Long-term prognostic and predictive factors in 107 stage II/III breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.

The heterogeneity of therapeutic modalities and eligibility criteria and the lack of long-term follow-up in most reports of neoadjuvant chemotherapy for breast cancer preclude us from drawing conclusions about its value in clinically relevant patient subgroups. The present study aims to identify predictive and prognostic factors in 107 non-inflammatory stage II/III breast cancer patients treated between November 1980 and October 1991 with an anthracycline-based induction regimen before locoregional surgery. Preoperative chemotherapy comprised 3-6 cycles of doxorubicin (pirarubicin after 1986), vindesine, cyclophosphamide and 5-fluorouracil. Type of subsequent surgery and adjuvant treatment were decided individually. In analysis of outcome, univariate comparisons of end points were made using the log-rank test, and significant (P < or = 0.05) pre- and post-therapeutic factors were incorporated in a Cox multivariate analysis. With a median follow-up of 81 months (range 32-164+ months), the median disease-free survival (DFS) is 90.5 months while median overall survival has not yet been reached. Cytoprognostic grade and histopathological response in both the primary and lymph nodes were independent covariates associated with locoregional relapse with or without DFS and overall survival. Eleven patients with pathological complete response remain free of disease with a 68-month median follow-up, while the 18 with residual microscopic disease on the specimen showed a 60% cumulative incidence of locoregional recurrence. Despite encouraging response rates based on clinical or radiological evaluation (87% or 70%), neither method showed any significant correlation with pathological response and failed to contribute prognostic information on patients'' outcome. Pathological evaluation of antitumoral activity of primary chemotherapy remains a major source of prognostic information and might be used to select patients in need of additional adjuvant treatment.     

Renal tubular dysfunction and urinary zinc excretion in breast cancer patients treated with anthracycline-based combination chemotherapy

The survival of breast cancer patients has significantly improved through the treatment with anthracyclines. Although anthracyclines are known to produce renal disease in experimental animals, little is known about the toxicity of anthracyclines at clinically relevant doses in humans. In a previous study on cancer patients we have observed an increase in the urinary activity of N-acetyl-beta-D-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction that was accompanied by increased urinary zinc loss. Because an increase in NAG activity was reported after the treatment with anthracyclines, we hypothesized that an increase in urinary NAG activity in breast cancer patients treated with anthracycline-based regimens will be accompanied by hyperzincuria and hypozincemia. Urinary and serum zinc, urinary NAG and serum creatinine were examined during chemotherapy in 26 breast cancer patients treated with anthracycline-based chemotherapy. A trend for increased NAG activity, as compared to baseline, was observed throughout the first 4 cycles of treatment. NAG activity was significantly elevated compared to pretreatment levels one week after the first, third and fourth dose of chemotherapy. Serum creatinine concentrations decreased significantly after the second cycle of therapy. On the other hand, urinary and serum zinc levels did not change significantly during the treatment. In conclusion, our data confirm the presence of mild renal tubular cell dysfunction in breast cancer patients treated with doxorubicin-based chemotherapy. Increased urinary NAG is accompanied by a decrease in serum creatinine which is consistent with hyperfiltration. These changes are not associated with abnormalities of renal zinc handling or a decrease in serum zinc concentrations.     

Neutrophil count is not associated with infection episodes in breast cancer patients treated with anthracycline-based chemotherapy

The aim was to evaluate the impact of anthracycline-based chemotherapy on neutrophil count and infections in breast cancer women. The medical records of patients were retrospectively and prospectively reviewed (8-year period). Patients were grouped according to anthracyclines at different doses: (1) Scheme 1 ( n  = 56, 224 courses): 50–60 mg/m²; and (2) Scheme 2 ( n  = 25, 100 courses): 65–75 mg/m², associated to cyclophosphamide and 5-fluorouracil, at 21-day intervals between courses. Neutrophil count was performed on diagnosis and 48–72 h before each chemotherapy course. Patients were followed up for neutrophil count and infection episodes for three consecutive courses. Multivariate analysis was used to determine independent factors for infection. After the first course, neutrophil count was reduced than baseline ( P  < 0.001) and maintained during the subsequent courses, without differences between courses or groups. There were 49 infection episodes (63.2% urinary, 18.4% neutropenic fever and 18.4% diverses), mainly between course 1–2 (39%) and course 3–4 (38%) of chemotherapy. Patients evaluated as presenting or not with infection episodes did not differ in neutrophil count. The number of chemotherapy courses ( P  < 0.05), but not age, neutrophil count or chemotherapy regimen, was associated with infection. We concluded that progressive chemotherapy, but not neutrophil count, was an independent factor for infection.     

Predictive factors for anthracycline-based chemotherapy for human breast cancer

Predictive factors for anthracycline-based chemotherapy have yet to be incorporated into daily practice. Meta-analyses of studies using anthracycline-based treatment regimens have shown an improved prognosis for human epidermal growth factor receptor type 2 (HER2)-positive tumors, but not for HER2-negative tumors compared with results of non-anthracycline regimens. Currently it is believed that the positive association between HER2 status and anthracycline sensitivity is indirect, that is, their association may be mediated through topoisomerase II alpha (TOP2A), a target molecule of anthracyclines, since TOP2A is near HER-2 and co-amplification of the TOP2A gene frequently occurs in HER2-amplified tumors. This strongly suggests that TOP2A gene amplification is a predictive factor for anthracyline-based regimens. The Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society has demonstrated that TOP2A-positive and BRCA1-negative subsets evaluated by immunohistochemical staining show a significantly higher pathological complete response when treated with preoperative epirubicin-containing regimens. Combining these findings with the observation that triple-negative tumors and basal-like tumors respond to anthracycline treatment suggests that not only HER2-positive tumors but also a distinct subset of HER2-negative tumors may be sensitive to anthracycline-based regimens.     

乳腺癌新辅助化疗患者上肢淋巴水肿的危险因素分析

背景与目的：局部晚期乳腺癌新辅助化疗后联合其他局部治疗,如手术、放疗后患者的上肢淋巴水肿的相关危险因素尚未完全明确。该研究旨在回顾性分析新辅助化疗后患者上肢淋巴水肿的发生率及相关危险因素。方法：回顾分析2007年1月—2012年12月共103例乳腺癌新辅助化疗后行手术(包含腋淋巴结清扫)的患者。所有患者术后接受了全乳或胸壁以及锁上野放疗。淋巴水肿的诊断采用上肢周径测量法。结果：中位随访时间4.5年,41例患者发生上肢淋巴水肿。4.5年淋巴水肿的累积发生率为39.8%。分析结果显示：腋窝淋巴结切取个数大于15(HR=2.455;P=0.006)与完成足疗程新辅助化疗(HR=2.199;P=0.014)为发生淋巴水肿的独立危险因素。结论：该研究患者中有超过1/3的患者在治疗完成后的4~5年内发生患侧上肢的淋巴水肿。腋窝淋巴结切取个数大于15以及完成足疗程新辅助化疗的患者发生淋巴水肿的风险较高,因而对这部分患者需要更加密切的随访以便使淋巴水肿能够被早期发现和治疗。     

蒽环类药物对乳腺癌患者月经状态的影响

目的研究乳腺癌患者年龄及不同蒽环类化疗药物对化疗诱导停经的影响,为临床合理用药提供依据。方法前瞻性研究绝经前乳腺癌患者接受化疗后月经变化情况,比较不同年龄段及使用不同化疗药物的患者月经状态变化的差异。结果137例乳腺癌患者,化疗致闭经（CIA）的发生率为73．72％（101／137）,长期闭经（LCIA）发生率为43．80％（60／137）。40岁以下患者CIA和LCIA的发生率均显著低于40岁以上的患者（X^2=25．32、18．42,P〈0．05）,并且40岁以下组发生CIA后月经恢复率为61．90％（13／21）,明显高于40岁以上组的35．00％（28／80）,差异有统计学意义（X^2=4．99,P=0．025）。40岁以上患者中表柔比星（商品名：法玛新）、表柔比星（商品名：艾达生）、吡柔比星诱导LCIA率差异有统计学意义（X^2=6．92,P=0．031）。结论年龄是CIA的重要因素,40岁以下患者月经受化疗影响较小,停经多为可逆性。40岁以上患者使用不同的蒽环类化疗药物对月经状态的影响差异有统计学意义。     

Response and long-term effect of patients with triple-negative breast cancer receiving neo-adjuvant anthracycline-based chemotherapy

OBJECTIVE The breast cancer lack of expression of estrogen receptor （ER）, progesterone receptor （PR）, and human epidermal growth factor receptor 2 （HER-2） is defined as the Triple-negative breast cancer （TNBC）. Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up （median, 5.4 years） of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival （RFS） and overall survival （OS） rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triplenegative phenotype （TNP）, tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission （pCR） rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 （21.5%） of the 326 patients suffered TNBC. Compared with the subjects in non-TNBC group, the patients with TNBC had a significantly higher pCR rate （P = 0.046） and clinical response rate （P = 0.037）, but also decreased 5-year RFS （P = 0.001） and OS （P = 0.004） rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression （P = 0.007, P = 0.028）, but negatively correlated with level of E-cadherin （P = 0.034）. CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor. The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.     

Mitotic index and benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer.

PURPOSE: We have evaluated whether the mitotic index could predict the benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines. PATIENTS AND METHODS: A total of 937 patients from a single institution were included in two randomized trials that compared adjuvant anthracycline-based chemotherapy with no chemotherapy. These patients account for 83% of the overall population included in these trials. The first trial included premenopausal patients with node-negative disease, and the second one included postmenopausal patients, regardless of lymph node status. The treatment benefit was assessed according to the number of mitoses per field (x400). RESULTS: The mitotic index was assessable in 888 patients (94%). All the patients presented as either node-positive or an average-risk breast cancer according to 2003 Saint Gallen consensus conference guidelines. The 5-year overall survival rates were 91% and 87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients with low/medium mitotic index (< three mitoses/field; n = 450), the 5-year overall survival rate was 95% for patients treated or not with adjuvant chemotherapy (P = .56). In patients with high mitotic index (>/= three mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for patients treated or not treated with adjuvant chemotherapy, respectively (P = .02). CONCLUSION: A high mitotic index is associated with the efficacy of adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant chemotherapy in daily practice.     

Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.     

Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy.

BACKGROUND AND PURPOSE: To evaluate radiation-induced defects in myocardial perfusion imaging in early breast cancer patients treated with modern technique radiotherapy. PATIENTS AND METHODS: Twenty-four patients with left-breast tumours and 12 control patients with right-breast tumours, relapse-free since treatment for primary disease, who had undergone radiotherapy at least 5 years previously and with no history of ischaemic heart disease prior to radiotherapy underwent study. In left-breast patients, at least 1 cm of heart was required to have been in the treatment field. Patients underwent cardiac assessment and single photon emission computerized tomography myocardial perfusion imaging. RESULTS: Myocardial perfusion tracer uptake was abnormal in 17 (70.8%) left-breast and two (16.7%) right-breast patients (P = 0.002). Of the 17 abnormal scans in left-breast patients, abnormalities were confined to the cardiac apex in 16 patients, and perfusion defects were reversible (n = 7), fixed (n = 7) or mixed (n = 3). Reversible perfusion defects that were not confined to the cardiac apex were observed in two right-breast patients. Left ventricular ejection fraction was normal in all 33 patients in whom it was measured, and no myocardial perfusion abnormalities were judged to require treatment or follow-up. CONCLUSIONS: In this selected study population modern technique radiotherapy to the left breast was associated with a significantly greater number of myocardial perfusion abnormalities than radiotherapy to the right breast. These abnormalities were both reversible and irreversible, suggesting that radiotherapy can lead to both myocardial damage and to epicardial coronary disease. With a minimum of 5 years follow-up since treatment, no abnormalities were considered to be clinically significant.     

Verbal fluency in breast cancer patients treated with chemotherapy

Background

Cognitive decline caused by chemotherapy used in the treatment of malignant diseases was reported in several studies. ICCTF recommends the diagnosis of cognitive function in patient treated with chemotherapy. One of the suggested method is Verbal Fluency Test (VFT).

Methods

Study was carried out on a group of 30 women with early breast cancer treated with adjuvant chemotherapy and 29 healthy controls. The patients underwent neuropsychological assessment using VFT at three time points: T1: before chemotherapy, T2: mid-chemotherapy and T3: post-chemotherapy. The examination in healthy controls was conducted at the same time intervals.

Results

In phonetic fluency task patients produced more words at T2 compared to T1 (Z = 2.02; p < 0.05) and at T3 compared to T1, both patients (Z = 2.36; p < 0.05) and controls (Z = 2.57; p < 0.01). The patients scored lower than controls (Z = ?2.04; p < 0.05) as well as on average cluster size in the same task (Z = ?2.38; p < 0.05) at T3, while they scored higher on the number of phonetic switches at T2 compared to T1 (Z = 2.62; p < 0.01) and at T3 compared to T1 (Z = 2.50; p < 0.01). In semantic task controls produced more words at T3 than at T1 (Z = 2.62; p < 0.01) and at T3 compared to T2 (Z = 2.89; p < 0.01) and semantic clusters at T3 compared to T2 (Z = 2.43; p < 0.05). In patients, number of clusters was smaller at T3 compared to T2 (Z = ?2.85; p < 0.05), while number of semantic switches was higher at T3 than at T2 (Z = 3.05; p < 0.01). Patients scored also lower than controls on number of semantic switches at T2 (Z = ?2.05; p < 0.05).

Conclusions

Chemotherapy does not decrease verbal fluency, but it has a negative impact on semantic memory.

     

Bisphosphonates and pathologic complete response to taxane- and anthracycline-based neoadjuvant chemotherapy in patients with breast cancer

BACKGROUND:

Several studies have suggested that bisphosphonates have an antitumor effect. In the current study, the authors sought to evaluate whether the use of bisphosphonates increased the rate of pathological complete response (pCR) in patients with breast cancer.

METHODS:

The authors identified 1449 patients with breast cancer who were receiving taxane‐ and anthracycline‐based neoadjuvant chemotherapy between 1995 and 2007 at The University of Texas MD Anderson Cancer Center. Patients who received bisphosphonates for osteopenia or osteoporosis while receiving chemotherapy were also identified. The primary outcome was the percentage of patients achieving a pCR. Groups were compared using the chi‐square test. A multivariable logistic regression model was fit to examine the relation between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan‐Meier method was performed; groups were compared using the log‐rank test.

RESULTS:

Of the 1449 patients included, 39 (2.7%) received bisphosphonates. Those receiving bisphosphonates were older (P < .001) and less likely to be obese (P = .04). The pCR rate was 25.4% in the bisphosphonate group and 16% in the nonbisphosphonate group (P = .11). In the multivariable model, patients treated with bisphosphonates tended to have higher rates of pCR (odds ratio, 2.18; 95% confidence interval, 0.90‐5.24); however, the difference was not found to be statistically significant. With a median follow‐up of 55 months (range, 3 months‐145 months), no differences in disease recurrence or survival were observed.

CONCLUSIONS:

The use of bisphosphonates at the time of neoadjuvant chemotherapy was not found to be associated with a statistically significant increase in the rates of pCR. The observed estimates suggest a positive effect; however, the small percentage of patients receiving bisphosphonates likely affected the power to detect a statistically significant difference. Cancer 2011;. © 2011 American Cancer Society.     

Prognostic factors and long-term survival in 585 patients with metastatic breast cancer treated with epirubicin-based chemotherapy

Background:Analysis of prognostic factors in patients withmetastatic breast cancer treated with epirubicin-based chemotherapy. Patients and methods:Data from 469 patients treated withepirubicin-based chemotherapy for metastatic breast cancer were used.Prognostic factors were identified (Cox multivariate analysis). A prognosticindex was compiled and risk groups were established accordingly. Theapplicability of the index was investigated in a series of 116 patients. Results:The prognostic factors identified were: liver, pleural,soft tissue, lung and bone metastases, performance status >2, advancingage, abnormal elevation of serum lactate dehydrogenase and negative/unknownoestrogen receptor status. Four risk groups were established: good,intermediate I, intermediate II and poor. The median and five-year survivalsin percentage were: good: 34 months (26%); intermediate I: 19 months(6%); intermediate II: 12 months (0%); poor: 7 months(1%). The corresponding values in the applicability group were: 32months (23%); 28 months (22%); 18 months (5%); and 6months (0%). Conclusions:It is more the number and impact on the organsinvolved, that predict the patients survival. The construction of aprognostic index could be helpful in assessing the outlook for patients,especially the quite dramatic difference in long-term survival between thegood and poor risk patients.     

Results of two randomized trials evaluating adjuvant anthracycline-based chemotherapy in 1146 patients with early breast cancer

Two randomized trials evaluated the effect of 6 courses of anthracycline-based chemotherapy in early breast cancer. A total of 1 146 patients were included: 311 high-risk node-negative premenopausal patients and 835 high-risk node-negative or node-positive postmenopausal patients. Patients were randomized after surgery to receive either no chemotherapy (control group) or 6 courses of anthracycline-based chemotherapy (CT group). Postmenopausal patients received adjuvant tamoxifen for at least two years. Radiotherapy was delivered after completion of chemotherapy in the CT group. The 10-year disease-free survival (DFS) rates were 60% in the control group and 65% in the CT group (log-rank test, p = 0.01). The 10-year distant metastasis rates were 28% and 23% (p = 0.02), and the 10-year local recurrence rates were 12% and 10%, respectively (p = 0.24). Chemotherapy was significantly less effective in post-menopausal patients with estrogen receptor-positive tumors. Adjuvant anthracyclin-based chemotherapy yielded a significant benefit for DFS by lowering the risk of distant metastases. After up to 10 years of follow-up, deferring radiotherapy after chemotherapy did not compromise local control.     

Chronic comorbid conditions associated with risk of febrile neutropenia in breast cancer patients treated with chemotherapy

Chemotherapy-induced febrile neutropenia (FN) is associated with increased patient mortality and health care costs. Comorbid conditions such as liver and renal dysfunction have been linked to increased risk of FN. However, the effects of other chronic comorbid conditions on risk of FN have not been well studied. To examine the association between chronic comorbid conditions and FN in breast cancer patients, we identified incident breast cancer patients from 2000 to 2009 treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. Patients who received primary prophylactic granulocyte colony-stimulating factor (G-CSF) were excluded. We assessed history of comorbid conditions prior to cancer diagnosis using ICD-9 codes and disease registries. FN events were identified in the first chemotherapy cycle using a combination of ICD-9 codes and hospital discharge diagnoses. For each comorbid condition, propensity scores that included patient characteristics and other predisposing comorbid conditions were calculated and adjusted for in Cox models to determine associations between that comorbid condition and FN. We also evaluated secondary models that additionally adjusted for cancer stage, baseline absolute neutrophil count (ANC), chemotherapy regimen, and dose reductions. A total of 7,127 breast cancer patients were included; median age was 55 years, and the majority had localized (47 %) or regional (49 %) disease at diagnosis. In the first chemotherapy cycle, 335 (4.7 %) patients developed FN. Congestive heart failure (HR = 3.0; 95 % CI: 1.3–5.9), osteoarthritis (HR = 2.0; 95 % CI: 1.4–2.8), previous cancer (HR = 3.4; 95 % CI: 1.2–7.5), and thyroid disorder (HR = 1.6; 95 % CI: 1.1–2.3) were associated with increased risk of FN. These estimates were similar to those from secondary models that also adjusted for additional cancer and treatment-related covariates. Our findings suggest that several chronic comorbid conditions may be associated with risk of FN. This information, if confirmed by others, may aid clinical decision making with respect to use of prophylactic G-CSF during chemotherapy treatment.     

HER2 and response to anthracycline-based neoadjuvant chemotherapy in breast cancer

BackgroundThe predictive role of human epidermal growth factor receptor 2 (HER2) to adjuvant anthracycline-based chemotherapy remains controversial. Here, we investigated the association between HER2 status and pathological response in breast cancer patients who received neoadjuvant anthracycline-based regimens.Patients and methodsWomen (n = 538) with operable primary breast cancer received neoadjuvant anthracycline-based chemotherapy. Pathological complete response (pCR) was defined as no invasive breast tumor cells in breast after completion of neoadjuvant chemotherapy. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core biopsy breast cancer tissue obtained before initiation of neoadjuvant chemotherapy.ResultsIn this cohort of 538 patients, 23.9% of patients achieved a pCR in their breast. HER2-positive tumors had a lower rate of pCR than did HER2-negative tumors (14.7% versus 25.7%, P = 0.013); negative HER2 status remained as an independent favorable predictor of pCR after adjusted for age, estrogen receptor, progesterone receptor, tumor size, chemotherapy cycles, and tumor grade in a multivariate analysis (odds ratio = 3.14; 95% confidence interval = 1.60–6.16, P = 0.001). Furthermore, patients with a pCR had a higher 3-year disease-free survival (DFS) rate than did patients without a pCR (P = 0.007).ConclusionWomen with HER2-negative breast cancers rather than HER2-positive tumors benefit from anthracycline-based neoadjuvant chemotherapy.     

Prognostic factors in metastatic breast cancer treated with combination chemotherapy.

Six hundred nineteen patients with metastatic breast cancer, treated with a combination of 5-fluorouracil, Adriamycin, and cyclophosphamide, or close variations of this program, with or without immunotherapy were analyzed retrospectively to identify those host, tumor, or treatment characteristics that might be of prognostic importance in predicting response to chemotherapy and survival from onset of the 5-fluorouracil-Adriamycin-cyclophosphamide treatments. Primary tumor characteristics such as size of primary, number of axillary nodes involved, stage at diagnosis, and type of surgery used for primary treatment were not found to be of prognostic significance. Host characteristics such as age, menstrual status, or family history of breast cancer were similarly unrelated to outcome. Non-Caucasian patients had a lower response rate and somewhat shorter survival than did Caucasians. Pretreatment weight loss, poor performance status, and abnormal biochemical and hematological values were of adverse prognostic significance. An estimate of total extent of disease based on criteria for rating extent of involvement at 12 potential sites was a much more important prognostic factor related to response and survival than actual sites of involvement or the traditional "dominant site" classification. There was a trend, however, for patients with bone involvement to have a longer survival than did patients with metastases to other organ sites. Shorter survival times were observed among patients exposed to extensive prior radiotherapy and those who failed to respond to prior hormonal treatment. The prognostic variables identified in this paper should be used for the design and comparison of clinical trials in the future.     

Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer

BACKGROUND: Radiation therapy (RT), a critical component of breast-conserving therapy for breast cancer, has been associated with coronary artery disease (CAD) in numerous older studies, but the risk may be lower with modern techniques. METHODS: Observed rates of cardiac events in 828 patients treated with breast-conserving surgery and RT at the University of Michigan were compared with expected rates. Relations between potential risk factors and actuarial rates of first CAD event were analyzed. RESULTS: Observed risks of cardiac events were lower than expected. The standardized incidence ratio (SIR) of myocardial infarction (MI) was 0.44 (95% confidence interval [CI]: 0.21-0.70). The SIR of MI or CAD requiring intervention was 0.50 (95% CI: 0.27-0.68). With a median follow-up of 6.8 years, 12 (1.4%) patients had at least 1 MI on follow-up and 20 (2.4%) had at least 1 MI or CAD requiring intervention. Median age at first cardiac event was 75.9 years (range, 43.1-91.5). Median interval from RT to occurrence of the first cardiac event was 3.7 years (range, 13 days to 15.4 years). The 10-year cumulative incidence of MI was 1.2% and cumulative incidence of MI or CAD requiring intervention was 2.7%. On multivariate analysis, age, diabetes mellitus, active smoking, and laterality of RT were significant predictors of MI. Age and active smoking were significant predictors of MI or CAD requiring intervention. CONCLUSIONS: Patients in this series had lower risk of ischemic cardiac events than expected. Although small in absolute magnitude, patients radiated to the left side did have a statistically significant increased risk of MI. These findings support further investigation of techniques to minimize the long-term cardiac risks faced by breast cancer patients.