Advanced Breast Cancer Cases Research Articles

晚期乳腺癌的中西医结合治疗

Objective: To observe the treatment of 15 cases of advanced breast cancer,and to explore effective treatment. Methods: Patients with advanced breast cancer were having intravenous infusion of ifosfamide 1.0,d1.7;intravenous cisplatin 20mg,d1.4.7;tegafur 0.4 veins 0.1 drip and leucovorin bolus,d1.4.7;paclitaxel 30mg intravenous drip,d2.8;epirubicin 30mg intravenous drip,d5;V-p16 100mg intravenous drip,d6.9; semustine 1 (50mg),before bedtime d6.9;prior chemotherapy herein are 5mg intravenous dexamethasone to prevent allergic reactions from June 2004 to June 2011. They had BOC chemotherapy radiotherapy for five weeks (one period of treatment). In the process of chemotherapy, they were having oral medicine, four weeks is a period of treatment. The total treatment was evaluated. Results Five cases recovered completely, eight cases partly alleviated and shrinkage of tumors is less than 50% in two cases. no tumor patients continues to increase,the total efficiency is 86.7%. Adverse reactions: The patients without Ⅲ-Ⅳ toxicity. Conclusion: The combination therapy, which carries features of efficacy,safety, and less adverse reactions,is an effective way to treat advanced breast cancer . ight-siS�ooؽq�uqis the most complicated and intractable trauma of abdomen. The reasonable surgery method, the proper therapeutic measure and the intensive nursing are keys to successful cure.

癌性胸水・腹水に対してS-1+CPT-11併用療法が奏効した乳癌の4例

癌性胸水・腹水に対してS-1+CPT-11併用療法が奏効した乳癌の4例

Abstract 471: A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine.

Abstract Introduction: All cases, so far we have experienced,of bone-metastatic breast carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy. We here report a case of advanced breast cancer that has been additively treated with autologous formalin-fixed tumorvaccine (AFTV) (Clin Cancer Res 10: 1574-9 2004). Case : A 53 years old female was diagnosed bearing a bone metastasis of breast cancer at vertebra Th7 by bone scintigraphy, MRI and SPECT. The breast was operated, irradiated according to palliative radiation therapy with 36 Gy, vaccinated with AFTV, and then chemotherapy (CEF) was done as the last step of adjuvant therapy. Afterwards aromatase inhibitor and zoledronic acid hydrate was used for maintenance therapy. Five years later, the bonemetastasis has disappeared and she was diagnosed complete remission. Tumor markers have been in normal level . QOL of this patient is good at present. Conclusion: Complete remission of bone metastasis of breast carcinoma is very rare. In this case, the preceded use of AFTV and radiation to the chemotherapy may have contributed to the cure. Additional use of AFTV should be considered in a larger scale clinicaltrial to improve therapeutic efficacy in bone-metastatic breast carcinoma. Citation Format: Fumito Kuranishi, Tadao Ohno. A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 471. doi:10.1158/1538-7445.AM2013-471

Abstract 450: Host-tumor immune response for breast cancer patients.

Abstract We demonstrated immune suppression of regulatory T cells (Treg) and M2 macrophage in breast cancer (BC) patients at AACR 2011. In summary, to compare between 38 early and 12 advanced BC cases, CD163-positive tumor cells and CCR4-positive tumor cells were detected more frequently in advanced cases than in early cases. Treg cells in PBMC significantly increased in percentage of the population in 37 BC patients than in 21 healthy volunteers. To explore host-tumor immune response, several cytokines were examined in the same cases. Plasma from 32 early and 9 advanced BC cases was preoperatively obtained. Human IL-2, IL-4, IL-6, IL-10, TNF, INFγ, and IL-17A were measured using cytometric beads array system. Statistical significance was analyzed using Mann-Whitney U-test. Plasma IL-17A had significantly higher levels in early BC than in advanced BC (103 pg/ml v.s. 51 pg/ml at mean level). Th17 cells may have some potential to control tumor progression in BC. In conclusions, induction of host-tumor immune response due to chemotherapy and anti-HER2 therapy and release from immune suppression such as CCR4 monoclonal antibody are important issues to explore a new strategy for BC patients. Citation Format: Shigeru Imoto, Noriko Nakatsugawa, Hirotsugu Isaka, Hiroki Ito, Kentaro Imi, Kaisuke Miyamoto, Tetsuya Nakatsura. Host-tumor immune response for breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 450. doi:10.1158/1538-7445.AM2013-450

The Aryl Hydrocarbon Receptor: A Target for Breast Cancer Therapy.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a battery of genes in response to exposure to a broad class of environmental poly aromatic hydrocarbons (PAH). AhR is historically characterized for its role in mediating the toxicity and adaptive responses to these chemicals, however mounting evidence has established a role for it in ligand-independent physiological processes and pathological conditions, including cancer. The AhR is overexpressed and constitutively activated in advanced breast cancer cases and was shown to drive the progression of breast cancer. In this article we will review the current state of knowledge on the possible role of AhR in breast cancer and how it will be exploited in targeting AhR for breast cancer therapy.

A Case of StageIV Advanced Breast Cancer Showing Clinical Complete Response with Paclitaxel as Neoadjuvant Chemotherapy

A Case of StageIV Advanced Breast Cancer Showing Clinical Complete Response with Paclitaxel as Neoadjuvant Chemotherapy

Clinical efficacy of NVB combined with cisplatin for 30 cases of advanced breast cancer after anthracycline chemotherapy

Objective To observe the clinical efficacy of NVB combined with cisplatin for patients with advanced breast cancer after anthracycline chemotherapy. Methods 60 cases of advanced breast cancer after anthracycline chemotherapy, admitted into our hospital from Sep 2010 to Aug 2011, were randomly divided into 2 groups： 30 patients in a test group got the treatment of NVB combined with cisplatin; 30 patients of the control group continued use of anthracycline chemotherapy. The treatment efficacy was calculated and observed.Results Effective rate （CR ＋ PR） in test group was 43.3%, which was higher than that （13.3%）in the control group, and the difference was statistically significant （P〈0.05）. After 3 courses of treatment, all patients had no severe liver functional damage occurred, and the main drug toxicity manifested as bone marrow suppression, gastrointestinal reactions, and hair loss; in addition, a small number of patients showed peripheral neurotoxicity and phlebitis; the difference of bone marrow suppression between 2 groups was statistically significant （P〈0.05）.Conclusion The treatment of NVB combined with eisplatin for the patients with advanced breast cancer after anthracycline chemotherapy is the best choice, which should be widely applied. Key words: Vinca alkali; Cisplatin; Breast cancer

Sonodynamic and photodynamic therapy in advanced refractory breast cancer.

118 Background: Sonodynamic therapy (SDT), a procedure related with photodynamic therapy, is a promising new modality for treating deep-seated cancer. Two new chlorophyll derived sono-photo-sensitizing agents, along with equipment for systemic SDT, have been developed by EEC Biotech and all approved by regulator for safety on human. Animal studies demonstrate that the sensitizers are specifically absorbed into tumor cells and SDT does inhibit growth of mouse S-180 sarcoma. An in vitro experiment with human breast cancer cell-line showed that SDT was strongly synergetic with chemotherapy. Using sono-photo-dynamic therapy (SPDT) as a supplementary or salvage treatment, we have got some positive results in advanced refractory breast cancers. Methods: Twelve patients were pathologically proven advanced breast carcinoma. Eleven had metastases in viscera including brain, and nine in bones. Ten had chemotherapy before, nine failed at least second lines of conventional chemotherapy. With SPDT, Patients took the sensitizers sublingually on days 1 and 2, red light and multiple ultrasound transducers irradiate tumor area and whole body on days 4 to 6. The treatment was repeated. Nine patients had concurrent chemo with range from moderate to ¼ conventional dosages selected to keep side effects at grade II or better. Results: The twelve patients achieved CR 3(25%), PR 6 (50%), MR 1, SD 2, with an overall response rate of 75%.Median overall survival exceeded 14.5 months. SPDT as sole therapy was effective in three cases. Four treated repeatly with SPDT also achieved positive result after tumor relapsed. One patient with brain metastases showed much reduced. The two SD were TNBC with inflammation-like metastases on the chest surface. The main SPDT side effects were easily reversible mild pain in tumor areas, tiredness and weakness.There was no skin sensitivity.SPDT/dose controlled chemo was well tolerated, even a terminally ill patient was treated safely and effectively. Conclusions: These preliminary data suggest that SPDT has almost no toxicity, and may dramatically enhance chemo efficacy in some refractory advanced breast cancer cases. SPDT has a good trend to be a new systemic, low toxicity tumor therapy and merit for further investigation.

P1-01-10: Immune Suppression of Regulatory T Cells and M2 Macrophage in Breast Cancer Patients.

Abstract Background: Recent multi-disciplinary treatments of breast cancer (BC) could decrease the mortality rate, but successful immune therapy remains uncertain. To explore new strategy of immune therapy of BC, we are investigating about host-tumor immune response in BC patients. Materials and methods: Tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were obtained from early and advanced BC patients. PBMC were also collected from healthy volunteers. Regulatory T (Treg) cells were examined by counting CD4+CD25highCD127low/−cells in PBMC with flow cytometry analysis. Immunohistochemical evaluation of tumor specimens was performed with monoclonal antibodies of HLA-ABC and DR, CD56, CD68, CD83, and CD163. The number of stained cells was analyzed using a semiquantitative ordinal scale ranging from 0 to 3 (0, +/−, ++, +++). Results: HLA-ABC and DR were stained negative in 44% and 82% of 50 BC cases. When host-tumor immune response were compared between 38 early BC cases and 12 advanced BC cases, numbers of CD68-positive cells significantly increased in peripheral tumor tissues of advanced BC cases than in those of early BC cases (92% versus 53%). CD163-positive tumor cells were also detected more frequently in advanced BC cases than in early BC cases (75% versus 16%). There were no significant differences of distribution of CD4, CD8, CD56, and CD83-positive cells in early and advanced BC cases. Treg cells in PBMC significantly increased in percentage of the population in 37 BC patients than in 21 healthy volunteers (4.2% versus 2.5% of CD4-positive cells at mean value). Interestingly, Treg cells decreased in percentage of the population in 36 postoperative BC patients. Conclusions: Our results suggest that Treg cells render BC patients under immune suppression and M2 macrophage plays an important role of tumor progression. Targeted therapy against M2 macrophage may be a promising strategy of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-10.

P5-13-20: TOP2A Amplification Have Associated with Response to Anthracycline-Based Preoperative Chemotherapy in Primary Breast Cancer.

Abstract Background: Recent studies have suggested that HER2 gene amplification or overexpression have association with sensitivity of anthracycline-based chemotherapy. Preclinical studies found that TOP2A amplification or deletion only could be detected in HER2 amplification or over-expressive cases. And TOP2A protein is the target of anthracycline. In fact, the value of HER2 for predicting response to anthracycline-based chemotherapy in breast cancer may be more likely related to the concomitant amplification of the TOP2A gene. In this study we studied the association between TOP2A gene amplification and response to anthracycline-based preoperative chemotherapy. Methods: 309 early and local advanced breast cancer cases were enrolled in our study. HER2 proteins were qualitatively analysed by IHC, and TOP2A gene alterations were quantified by real-time polymerase chain reaction (RT-PCR) in primary tumor core biopsies from all HER2 over expressive cases. The enrolled patients received an intense dose dense (IDD) (CE, Cyclophosphamide + Epirubicin) or conventionally (TE, Paclitaxel+Epirubicin) scheduled anthracycline- based preoperative chemotherapy. The tumor was evaluated every two cycles. Median time on study for 309 patients with follow-up was 38 months. Results: The pCR was 14.3%. HER2 overexpression was found in 80/309 (25.9%) breast cancer cases, of which 61/80 cases have been tested for TOP2A status. 19/80 cases have not been tested for TOP2A status because of lacking core biopsies tumor tissue after pathological diagnosis. HER2 overexpression was associated with a significantly higher pCR rate compared to HER2 lower expression (27.5% vs. 9.6%, P<0.001). Further analysis was carried on and found the significantly higher pCR rate in TOP2A co-amplified cases compared to TOP2A deleted or normal cases (56.3% vs. 13.8%, P=0.001). HER2 overexpression was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (56.3% vs. 9.6%, P<0.001), but not when deleted or normal (13.8% vs. 9.6%, P=0.183), compared to HER2 lower expression tumors. The interaction between HER2 or TOP2A and anthracycline-based regiment was observed not only in IDD but conventionally scheduled preoperative chemotherapy. Discussion: Previous studies demonstrate that TOP2A gene amplification may define a subtype of HER2−positive breast cancer, This subtype of breast cancer may be highly sensitive to anthracycline-based chemotherapy, which may improve progression in HER2 and TOP2A co-amplification cases. Howerver, this viewpoint needs suppose from preoperative chemotherapy. Using RT-PCR to test TOP2A statue from 61 primary breast cancer tumor tissue, we demonstrate that TOP2A amplification breast cancer have highly sensitive to anthracycline-based preoperative chemotherapy. This finding suggests that TOP2A as a predictive marker in breast cancer should be included in future studies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-20.

Estrogen receptor-beta mediates the protective effects of aromatase induction in the MMTV-Her-2/neu x aromatase double transgenic mice.

Breast cancers amplified for the tyrosine kinase receptor Her-2/neu constitute ~30% of advanced breast cancer cases, and are characterized by hormone independence and aggressive growth, implicating this pathway in breast oncogenesis. The induction of Her-2/neu leads to tumor development in 60% of transgenic mice. We have previously examined the effects of estrogen in the MMTV-Her-2/neu background by generating the MMTV-Her-2/neu x aromatase double transgenic mouse strain. MMTV-Her-2/neu x aromatase mice developed fewer mammary tumors than the Her-2/neu parental strain. Our present data show the induction of several estrogen-related genes, including the tumor suppressors BRCA1 and p53, and a decrease in several angiogenic factors. The phosphorylated forms of MAPK p42/44 and AKT were lower in the MMTV-Her-2/neu x aromatase double transgenic mice compared to the MMTV-Her-2/neu parental strain; conversely, phospho-p38 levels were higher in the double transgenic strain. The ERβ-selective antagonist THC reversed these changes. The regulation of these factors by ERβ was confirmed in clones of MCF7 breast cancer cells overexpressing Her-2/neu in combination with ERβ, suggesting that ERβ may play a direct role in regulating MAPK and AKT pathways. In summary, the data suggest that ERβ may play a major role in decreasing tumorigenesis and that it may affect breast cancer cell proliferation and survival by altering MAPK and AKT activation as well as modulation of tumor suppressor and angiogenesis factors. Treatment with selective ERβ agonist may provide therapeutic advantages for the treatment and prevention of breast cancer.

Influence of whole arm loss of chromosome 16q on gene expression patterns in oestrogen receptor‐positive, invasive breast cancer

A whole chromosome arm loss of 16q belongs to the most frequent and earliest chromosomal alterations in invasive and in situ breast cancers of all common subtypes. Besides E-cadherin, several putative tumour suppressor genes residing on 16q in breast cancer have been investigated. However, the significance of these findings has remained unclear. Thus, other mechanisms leading to gene loss of function (eg haploinsufficiency, or distortion of multiple regulative subnetworks) remain to be tested as a hypothesis. To define the effect on gene expression of whole-arm loss of chromosome 16q in invasive breast cancer, we performed global gene expression analysis on a series of 18 genetically extensively characterized invasive ductal breast carcinomas and verified the results by quantitative real-time PCR (qRT-PCR). The distribution of the differential genes across the genome and their expression status was studied. A second approach by qRT-PCR in an independent series of 30 breast carcinomas helped to narrow down the observed effect. Whole-arm chromosome 16q losses, irrespective of other chromosomal changes, are associated with decreased expression of a number of candidate genes located on 16q (eg CDA08, CGI-128, SNTB2, NQO1, SF3B3, KIAA0174, ATBF1, GABARAPL2, KARS, GCSH, MBTPS1 and ZDHHC7) in breast carcinomas with a low degree of genetic instability. qRT-PCR provided evidence to suggest that the expression of these genes was reduced in a gene dosage-dependent manner. The differential expression of the candidate genes according to the chromosomal 16q-status vanished in genetically advanced breast cancer cases and changed ER status. These results corroborate previous reports about the importance of whole-arm loss of chromosome 16q in breast carcinogenesis and give evidence for the first time that haploinsufficiency, in the sense of a gene dosage effect, might be an important contributing factor in the early steps of breast carcinogenesis.

Abstract 1555: Immune suppression of regulatory T cells and M2 macrophage in breast cancer patients

Abstract Background: Recent multi-disciplinary treatments of breast cancer (BC) could decrease the mortality rate, but successful immune therapy remains uncertain. To explore new strategy of immune therapy of BC, we are investigating about host-tumor immune response in BC patients. Materials and methods: Tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were obtained from early and advanced BC patients. PBMC were also collected from healthy volunteers. Regulatory T (Treg) cells were examined by counting CD4+CD25highCD127low/-cells in PBMC with flow cytometry analysis. Immunohistochemical evaluation of tumor specimens was performed with monoclonal antibodies of HLA-ABC and DR, CD56, CD68, CD83, and CD163. The number of stained cells was analyzed using a semiquantitative ordinal scale ranging from 0 to 3 (0, +/-, ++, +++). Results: HLA type I and type II were stained negative in 44% and 82% of 50 BC cases. When host-tumor immune response were compared between 38 early BC cases and 12 advanced BC cases, numbers of CD68-positive cells significantly increased in peripheral tumor tissues of advanced BC cases than in those of early BC cases (92% versus 53%). CD163-positive tumor cells were also detected more frequently in advanced BC cases than in early BC cases (75% versus 16%). There were no significant differences of distribution of CD4, CD8, CD56, and CD83-positive cells in early and advanced BC cases. Treg cells in PBMC significantly increased in percentage of the population in 46 BC patients than in 16 healthy volunteers (3.8% versus 2.1% of CD4-positive cells at mean value). Interestingly, Treg cells decreased in percentage of the population in postoperative BC patients. Conclusions: Our results suggest that Treg cells render BC patients under immune suppression and M2 macrophage plays an important role of tumor progression. Targeted therapy against M2 macrophage traits may be a promising strategy of breast cancer. Host-tumor immune response will be reported for BC patients treated with primary chemotherapy or radiofrequency ablation therapy in comparison with those who underwent breast surgery first. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1555. doi:10.1158/1538-7445.AM2011-1555

Indian experience with diethylstilbestrol in hormone-positive metastatic breast cancer after failure of standard hormone therapy.

e11502 Background: Blocking estrogen receptor or production is standard of care for hormone receptor positive advanced breast cancer patients. A paradoxical approach of using estrogens in such patients has been used for the last 5-6 decades. The mechanism of action of diethylstilbestrol (DES) focuses on induction of apoptosis. Methods: Fifteen cases of hormone receptor positive advanced breast cancer were treated with DES after failure of standard hormonal chemotherapy. Median age was 55 years. Median time before starting DES for metastatic disease was 2.5 years. Median lines of chemotherapy received before starting DES was two. All patients had received aromatase inhibitors, tamoxifen. Ten patients had also received fulvestrant. Nine patients had liver, nine had bone, six had lymph node, four had lung, and two had skin metastasis. Results: 5 mg BID dose of DES was started. After a period of median 6 month therapy, there were four partial responses, six patients had stable disease, and five had progressive disease. Reduction in serum markers CA15.3 and CEA was seen in eight patients. The therapy was well tolerated. There was mild elevation of liver enzymes – SGOT and SGPT in four cases. There were no other untoward toxicity. Conclusions: In post menopausal hormone receptor positive cases of advanced breast cancer, after failure of standard hormone therapy, DES offers safe, cheap, and effective palliative treatment. No significant financial relationships to disclose.

A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma.

TNM staging and classification (familial and nonfamilial) of breast cancer in Jordanian females

Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS) cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

Retrospective analysis of 119 Chinese noninflammatory locally advanced breast cancer cases treated with intravenous combination of vinorelbine and epirubicin as a neoadjuvant chemotherapy: a median follow-up of 63.4 months

BackgroundThis study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC).MethodsOne-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67).ResultsPatients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively).ConclusionThis study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.

A case of HER2-positive male breast cancer with lung metastases showing a good response to trastuzumab and paclitaxel treatment

We present a case of advanced HER2-positive male breast cancer, which showed a good response to a combined treatment of trastuzumab and paclitaxel. A 78-year-old man was diagnosed with invasive ductal carcinoma (T4d N3 M1, stage IV). He had advanced breast cancer consisting of multiple tumors with skin involvement and redness over the entire left chest region. A computed tomography (CT) scan of the chest revealed a metastatic tumor in the left lung. Histologically, both the primary breast cancer and the metastatic lung tumor were identified as invasive ductal carcinoma that was estrogen receptor-negative (ER)(-) and progesterone receptor-negative (PgR)(-), with a HER2 score of 3+ (IHC). The patient received a combination chemotherapy using trastuzumab and paclitaxel. Two months later, a follow-up chest CT scan showed that the left lung tumor had disappeared, suggesting a good response to trastuzumab and paclitaxel. During trastuzumab treatment, no severe adverse events above grade 3 were observed. This is the first reported case of advanced HER2-positive male breast cancer in which a good response to trastuzumab and paclitaxel was demonstrated at both primary breast cancer and metastatic sites.

Mitochondrial DNA G10398A variant is not associated with breast cancer in African-American women

Mitochondria play important roles in cellular energy production, free radical generation, and apoptosis. In a previous report, the mitochondrial DNA (mtDNA) G10398A (Thr→Ala) polymorphism was associated with breast cancer risk in African-American women [Cancer Res 2005;65:8028–33]. We sought to replicate the association by genotyping the G10398A polymorphism in multiple established population-based case-control studies of breast cancer in African-American women. The 10398A allele was not significantly associated with risk in any of the studies: San Francisco (542 cases, 282 controls, odds ratio OR = 1.73, 95% confidence interval CI = 0.87–3.47, P = 0.12); Multiethnic Cohort (391 cases, 460 controls, OR = 1.08, 95% CI = 0.62–1.86, P = 0.79); and CARE and LIFE (524 cases, 236 controls, OR = 0.81, 95% CI = 0.43–1.52, P = 0.50). With data pooled across the studies (1,456 cases and 978 controls), no significant association was observed with the 10398A allele (OR = 1.14, 95% CI = 0.80–1.62, P = 0.47, test for heterogeneity = 0.30). In analysis of advanced breast cancer cases ( n = 674), there was also no significant association (OR = 1.18, 95% CI = 0.76–1.82, P = 0.46). Our results do not support the hypothesis that the mtDNA G10398A polymorphism is, as has previously been reported, a marker of breast cancer risk in African Americans.

Molecular Subtypes in Breast Cancer Evaluation and Management: Divide and Conquer

In the 19th century, the Scottish surgeon, Dr. Thomas Beatson, recognized that some, but not all, cases of advanced breast cancer would regress in response to “hormonal therapy,” which he administe...