Whole Grain Consumption and Breast Cancer: A Case-Control Study in Women.

OBJECTIVE: Whole grain consumption has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between whole grain consumption and breast cancer in women. METHODS: A case-control study was designed. Two hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched controls were enrolled. A standardized, validated questionnaire assessing various sociodemographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews. Moreover, data on regular consumption of whole grains (i.e., never/rarely, 1-6 times/week, >7 times/week) were recorded. Overall dietary habits were assessed through the level of adherence to the Mediterranean diet using the MedDietScore (theoretical range 0-55). RESULTS: Whole grain consumption of more than 7 times/week was associated with a 0.49-fold (odds ratio = 0.49; 95% confidence interval, 0.29, 0.82) lower likelihood of having breast cancer, after adjustments were made. CONCLUSIONS: This study suggested that whole grain consumption more than 7 times/week was consistently associated with reduced risk of breast cancer.

Dietary patterns and breast cancer: a case-control study in women.

PURPOSE: Since dietary habits have been associated with breast cancer, the tested research hypothesis was the associations between food patterns, as derived through multivariate methods, and breast cancer. METHODS: In a case-control study, Two-hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched, healthy controls were studied. A standardized, validated questionnaire assessing various socio-demographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews. Factor analysis, with principal components method, was applied to extract dietary patterns from 86 foods or food groups consumption reported by the controls. RESULTS: Three components were derived explaining 43% of the total variation in consumption. Component 1 was characterized by the consumption of potatoes, red meat and its products, poultry and white meat, dairy products, use of margarine/butter in cooking or at the table, consumption of sausages, fried food as well as grilled meat or fish; component 2 was characterized by the consumption of whole grains, fruits, and vegetables; and component 3 was characterized by olive oil and fish consumption. After adjusting for various confounders, components 2 and 3 were favorably associated with the absence of having breast cancer [odds ratio (OR) 0.60, 95% CI 0.47-0.75 and OR 0.81, 95% CI 0.66-0.99, respectively], while component 1 was not significantly associated with the disease. CONCLUSIONS: Adherence to healthy dietary patterns (including whole grains, fruits, and vegetables, olive oil, and fish) seems to be favorable in not having breast cancer, among middle-aged women.

Dose-dense paclitaxel versus docetaxel following FEC as adjuvant chemotherapy in axillary node-positive early breast cancer: a multicenter randomized study of the Hellenic Oncology Research Group (HORG).

Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive early breast cancer. However, which is the preferable taxane in a dose-dense regimen remains unknown. We conducted a randomized study to compare the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with node-positive early breast cancer. Following surgery women with HER2-negative breast cancer and at least one infiltrated axillary lymph node were randomized to receive four cycles of FEC (700/75/700 mg/m(2)) followed by four cycles of either paclitaxel (175 mg/m(2)) or docetaxel (75 mg/m(2)). All cycles were administered every 14 days with G-CSF support. The primary endpoint was disease-free survival (DFS) at 3 years. Between 2004 and 2007, 481 women were randomized to paclitaxel (n = 241) and docetaxel (n = 240). After a median follow-up of 6 years, 51 (21%) and 48 (20%) women experienced disease relapse (p = 0.753) and there was no significant difference in DFS between the paclitaxel- and docetaxel-treated groups (3-year DFS 87.4 vs. 88.3%, respectively; median DFS not reached; p = 0.633). Toxicities were manageable, with grade 2-4 neutropenia in 21 versus 31% (p = 0.01), thrombocytopenia 0.8 versus 3.4% (p = 0.06), any grade neurotoxicity 17 versus 7.5% (p = 0.35) and onycholysis 4.9 versus 12.1% (p = 0.03) for patients receiving paclitaxel and docetaxel, respectively. There were no toxic deaths. Dose-dense paclitaxel versus docetaxel after FEC as adjuvant chemotherapy results in a similar 3-year DFS rate in women with axillary node-positive early breast cancer. Due to its more favorable toxicity profile, paclitaxel is the taxane of choice in this setting.

Adherence to the Mediterranean diet is associated with lower likelihood of breast cancer: a case-control study.

Mediterranean diet has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between adherence to the Mediterranean diet and its inherent constituents, with breast-cancer. Two-hundred-and-fifty consecutive, newly diagnosed breast-cancer female patients (56 ± 12 yr) and 250, 1-to-1 age-matched with the patients, controls, were studied. A standardized, validated questionnaire assessing various sociodemographic, clinical, lifestyle, and dietary characteristics, was applied through face-to-face interviews. Adherence to the Mediterranean diet was evaluated using the 11-components MedDietScore (theoretical range 0-55). Multiple logistic regression was applied to test the research hypothesis, whereas discriminant analysis was used to explore the strength of each component in relation to the outcome. One unit increase in the MedDietScore (i.e., greater adherence to the Mediterranean diet) was associated with 9% lower likelihood of having breast cancer (odds ratio = 0.91; 95% confidence interval, 0.86, 0.97). Decomposition of the MedDietScore revealed that the most important components and with beneficial effect were nonrefined cereals, vegetables, fruits, and alcohol, followed by red meat, but with unfavorable effect. A dietary recommendation for healthy eating, close to the Mediterranean dietary pattern, seems promising for breast cancer prevention.

The role of Ki-67 in the proliferation and prognosis of breast cancer molecular classification subtypes.

The Ki-67 antigen was identified in the early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that this protein has an important function in cell division, its exact role is still unclear and there is little published work on its overall function. The aim of the present study was to evaluate the contribution of the level of Ki-67 with respect to tumor recurrence in molecularly classified groups of breast cancer patients. Ki-67 was divided into the percentage levels up to and including 20% and over 20%. Immunohistochemistry and fluorescence in-situ hybridization are described for the results of estrogen receptor, progesterone receptor, c-erb-B2, and Ki-67 biomarkers. Formaldehyde-fixed breast samples were paraffin wax embedded and processed for paraffin sections. The protocol of the present study started in 1995 and finished in 2010. Nine hundred and sixteen patients with breast cancer were examined: 291 were grouped as luminal A, 228 as luminal B, 221 as the Her-2 subtype, and 107 as basal cell (triple negative). Follow-up ranged from 3 to 15 years following diagnosis. It was found that in luminal A patients, only one had a Ki-67 level higher than 20%. In luminal B, the Ki-67 was higher than 20% in 51.16% of the patients and recurrence occurred in 23.68%. In the Her-2 subtype, the Ki-67 level was more than 20% in 48.63%. In basal cell triple-negative patients, Ki-67 was more than 20% in 63.86%. The data presented here indicate that the level of Ki-67 may be considered one of the valuable biomarkers in breast cancer patients with respect to process and recurrence.

FEC versus sequential docetaxel followed by epirubicin/cyclophosphamide as adjuvant chemotherapy in women with axillary node-positive early breast cancer: a randomized study of the Hellenic Oncology Research Group (HORG).

A randomized multicenter phase III study was conducted to compare the sequential docetaxel followed by epirubicin/cyclophosphamide combination with that of FEC regimen as adjuvant chemotherapy in women with axillary node-positive early breast cancer. Seven hundred and fifty-six women with axillary lymph node-positive breast cancer were randomized to receive either 4 cycles of docetaxel (100 mg/m(2)) followed by 4 cycles of epirubicin (75 mg/m(2)) plus cyclophosphamide (700 mg/m(2)) (experimental arm) or 6 cycles of FEC (epirubicin 75 mg/m(2), cyclophosphamide 700 mg/m(2), and 5-fluorouracil 700 mg/m(2); control arm). All regimes were administered every 3 weeks. The primary end point was five-year disease-free survival (DFS). After a median follow-up period of 5 years, 233 (30.8%) relapses had occurred (108 and 125 in the experimental and control arms, respectively; P = 0.181). The five-year DFS was 72.6% (95% CI 63.8-81.3%) and 67.2% (95% CI 58.0-76.4%) for women randomized in the experimental and control arms, respectively (P = 0.041; log rank test). There was no difference in the overall survival between the two arms (83.8 and 81.4% in the experimental and control arms, respectively; P = 0.533). The experimental arm was associated with increased neutropenia requiring administration of granulocyte colony-stimulating factor in 90.5% of the patients as compared with 74.1% in the control arm (P = 0.0001). The sequential docetaxel followed by epirubicin/cyclophosphamide adjuvant chemotherapy regimen resulted in improved five-year DFS in women with axillary node-positive early breast cancer at the expense of increased but manageable myelotoxicity.

Comparison of HER2 detection methods between central and regional laboratories in Greece.

PURPOSE: HER2 gene amplification and overexpression is associated with aggressive breast cancer and poor prognosis. Accurate HER2 testing of patients with breast cancer before treatment is important to ensure that as many patients with HER2-positive breast cancer as possible receive the most appropriate treatment and that women with HER2-negative disease avoid a potentially toxic therapy. This study compares immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) HER2 testing at central and regional laboratories in Greece. PATIENTS AND METHODS: The HER2 status of 458 breast cancer samples was determined by IHC in central and regional laboratories using commercially available anti-HER2 antibodies. FISH analysis, scored as number of signals or a ratio, was subsequently performed by the central laboratory on most samples. Various statistical analyses were used to examine concordance between test center results. RESULTS: Immunohistochemistry HER2 testing was successfully performed on 445 samples in the central laboratory and 381 samples in regional laboratories, with good concordance between central and regional laboratories. After FISH analyses of a large proportion of these samples, good correlation was observed between FISH HER2 status and IHC results from the central laboratory but not from regional laboratories. These data suggest that HER2 status determined by IHC in a central laboratory is generally more accurate than that determined by a regional laboratory. CONCLUSION: This study emphasizes the importance of accurate HER2 testing and the need to continually check the reproducibility and reliability of the test.

Evaluation of serum procalcitonin and interleukin-6 levels as markers of liver metastasis.

OBJECTIVES: Procalcitonin (PCT) and interleukin-6 (IL-6) are established markers of tissue inflammation and injury. The aim of the present study was to investigate the possible correlation of PCT and IL-6 with liver metastasis. DESIGN AND METHODS: The study consisted of fifteen healthy controls (group A), twenty-one patients with solid tumors without metastases (group B), eleven patients with liver metastasis only (group C) and eleven patients with generalized metastatic disease (group D). RESULTS: Serum PCT levels were significantly increased in group D compared to groups A (p<0.001) and B (p=0.004), but no difference was observed in PCT levels between groups C and B or C and D. IL-6 serum levels were markedly elevated in group C compared to group A (p<0.001) or to groups B (p<0.001) and D (p=0.02). A positive correlation was observed between PCT and IL-6 serum levels (r=0.357, p=0.019). CONCLUSIONS: PCT levels are related to disease stage in cancer patients, whereas IL-6 concentration seems to be a more specific marker of liver metastasis.

Pegylated liposomal doxorubicin in combination with vinorelbine as salvage treatment in pretreated patients with advanced breast cancer: a multicentre phase II study.

PURPOSE: To investigate the activity and tolerance of pegylated liposomal doxorubicin in combination with vinorelbine in pretreated patients with metastatic breast cancer. PATIENTS AND TREATMENT: Thirty-six women with metastatic breast cancer were enrolled. The median age was 64 years, 80% of the patients had a performance status of 0-1, 30 (83%) had visceral disease and 83% had received prior taxanes while 50% anthracyclines. Treatment consisted of pegylated liposomal doxorubicin (40 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 15) every 4 weeks. RESULTS: In an intention-to-treat analysis 2 (6%) complete and 12 (33%) partial responses were observed (overall response rate 39%; 95% CI: 23-54.8%); 8 (22%) and 14 (39%) patients experienced stable and progressive disease, respectively. The median TTP was 6.5 months and the median survival time 14.2 months. The 1-year survival rate was 54.1%. Grade 3 and 4 neutropenia occurred in 21 (58%) patients, grade 3-4 anemia in four (11%) and grade 4 thrombocytopenia in one (3%). Two (6%) patients developed febrile neutropenia. Non-hematologic toxicity was mild and easily manageable. There was no clinically important cardiac toxicity or treatment-related deaths. CONCLUSIONS: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated salvage regimen in patients with metastatic breast cancer which merits further evaluation.

Evaluation of HER2 gene status in breast cancer by chromogenic in situ hybridization: comparison with immunohistochemistry.

BACKGROUND: The purpose of this study was to evaluate HER2 gene status in relation to chromosome 17 polysomy with the chromogenic in situ hybridization (CISH) technique and to compare the results with those of immunohistochemistry (IHC). METHODS AND RESULTS: Sixty six cases of breast carcinoma with an immunohistochemical HER2 protein score of 1+, 2+ 3+ (HercepTest) were investigated. HER2 gene status was evaluated on paraffin sections with the CISH technique using a digoxigenin-labeled DNA probe. In HER2 positive cases with low level amplification (LLA), the copy number of chromosome 17 was determined. Thirty four tumors (51.5%) were negative and 32 (48.5%) were positive for HER2 gene amplification. Of these 10 tumors (15%) showed LLA and 22 tumors (33.5%) high level amplification (HLA). Nine of ten tumors with LLA had an equal or greater than two ratio of HER2 to chromosome 17 signals. The correlation of the results obtained by CISH and IHC showed that the concordance of the two methods was highest in the 3+ group (100%) and lower in 1+ group (89%), whereas a high degree of discordance was found in the 2+ group (69%). CONCLUSIONS: CISH is an accurate and practical technique for the evaluation of both HER2 gene and chromosome 17 status and its application is considered necessary especially for the clarification of the 2+ results of IHC.

Meat consumption and breast cancer: a case-control study in women.

BACKGROUND: The relationship between meat intake and breast cancer has been inconsistent . OBJECTIVE: The aim of this work was to evaluate the association between meat intake and breast cancer, in women. DESIGN: A case-control study with 250 consecutive, newly diagnosed breast-cancer-female-patients (56 ± 12 years) and 250, one-to-one age-matched controls was conducted. A standardized, validated questionnaire assessing various socio-demographic, clinical, lifestyle and dietary characteristics was applied through face-to-face interviews. Data on consumption of red, white, processed and grilled meat were also recorded. Overall dietary habits were assessed through the level of adherence to the Mediterranean diet using the MedDietScore (theoretical range 0-55). RESULTS: Processed meat intake, even for 1-2 times/week,was associated with a 2.7-fold (OR= 2.65, 95% CI 1.36, 5.14) (p= 0.004) higher likelihood of having breast cancer, while daily intake increased the likelihood by a 2.8-fold (OR = 2.81, 95% CI 1.13, 6.96) (p = 0.026), after various adjustments made. Red, white and grilled meat intake was not significantly associated with the outcome when the same adjustments were made. CONCLUSIONS: This study suggested that only daily processed-meat intake was consistently associated with increased odds of breast-cancer.

Aims, design and methods of a case-control study for the assessment of the role of dietary habits, eating behaviors and environmental factors, on the development of breast cancer.

In this work the aims, methodology and procedures of a case-control study that was developed for assessing the role of dietary habits, eating behaviors and environmental factors on the development of breast cancer, is presented. During 2010-2012, 250 consecutive women patients, newly diagnosed with breast cancer and 250 population-based, healthy subjects (controls) age-matched to the cases, were enrolled. Socio-demographic, dietary, psychological, lifestyle as well as environmental characteristics (i.e., exposure to pollution, pesticides, electromagnetic fields and radon) were recorded through face-to-face interviews with the participants. Dietary habits and eating behaviors were evaluated with a special questionnaire that had been developed for the study, and was found relatively valid and reliable.

A phase I trial of oral metronomic vinorelbine plus capecitabine in patients with metastatic breast cancer.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of oral metronomic vinorelbine with capecitabine in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Escalated doses of oral metronomic vinorelbine (starting dose 30 mg) every other day continuously and capecitabine (starting dose 800 mg/m(2) bid) on days 1-14 every 21 days were administered. DLTs were evaluated during the first cycle. RESULTS: Thirty-six women were enrolled at eight escalating dose levels. For twenty-four patients, treatment was first line, for eight second line, and for four third line. The DLT level was reached at oral metronomic vinorelbine 70 mg and capecitabine 1,250 mg/m(2), and the recommended MTD doses are vinorelbine 60 mg and capecitabine 1,250 mg/m(2). DLTs were febrile neutropenia grade 3 and 4, diarrhea grade 4, and treatment delays due to unresolved neutropenia. There was no treatment-related death. The main toxicities were grade 2-3 neutropenia in 16.6% of patients each, grade 2-3 anemia 16.5%, grade 2-4 fatigue 27.5%, grade 2-3 nausea/vomiting 11%, and grade 3-4 diarrhea 8.2%. Two complete and 10 partial responses were documented. CONCLUSION: Oral metronomic vinorelbine with capecitabine is a well-tolerated and feasible regimen that merits further evaluation in MBC.

Final results of an international retrospective observational study in patients with advanced breast cancer treated with oral vinorelbine-based chemotherapy.

BACKGROUND: Full oral chemotherapy (CT) is an active and convenient therapeutic option for patients with advanced breast cancer (ABC). In this retrospective analysis, we reviewed the characteristics and the outcome of patients treated by oral vinorelbine either as a single-agent or in combination with capecitabine as first- or second-line CT in the metastatic setting. PATIENTS AND METHODS: We analysed 216 patients with ABC who started treatment with a full oral CT at 13 centers and seven countries between 2006 and 2008. To be eligible, patients must have received either as a first-(56%) or second-line (44%) therapy oral vinorelbine as a single-agent (54%) or in combination with capecitabine (46%). RESULTS: Main patients' characteristics in the full population (n=216): median age (range): 61 (32-87) years; categories of age: <50 years: 18%, 50-65 years: 44%, ≥ 65 years: 38%; hormone receptor-positive: 63%; ≥ 2 metastatic sites: 58%; visceral metastases: 49%; prior CT: 86%; prior CT for ABC: 44%; prior anthracycline treatment: 69%; prior taxane treatment: 43%, prior anthracycline plus taxane: 38%; prior endocrine therapy: 63%. Median number of cycles: 6 (range=1-54); 48% of patients received more than 6 cycles. G3/4 toxicities: neutropenia 8%, anaemia 2%, thrombocytopenia 1%, febrile neutropenia/neutropenic infection 2%, nausea 6%, vomiting 4%, diarrhea 6%, fatigue 6%, hand-foot syndrome 14% (combination with capecitabine), neuropathy 1%, alopecia (grade 2) 1%. EFFICACY: disease control was achieved in 77% of patients [95% confidence interval=71-83%], 74% as single-agent, 81% in combination, 82% in first-line, 71% in second-line. Median progression-free survival was 9.7 months [95% confidence interval=8.2-12.6 months] in first-line and 6.6 months [95% confidence interval=5.5-8.5 months] in second-line therapy. Caregivers described these oral regimens as convenient (81%), well-tolerated (84%) and with a good compliance by patients (76%). CONCLUSION: These data from everyday practice confirm, as shown in different clinical trials, that oral vinorelbine is an active and well-tolerated CT for ABC, either as a first- or second-line in patients pre-treated with anthracyclines or taxanes. The convenience of its oral administration in association with its good tolerance profile, allows for continuation of treatment until disease progression without a pre-planned maximum of cycles.

Effect of once-weekly epoetin beta on survival in patients with metastatic breast cancer receiving anthracycline- and/or taxane-based chemotherapy: results of the Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study.

PURPOSE: The Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study evaluated whether epoetin beta would improve survival in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: BRAVE was an open-label, randomized, multicenter study in patients with MBC treated with anthracycline- and/or taxane-based chemotherapy. Patients (hemoglobin [Hb] < 12.9 g/dL) were randomly assigned (1:1) to epoetin beta 30,000 U subcutaneously once weekly or control for 24 weeks. The primary efficacy variable was overall survival. Secondary efficacy outcomes included progression-free survival, transfusion- and severe anemia-free survival, Hb response, safety, and quality of life (QoL). RESULTS: After 18 months of follow-up, 62 (27%) of 231 patients survived with epoetin beta therapy and 63 (27%) of 232 with control. No difference was detected in overall survival (hazard ratio [HR] = 1.07; 95% CI, 0.87 to 1.33, P = .522) or progression-free survival (HR = 1.07; 95% CI, 0.89 to 1.30, P = .448). There was a statistically significant benefit on transfusion- and severe anemia-free survival compared with control (HR = 0.59; P = .0097). Median Hb level increased with epoetin beta (11.7 g/dL at baseline to 13.3 g/dL at 24 weeks) but did not change with control (11.5 v 11.4 g/dL). Patients receiving epoetin beta experienced more thromboembolic events (TEEs) compared with controls (13% v 6%; P = .012) with no difference in serious TEEs (4% v 3%). Epoetin beta did not significantly improve QoL in this study where patients had a high baseline Hb value. CONCLUSION: In patients with MBC receiving chemotherapy and initial Hb less than 12.9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.

Docetaxel-ifosfamide combination in patients with HER2-non-overexpressing advanced breast cancer failing prior anthracyclines.

The feasibility of the docetaxel-ifosfamide combination, as well as the definition of maximum tolerated doses (MTD) in a previous phase I study, led us to continue evaluating the regimen in an extended phase II study in patients with HER2-non-overexpressing, anthracycline pre-treated advanced breast cancer. Patients with histologically confirmed metastatic breast cancer failing prior anthracycline-based chemotherapy were treated with docetaxel 100 mg/m2 over 1 h on day 1 followed by ifosfamide 5 g/m2 divided over days 1 and 2 (2.5 g/m2/day over 1 h), and recycled every 21 days with prophylactic granulocyte-colony stimulating factor (G-CSF) administration from day 3-until a neutrophil count >10,000/microl. Between March 1999 and June 2002, 71 patients with a median age of 55 years (range, 28-72) and performance status (World Health Organization; WHO) of 1 (range, 0-2) were treated; all were assessable for toxicity and 70 patients for response. Clinical response rates (RRs), on an intention-to-treat basis were: 41/71 [58%; 95% CI, 46.5-69.5%]; 7 complete remissions (CRs), 34 partial remissions (PRs), 15 stable disease (SD) and 15 progressive disease (PD). The median response duration was 7.5 months (2-28 months), median time-to-progression (TTP) 6 months (0.1-30 months), and median overall survival (OS) 12 months (0.1-36 months). Grade 3/4 toxicities included; neutropenia in 63% of patients-with 52% developing grade 4 neutropenia (>or=7 days) and in 11% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included; peripheral neuropathy grade 2 only in 7%, grade 1/2 reversible central nervous system (CNS) toxicity in 11%, no renal toxicity, grade 2 myalgias in 7%, grade 3 diarrhea in 4%, skin/nail toxicity in 11%, and grade 1/2 fluid retention in 28% of patients. The present report has demonstrated encouraging activity of the docetaxel-ifosfamide combination in anthracycline-pretreated, HER2-negative advanced breast cancer. Therefore, future randomized phase III studies versus single-agent docetaxel or currently established combinations of the latter with other agents in this setting with established clinical activity, such as capecitabine or gemcitabine, will be warranted.

Leptomeningeal carcinomatosis after major remission to taxane-based front-line therapy in patients with advanced breast cancer.

AIM: To determine the incidence of leptomeningeal carcinomatosis (LMC), as the first manifestation of systemic progression, in breast cancer patients after obtaining a major response (complete response, CR or >80% partial response, PR) to first-line taxane-based chemotherapy treated between 1996 and 2000 in our Medical Oncology Unit. PATIENTS AND METHODS: Patients with histologically proven breast cancer having either metastatic disease, or high-risk locoregional disease that were entered into treatment protocols with first-line taxane (paclitaxel or docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as the first evidence of progression after major response (CR or >80% PR) were analyzed in the present study (n = 155). RESULTS: Seven patients with a median age of 54 (range: 40-70) years developed LMC as their first evidence of progression after taxane-based regimens with a median interval of 6 months (range: 2-18) from start of treatment to diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT), while one patient received i.t. methotrexate and RT to lumbar spine. Two patients responded to treatment for LMC, while two achieved stable disease and three progressed. Two patients had elevated cerebrospinal fluid tumor markers (more than serum marker levels) that proved useful in monitoring response to treatment. Median survival after LMC was 3.6 months (range: 1-31+) and correlated positively to the interval from the initiation of taxane-based therapy to LMC (r = 0.84, P = 0.019). Seven out of 86 responders (8.1%; 95% confidence interval, 2.4-13.9) developed LMC as the first sign of progression after a major response to first-line chemotherapy. CONCLUSIONS: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased when compared in retrospect to non-taxane-treated patients. Prospective evaluation of the incidence of LMC after taxane versus non-taxane-based treatment from large randomized multiinstitutional trials is warranted and identification of potential prognostic factors might help identify patients requiring appropriate prophylactic therapy.

Isolated leptomeningeal carcinomatosis (carcinomatous meningitis) after taxane-induced major remission in patients with advanced breast cancer.

OBJECTIVES: To identify the incidence of leptomeningeal carcinomatosis (LMC), as the first site of systemic progression, in breast cancer patients after having obtained a major response (CR or near CR) to first-line taxane-based chemotherapy and compare these findings in retrospect with a matched-pair group of historical control patients from our database treated with nontaxane regimens. PATIENTS AND METHODS: Patients with histologically proven breast cancer having either metastatic disease or high-risk locoregional disease that were entered into treatment protocols with first-line taxane (paclitaxel or docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as the first evidence of progression after major response (CR or >80% PR) were analyzed in the present study (n = 155), and compared, as regards the incidence of LMC, to a matched-pair retrospective group of 155 patients treated with nontaxane regimens in our unit. RESULTS: Seven patients with a median age of 54 years (range 40-70) developed LMC as their first evidence of progression after taxane-based regimens with a median interval of 6 months (range 2-18) from start of treatment to diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT), while 1 patient received i.t. methotrexate and RT to the lumbar spine. Two patients responded to treatment for LMC, while 2 achieved stable disease and 3 progressed. Two patients had elevated cerebrospinal fluid tumor markers (more than serum marker levels) that proved useful in monitoring response to treatment. Median survival after LMC was 3.6 months (range 1-17+) and correlated positively to the interval from the initiation of taxane-based therapy to LMC (r = 0.84, p = 0.019). Seven out of 86 responders (8.13%) in the taxane group versus 1 out of 72 responders (1.4%) in the non-taxane-treated group developed LMC as the first sign of progression after a major response to first-line chemotherapy (p < 0.1). CONCLUSIONS: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased, but not significantly so, when compared retrospectively to non-taxane-treated patients. Prospective evaluation of the incidence of LMC after taxane versus non-taxane-based treatment from large randomized multi-institutional trials is warranted and identification of potential prognostic factors might help to identify patients requiring appropriate prophylactic therapy.