PR Positive Status Research Articles

Analysis of the clinicopathologic characteristics and prognosis of breast cancer patients with ER or PR single-positive status

Objective:To investigate the clinicopathologic characteristics and prognosis of primary invasive breast cancer patients with ER/PR single-positive status.Methods:A total of 1,054 patients with primary invasive breast cancer with different ER or PR status seen in our hospital between October 1998 and May 2004 were analyzed.Patients were stratified according to ER and PR expression.The study was focused on the single-positive groups (ER+/PR-and ER-/PR+) and assessed their main characteristics and evaluated the prognostic difference between the double positive and negative tumors. The survival rate of breast cancer was calculated by Kaplan-Meier analysis and log-rank test.COX multivariate analysis was conducted to determine the independent risk factors of prognosis.Results:The prognosis of double-positive tumors was best in different receptor groups and was better in single-positive group than in double-negative group.The majority of ER+/PR- tumors were small and well-differentiated.They were more frequently seen in elder and postmenopausal women. The survival analysis showed no difference in overall survival between the two groups (P=0.890).However,disease-free survival was better in ER+/PR- patients than in ER-/PR+ patients (P=0.035).Compared with the double-negative phenotype, ER+/PR- group was associated with better outcome.In patients with single-positive receptor who received adjuvant hormone therapy,different ER or PR positive status was an independent risk factor for disease-free survival (P=0.023). Conclusion:ER+/PR- and ER-/PR+ tumors were two distinct groups of breast cancer in clinicopathologic characteristics and prognosis.ER-/PR+ breast cancer patients might need active treatment because of its aggressive behaviors.

Determinants of outcome in elderly patients with positive sentinel lymph nodes

614 Background: Older women are less likely to receive standard of care treatment for breast cancer. This undertreatment may be linked to the perception that elderly patients (pts) may not tolerate or derive benefit from treatment that is often viewed as “too toxic.” Methods: From July 1997 to July 2003, 1,470 pts with invasive cancer with positive sentinel lymph nodes (PSLN) by intraoperative frozen section or final pathologic exam by hematoxylin-eosin and/or immunohistochemistry (IHC). We examined sociodemographic, pathologic, and therapeutic variables that affected the outcome of elderly pts ≥70 years old. A comorbidity score was assigned using Adult Comorbidity Evaluation-27 system. Chi-square, Fisher's exact Wilcoxon tests, and multivariate logistic regression analysis were used. Results: The median age was 53 years (range 21–89) and median tumor size 1.6 cm (range 0.1–11). 1,265 (86.1%) pts were <70 years old and 205 (13.9%) pts were ≥70 years old. 183 (12.5%) pts had IHC only PSLN, 1,021 (69.5%) had 1–3 PSLN, and 266 (18%) ≥4 PSLN. Breast conservation therapy (BCT) was performed in 59.7% of pts. Elderly pts were more likely to have moderate to severe comorbidities (46% vs. 11%, p < 0.0001) and BCT (67% vs. 59%, p = 0.026), compared to pts <70 years old. Elderly pts were less likely to undergo completion ALND (73% vs. 89%, p < 0.0001), adjuvant chemotherapy (43% vs. 90%, p < 0.0001) and radiotherapy following BCT (82% vs. 90%) compared to pts <70 years old. The 5-year disease-free survival (DFS) was not significantly different for elderly pts compared to non-elderly pts (87.7% vs. 91.9%, p = 0.21), on the other hand the 5-year overall survival was significantly worse for elderly pts (80.4% vs. 93.2%, p < 0.0001), a difference that was mainly due to a significantly higher 5-year cumulative incidence of death due to other causes (13.2% vs. 1.9%, p < 0.0001). On multivariate analysis, ER or PR positive status, IHC only PSLN and T1 tumors were the only factors independently associated with improved odds of 5-year DFS. Conclusions: Tumor rather than patient factors were the primary determinants of breast cancer outcomes in our cohort of node positive breast cancer pts. Elderly breast cancer pts with an estimated life expectancy beyond 5 years should receive the same standard of care therapy as their younger counterparts. No significant financial relationships to disclose.

Do Clinical and Immunohistochemical Findings of Pure Mucinous Breast Carcinoma Differ from Mixed Mucinous Breast Carcinoma ?

Mucinous carcinoma of the breast is a relatively rare histologic type with two subtypes: pure and mixed. It has a favourable prognosis with a low risk of axillary metastases.The prognosis for pure mucinous carcinoma (PMC) was much better than for the mixed mucinous carcinoma (MMC). The aim of the study is to determine suitable candidates for breast or axillary conservation in mucinous carcinoma subtypes.The slides of 26 pure and 23 mixed mucinous carcinomas of the breast were evaluated. The clinical, pathological and immunohistochemical features between PMCs and MMCs were compared.MMC displayed greater metastatic potential (p < 0.05), p53 positivity (p < 0.05) and c-erbB-2 positivity (p < 0.001) than PMCs. PMCs smaller than 2 cm had less metastatic capacity and extranodal invasion compared to MMCs smaller than 2 cm (p < 0.001 and p < 0.01, respectively). MMCs smaller than 2 cm displayed weaker ER positivity but greater c-erbB-2 positivity than PMCs smaller than 2 cm (p < 0.01).In conclusion, MMC had worse prognostic factors than PMC with both types of mucinous carcinoma showing similar ER and PR positive status. Even if PMCs and especially smaller PMCs display more favourable prognostic features, including less axillary lymph node involvement, it is appropriate to use sentinel lymph node biopsy to make better axillary assessment.

Male breast cancer: An analysis of clinical features, disease outcome and treatment efficacy

11539 Background: Male breast cancer (MBC) accounts for about 1% of all cases of breast cancer. This scarcity explains the difficulty in assessing clinical features and evolution of management over time. Methods: A retrospective chart analysis of MBC, diagnosed and treated between 1976 and 2006 in two cancer departments in Poland, has been performed. This evaluation included 25 MBC patients (pts) with a median age at diagnosis of 60 (range 42–74). Median delay to diagnosis was 19 months (range 3–84). All the patients had pathology-confirmed invasive ductal adenocarcinoma of the breast. The most frequent G-score (according to Bloom-Richardson Grading System) was G2 and was detected in 12/25 pts (48%). The ER and/or PR positive status was confirmed in half of the patients (13/25) (52%). HER2 status was assessed only in 5 cases with HER2-overexpression in 2 of them. Results: Stage IV was diagnosed in 2 pts, stage III in 16 pts, stage IIB in 6 and stage I in 1. More then half of stage III pts had T4 tumor feature at presentation. Radical mastectomy undergone 19 pts (76%), and in 4 cases lumpectomy was performed. Chemotherapy received 16/25 pts (64%): 10 pts (40%) as induction/neoadjuvant, adjuvant 4 pts (16%), and palliative 2 (8%). CMF regimen was used in 12/16 pts (75%) and anthracycline-based chemotherapy received 4/16 pts (25%). Hormone therapy was applied to 13/25 pts (52%), usually tamoxifen; only 1 patient received anastrozole. Two pts with metastatic disease were treated with trastuzumab-based therapy. Radical breast irradiation (50 Gy) was performed in 16/25 cases (64%), 2 patients received palliative breast radiotherapy. Clinical overall response rate reached 86%. Survival analysis was performed using Kaplan-Meier survival curves. Overall 5-year and estimated 10-year survival were 66% and 35%, respectively. After the median follow-up of 51 months (range 12–162) 13 patients died, most of them due to MBC progression. Conclusions: MBC is a very rare disease comparing to female breast cancer, and therefore its rarity can be the major reason for a diagnostics and treatment delay. Despite growing awareness of this disease over time, MBC is still detected in more advanced stages than in women, which results poor clinical outcome. The optimal management of this entity needs to be defined. No significant financial relationships to disclose.

Expression and Clinical Significance of Angiopoietin-2 and its Receptor Tie-2 in Invasive Breast Cancer

Purpose: Breast carcinomas are highly malignant tumor that the angiogenesis factor, vascular endothelial growth factor and its receptors are overexpressed. To elucidate the role of Angiopoietin-2 (ANG2) and ANG2 receptor Tie-2 in invasive ductal carcinoma, we examined the expression of ANG2, and Tie-2 at the mRNA and protein levels in human breast cancer cell lines and samples. Methods: Total RNA from 22 breast cancer patient biopsies were extracted. ANG2 and Tie-2 mRNA expression was measured by means of reverse transcription-PCR assay. Results: RT-PCR indicated that the ANG2 and Tie-2 mRNA levels in carcinoma samples were significantly higher than those of the adjacent non-neoplastic breast tissues. For ANG2 and Tie-2, 41 of 71 invasive ductal carcinomass (58%) showed high expressions in Immunohistochemistry. Immunohistochemical analysis demonstrated that ANG2 and Tie-2 were expressed by both tumor cells and endothelial elements. Expression in tumor cells were confirmed by studying a panel of human breast carcinoma cell lines cultured by RT-PCR. Our study showed that the ANG2 positivity was correlated with axillary lymph node metastasis among the clinicopathological parameter and confirmed that high expressions of ANG2 correlated highly with the axillary lymph node metastases, histological grade, positive PR status, and age, and Tie-2 expression correlated significantly with the p53 status. Moreover, ANG2 and Tie-2 co-expression correlated significantly with the axillary lymph node metastases, compared with ANG2(-)/Tie-2 (-) and ANG2 (+)/Tie-2 (-) or ANG2 (-)/Tie-2 (+) cases. Conclusion: These findings suggested that ANG2 and Tie-2 might be involved in the progression of invasive ductal carcinomas through autocrine and paracrine signaling and that it may be clinically useful in selecting patients who could benefit from adjuvant treatment by further study. (Journal of Korean Breast Cancer Society 2004;7:84-91) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome.

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB- 1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB- 1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE epsilon2 or epsilon4 alleles and the parameters investigated. Although there is evidence to suggest that APOE epsilon4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.

Tamoxifen as initial endocrine therapy for metastatic breast cancer: Long term follow-up of two Piedmont Oncology Association (POA) trials

To examine the outcomes of endocrine naive patients treated with tamoxifen as initial endocrine therapy for metastatic breast cancer. Data were obtained from the long-term follow-up of two previously published randomized trials. All patients received tamoxifen 20 mg po in a single daily dose. Eligibility required patients to be age > or = 18, performance status 0-3, and estrogen or progesterone receptor positive or unknown. Patients were ineligible if they had any prior endocrine therapy in either the adjuvant or metastatic setting. 156 patients have been followed for a median of 8.3 years. Median age was 61 years, 83% were > or = 50 years, 84% performance status of 0-1, 43% were both ER and PR positive, 33% had prior chemotherapy, 62% had a disease-free interval of > 2 years, and 59% had only one metastatic site. The complete (14%) and partial (6%) response rate for 147 evaluable patients was 20% (95% CI for CR + PR of 14-27%). Multivariate analysis revealed that improved response was related to soft tissue involvement and positive PR status. The majority of patients with soft tissue, nodal or lung metastases had responses noted within three months. Median time to disease progression was 6.7 months. Multivariate analysis revealed that older patients, those with one metastatic site and those with positive PR status had the longest time to progression. Median survival was 27.2 months. Better performance status, fewer metastatic sites and being PR positive were associated with significantly improved survival. The patient population in this series is not likely to be studied in future trials because of the wide use of tamoxifen in the adjuvant setting. In a small percentage of patients with metastatic breast cancer, tamoxifen therapy is associated with prolonged remission and survival. Pretreatment characteristics can help identify such patients.