Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis

Summary A series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available.Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately.Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.Including the Departments of Surgery (Th. Wobbes, R.F. v.d. Sluis), Radiotherapy (W.A.J. v. Daal), Pathology (R. Holland), Radiology (J.H.C.L. Hendriks), and Medical Oncology (D. Wagener)     

Estrogen and progesterone receptors as prognostic factors in breast cancer

The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone.     

Prognostic factors predicting survival from first recurrence in patients with metastatic breast cancer: analysis of 439 patients

We have analyzed retrospectively 439 women with recurrent breast cancer, followed at a single institution, in order to define potential prognostic factors for survival at the time of first recurrence. Median age at the time of first recurrence was 58 and the median disease free interval (DFI) from initial diagnoses to recurrence was 33 months. Thirteen percent of the patients did not receive any adjuvant therapy while 87% received different combinations of chemotherapy, radiotherapy and hormone therapy as adjuvant treatment. With a median followup of 44 months from the time of recurrence the median survival (MSR) was 24 months (SE 1.24) and fiveyear overall survival was 18% (SE 2.02). On the univariate analysis, pathological tumor size (pT) at diagnosis (p<0.0006), axillary lymph node status at diagnosis (p<0.00001), negative estrogen receptor (ER) status (p<0.0001), negative progesterone receptor (PgR) status (p<0.0001), adjuvant chemotherapy (p<0.001), disease free interval (p<0.00001), location of recurrence (p<0.0002) and number of metastatic sites (3: p, 0.0003), were significantly associated with shorter survival from first relapse. On the multivariate analysis, only the site of recurrence, axillary lymph node status at diagnosis, ER status and DFI remained independently associated with decreased MSR after first relapse.     

Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population

Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone metastasis.     

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

The prognostic value and relationships of patient characteristics, estrogen and progestin receptors, and site of relapse in primary breast cancer

Estrogen and progestin receptor levels (ER and PgR) in tumors from 506 patients with primary breast cancer diagnosed in 1979, 1980, and 1981 were measured by a Scatchard plot analysis. At a median follow-up time of 3.5 years the prognostic value of the receptor levels was evaluated and compared with other tumor and patient characteristics. No relation was found between receptor levels and tumor, lymph node, metastasis (TNM) classification or location of the primary tumor. A significant positive rank correlation was observed between ER and PgR levels (rs = 0.57) and between ER level and age of the patients (rs = 0.39, P less than 0.001). The observed association between ER level and menopause status could not be maintained after correction for age. Independent prognostic factors for overall survival were tumor size (P = 0.002), the number of positive lymph nodes (P less than 0.001), age at primary surgery (P less than 0.001), the PgR level of the tumor (P less than 0.001), but not ER level. Independent prognostic factors for relapse were tumor size (P = 0.003), number of positive lymph nodes (P less than 0.001), age (P = 0.006), menopause status (P = 0.02), PgR level (P = 0.007), but not ER level. Finally, for death rate after relapse the following prognosticators were identified: size of the primary tumor (P = 0.03), number of positive lymph nodes (P = 0.03), age (P = 0.003), site of relapse (P less than 0.001), ER level (P = 0.02), and PgR level (P = 0.04). Patients with tumors containing low positive PgR levels (10 to 20 fmol/mg protein) had a slightly better prognosis than patients with PgR-negative tumors. It is concluded that the PgR level of the primary tumor is a better prognosticator than the ER level. The ER offered no additional ability for discriminating between low- and high-risk patients once PgR was included in the model. In contrast, PgR was capable of improving on the discriminating ability of ER. In addition, patients with tumors containing both PgR and ER showed the best prognosis. Therefore, it is recommended that ER and PgR should be assayed in all breast cancer biopsies.     

Prognostic significance of progesterone receptors alone or in association with estrogen receptors in human breast cancer

Estrogen (ER) and progesterone (PgR) receptors were measured simultaneously in 1144 consecutive breast cancer patients to determine the distribution of patients according to receptor and menopausal status when receptor occurrence rates were considered. The prognostic significance of PgR, either alone or in association with ER, was studied on 187 consecutive breast cancer patients treated only by radical mastectomy. All the cases, as regards axillary node status, were pathologically assessed as node negative. These patients did not receive any adjuvant treatment after mastectomy. At 36 months after mastectomy, the follow-up indicated that PgR- patients have a worse prognosis than PgR+ ones. This is evident when PgR alone is considered as a prognostic factor as well as when it is used to identify, within ER+ cases, those with a higher probability of relapse. In conclusion, it can be stated that although PgR status is an independent prognostic factor, it is useful to evaluate ER and PgR simultaneously for better patient management.     

Estrogen receptor negative and progesterone receptor positive primary breast cancer: Pathological characteristics and clinical outcome

The expression of estrogen (ER) and progesterone (PgR) receptors was analyzed in a retrospective series of 3000 patients who had operable primary breast cancer. Patients were stratified according to ER and PgR status and the study was focused on the two groups (ER–PgR+ and ER–PgR–) of patients whose tumors contained low levels of ER (< 15 fmol/mg protein), regarding potential response to endocrine therapy. The comparison of clinical or histological characteristics between ER–PgR+ and ER–PgR– patients was analyzed as well as the disease-related death and survival. The mean follow-up was 86.3 months. Among the 529 ER–patients, 62 were PgR+ (12%), whereas 467 were PgR– (88%). The ER–PgR+ and ER–PgR– populations represented 2% and 15.6% of the overall population, respectively. In ER– tumors, the PgR status was significantly related to: age, menopausal status, tumor size, SBR grade, and histological type, but not to the type of surgical treatment or to lymph node involvement. ER–PgR+ tumors had smaller size (64% T1 vs 43%) (p=0.004) and were more frequently grade I (28% vs 12%) than ER–PgR– ones (p < 0.001). In addition, the patients with ER–PgR+ tumors were significantly younger (49.4 years vs 58.4 years; p < 0.0001), and were more frequently premenopausal (76% vs 36%; p < 0.001). The disease-free interval and the metastasis-free survival tended to be worse for ER–PgR– than for ER–PgR+ patients, but the difference was not statistically significant at 10 years. However, a small but significant difference in overall survival, in favor of the PgR+ group, was observed between the two groups during the first 5 years (p=0.03).We conclude that in combination with ER, PgR status defines a group of patients with clinical and biological specificity, which could be considered for specific endocrine therapy.     

Survival after first recurrence of breast cancer. The Miami experience.

BACKGROUND. Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976-1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS. In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS. In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS. This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution.     

Steroid hormone receptors and prognosis in breast cancer

Summary The importance of steroid receptors for the prognosis of mammary carcinoma has been evaluated by investigating the course of disease in 163 patients for a median follow up time of 66 months after mastectomy. Multivariate analysis including estrogen receptor (ER), progesterone receptor (PgR), the presence of 8S and 4S ER together or 4S ER only, and the lymph node status revealed only the latter to have significant (p<0.001) predictive potency. Lymph node positive (N-pos) patients had a 3.3 (1.7–6.2) fold risk of death and 2.8 (1.7–4.7) fold risk of recurrence relative to node negative (N-neg) patients.When we compared overall survival (OAS) and disease-free survival (DFS) in the various receptorpositive groups with the groups that displayed neither ER nor PgR, significant differences in prognosis were only seen in N-neg patients. PgR did not turn out to be a better prognostic factor than ER, nor was the 8S ER a sing of increased OAS and DFS compared to total ER. However, the number of patients in this group was too small to allow a definite statement.     

Oestrogen receptors in primary and advanced breast cancer: an eight year review of 704 cases

ER content of primary tumour tissue has been examined in 704 patients presenting with operable breast cancer. The median follow-up is now 84 months and no patient has received adjuvant therapy of any kind. ER status is related to histological grade, menopausal status, initial site of metastases and subsequent response to endocrine therapy. A significant advantage in terms of survival is found in ER positive patients which is confined to those lymph node positive at mastectomy. DFI is also significantly related to ER status in lymph node positive patients. Survival after the symptomatic presentation of metastases and the institution of endocrine therapy is prolonged in patients with ER positive tumours. The overall response rate to endocrine therapy in assessable patients with ER positive tumours is 32%. By combining the ER status and histological grade of tumour tissue, a group of patients comprising 28% of those assessable to endocrine therapy can be identified (ER positive, grade I and II) with a response rate of 46%.     

Long term survival and the prognostic factors of advanced breast cancer patients treated with adreno-oophorectomy

Summary Longer survival data are necessary to elucidate the prognostic factors for survival in advanced breast cancer patients. Univariate and multivariate analyses were performed in 159 patients treated with adreno-oophorectomy alone as the first-line treatment for advanced or recurrent breast cancer, between 1972 and 1983. Nine clinical factors included age, menopausal status, estrogen (ER)- and progesterone receptors (PgR) in recurrent tumors, disease-free interval (DFI), number of metastatic organs, performance status, and adjuvant therapy performed. Response was evaluated according to the UICC criteria. A 31% (50/159) response with 16 CR, 34 PR, 48 NC, and 61 PD was obtained. The logistic regression model of the factors showed that ER was the single affecting factor for the response. According to the Cox proportional hazard model, ER and the dominant site of metastasis were indicated to be significant for survival. According to the landmark method, the response significantly correlated to survival. Using the backward elimination procedure of the Cox proportional hazard model in the patient group defined by the landmark time of 3 months after therapy, the survival of the patients with advanced breast cancer was shown to be primarily influenced by the tumor response which was solely affected by ER status, and the dominant site, particularly the presence of liver metastasis, independently modified the survival length. These results may be useful in future studies of total estrogen blockade trials for breast cancer.     

Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor

BACKGROUND: Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma. METHODS: The prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S-phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c-erbB-2, p53, and bcl-2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs). RESULTS: The median duration of survival was 17.8 months (95% confidence interval, 15.2-21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl-2 expression, together with c-erbB-2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl-2 expression were significant predictors of worse survival (P < 0.05). CONCLUSIONS: In addition to traditional risk factors, bcl-2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting.     

Significance of axillary lymph node metastasis in primary breast cancer.

PURPOSE: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS: Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (locoregional v distant), disease-free interval (< 1.5 years v 1.5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). RESULTS: Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. CONCLUSION: Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.     

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.     

Patients with Recurrent Breast Cancer: Does the Primary Axillary Lymph node Status Predict more Aggressive Tumor Progression?

BACKGROUND: The extent of axillary lymph node involvement represents the foremost important prognostic parameter in primary breast cancer, and, thus, is one of the main determinants for subsequent systemic treatment. Nevertheless, the relevance of the initial axillary lymph node status on survival after disease recurrence is discussed controversially. Persisting prognostic impact after relapse would identify lymph node status as a marker for tumor biology, in contrast to a simply time-dependent phenomenon. METHOD: Retrospective analysis of 813 patients with locoregional or distant recurrence of primary breast cancer, who were primarily diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians-University, Munich, and the University Hospital in Berlin-Charlottenburg, Germany, between 1963 and 2000. To be eligible, patients were required to have been treated for resectable breast cancer free of distant disease at the time of primary diagnosis, and must have undergone systematic axillary lymph node dissection. Patients with unknown tumor size or nodal status were excluded from the study. All data were gathered contemporaneously and compared with original patients files, as well as the local cancer registry, ensuring high quality of data. The median observation time was 60 (standard deviation 44) months. RESULTS: At time of primary diagnosis, 273 patients (33.6%) were node-negative, while axillary lymph node metastases were detected in 540 patients (66.4%). In univariate analysis tumor size, axillary lymph node status, histopathological grading, hormone receptor status, as well as peritumoral lymphangiosis and haemangiosis carcinomatosa were significantly correlated with survival after relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival time after relapse in node-negative patients to be 42 months (31-52 months, 95% CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24 months, 95% CI), compared to 13 months in patients with at least 4 involved axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis, allowing for tumor size, axillary lymph node status, histopathological grading, presence of lymphangiosis carcinomatosa, relapse site and disease-free interval confirmed all parameters, except of histopathological grading (P = 0.14), as significant, independent risk factors for cancer associated death. Subgroup analyses, accounting for site of relapse and duration of disease-free interval, confirmed primary lymph node status as independent predictor for cancer-associated death after relapse. CONCLUSION: Lymph node involvement at primary diagnosis of breast cancer patients predicts an unfavorable outcome after first recurrence, independently of the site of relapse and disease-free interval. These observations support the hypothesis that primary lymph node involvement is not a merely time-dependent indicator for tumor progression, but indicates tumors with aggressive biological behavior.     

同期腋窝转移淋巴结受体检测在激素受体阴性乳腺癌中的临床意义

  目的   探讨同期腋淋巴结转移病灶雌激素受体（estrogen receptor,ER）和孕激素受体（progesterone receptor,PR）补测在激素受体阴性浸润性乳腺癌中的临床意义。   方法   观察2012年7月至2013年1月,重庆医科大学附属第一医院内分泌乳腺外科门诊随访及住院患者中补测激素受体阴性乳腺癌同期腋淋巴结转移病灶ER和PR的表达情况,所有标本（包括原发癌病灶及同期腋淋巴结转移病灶）的免疫组织化学检测均由重庆医科大学病理检测中心进行,根据检测报告,原发病灶阴性而腋淋巴结转移病灶ER和/或PR阳性者补加内分泌治疗。   结果   56例激素受体阴性乳腺癌中,同期腋淋巴结转移病灶ER阳性8例（14.3%）,PR阳性2例（3.6 %）,ER和PR均阳性3例（5.4%）,共13例（23.3%）因补查腋淋巴结转移病灶ER和/或PR变阳性而在随访中加用内分泌治疗。肿瘤原发病灶与腋转移淋巴结ER和PR均阴性43例（76.7%）,即肿瘤原发癌病灶与腋转移淋巴结ER和PR均为阴性表达的总符合率为76.7%,不一致率为23.3%。   结论   受体阴性浸润性乳腺癌原发病灶与腋淋巴结转移病灶ER和PR表达具有一定的不一致性,对原发癌病灶激素受体阴性乳腺癌患者应检查其同期腋淋巴结转移病灶受体的表达,可能筛查出原发病灶受体阴性而复发转移病灶受体阳性患者,及时加用内分泌治疗,提高该类患者的疗效,亦可解释部分激素受体阴性而内分泌治疗也有一定疗效的原因。      

乳腺癌患者人表皮生长因子受体2基因扩增状态与临床病理特征的关系

目的探讨乳腺癌患者人表皮生长因子受体2(HER2)基因的扩增状态与患者临床病理特征相关性,并分析乳腺癌患者腋窝淋巴结转移的影响因素。方法收集2016年1月至2019年3月在滕州市中心人民医院病理科做常规病理检查且HER2免疫组织化学(IHC)结果为++的262例乳腺癌患者病理资料,包括年龄、肿瘤长径、组织学分级、病理类型、是否有淋巴结转移、肿瘤数量、肿瘤部位;用IHC法检测石蜡标本p53、Ki-67、雌激素受体(ER)、孕激素受体(PR)的表达结果;用荧光原位杂交(FISH)法检测HER2基因的扩增状态;分析HER2基因扩增是否与上述临床病理特征相关,以及腋窝淋巴结转移是否与上述特征相关。结果262例乳腺癌患者有69例HER2扩增阳性,阳性扩增率为26.3%;HER2基因扩增与Ki-67增殖指数和ER、PR的表达状态相关,差异有统计学意义(χ^2=13.27,P<0.01;χ^2=34.97,P<0.01;χ^2=38.31,P<0.01);与年龄、肿瘤长径等其余临床病理特征均无关(均P>0.05)。262例乳腺癌患者中发生腋窝淋巴结转移106例(40.5%);淋巴结转移与肿瘤长径显著相关(χ^2=29.10,P<0.01),与其余临床病理特征均无相关(均P>0.05)。结论乳腺癌HER2基因扩增状态与Ki-67增殖指数和ER、PR的表达相关,肿瘤大小为影响乳腺癌患者腋窝淋巴结转移的因素,准确判断上述指标能更好地指导乳腺癌患者的治疗和评估预后。     

Comparison of estrogen and progesterone receptor status to lymphocyte immunity against tumor antigens in breast cancer patients

Summary Estrogen (ER) and progesterone receptor (PgR) content of tumors were determined by both the dextrancoated charcoal (DCC) cytosol and immunocytochemical assays (ICA), and these hormone receptor results were compared to lymphocyte immunity against tumor antigen(s) for 52 breast carcinoma patients. Hormone receptor analysis by both methods demonstrated that 60% of the patients' tumors had ERs, while 44% were positive for PgRs. The ICA procedure was more sensitive than the cytosol technique for determining PgR content of the tumors. This increased sensitivity was not observed for ER by ICA. Patient age, tumor size, and nodal status were not related to the ER and PgR receptor status. A total of 21/52 (40%) of the patients had positive lymphocyte immunity against tumor antigen. This immunity was independent of patient age, tumor size, and nodal status. There was no significant relationship between lymphocytic immunity against tumor antigen and ER or PgR content of tumors, suggesting that patient lymphocyte immunity against tumor is independent of hormone receptor status. This is further evidence that lymphocyte immunity against tumor antigen status is an independent prognostic indicator that may be useful in the selection of a subset of node negative patients for adjuvant chemotherapy.     

Prediction of supraclavicular lymph node metastasis in breast carcinoma

PURPOSE: Supraclavicular lymph node metastasis in breast cancer patients has a poor prognosis, and aggressive local treatment has usually resulted in severe morbidity. The purpose of this study was to select high-risk neck metastasis patients for prophylactic radiotherapy. METHODS: Between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22-92). The median follow-up period was 39 months. The following factors were analyzed: age, tumor size, tumor location, histologic type, histologic grade, estrogen and progesterone receptor status, DNA flow cytometry study results, number of positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal therapy, and level of involved axillary nodes. RESULTS: Of the 2658 patients, 113 (4.3%) developed supraclavicular lymph node metastasis during this period. Young age (< or =40 years), tumor size >3 cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Three predictive factors were significant after multivariate analysis: high histologic grade, >4 positive nodes, and axillary level II or III involved nodes. In patients with axillary level I involved nodes and < or =4 positive nodes, the incidence was 4.4%. If axillary level III was involved, the rate of supraclavicular lymph node metastasis was 15.1%. CONCLUSION: The incidence of supraclavicular lymph node metastasis was higher in the groups with >4 positive nodes and in those with axillary level II or III involved nodes. Selective use of comprehensive radiotherapy for these high-risk patients will achieve good locoregional control.