 95% (HR+/Her2-), 89% (TP), 84% (TN), and 76% (HR-/Her2+) (log rank test = 20.29, p < 0.001). In a model adjusted for age, race, TNM stage, and treatment using HR+/Her2- patients as the reference group, recurrence risk was 1.98 for TP (95% CI = 1.02 to 3.84), 2.32 for TN (95% CI = 1.32 to 4.08), and 4.25 for HR-/Her2+ patients (95% CI = 2.33, 7.75). A hierarchy of BC phenotypes defined by HR and Her2 status exists with progressively worse disease outcomes by category.     

Pregnancy‐associated breast cancer in a contemporary cohort of newly diagnosed women

Pregnancy‐associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy, lactation, or in the postpartum period. There is evidence that PABC is associated with a poorer prognosis, and that the development of the disease is influenced by the unique hormonal milieu of pregnancy. The purpose of this study was to investigate the clinicopathologic characteristics associated with PABC in a contemporary cohort of women with newly diagnosed BC. Our institutional Breast Cancer Database was queried for women diagnosed with BC between 2009‐2018 who had at least one full‐term pregnancy (FTP). Variables of interest included patient demographics and clinical and tumor characteristics. PABC was defined as breast cancer diagnosed within 24 months of delivery. Statistical analyses included Pearson's chi‐square and logistic regression. Out of a total of 2202 women, 46 (2.1%) had PABC. Median follow‐up in the total cohort was 5.5 years. After adjusting for age at first FTP, PABC was associated with younger age at diagnosis, older age at first FTP, non‐Caucasian race, BRCA positivity, presentation with a palpable mass, higher pathologic stage, higher histologic grade, and ER‐negative and triple‐negative receptor status. The association of PABC with non‐Caucasian race may be reflected in the increased proportion of triple‐negative breast cancers in the PABC group. PABC was also associated with older age at first FTP. As more women delay childbearing, risk for PABC may increase. Our findings suggest that women who become pregnant at older ages should be followed carefully during pregnancy and the postpartum period, especially if they are BRCA mutation carriers. The optimal approach for monitoring older women during pregnancy and the postpartum period is unclear.     

Heterogeneity of Breast Cancer Clinical Characteristics and Outcome in US Black Women—Effect of Place of Birth

Breast cancer mortality in black women is disproportionately high; reasons for this phenomenon are still unclear. In addition to socioeconomic factors, the biology of the tumor may play a role. We analyzed 1,097 incident invasive breast cancer cases diagnosed between 2000 and 2010 in black US women from Long Island and Brooklyn. Thirty‐five percent of women had an estrogen receptor (ER) negative tumor, 46% a progesterone receptor (PR) negative tumor. ER, PR negative tumors were diagnosed at an earlier age (55.8 versus 55.3 years), at a later stage (p = 0.06), were larger in size (p = 0.04), and more frequently treated with neo‐adjuvant chemotherapy (p = 0.06) than ER, PR positive tumors. Determinants of shorter survival were: ER, PR negativity (HR: 2.2, 95% CI: 1.4–3.4), age, and stage at diagnosis (HR: 2.0; 95% CI: 1.5–2.7). ER, PR negative breast cancer born outside of the US experienced a significantly worse survival than ER, PR negative women who were born in the US. ER, PR negative tumors in black women born outside the US, mainly in the Caribbean, are biologically more aggressive than the same size and age‐matched tumors in black women born in the US. Our study suggests that environmental exposures in the country of origin may impact on host cancer interactions and cancer outcome.     

The biology of male breast cancer

Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare. Using hierarchical clustering in FBC, ERα clustered with PR, whereas in MBC, ERα associated with ERβ and AR. Based on limited data it appears that Oncotype DX is effective in determining recurrence risk in selected MBC. In future, tailored therapies based on genomics will probably yield the most promising approach for both MBC and FBC.     

Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival

BackgroundTo understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors.Materials and methodsWe conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS).Results1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes.ConclusionsSurgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.     

雌、孕激素受体和表皮生长因子受体2在乳腺癌分型中的应用

目的 研究乳腺癌分子亚型的临床病理特征及预后.方法 SP法检测509例手术切除的乳腺癌雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、表皮生长因子受体2(erbB-2,Her-2)表达并对其分型,Her-2-、ER/PR+为腔上皮样A亚型(Luminal A),Her-2+、ER/PR+为腔上皮样B亚型(Luminal B),Her-2-、ER-、PR-为三阴性型(Tripie-negative)、Her-2+、ER-、PR-为ERBB2+亚型(ERBB2+).χ~2检验比较亚型的临床病理特征,Kaplan-Meier法分析5年无瘤生存率(DFS),单因素和Cox多因素分析与复发和转移相关的因素.结果 Luminal A占所有病例40.5%(206/509),Luminal B占18.5%(94/509),Tripie-negative占21.4%(109/509),ERBB2+19.6%(100/509).三阴性型乳腺癌中髓样癌的比例高于其他类型乳腺癌(P<0.05),4种亚型复发转移率差异有统计学意义(P=0.029).多因素分析发现淋巴结状态和l临床分期是独立的预后影响因素(P=0.000).ERBB2+和Triple-negative的DFS分别为81%、78.9%,低于Luminal A和Luminal B的DFS(88.8%、90.4%)(P=0.025).结论 在本组乳腺癌患者中,Luminal A亚型所占比例最高,Triple-negative和ERBB2+复发转移率高,预后较Luminal A和Luminal B亚型差.     

Comparison of estrogen receptor, progesterone receptor and Her-2 status in breast cancer pre- and post-neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NAC) is now a relatively standard treatment for breast carcinoma. However, some tumors are known to develop resistance to chemotherapies. We investigated whether the status of estrogen receptor (ER), progesterone receptor (PR) and Her-2 expressions in breast cancer cases prior to NAC could be changed after NAC. We used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. No differences were found in ER or Her-2 status, but a significant difference was found in PR status. Changes in Her-2 status were suspected in four specimens after NAC (3+ to 1+ for 3 patients, and 1+ to 3+ for one patient) according to the IHC results. However, in all four of these cases, FISH of the resections showed no change. When IHC indicates a change in Her-2 expression after NAC, FISH is recommended.