Breast cancer with cartilaginous and/or osseous metaplasia

We report a rare case of breast cancer with cartilaginous and/or osseous metaplasia. A 59-year-old woman had a large lump in her left breast, which had enlarged gradually over a period of 2 years. Mammography, ultrasonography and aspiration cytology suggested phyllodes tumor with carcinoma. She underwent wide excision and sentinel lymph node biopsy. Because of the existence metastatic tumor cells in the sentinel lymph node on frozen section, sequential axillary lymph node dissection was conducted consequently. Histologically, the tumor consisted of invasive ductal carcinoma and spindle-cell carcinoma, including cartilaginous metaplasia. Adjuvant chemotherapy and whole-breast irradiation were performed. However, she died of multiple metastases to the liver 2 years after surgery. Breast cancer with cartilaginous and/or osseous metaplasia belongs to a special type of invasive carcinoma, and the incidence is very low. We here present our case and a review of the literature.     

A Case of breast cancer with predominant cartilaginous and osseous components

Primary breast cancers with cartilaginous and osseous components are quite rare. We recently treated a 51-year-old woman suffering from primary breast cancer with predominant cartilaginous and osseous components, adjacent to a component of intraductal carcinoma. We discuss the management of this tumor with a review of the literature.     

A case of breast carcinoma with cartilaginous and osseous metaplasia

We report a case of a 49-year-old Japanese woman diagnosed with breast carcinoma with osseous and cartilaginous metaplasia with a poor outcome. Histological examination revealed invasive ductal carcinoma with undifferentiated sarcomatous components including chondrosarcomatous areas. Osseous metaplasia was also noted in a very limited area. Neither axillary lymph node metastases nor vessel invasion were observed. Immunohistochemical examination was negative for estrogen receptor, progesterone receptor and HER2 overexpression. Stage II A T2N0M0 carcinoma was diagnosed postoperatively. Five months after the operation, she developed lung metastases. Although she received systemic chemotherapy, the lesions increased in number and grew rapidly. She died of pulmonary distress 5 months after relapse.     

Two case of breast cancer with cartilaginous and osseous metaplasia

Invasive breast cancer (IBC) with cartilaginous or osseous metaplasia is rare. Here we report two cases of this unusual variation. Case 1: The patient was a 33-year-old woman with a right breast tumor, 2.2 cm in size. Mammograms (MMG) presented no specific findings, but ultrasound (US) showed a cystic-like lesion. Excisional biopsy confirmed IBC with cartilaginous and osseous metaplasia. Biopsy was followed with a modified radical mastectomy. One lymph node was positive, and both estrogen receptor (ER) and progesterone receptor (PgR) were negative. Case 2: The patient was a 43-year-old woman with a left breast tumor, 4.2 cm in size. MMGs presented no findings but US showed an irregular shaped, low-echoic area, suggesting malignancy. Core needle biopsy confirmed IBC with cartilaginous metaplasia. A total adenectomy and lymph node dissection with breast reconstruction using a lattisimus dorsi muscle flap were performed. Two of 18 lymph nodes were positive for metastasis and both ER and PgR were negative. IBC with cartilaginous or osseus metaplasia seem to be divided into two types pathologically, with or without intervening spindle cells, which is related to the prognosis. Matrix producing carcinoma (MPC) has no intervening spindle cells and a better prognosis than other types, however, MPC has been reported to have the same prognosis as ordinary breast cancer after for adjusting its stage. Our two cases were MPC's and no recurrence has been detected 5 and 3 years from the initial therapy, respectively.     

Systemic chemotherapy in locally advanced and/or metastatic bladder cancer

Transitional cell carcinoma of the bladder is a common malignancy. Advanced urothelial cancer is a chemosenstive neoplasm. Whereas the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was long-considered the standard of care for patients with advanced disease, the evaluation of newer agents with retained activity and improved tolerability has been the focus of much investigation over the past decade. Combinations such as cisplatin-gemcitabine (GC) and intensified, G-CSF supported MVAC have shown more favourable toxicity profile and equal or even improved efficacy. Specific groups of patients (elderly, patients with renal dysfunction or poor performance status or co-morbidities) who cannot tolerate cisplatin-based therapy, should receive carboplatin, gemcitabine or taxane-based treatment. Continuing improvements in our understanding of the molecular phenotype of individual patient tumors may lead to the appropriate therapies that target molecular aberrations unique to this malignancy. This review will summarize recent developments in the management of locally advanced (T4b, N 2-3) and/or metastatic (M1) bladder cancer.     

Cytogenetic profile of locally advanced and metastatic Schistosoma-related bladder cancer and response to chemotherapy

Bladder cancer is a common malignancy in developing countries in which bladder infection with the parasite Schistosoma haematobium is prevalent. Several epidemiological, histopathological, and clinical characteristics of schistosoma-associated bladder cancer suggest that it is distinct from bladder cancer seen in other places in the world. The aim of this study was to extend establishing the cytogenetic profile of this type of malignancy in advanced and metastatic cases, and to demonstrate its relation to the end results of systemic therapy. Fluorescence in situ hybridization was applied to interphase nuclei to detect numerical chromosome changes in 41 patients with bladder cancer. Numerical chromosome aberrations were detected in 27 of 41 cases (66%). In 17 (41%) cases, a gain of chromosome 7 was observed, while losses in chromosomes 9 and 17 were detected in 20 (49%) and 18 (44%) cases, respectively. Loss of chromosome Y was detected in 7 of the 32 male patients included in this study (22%). There was a statistically significant association between stage of the disease and overall survival; Bajorin score and time to disease progression and overall survival; and between response to systemic therapy and time to disease progression and overall survival. The only chromosomal abnormality that had a significant relationship with overall survival was the gain of chromosome 4. When the genetic basis of schistosoma-associated bladder cancer is fully understood, new diagnostic and therapeutic strategies could be developed, which in turn may promote better clinical management and survival.     

Predictive factors of response to first-line chemotherapy in 1426 women with metastatic breast cancer

Since response to chemotherapy is a major determinant of survival in metastatic breast cancer, the purpose of our study was to analyse the predictive factors of response. 1426 patients enrolled into eight consecutive randomised trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, between 1977 and 1992, were analysed. A forward stepwise logistic regression analysis was used. The objective response rate (ORR) to chemotherapy in the total population was 63.6% (95% confidence interval (CI): 61.5–67.7). The complete response rate was 17.5%. Multivariate analysis defined adjuvant chemotherapy, lactate dehydrogenase (LDH), Karnofsky index (KI), and pleural and lung metastases to be the five main variables correlated with ORR. A predictive score was calculated using the coefficient of these five variables. The score was established as follows: −1.32+0.54 (if prior adjuvant chemotherapy)+0.80 (low KI)+0.75 (raised LDH)+0.49 (lung metastases)+0.51 (pleural metastases). A low score (less than −0.78) was associated with an ORR greater than 70.0%, representing 41.2% of our population. An intermediate score (between −0.78 and 0) was associated with an ORR of 50 to 70%, representing 37.5% of our population and a positive score was associated with an ORR of less than 50%, representing 21.3% of our population. This score can be used to predict objective response rates to first-line anthracycline-based chemotherapy. This method now needs to be evaluated prospectively in phase II trials. Identification of various risk groups may also be useful for interpretation and design of clinical trials.     

Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy

ObjectiveTo evaluate the pathologic response after neoadjuvant chemotherapy in patients with breast cancer according to the stromal tumor-infiltrating lymphocytes (TILs) as well as the evaluation of overall and disease-free survival according to TILs.MethodsA six years (2008–2013) review was done including patients with locally advanced breast cancer that received neoadjuvant therapy and then surgery. An evaluation of the percentage of TILs was done in the pretreatment biopsies and a correlation analysis and survival curves were done.Results187 patients were evaluated. The pathological complete response (pCR) in patients with TILs ≥30% was 58.5%, and in patients with TILs < 30% was 11% (p < 0.001). An Odds Ratio of 8.85 was obtained in patients with TILs ≥30% to achieve a pCR. This relationship was seen in patients with HER2-enriched and triple-negative subtypes. No correlation between TILs and survival was obtained (OS: log-rank; p = 0.834; DFS: log-rank; p = 0.937).ConclusionsThe study of TILs is important because they represent an additional tool to predict the response to neoadjuvant treatment mostly in HER2-enriched and triple-negative subtypes of breast cancer.     

Histological features of breast cancer, highly sensitive to chemotherapy

Background  To establish tailor-made therapy for breast cancer, we investigated the possibility of predicting chemotherapy sensitive cases based on pre-therapeutic histological features. as]Methods: A total of 87 breast cancer patients underwent neoadjuvant chemotherapy with a paclitaxel (80 mg/m²/qlw, 12 courses) or an epirubicin regimen (90 mg/m²/q3wks, 4 courses). We investigated the chemo-sensitivity of invasive ductal carcinoma, solid-tubular carcinoma consisting of highly malignant cancer cells with many mitoses. We refer to this type of carcinoma as“chemo-sensitive carcinoma”and compared the histological therapeutic effects of chemo-sensitive and chemo-insensitive carcinomas. Results  1) Out of 87 patients, 20 cases (23%) showed the histological features of chemo-sensitive carcinomas on pre-therapeutic needle biopsy specimens. The remaining 67 cases (77%) were classified as chemo-insensitive carcinoma. 2) Histologically marked or complete response were observed in 50% (10/20) of chemo-sensitive carcinomas and 10% (7/67) of chemo-insensitive carcinomas (x² = 15.33, P=0.0001). Multivariate analysis of chemo-sensitive carcinoma, including HER2, hormone receptor and p⁵³ status, revealed that chemo-sensitive carcinoma had a significant correlation with the histological therapeutic effects (P=0.01119). 3) Pathological complete response (pCR) was achieved in 35% (7/20) of chemo-sensitive carcinomas and 1.5% (1/67) of chemo-insensitive carcinomas (x²=20.71,P<0.0001). Multivariate analysis revealed that chemo-sensitive carcinoma had a significant correlation with pCR (p=0.0091) Conclusion  The histological features of chemo-sensitive carcinoma were significant predictive factors for chemotherapeutic efficacy.     

Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer

Background

Racial disparities in breast cancer outcomes are attributed to differences in baseline tumour characteristics and biology, stage, age, ethnic background and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesised that racial/ethnic differences result in differential tolerance to chemotherapy potentially, leading to compromised dose intensity/density of chemotherapy in patients with early-stage breast cancer.

Methods

Data were collected from patients treated at five international centers for early breast cancer with the same adjuvant/neoadjuvant chemotherapy (FEC 100: fluorouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m²,every 21 d for 3-6 cycles). Toxicities were assessed by first episode of ?grade 2 toxicity.

Results

Toxicities were compared according to four race/ethnicity groups (103 Caucasian, 30 African American, 164 Asian, and 34 Hispanic patients). Tumour characteristics across four race/ethnicity groups were similar. Asians had a significantly higher rate of grade 3 haematologic toxicity than Caucasians, African Americans or Hispanic women (32%, 16%, 10%, and 15%, respectively; p < 0.05). In multivariate analysis, only lower BMI was associated with a higher incidence of ?grade 3 toxicities. However, no significant differences in chemotherapy dose intensity/density were shown across the four race/ethnicity groups.

Conclusion

Racial differences in acute toxicity were noted in women with breast cancer who were treated with FEC 100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy across ethnicities is not possible and emphasising the need to validate safety of chemotherapeutic regimens in patients of different ethnicities by enhancing the participation of minorities in clinical trials.     

化疗有效后内分泌维持治疗晚期乳腺癌八例临床分析

 【摘要】　目的　观察复发转移性乳腺癌化疗缓解后序贯内分泌治疗的疗效。方法　8例复发转移性乳腺癌患者先根据既往用药给予化疗,疾病缓解后采用单药内分泌维持治疗。结果　8例患者接受 2～8个（中位4个）周期化疗,最佳疗效均达部分缓解,治疗持续时间为1～6个月（中位2个月）,化疗中位治疗失败时间为4个月。随访至2010年12月31日,8例患者的疾病进展时间为 6～86个月（中位为13.5个月）。中位生存期21.5个月（6～86个月）。7例患者分别因严重的骨髓毒性、乏力或消化道反应而终止化疗,1例因紫杉醇变态反应停止化疗。结论　复发转移性乳腺癌经化疗疾病缓解后,采用内分泌维持治疗可改善患者生活质量,延长有效治疗时间。     

HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer

Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each Hercep Test immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p=0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p=0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p=0.26]) or overall survival (81% vs 84% [p=0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer’s approved guidelines failed to demonstrate a predictive or a prognostic role.     

HEP方案与NP方案治疗难治性晚期乳腺癌的临床观察

目的:观察比较含羟基喜树碱(HCPT)的HEP方案与含长春瑞滨(NVB)的NP方案治疗多次化疗失败的晚期乳腺癌患者的有效性和安全性。方法:经病理学检查证实,治疗复发或转移后经至少一种化疗方案治疗失败的同期晚期乳腺癌患者53例,分为HEP组和NP组。HEP组23例采用HCPT6mg/m2静脉滴注,d1~d5,足叶乙甙(VP-16)100mg静脉滴注,d1~d5,顺铂(PDD)20mg静脉滴注,d1~d5。NP组30例采用长春瑞滨(NVB)25mg/m2,静脉滴注d1、d5,顺铂(PDD)20mg静脉滴注,d1~d5。均为4周重复,治疗2~4个周期。2个周期治疗结束后按照WHO标准评价疗效和毒性。结果:HEP组近期有效率为17.4%(4/23),其中CR0例,PR4例(17.4%),NC14例(60.9%),PD5例(21.4%),RR为17.4%,DCR为78.3%,中位TTP为7.0个月。NP组近期有效率16.7%(5/30),其中CR0例,PR5例(16.7%),NC17例(56.7%),PD8例(26.7%),RR为17.4%(5/30),DCR为73.3%(22/30),中位TTP为6.5个月。两组的有效率及TTP比较未见有统计学差异(P>0.05)。主要毒副反应为恶心、呕吐、脱发及骨髓抑制等,发生率相似。所有毒副反应均能耐受。结论:HEP方案治疗多次化疗失败的晚期乳腺癌患者疗效可靠,毒副反应可耐受,经济花费少,可以考虑作为晚期乳腺癌经多次化疗失败后的另一优选方案。     

多烯紫杉醇/吉西他滨联合顺铂序贯治疗转移复发性乳腺癌临床观察

目的观察多烯紫杉醇(DXL)联合顺铂(DDP)和吉西他滨(GEM)联合顺铂(DDP)序贯治疗转移复发性乳腺癌的临床疗效及毒副作用。方法53例经病理确诊为转移复发性乳腺癌,随机分为TP(多烯紫杉醇 顺铂)/GP(吉西他滨 顺铂)序贯组和TP组(多烯紫杉醇 顺铂)。TP:25例,多烯紫杉醇35 mg/m~2,静滴d1,d 8;顺铂25 mg/m~2静滴,d1～3,28 d为一个周期,共治疗4～6周期。TP/GP序贯组28例,先用TP方案化疗3～4周期,方案同上,后改用GP方案:GEM 1 000 mg/ m~2,静滴d 1,8;DDP 25 mg/m~2,静滴,d 1～3;28 d为一个周期,治疗3～4周期。或先用GP方案3～4周期,后改用TP方案3～4周期。至少应用4个周期。结果TP/GP组与TP组有效率(RR)分别为67.9%和56.0%(x~2=0.790,P=0.374);疾病控制率(DCR)分别为92.9%和88.0%(x~2=0.365,P =0.658)。其中TP/GP组一线治疗6例,CR 2例,PR 4例,有效率为100.0%;二线治疗22例,CR 2例,PR 11例,有效率59.1%。TP组一线治疗5例,CR 2例,PR 3例,有效率为100.0%,二线治疗20例,CR 0例,PR 9例,有效率45.0%。TP/GP、TP组中位无进展生存时间分别为9.5和8.0个月;中位生存时间分别为19.0和19.0个月(P=0.3894)。1年生存率分别为82.2%和60.0%,2年生存率分别为28.6%和30.0%,两组差异无显著性(P>0.05)。主要不良反应为骨髓抑制。结论多烯紫杉醇/吉西他滨联合顺铂序贯治疗转移复发性乳腺癌临床疗效好,不良反应轻,值得进一步扩大样本研究。     

Adjuvant chemotherapy in breast cancer: To use or not to use,the anthracyclines

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclines in the adjuvant setting for patients with breast cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.     

Association between c-myc amplification and pathological complete response to neoadjuvant chemotherapy in breast cancer

Background

The aim of this study was to investigate whether c-myc amplification in human breast cancer is associated with response to neoadjuvant chemotherapy comprising paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC).

Methods

Tumour tissue samples were obtained before neoadjuvant chemotherapy (P-FEC) from 100 primary breast cancer patients (stage II/III). C-myc and HER2 amplification were examined by FISH, and oestrogen receptor (ER), progesterone receptor (PR), Ki67, and topoisomerase 2α (TOP2A) expression were examined immunohistochemically. Pathological complete response (pCR) was defined by a complete loss of tumour cells in the breast without any lymph node metastasis.

Results

C-myc amplification was observed in 40% (40/100) of breast tumours, and was significantly associated with ER-negative tumours (23/40 for ER(-) versus 17/60 for ER(+), P = 0.004), high histological grade tumours (11/18 for grade 3 versus 29/82 for grades 1 + 2, P = 0.043) and TOP2A-positive tumours (28/51 for TOP2A(+) versus 12/49 for TOP2A(-), P = 0.002). pCR rate was 20% for total patients (10.0% for ER(+) and 35.0% for ER(-)). Further, breast tumours with c-myc amplification (c-myc(+)) showed a significantly (P = 0.041) higher pCR rate (12/40) than those without such amplification (c-myc(-)) (8/60). This association between pCR and c-myc amplification was observed in ER-positive tumours (4/17 for c-myc(+) versus 2/43 for c-myc(-), P = 0.048) but not in ER-negative tumours (8/23 for c-myc(+) versus 6/17 for c-myc(-), P = 0.973).

Conclusion

Our results suggest that c-myc amplification is significantly associated with a high pCR rate to P-FEC in breast tumours, especially in ER-positive tumours.     

An evaluation of predictive factors involved in clinical or pathological response to primary chemotherapy in advanced breast cancer

BACKGROUND: The usefulness of primary chemotherapy has been widely recognized and applied to routine clinical practice to improve prognosis by downstaging. Nevertheless, none of many trials has been able to show a positive effect of primary chemotherapy in terms of prognosis, and predictive factors of outcome have not been defined and are still under investigation. METHODS: Primary chemotherapy was given to 50 patients with advanced breast cancer. Predictive factors involved in clinical or pathological response to primary chemotherapy (3 cycles of CE(F) therapy ) were investigated. RESULTS: The response rate in all patients was 56.0% (CR: 3 patients PR: 25 patients) and 64.1% in patients without distant metastases. MIB-1 was related to the clinical response and EIC (extensive intraductal component) was related to the pathological response; the response was high in patients with EIC negative tumors. Responders had tumors with higher proliferative activity, which decreased significantly after chemotherapy. Patients with a decrease of more than 30% in proliferative activity after chemotherapy had significantly higher disease-free survival rates. CONCLUSION: The proliferative activity and EIC status were useful predictors of clinical or pathological response to primary chemotherapy. A decrease in proliferative activity by chemotherapy significantly correlated with clinical response and reflected a favorable prognosis. The number of patients benefiting from primary chemotherapy might steadily increase by detecting these predictive factors.     

榄香烯在老年复发、转移性乳腺癌铂类联合化疗中的应用

目的对比含铂方案足量化疗与减量化疗联合榄香烯在老年复发、转移性乳腺癌患者中的疗效及不良反应。 方法回顾性分析2009年12月至2015年6月在大连医科大学附属第一、第二医院诊治具有完整随访资料的72例老年复发、转移性乳腺浸润性导管癌患者的临床资料。按治疗方法分为常规组(37例)：顺铂75 mg/m²,分2～3 d静脉滴注,联合吉西他滨1 000 mg/m²或长春瑞滨25 mg/m²,第1、8天静脉滴注,每3周重复;联合组(35例)：顺铂60～75 mg/m²,分2～3 d静脉滴注,联合吉西他滨800 mg/m²或长春瑞滨20 mg/m²,第1、8天静脉滴注,每3周重复,同时注射榄香烯400 mg/d, 2周为1个疗程。分析2组患者的近期及远期疗效、不良反应及生活质量差异。组间例数比较用χ²检验,等级资料比较采用秩和检验,生存分析采用Kaplan-Meier和Log-rank法。 结果常规组患者完全缓解(CR)率为10.81%(4/37)、部分缓解(PR)率为37.84%(14/37)、病情稳定(SD)率为24.32%(9/37)、病情进展(PD)率为27.03%(10/37),联合组CR率为11.43%(4/35)、PR率为34.28% (12/35)、SD率为22.86%(8/35)、PD率为31.43%(11/35), 2组差异无统计学意义(Z＝－0.289,P＝0.773)。联合组白细胞减少的发生率低于常规组[45.71%(16/35)比70.27%(26/37), Z＝－2.025,P＝0.043]。消化道不良反应主要是恶心、呕吐,常规组和联合组发生率分别为97.30%(36/37)和80.00%(28/35),差异有统计学意义(Z＝－2.080,P＝0.038)。其他不良反应的发生率,常规组与联合组比较,差异均无统计学意义(血小板减少：35.14%比20.00%,Z＝－1.425,P＝0.154;贫血：35.14%比37.14%,Z＝－0.066,P＝0.947;肝功能损害：29.73%比25.71%,Z＝－0.265,P＝0.791)。2组患者生活质量差异无统计学意义(Z＝－1.760,P＝0.078)。常规组、联合组中位无进展生存时间分别为8.9、6.5个月,差异无统计学意义(χ²＝0.226,P＝0.634)。 结论老年复发、转移性乳腺癌患者减量化疗联合榄香烯治疗,与常规足量化疗疗效相近,安全性更佳。     

A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with breast cancer

Background  We aimed to identify, through a review of the literature, candidate genes for a prospective predictive chemosensitivity test in patients with breast cancer. Methods  Papers demonstrating an association between gene alterations in tumor tissue and clinical chemosensitivity in breast cancer patients were selected by Medline searches. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) of response rates for patients who had tumors with or without gene alteration. Combined ORs and CIs were estimated using the DerSimonian-Laird method. Results  A total of 18 genes were evaluated for association with clinical chemosensitivity in 6378 patients registered in 69 studies. The median (range) number of patients in each study was 73 (29–319). Overexpression of ABCB1 (P-glycoprotein) was associated with poor responses to first-line chemotherapy (combined OR [CI], 0.16 [0.05–0.59]; n = 322). Overexpression and amplification of TOP2A (topoisomerase II-alfa) were more frequently observed in patients who responded to first-line chemotherapy (combined OR [CI], 2.73 [1.02–7.27]; n = 323). Overexpression of ERBB2 (c-erbB2) was associated with favorable responses in patients treated with both first-line anthracycline-based chemotherapy and second-line taxane-based chemotherapy (combined ORs [CIs], 1.60 [1.19–2.17]; n = 1807 and 2.24 [1.06–4.74]; n = 259, respectively). BCL2 overexpression was associated with resistance to first-line chemotherapy (combined OR [CI], 0.44 [0.21–0.91]; n = 816). Conclusion   ABCB1, TOP2A, ERBB2, and BCL2 were good candidates for future clinical trials of predictive chemosensitivity tests in patients with breast cancer.     

Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study

Purpose: To compare the efficacy and toxicity of epirubicin to that of the combination of epirubicin and cisplatin in patients with advanced breast cancer. Patients and methods: A total of 155 patients were randomized to receive either epirubicin (70 mg/m²) days 1 and 8 every 4 weeks or epirubicin (60 mg/m²) days 1 and 8 plus cisplatin (100 mg/m²) day 1 every 4 weeks. Epirubicin was continued until disease progression or to a cumulative dose of 1000 mg/m². Cisplatin was discontinued after six cycles. In 45 premenopausal women an oophorectomy was performed. None of the evaluable patients had received chemotherapy for metastatic disease. Results: Among evaluable patients (74 in the epirubicin group and 65 in the epirubicin plus cisplatin group) there were 19% vs 29% complete responses, and 42% vs 37% partial responses, with no significant difference. In the epirubicin plus cisplatin group the response rate was significantly higher in previously untreated patients as compared with patients who had received adjuvant chemotherapy (74% vs 55%, P=0.002). Median times to disease progression were 8.4 months in the epirubicin group and 15.3 months in the epirubicin plus cisplatin group (P=0.045). Median survival times were 15.1 and 21.5 months, respectively (P=0.41). In the epirubicin plus cisplatin group leukopenia and thrombocytopenia were significantly more frequent, 29% of the patients developed mild to moderate peripheral neurotoxicity, 34% reported tinnitus and hearing changes, 6 patients developed nephrotoxicity (one died due to nephrotic syndrome), and 3 patients developed leukaemia (two died of this cause). Congestive heart failure occurred in six patients in the epirubicin group and three patients in the epirubicin plus cisplatin group. Conclusion: Cisplatin plus epirubicin is an active, although highly toxic regimen when used as first-line therapy in advanced breast cancer. The time to disease progression was significantly longer in the cisplatin plus epirubicin group (increased by 82%). Due to toxicity, the combination regimen cannot be recommended. However, the study indicated a very high activity of cisplatin in advanced breast cancer. Studies of first-line therapy in advanced breast cancer including cisplatin or other platin derivatives in combination with, for example, the taxanes are suggested. Received: 8 December 1999 / Accepted: 17 July 2000