Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PURPOSE: The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. PATIENTS AND METHODS: Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. RESULTS: Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. CONCLUSION: After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). PATIENTS AND METHODS: Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. RESULTS: One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. CONCLUSION: VNB is an active drug against ACC with moderate toxicity. Its activity is among the highest reported for single agents. Further evaluation in association with other agents is clearly justified.

Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. RESULTS: Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). CONCLUSION: IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.

High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.

From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.

Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia.

BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male-pattern baldness. Based on this potential, the effectiveness of Mx 2% topical solution was evaluated in cancer patients (pts) to prevent doxorubicin-induced alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid tumors treated with doxorubicin-based chemotherapy in a dose range of 50-60 mg/m2/cycle were randomly assigned to receive Mx 2% topical solution or placebo. RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p = ns). No adverse effects were observed. CONCLUSION: In this study Mx 2% topical solution was non-toxic but was not effective in the prevention of chemotherapy-induced alopecia.

Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION: VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

Marcadores moleculares para predecir el pronóstico del cáncer de mama / Molecular markers to predict the prognosis of breast cancer

En la mujer, el cáncer de mama representa el 25-30 por ciento de los tumores malignos siendo la enfermedad con mayor índice de mortalidad. Para identificar pacientes con carcinomas de mama de mal pronóstico, se usan diferentes parámetros relacionados con el tumor primario. De todos los parámetros usados rutinariamente, el grado de invasión tumoral en los ganglios linfáticos axilares es considerado uno de los más importantes. A pesar de ello, 30 por ciento de los pacientes con ganglios linfáticos libres de metástasis (considerados como de buen pronóstico) presentam recurrencia y mueren dentro de los 10 años de realizado el diagnóstico. Esto, al igual que otras observaciones, permiten concluir que los parámetros usados de rutina no serían suficientes - por sí solos - para predecir el curso de la enfermedad tumoral. Gracias a los últimos avances de la biología celular y molecular los eventos cruciales de la carcinogenesis, progresión tumoral y la metástasis están siendo analizados a nivel molecular. En algunos tumores estos adelantos ya están siendo incorporados a la páctica clínica. Recientemente se ha observado que, en determinados tumores, anormalidades de varios genes están correlacionados con el pronóstico de cada paciente. Por medio de la determinación de diferentes macromoléculas marcadoras, los laboratorios de biología molecular puedem brindar importante información pronóstica y de ayuda en al selección de las estrategias terapéuticas. Entre estos nuevos marcadores podemos citar: amplificación y/o sobreexpresión de oncogenes, secreción aumentada de factores de crecimiento, el índice de proliferación celular y la ploidía, proteinas inducidas por los estrógenos, expresión de moléculas relacionadas con el proceso de matástasis, proteínas asociadas con la resistencia farmacológica, etc. En este artículo realizamos un breve análisis de la metodología utilizada para evaluar estos marcadores tumorales y mencionamos algunas de sus aplicaciones clínicas. Nos acercamos al momento en el cual el diagnóstico clínico deberá realizarse a nivel molecular. Esto será posible combinando la histopatología convencional con las técnicas modernas de biología celular y molecular. Esta nueva información llevará a una reevaluación de los sistemas de los tumores, que no estarán basados en la aparencia morfológica o en el origen de las células, sino por la caracterización de sus genes asociados con estadios particulares de cada tumor

Marcadores moleculares para predecir el pronóstico del cáncer de mama / Molecular markers to predict the prognosis of breast cancer

En la mujer, el cáncer de mama representa el 25-30 por ciento de los tumores malignos siendo la enfermedad con mayor índice de mortalidad. Para identificar pacientes con carcinomas de mama de mal pronóstico, se usan diferentes parámetros relacionados con el tumor primario. De todos los parámetros usados rutinariamente, el grado de invasión tumoral en los ganglios linfáticos axilares es considerado uno de los más importantes. A pesar de ello, 30 por ciento de los pacientes con ganglios linfáticos libres de metástasis (considerados como de buen pronóstico) presentam recurrencia y mueren dentro de los 10 años de realizado el diagnóstico. Esto, al igual que otras observaciones, permiten concluir que los parámetros usados de rutina no serían suficientes - por sí solos - para predecir el curso de la enfermedad tumoral. Gracias a los últimos avances de la biología celular y molecular los eventos cruciales de la carcinogenesis, progresión tumoral y la metástasis están siendo analizados a nivel molecular. En algunos tumores estos adelantos ya están siendo incorporados a la páctica clínica. Recientemente se ha observado que, en determinados tumores, anormalidades de varios genes están correlacionados con el pronóstico de cada paciente. Por medio de la determinación de diferentes macromoléculas marcadoras, los laboratorios de biología molecular puedem brindar importante información pronóstica y de ayuda en al selección de las estrategias terapéuticas. Entre estos nuevos marcadores podemos citar: amplificación y/o sobreexpresión de oncogenes, secreción aumentada de factores de crecimiento, el índice de proliferación celular y la ploidía, proteinas inducidas por los estrógenos, expresión de moléculas relacionadas con el proceso de matástasis, proteínas asociadas con la resistencia farmacológica, etc. En este artículo realizamos un breve análisis de la metodología utilizada para evaluar estos marcadores tumorales y mencionamos algunas de sus aplicaciones clínicas. Nos acercamos al momento en el cual el diagnóstico clínico deberá realizarse a nivel molecular. Esto será posible combinando la histopatología convencional con las técnicas modernas de biología celular y molecular. Esta nueva información llevará a una reevaluación de los sistemas de los tumores, que no estarán basados en la aparencia morfológica o en el origen de las células, sino por la caracterización de sus genes asociados con estadios particulares de cada tumor (AU)

[Molecular markers to predict the prognosis of breast cancer]. / Marcadores moleculares para predecir el pronóstico del cáncer de mama.

The incidence of breast cancer is 25-30% of all malignant female tumors and represents the highest rate of mortality. To define those breast cancer patients at higher risk several prognostic factors are routinally evaluated in the primary tumor. Among them, the presence and degree of tumor involvement in axillary lymph node is one of the most powerful prognostic indicator. However, around 30% of node negative patients (good prognosis group) have recurrences and die within the next 10 years from diagnosis. Therefore, there is a need for markers to better discriminate biologic differences in the primary tumors. The techniques of molecular biology are shedding new insight into the subcellular pathology of malignancy. The crucial events of carcinogenesis, tumor progression, and metastatic spread are coming into focus at a molecular level. In some tumors, these advances in the laboratory are beginning to have applications at the bedside. Recently, abnormalities in the copy number and expression of several genes have been correlated with prognosis of individual patients with selected types of cancer. Molecular biology laboratories can provide useful predictive information that can be used to influence decision on the selection of treatment and to estimate a better risk stratification. Among these new markers are: oncongene amplification and/or over-expression, growth factors, cellular proliferation rate and ploidy, estrogens induced proteins, expression of metastasis related molecules, drug resistance associated proteins, etc. In this article we attempt to present a brief evaluation of a new technology that promises to add greater precision in evaluating molecular tumor markers and we mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Marcadores moleculares para predecir el pronóstico del cáncer de mama. / [Molecular markers to predict the prognosis of breast cancer]

The incidence of breast cancer is 25-30

of all malignant female tumors and represents the highest rate of mortality. To define those breast cancer patients at higher risk several prognostic factors are routinally evaluated in the primary tumor. Among them, the presence and degree of tumor involvement in axillary lymph node is one of the most powerful prognostic indicator. However, around 30

of node negative patients (good prognosis group) have recurrences and die within the next 10 years from diagnosis. Therefore, there is a need for markers to better discriminate biologic differences in the primary tumors. The techniques of molecular biology are shedding new insight into the subcellular pathology of malignancy. The crucial events of carcinogenesis, tumor progression, and metastatic spread are coming into focus at a molecular level. In some tumors, these advances in the laboratory are beginning to have applications at the bedside. Recently, abnormalities in the copy number and expression of several genes have been correlated with prognosis of individual patients with selected types of cancer. Molecular biology laboratories can provide useful predictive information that can be used to influence decision on the selection of treatment and to estimate a better risk stratification. Among these new markers are: oncongene amplification and/or over-expression, growth factors, cellular proliferation rate and ploidy, estrogens induced proteins, expression of metastasis related molecules, drug resistance associated proteins, etc. In this article we attempt to present a brief evaluation of a new technology that promises to add greater precision in evaluating molecular tumor markers and we mention some of its clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)