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Hormone receptor-positive and human epidermal growth factor receptor 2-positive (HR+/HER2+ breast cancer comprise approximately 5-10% of all invasive breast cancers. However, the lack of knowledge regarding the complexity of tumor heterogeneity in HR+/HER2+ disease remains a barrier to more accurate therapies. This study aimed to describe the tumor heterogeneity of HR+/HER2+ breast cancer and to establish a novel indicator to identify the HER2-enriched subtype in patients with HR+/HER2+ breast cancer.First of all, a comprehensive analysis was performed on HR+/HER2+ breast cancer samples from the TCGA (n = 141) and METABRIC (n = 104) databases. We determined the distribution of PAM50 intrinsic subtypes within the two cohorts and compared the somatic mutational profile and RNA expression features between HER2-enriched and non-HER2-enriched subtypes. From this, we constructed a novel marker termed rH/E, which was calculated as ERBB2 expression quantity/(ESR1 expression quantity + 1). Secondly, we performed multiplex immunofluorescence (mIF) to evaluate HER2 and estrogen receptor (ER) expression simultaneously in the third cohort, enrolling 43 cases of early HR+/HER2+ breast cancer from Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). When using mIF, rH/E was adjusted to prH/E, which was calculated as HER2-positive cells%/(ER-positive cells + 1)%.All four main intrinsic subtypes were identified in HR+/HER2+ breast cancer, of which the luminal B subtype was the most common, followed by the HER2-enriched and luminal A subtypes. Significantly increased TP53 and ERBB3 and decreased PIK3CA somatic mutation frequency were observed in the HER2-enriched subtype compared with the non-HER2-enriched subtype. In addition, the HER2-enriched subtype was characterized by significantly higher ERBB2 and lower ESR1 expression. We then constructed a marker termed rH/E to reflect the relative expression of ERBB2 to ESR1 in each patient. rH/E discriminates the HER2-enriched subtype from the better than the expression of ERBB2 or ESR1 alone. In the CAMS cohort, we observed four subtypes of tumor cells: ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-. Tumor cell diversity was common, with 86% of patients having all four subtypes of tumor cells. Moreover, prH/E showed a significant prognostic association in the CAMS cohort.This study furthers our understanding of the complexity of tumor heterogeneity in HR+/HER2+ breast cancer, and suggests that the combined analysis of ERBB2 and ESR1 expression may contribute to identifying patients with specific subtypes in this population.

Early prediction of treatment response is crucial for the optimal treatment of advanced breast cancer. We aimed to explore whether monitoring early changes in plasma human epidermal growth factor receptor 2 (HER2) levels using digital PCR (dPCR) could predict the treatment response in advanced breast cancer.This was a multicenter, prospective, noninterventional clinical study of patients with advanced breast cancer. All enrolled patients underwent blood testing to measure the HER2 levels by digital PCR before treatment initiation and once every 3 weeks during the study. The primary endpoints wereOverall, 85 patients were enrolled between October 9, 2018, and January 23, 2020. dPCR had a specificity of 91.67% (95% CI: 80.61% to 97.43%) for detecting HER2 amplification, and the area under the receiver operating characteristic (ROC) curve was 0.84 (p 0.01). A clinically relevant specificity threshold of approximately 90%, which was equivalent to a ≥15% decrease in the plasma HER2 ratio at 3 weeks from baseline, showed a positive predictive value of 97.37% (95% CI: 77.11% to 98.65%) in terms of predicting clinical benefit. Patients whose plasma HER2 ratio was reduced by ≥15% had a longer median progression-free survival (PFS) than those whose ratio was reduced by15% (9.20 months vs. 4.50 months, p 0.01).Early changes in the plasma HER2 ratio may predict the treatment response in patients with advanced breast cancer and could facilitate optimal treatment selection.

BackgroundHormone receptor-positive and human epidermal growth factor receptor-2-positive (HR+/HER2+) breast cancer comprise approximately 5-10% of all invasive breast cancers. However, the lack of knowledge regarding the complexity of tumor heterogeneity in HR+/HER2+ disease remains a barrier to more accurate therapies. This study aimed to describe the tumor heterogeneity of HR+/HER2+ breast cancer and to establish a novel indicator to identify the HER2-enriched-like subtype in patients with HR+/HER2+ breast cancer.MethodsFirst, a comprehensive analysis was performed on HR+/HER2+ breast cancer samples from the TCGA (n=141) and METABRIC (n=104) databases. We determined the distribution of PAM50 intrinsic subtypes within the two cohorts and compared the somatic mutational profile and RNA expression features between HER2-enriched and non-HER2-enriched subtypes. We then performed multiplex immunofluorescence to evaluate HER2 and estrogen receptor (ER) expression simultaneously in the third cohort, enrolling 43 cases of early HR+/HER2+ breast cancer from Cancer Hospital, Chinese Academy of Medical Sciences (CAMS). ResultsAll four main intrinsic subtypes were identified in HR+/HER2+ breast cancer, of which the luminal-B subtype was the most common, followed by the HER2-enriched and luminal-A subtypes. Significantly increased TP53 and ERBB3 and decreased PIK3CA somatic mutation frequency were observed in the HER2-enriched subtype compared with the non-HER2-enriched subtype. In addition, the HER2-enriched subtype was characterized by significantly higher ERBB2 and lower ESR1 expression. We then constructed a marker termed rH/E to reflect the relative expression of ERBB2 to ESR1 in each patient. rH/E discriminates the HER2-enriched subtype from the non-HER2 subtypes better than the expression of ERBB2 or ESR1 alone. In the CAMS cohort, we observed four subtypes of tumor cells: ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-. Tumor cell diversity was common, with 86% of patients having all four subtypes of tumor cells. Moreover, rH/E showed a significant prognostic association in the CAMS cohort. ConclusionsThis study furthers our understanding of the complexity of tumor heterogeneity in HR+/HER2+breast cancer, and suggests that the combined analysis of ERBB2 and ESR1 expression may contribute to identifying patients with specific subtypes in this population.

Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers.The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis.A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P0.05). Patients aged35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P0.05). Compared with patients aged35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRAge at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.

Jian-wei Li,1,2,* Guang-yu Liu,1,2,* Ya-jie Ji,3,* Xia Yan,1,2 Da Pang,4 Ze-fei Jiang,5 De-dian Chen,6 Bin Zhang,7 Bing-he Xu,8 Zhi-ming Shao1,2 1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Breast Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Breast Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 5Department of Oncology, 307 Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 6Department of Breast Diseases, Cancer Hospital of Yunnan Province, Kunming, People’s Republic of China; 7Department of Breast Surgery, Cancer Hospital of Liaoning Province, Shenyang, People’s Republic of China; 8Department of Oncology, Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2–3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years. Patients and methods: Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2–3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2–3 years (total treatment duration 5years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events. Results: A total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3–4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group. Conclusion: For early-stage breast cancer patients who remain premenopausal following 2–3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment. Trial Registration: ClinicalTrials.gov (identifier NCT01352091). Keywords: breast cancer, adjuvant therapy, anastrozole, tamoxifen, GnRH analogs, aromatase inhibitors

Supplemental Digital Content is available in the text, The aim of this study was to understand current trends in trastuzumab use in China as a neoadjuvant/adjuvant therapy for human epidermal growth factor receptor-2 positive (HER2+) breast cancer and identify factors influencing trastuzumab use. This was a retrospective, multicenter, cross-sectional study of patients diagnosed with HER2+ breast cancer (stage I–III), between July 2013 and June 2014, at 155 hospitals in 29 provinces/cities in China. Demographic and clinical data, including tumor characteristics and details of adjuvant/neoadjuvant therapies used, were collected. Data analysis included univariate analysis, multivariate logistic regression, and subgroup analyses. Of 4994 HER2+ patients (mean age 51.1 ± 9.9 years) included, only 29.8% received trastuzumab, with 30.5% in adjuvant therapy and 18.3% in neoadjuvant therapy. The highest rates of adjuvant trastuzumab were in Beijing (59.3%), Jiangsu (57.1%), and Ningxia (50.0%), while those of neoadjuvant trastuzumab were in Guangdong (24.8%), Beijing (14.1%), and Zhejiang (10.7%). Multivariate regression results revealed that factors associated with trastuzumab use were medical insurance cover for trastuzumab, residing locally to the hospital, more lymph node involvement, and more advanced tumor stage. Subgroup analysis revealed that patients receiving neoadjuvant therapy were likely to be younger, premenopausal and non-local, and had lymph node metastases, more advanced tumor, and progesterone receptor positive tumor. Trastuzumab use in patients with HER2+ breast cancer is relatively low in China, especially for neoadjuvant therapy. Insurance coverage seems to be the most correlated factor that influences the use of trastuzumab in Chinese patients with HER2+ breast cancer.

Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m 2 on day 1 and gemcitabine 1250 mg/m 2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov, number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; p non-inferiority superiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight [7%] vs one [ vs one [ vs ten [8%]), anaemia (39 [33%] vs six [5%]), and thrombocytopenia (38 [32%] vs three [3%]), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 [10%] vs 42 [36%]) and peripheral neuropathy (27 [23%] vs 60 [51%]), but more grade 1–4 anorexia (33 [28%] vs 10 [8%]), constipation (29 [25%] vs 11 [9%]), hypomagnesaemia (27 [23%] vs five [4%]), and hypokalaemia (10 [8%] vs two [2%]). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

To evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis.Thirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis.During the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005).The incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.

Retrospective and prospective studies have shown that continuous administration of trastuzumab with different chemotherapy regimens resulted in better clinical outcomes than the administration of chemotherapy alone in women with HER2-positive, trastuzumab-refractory metastatic breast cancer (MBC). However, there are limited data to evaluate the activity of trastuzumab in patients progressed after other anti-HER2 therapies, e.g. lapatinib. The aim of the present study was to evaluate retrospectively the clinical value of trastuzumab in patients with lapatinib-resistant HER2-positive advanced breast cancer treated in our center.Patients with HER2-positive MBC who experienced progression after first-line lapatinib-based regimens were assigned to receive either conventional treatment without trastuzumab or in combination with trastuzumab as second-line therapy. The efficacy end points included progression-free survival (PFS) and overall survival (OS).Thirty-five eligible patients progressed after treatment with lapatinib-based regimens were collected. None of the patients had received prior trastuzumab in either the adjuvant or metastatic setting. Twenty-two patients were assigned to receive conventional treatment without trastuzumab as second-line therapy (non-T arm) and 13 patients received conventional treatment combined with trastuzumab (T arm). There were no significant differences in the main clinical factors between the two arms, such as age, PS status, ER/PR, metastatic status, etc. Both the two cases with no disease progression after the second-line therapy were trastuzumab-treated patients, and all the other 33 cases were patients with progression despite the second-line therapy. Twenty-seven patients died due to disease progression, and eight survived (six cases of the T-arm and two cases of the non-T arm). The median PFS was 3.3 months in the non-T arm and 10.0 months in the T arm (P = 0.001). The median OS was 7.0 months in the non-T arm and 31.1 months in the T arm (P = 0.015).Trastuzumab plus conventional treatment is superior to conventional treatment in women with lapatinib-resistant HER2-positive metastatic breast cancer. Continuous anti-HER2 management can provide survival benefit to patients with HER2-positive breast cancer.

To analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases.Seventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed.The frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P0.05).The prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.

To investigate the relationship between genetic variantions of circadian clock genes and risk of breast cancer.A case-control study including 406 breast cancer patients and 412 controls was conducted and genes Clock (rs2070062) and Per2 (rs2304672, rs2304669, rs934945) were genotyped by TaqMan real-time PCR. Unconditional logistic regression model was used to analyze the association between the genetic polymorphisms and breast cancer.Individuals with the rs2304669-TT genotype showed significantly increased breast cancer risk with the OR of 2.33 when compared with the individuals with rs2304669-CC and CT genotypes (P = 0.001). In addition, the three haplotypes containing the risk T allele of rs2304669 were identified to be associated with increased breast cancer risk. However, it was found that rs2304672, rs2070062 and rs934945 polymorphisms were not related with breast cancer risk.The locus rs2304669 on Per2 gene is associated with breast cancer risk. Genetic variation of circadian clock genes may increase the susceptibility to breast cancer. Therefore, it may become an important biomarker of susceptibility to breast cancer.

To explore the effects of polysomy 17 on human epidermal growth factor receptor-2 (HER-2) testing and study its clinicopathologic significance.We retrospectively analyzed the HER-2 status by fluorescence in situ hybridization (FISH) and HER-2 protein expression by immunohistochemistry (IHC) in a cohort of 619 patients with invasive breast cancer. The relationship between polysomy 17 and various clinicopathologic parameters was assessed.Polysomy 17 was observed in 31.8% of cases, but more frequently in the IHC(3+) (41.9%) than in the IHC(2+)(27.7%) and IHC(1+/0) (11.1%) subgroup (P = 0.001). There was no significant correlation between the frequency of polysomy 17 and HER-2 status in each IHC subgroup (P0.05). Among the cases without gene amplification by FISH, 9 of 15 IHC(3+) cases showed polysomy 17. As compared with the amplified group, un-amplified polysomy 17 patients were associated with such good prognostic indicators as greater hormone receptor positivity (P0.001) and lower Ki-67 index (P = 0.003) with a trend towards those with neither amplification or polysomy.The frequency of polysomy 17 is partially correlated with HER-2 protein expression but not HER-2 amplification. And polysomy 17 is a major factor in strong HER-2 protein overexpression in 3+ non amplified cases. Tumors displaying un-amplified polysomy 17 resemble more HER-2-negative than HER-2-positive counterparts.

To explore the therapeutic outcomes of various first-line regimens and prognostic factors for hormone receptor positive (HR+) breast cancer (BrCa) patients with bone-only metastases.A total of 139 HR+ BrCa patients with bone-only metastases between January 1, 2005 and October 31, 2010 were retrospectively reviewed. Their clinicopathologic characteristics, various treatment regimens and clinical survival factors were analyzed. Furthermore, the effects of various therapeutic regimens on skeletal-related events (SREs) were explored.In this cohort, 99 patients received first-line chemotherapeutic regimens and 40 had first-line endocrine drugs. Their median overall survival time was 61 months. No significant difference was noted in 5-year overall survival rate between first-line chemotherapy group (49.4%) and first-line endocrine group (44.3%) (hazard ratio (HR) 0.687, 95% confidence interval (CI) 0.307 - 1.539, P = 0.362). Furthermore, interval of disease-free survival3 years and number of positive lymph nodes10 were favorable prognostic factors by univariate analyses (HR = 0.333, 95%CI 0.138 - 0.803, P = 0.014; HR = 0.239, 95%CI 0.102 - 0.562, P = 0.001); they were also independent favorable prognostic factors by multivariate Cox-regression analyses. The proportion of patients with SREs decreased in the first-line chemotherapy group compared with the first-line endocrine group (45/99 (45.4%) vs 25/40 (62.5%)). Nonetheless, the difference was insignificant (P = 0.092).Interval of disease-free survival3 years and number of positive lymph nodes10 are independent favorable prognostic factors. The overall survival of HR+ BrCa patients with bone-only metastases is not significantly different between two groups. First-line chemotherapy may lower the incidence of SREs. Both endocrine therapy and chemotherapy are effective for HR+ BrCa patients with bone-only metastases and they should be individualized.

To evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.Patients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.Overall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.As a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.

To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection.A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors.Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P0.001), tumor location (P = 0.001), pathological grade (P0.001), TNM stage (P0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival.The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.

Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for ∼ 15% of overall breast cancer and associated with a poor prognosis. There is a short of standard adjuvant chemotherapy regimens for TNBC. A number of studies have shown that TNBC might be sensitive to cisplatin and carboplatin on the basis that dysfunction of BRCA1 and its pathway is associated with a specific DNA-repair defect, but data of adjuvant setting about this is limited.From January 2010 to September 2011, 95 early triple-negative breast cancer patients confirmed by pathology were randomly assigned to receive TP (docetaxel 75 mg/m², carboplatin AUC = 5, day 1, 21 days a cycle for 6 cycles) or EC-T (epirubicin 90 mg/m², cyclophosphamide 600 mg/m², d1, 21 days a cycle for 4 cycles, followed by docetaxel 80 mg/m², d1, 21 days a cycle for 4 cycles) chemotherapy. Adjuvant radiation therapy was given selectively after chemotherapy. Here we report a preliminary safety analysis with the chi-square test.Seventy-six out of the 95 patients had completed the chemotherapy and could be assessed for the safety profiles of the regimens. Thirty-seven of them were in the EC-T group with a median age of 47 years, and 21 out of these 37 patients were premenopausal (56.8%). Another 39 patients came from the TP group with a median age of 46 years, and 22 out of these 39 patients were premenopausal (56.4%). All of the 37 patients in EC-T group completed the planned treatment whereas 2 patients of the 39 cases in TP group did not because of bone marrow suppression. During the treatments, 9 patients had dose adjustment in each group. Adverse events of grade 1/2 were common. Specific incidence of adverse events with grade 3/4 in each group was as follows: alopecia, 29.7% vs. 10.3% (P = 0.033), vomiting 21.6% vs. 7.7% (P = 0.085), leukopenia 54.1% vs.25.6% (P = 0.011) and neutropenia 51.4% vs. 35.9% (P = 0.174). Other grade 3/4 toxicities were rare. All the adverse events (except peripheral neuropathy and pigmentation) recovered within 1 month after the chemotherapy.Both EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the treatment of triple-negative breast cancer patients, while the TP regimen has advantages with less grade III/IV alopecia and leukopenia.

Endobronchial metastases (EBM) secondary to extrapulmonary solid malignant tumors are rare but may occur. The most common extrathoracic malignancies associated with EBM are colorectal, renal and breast cancer. This study aimed to evaluate the clinicopathological aspects of EBM from breast cancer and the prognosis of the patients.Clinicopathological data of 11 cases diagnosed as EBM from breast cancer treated in our hospital from 2003 to 2010 were re-evaluated. Their symptoms, recurrence interval, radiological features, histopathological properties, and prognosis were assessed.Eleven cases were diagnosed by bronchoscopic bronchial biopsy. The median interval from diagnosis of breast cancer was 57 months (range: 11 - 189 mo). All patients had other proven metastases when the EBM was diagnosed. The most frequently observed symptoms were cough (8 cases). Interestingly, two patients were asymptomatic. Hilar mass (5 cases) was a common radiological finding. No disaccordance between the hormone receptor status in the primary and metastatic lesions in these patients was found. The median survival after EBM diagnosis was 21 months (range: 6 - 36) with four patients still alive and one of these four patients was surviving more than 7 years.On average, EBM is diagnosed about 5 years after the diagnosis of breast cancer, which is a relatively long lead time, but the median survival time is short, as 21 months in our group. The treatment plan must be individualized, because in some cases, long-term survival can be expected.

Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.

Treatment option for metastatic breast cancer (MBC) patients pre-treated with chemotherapy is limited. Oral etoposide has shown some promises in these patients. However, patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure. This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.MBC patients receiving at least two chemotherapy regimens prior to the enrollment were treated with repeated cycles of oral etoposide (60 mg×m(-2)×d(-1) on days 1-10, followed by 11 days of rest). The primary end point was the progression free survival (PFS). The secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and toxicity profiles.Thirty-two patients received 230 cycles of oral etoposide with a median of 6 cycles (range, 2-20 cycles) per patient. Eight patients (25%) had partial response (PR) and 14 patients achieved stable disease (SD). The ORR was 25%. Nine patients achieved SD for more than 24 weeks and CBR was 53%. The median PFS and OS were 5 (range, 1.5-17.0 months) and 16 months (range, 3.0-51.0 months), respectively. The patients who achieved clinical benefit had longer survival time than those who did not (25.0 versus 11.0 months, P0.01). Among the 16 patients who received more than four regimens prior to this study, four patients achieved PR and four achieved SD for more than 24 weeks, with a CBR of 50%. The most common hematologic adverse events were anemia (43.8%) and neutropenia (38.5%). Nausea/vomiting (75.0%) and alopecia (62.5%) were the most frequent non-hematologic toxicities.Oral etoposide is effective and well tolerated in Chinese women with heavily pretreated MBC.

The aim of this study was to evaluate the effect of anastrozole, a new generation aromatase inhibitor, on the lipid metabolism in postmenopausal Chinese women with early breast cancer, and observe the adverse reactions as well.Postmenopausal women with early breast cancer patients took anastrozole 1 mg per day. The lipid profiles of total cholesterol, triglyceride, low density lipoprotein, and high density lipoprotein were assessed before taking the drug, 3 months, 6 months after taking medication, and later once a year, until the end of medication or follow-up. Patients taking lipid-lowering drugs were excluded. The adverse reactions during the process of taking medication was followed-up by telephone.Two hundred and eighty-five postmenopausal breast cancer patients took part in the trial from Jan. 2003 to Jun. 2009. All patients had completed primary surgery and demonstrated a postmenopausal status. ER or PR positivity was confirmed by histopathology. Taking the medication from a minimum of one year to a maximum of 5 years, with a median time of 3.61 years. During the medication time, anastrozole significantly increased the levels of low density lipoprotein-cholesterol after 6 months of treatment, continuing to 5 years, from (3.08 ± 0.90) mmol/L to (3.59 ± 0.59) mmol/L, with a maximal increase of 18.2% higher than that before medication. Anastrozole significantly increased the levels of total cholesterol and high density lipoprotein-cholesterol after 1 years of treatment. Anastrozole significantly reduced the levels of triglycerides after 1 years of treatment. Anastrozole showed no significant effect on serum lipids in the patients with pre-existing hyperlipidemia. A more significant effect on blood lipids was observed in patients aged ≥ 60-years than that in patients less than 60 years of age. The rate of other adverse events were similar to that reported in foreign patients.For the postmenopausal patients with breast cancer, taking anastrozole may lead to an abnormal lipid metabolism. Anastrozole significantly increases the levels of low density lipoprotein-cholesterol, total cholesterol and high density lipoprotein-cholesterol, and significantly reduces the level of triglycerides. The rate of other adverse events were similar to that reported in foreign patients. it is suggested that the blood lipid levels should be regularly assessed in patients with long-term anastrozole treatment. The rate of other adverse events similar to that reported with foreign patients, and patients tolerate this treatment well.

To characterize the sites of distant recurrence and clinical outcomes in a cohort of Chinese patients with metastatic triple-negative breast cancer (TNBC).One hundred and thirty-four patients with metastatic TNBC treated at Cancer Hospital of CAMS from January 1999 to December 2007 were included in this study. The clinicopathological features and long-term survival of the patients were retrospectively analyzed.The median age of the patients was 45 years. Most patients (72.7%) had a higher predilection for visceral metastasis and early recurrence within the first two years of follow-up. Six patients (4.5%) presented with stage IV disease, 14 patients were diagnosed with locoregional recurrence after mastectomy, 75 patients with distant metastases, and 45 patients with both locoregional recurrence and distant metastasis. The most common site of first recurrence was the lung, and 62(51.7%)of the patients had more than two sites of metastasis. By July 30, 2009, 75 patients died of breast cancer (56.0%). The median overall survival (OS) was 26.5 months [95% confidence interval (CI), 20.5 - 32.6 months]. The 1-, 3- and 5-year overall survivals (OS) were 80.9%,37.1% and 30.1%, respectively. The median overall survival time of 58 patients with single site of metastasis was 28.5 months, longer than that of patients with more than two sites of metastases. Patients whose initial distant recurrence was bone metastasis only (7 patients) had better prognosis, with a median OS of 84.2 months. The median OS (28.5 vs. 12.6 months, P = 0.0001) differed significantly between patients who received first-line chemotherapy and those who did not. Forty-five of the 96 patients with measurable disease achieved complete/partial response (CR/PR), 39 patients had stable disease (SD), and 12 patients had disease progression (PD). The median OS was 36.1 months in patients with CR/PR, 20.8 months with SD, and 14 months with PD, respectively. The median OS of patients with CR/PR was significantly longer than that of patients with SD/PD (P = 0.0108). Distant metastasis, first-line chemotherapy and clinical response were significantly related with OS by univariate analysis. Furthermore, first-line chemotherapy and the clinical response were demonstrated to be an independent prognostic factor by multivariate analysis.Recurrence risk and mortality are considerably higher in TNBC patients within the early years of follow-up. TNBC patients have a higher risk of multiple and visceral metastases, and poorer survival, which might attribute to its aggressive clinical behavior and lack of effective regimens. Our findings also suggest that chemotherapy can effectively improve the clinical outcome of those patients.

To investigate the concordance and correlation between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) assessment for HER-2 status in breast cancer patients and analyze their relationship to clinical characteristics.A total of 128 samples of breast cancer tissue were analyzed retrospectively. FISH was employed to detect the HER-2 gene amplification. And the FISH findings were compared with IHC test results by analyzing the concordance and correlation between two results. And their relationships to the clinical characteristics were analyzed.The overall coincidence rate of IHC and FISH was 90.6% (kappa = 0.405, P = 0.000). And the discordance was mainly found in the IHC (++) group. A positive correlation was found between the two results (r = 0.655, P = 0.000). The ER (estrogen receptor) expression was negatively correlated with HER-2 gene amplification and the expression of Her-2 protein (r = -0.300, P = 0.001; r = -0.223, P = 0.011). There was a negative correlation between ER/PR status and HER-2 gene amplification (r = -0.213, P = 0.016). The similar results were found in subgroup analysis. Tumor grade was negatively correlated with the expression of Her-2 protein (r = -0.293, P = 0.008), but not with HER-2 gene amplification (P0.05).IHC is a preferred method to detect the Her-2 status in breast cancer. The strong positive expression (+++) of HER-2 protein tested by IHC is strongly consistent with HER-2 gene amplification by FISH. But HER-2 gene amplification should be further detected by FISH in patients with HER-2 positive expression (+-++) in order to guide the clinical diagnosis and treatment. ER, ER/PR (progesterone receptor) status and tumor grade are correlated with HER-2 gene amplification and/or the expression of Her-2 protein. This study helps improve the accuracy of judging HER-2 gene amplification according to the clinical and pathological features such as ER status and the results of IHC.

Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.

To analyze the relationship between P-glycoprotein function in peripheral blood cells and primary multidrug resistance in breast carcinoma.P-gp function was investigated by flow cytometry in NK cells of 16 breast cancer patients treated with anthracyclines and taxanes. Among all the patients, 8 were in chemotherapy-sensitive group and 8 in chemotherapy-resistant group. P-gp function was determined by rhodamine 123 (Rh123)-ejection test. Mathematical model was established by a regression of the fluorescence-time curve. The efflux rate constants of the chemotherapy-sensitive and -resistant groups were compared.There was no significant difference of Rh123 accumulation, retention or efflux between the two groups. The mathematical model of F(t) = F(0) · e(-kt) was established. K was the efflux rate constant, which was significantly different between the chemotherapy-sensitive and -resistant groups (P = 0.025). When k3.9 was used as diagnostic criterium for primary resistance, the sensitivity, specificity and accuracy were 75.0%, 100% and 87.5%, respectively.P-glycoprotein function in peripheral blood cells is associated with primary multidrug resistance in breast carcinoma. The efflux rate constant may be a good predictor for chemotherapy sensitivity.

To investigate the clinicopathological characteristics and prognosis in young patients with estrogen receptor (ER)-negative, progesterone receptor(PR)-negative, and Her-2-negative (triple-negative) breast cancer (TNBC).94 young patients (or = 35 years old) with TNBC at the Cancer Hospital of CAMS between January 1999 and December 2007 were included in this study. The clinicopathological features and prognosis of those 94 patients were retrospectively evaluated.Among 786 young patients with breast cancer, 94 patients (12.0%) were triple-negative. The median age of the 94 young TNBC patients was 31 years.81 patients (86.2%) were diagnosed with invasive ductal carcinoma. 82.0% of the patients were classified as T1 or T2. The TNM stages included: 17 patients in stage I (18.1%), 48 in stage II (51.1%), 28 in stage III (29.8%) and 1 in stage IV (1.1%). 14 patients (14.9%) were diagnosed with lymphovascular invasion. The 1-, 3-, 5- and 7-year disease-free survival (DFS) was 88.3%, 66.9%, 59.7% and 59.7%, respectively. The corresponding overall survival (OS) rate was 98.9%, 85.6%, 72.9% and 69.6%, respectively. The univariate analysis showed that T stage, lymph node metastasis, clinical stage and lymphovascular invasion were correlated with the overall survival. However, only vascular invasion was showed to be an independent prognostic factor assessed by multivariate analysis. 33 patients developed recurrence or metastatic TNBC during the follow-up period. Among those 33 cases, 29 had recurrent or metastatic diseases within 3 years postoperatively and the other 4 cases after 3 years following surgery.Young patients with TNBC represent distinctive clinicopathological and prognostic characteristics. Progression on tailored treatment for such population is still crucial. Further studies on rational individualized treatment regimen are warranted.

To investigate the efficacy and safety of goserelin plus anastrozole in advanced premenopausal breast cancer patients.We summarized a single-centre experience with goserelin plus anastrozole in 32 premenopausal women with metastatic breast cancer (MBC). All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks concurrently with anastrozole 1 mg daily. The median duration of treatment was 12 months.No patient achieved complete remission (CR) (0%), 6 partial remissions (PR) (18.8%), 21 stable diseases (SD) (65.6%) and 5 progressive diseases (PD) (15.6%). Objective response rate (ORR) was achieved in 18.8% and clinical benefit (CR + PR + SD6 months) in 68.8%. The median progression-free survival (PFS) was 12 (2 - 57) months. One-year overall survival rate (OS) was 87.4% and two-year OS 66.9%. The OS of patients without visceral metastasis was significantly longer than that of patients with visceral metastasis (P = 0.04). Hot flushes and nausea were predominant toxicities.The combination of goserelin and anastrozole appears to be an efficient and well-tolerated regimen in premenopausal MBC women.

To evaluate the clinicopathological characteristics and prognosis of breast cancer with estrogen- and progesterone-receptor negative (ER-/PR-) and HER-2 overexpression (HER+++) in a Chinese population.The data of patients with ER-/PR- and HER+++ breast cancer treated in our hospital from March 1999 to December 2004 were retrospectively reviewed. The influence of clinicopathological characteristics and molecular markers on the survival was analyzed.A total of 111 breast cancer patients with ER and PR negative but HER+++ were identified, accounting for 4.9% of all the breast cancer patients treated during the same period. There were 25 cases (22.5%) in stage I, 44 (39.6%) in stage II and 36 (32.4%) in stage III, respectively, with a median age of 49 years. Axillary lymph node metastasis was found in 54 cases. The 5-year disease free survival (DFS) and overall survival rates (OS) were 70.7% and 73.1%, respectively. Univariate analysis showed that lymph node status, primary tumor size and pathological stage were prognosis-related factors influencing the DFS and OS. However, by multivariate analysis, only primary tumor size and lymph node status were independent factors influencing survival.The breast cancer with estrogen- and progesterone-receptor negative but HER-2 overexpression is a particular subtype of breast cancers, with unfavorable clinicopathological characteristics and poor survival. Lymph node status and primary tumor size are two independent prognostic factors.

To investigate the safety and tolerance of adjuvant dose-dense chemotherapy with paclitaxel and epirubicin for high-risk breast cancer.From January 2004 to December 2006, 101 patients with high-risk breast cancer after surgical resection were enrolled into this study. The patients were divided into two groups: dose-dense and regular groups. Each patient received 6 cycles of chemotherapy with intravenous administration of paclitaxel (175 mg/m2, on D3) and epirubicin (60 mg/m2, on Dl and D2). The dose-dense group had repeated treatment every two weeks, while the regular group repeated it every three weeks. G-CSF was used in a dose of 3 microg/kg on D5-D9 during each cycle in the dose-dense group. While in the regular group, it was used only under the condition that grade II neutropenia occurred.The toxicity could be evaluated in 101 patients. Major grade II-IV toxicities included: neutropenia, nausea, vomiting and alopecia. The incidence of grade III-IV neutropenia was 16.0% in the dose-dense group versus 54.9% in the regular group (P = 0.000); postponing of chemotherapy was 2.4% versus 6.0% (P = 0.027). Ninety-eight patients completed the chemotherapy as planed. After a median follow-up of 24 months, the median DFS and OS were not reached. The relapse-free rate and survival rate were 89.8% and 100% in the dose-dense group, which were 87.8% and 93.9% in the regular group. The relapse-free rate of the high-risk patients in the dose-dense group was 86.8% versus 81.3% in the regular group, and the corresponding survival rate was 100% versus 90.6%.Adjuvant dose-dense chemotherapy with paclitaxel and epirubicin is safe, tolerable and promising for high-risk breast cancer.

To analyze the incidence, clinical and pathological characteristics, survival and prognostic factors of so-called triple negative breast cancer (TNBC) with negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2).Clinical and pathological as well as follow-up data of TNBC patients between Jan. 1999 to Dec. 2002 were collected and analyzed.Totally, the pathological result of 1175 breast cancer patients were retrospectively reviewed, and 158 patients were found with negative ER, negative PR and HER-2 scored as 0 or 1 + by immunohistochemistry staining. Eventually, only 108 patients with ER-negative, PR-negative and HER-2-negative (score: 0 ) were analyzed. Of the 108 patients, 8 had breast cancer family history, 3 oophoroma family history and one had ever suffered from oophoroma herself. The median age of the 108 TNBC patients was 47.0 years, and 75.0% of them had stage I or II disease. The majority of pathological types were grade II or III invasive ductal carcinomas, and 92.6% of the tumors were staged as T1 or T2. Lymph node metastases were detected in 49. 1% of these patients. Event-free survival, distant metastasis-free survival, local relapse-free survival and overall survival at 5 years were 68.1%, 70.9%, 72.1% and 76.9%, respectively. Though lymph node metastasis and lymph-vascular invasion were all found to be correlated with overall survival, however, only the lymph node metastasis was an independent factor that affected the overall survival revealed by the Cox proportional hazard model analysis.Triple negative breast cancer has distinct clinical and pathologic characteristics. The incidence of triple negative breast cancer in Chinese is similar to that in white but lower than that in black women. Most of the triple negative breast cancer in China is composed of sporadic breast cancer. Lymph node metastasis is an important independent prognostic factor. Clinical outcome of this series is similar to that in white women, while better than that in black women after appropriate radiotherapy and anthracycline-based chemotherapy. Further study is still necessary to explore new treatment in order to improve the prognosis of triple negative breast cancer.

To analyze the clinical characteristics, survival, and prognosis of female breast cancer patients with 10 or more positive lymph nodes.The data of 128 female breast cancer patients with 10 or more positive lymph nodes from JAN 1998 to Mar 2002 were retrospectively reviewed. The clinical characteristics, survival, and prognostic factors were analyzed by SPSS 10.0 statistic software.The 1-, 3-, 5, and 7-year overall survival (OS) rates were 91.4%, 68.8%, 53.1%, and 40.2%, and the disease free survival (DFS) rates were 80.9%, 54.1%, 44.7%, and 36.0% respectively. Log Rank test showed that tumor size was not related to prognosis; patients with more than 20 positive lymph nodes (P = 0.029), positive lymph node ratio greater than 0.8 (P = 0.027), and infiltration of vessel (P = 0.037) had a poorer DFS and shorter OS; patients with negative hormonal receptor had a poorer OS than those with positive hormonal receptor (P = 0.019); radiotherapy improved DFS (P = 0.000), and adjuvant chemotherapy for 4 - 6 cycles (P = 0.000) or more than 6 cycles (P = 0.004) and endocrine therapy (P = 0.001) might improve DFS and OS; patients with multiple metastasis had a poorer survival than those with local recurrence (P = 0.004) and single metastasis (P = 0.058). COX proportional hazard model analysis showed that positive lymph node ratio and infiltration of vessel were independent prognostic factors for both DFS and OS; adjuvant endocrine therapy decreased relapse and death hazard ratio for 43% (RR = 0.57, P = 0.035) and 65% (RR = 0.35, P = 0.000) respectively; adjuvant radiotherapy decreased the relapse hazard ratio for 72% (RR = 0.28, P = 0.000); and adjuvant chemotherapy for more than 4 cycles decreased death hazard ratio for 51% (RR = 0.49, P = 0.001); patients with recurrence and/or metastasis had a higher death hazard ratio (RR = 2.738, P = 0.000), hormonal receptor was an independent prognostic factor, and active treatment might improve the survival.Breast cancers with 10 or more positive lymph nodes have higher aggressively biologic characteristics; the prognosis of this subgroup has no relationship with tumor size and inverse correlation with the numbers of positive lymph nodes; Positive lymph node ratio and infiltration of vessel are important independent factors. Multidiscipline therapy including adjuvant radiotherapy, endocrine therapy, and at least 4 cycles chemotherapy increases the therapeutic effect, decreases relapse and death hazard ratio, and improves the survival.

To analyse the clinical features and prognostic factors of small breast cancer patient (Tor =2 cm) with multiple axillary lymph node metastasis (Nor =4).The data of 118 small breast cancer patients (Tor =2 cm) with multiple axillary lymph node metastasis (Nor =4) surgically treated from 1993 to 2003 were retrospectively analysed by SPSS 13.0 software.The overall 5-year survival rate was 75.0% in this series. It was found by single-variant Kaplan-Merier analysis that the stage, adjuvant chemotherapy and adjuvant endocrine therapy significantly influenced the outcome of the patients. For patients with 4-9 oror =10 metastatic axillary lymph nodes, the 5-year OS was 89.5% and 59.8%, respectively (P = 0.009). It was 82.1% and 53.3% in the patients with or without adjuvant chemotherapy (P = 0.001), respectively. For patients with or without adjuvant endocrine therapy, the 5-year OS was 89.2% and 61.9% (P = 0.001). Multi-variant Cox regression analysis showed that the stage, adjuvant chemotherapy and adjuvant endocrine therapy were independent prognostic factors.Small breast cancer with multiple axillary lymph node metastasis usually has a tendency of metastasis with a poor prognosis, especially in those withor =10 metastatic axillary lymph nodes. The stage, adjuvant chemotherapy and adjuvant endocrinetherapy were independent prognostic factors. Reasonable multi-modality therapy may be able to improve the outcome of these patients.

To evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).From January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.The median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95% CI: 5.1-8.9). Median overall survival was 29.0 months (95% CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade III to IV adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%) , and alopecia in 6 cases (13.3%).Combination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

To analyze the clinicopathological features, parameters of molecular biology, survival rate, and prognostic factors in breast cancer patients with vascular invasion.The data of 262 breast cancer patients with vascular invasion surgically treated between January 1995 and December 2003 in our institution were retrospectively analyzed. Clinicopathological characteristics, parameters of molecular biology, disease free survival rate and overall survival rate were surveyed.Of all breast cancer patients registered in our institution during the same period, these 262 breast cancer patients with vascular invasion accounted for 5.3% with a median age of 43 years. The major pathological type was invasive ductal carcinoma (93.3%). The stages included stage I in 5% , stage II 31. 3% , stage III 58.8% , stage IV 1.1% , and unknown 3.8%. Immunohistochemical staining showed that ER positive in 67.7%, PR(+) 68.0%, p53(+) 54.2%, PCNA(+) 93.3%, c-erbB2( +++) 20.8% and c-erbB2(++) 16.9%. The 5-year and 10-year cumulative disease free survival and overall survival were 57.6% , 50.7% and 62.8%, 52.9% , respectively. The factors which were found to compromise disease free survival were the tumor size, lymph node status, stage, and radiotherapy in the univariate analysis, and for overall survival, were the tumor size, lymph node status, stage, location of vascular invasion and radiotherapy. The tumor size and radiotherapy were found to be independent prognostic factors for disease free survival and overall survival in the multivariate analysis.Breast cancers with vascular invasion have poor biological behavior though having been treated by surgery, radiotherapy and chemotherapy. The independent prognostic factors of such patients are tumor size and radiotherapy. Anti-angiogenesis and antilymphangiogenesis may gradually become promising target treatment for such patient.