De la anatomía patológica convencional a los nuevos perfiles genéticos del cáncer de mama / No disponible

La mortalidad por cáncer de mama se ha reducido graciasal diagnóstico precoz y a los tratamientos adyuvantes. Losefectos secundarios, toxicidades potenciales y el coste de lostratamientos sistémicos condicionan la individualización terapéuticacon una mejor selección de las pacientes. La heterogeneidaddel cáncer de mama nos obliga a considerar los factorespronósticos y predictivos.Desde hace 25 años clasificamos el cáncer de mama según sutipo histológico, grado y expresión de los receptores hormonales.Desde hace 15 años, gracias a la aplicación de las técnicas dehibridación in situ de los ácidos nucleicos, los tumores se clasificanen HER2 sobre-expresado o no sobre-expresado. Desdehace menos de 5 años se han definido distintos patrones de expresióngenética que nos aportan una nueva clasificación molecular.Perou y Sorlie publicaron el estudio pionero en Nature2000, demostrando que la heterogeneidad morfológica de los tumoresmamarios puede reclasificarse en 4 grupos principales: luminalA, luminal B, HER2 amplificado y similar a basal (basallike)en base a los estudios de reordenamiento genético. Los dosprimeros son de mejor pronóstico y el basal-like está relacionadocon un comportamiento más agresivo, con tendencia a desarrollarmetástasis y con un fenotipo “triple negativo” (para los receptoresde estrógenos, de progesterona y para el HER2), quelos excluye de las terapias diana hormonal y anti HER2, y aunquepueden responder bien a la quimioterapia neoadyuvante yadyuvante, su pronóstico es malo.De la misma manera la cuantificación de ciertos genes y suponderación según el impacto en su valor predictivo, ha sidocrucial para obtener los llamados tests genéticos predictivos...(AU)

Breast cancer mortality has declined as a result of early detectionand application of adjuvant systemic therapy. Individualisationof this therapy regarding the selection of patientsmay avoid side effects, potential toxicities and cost of adjuvanttherapy. The heterogenecity of breast cancer oblige us to considerprognostic and predictive factors.Invasive breast carcinomas were classified, since 25 yearsago, according to histological type, grade and expression ofhormone receptors. Fifteen years ago and thanks to the introductionof the hybridization in situ of nucleic acids techniques,we could classify breast tumors in HER2 amplified and not amplifiedHER2. More recently, the molecular portraits or variationin gene expression patterns by Perou and Sorlie (Nature2000), have demonstrated that the morphological heterogenecityof breast cancer could be reclassified based in theDNA microarrays analysis studies. These studies have shownthat the expression profiles of breast cancer display a systematicvariation and allowed the classification of breast cancer into4 main groups: luminal A, luminal B, amplified Her2 and basallikebreast carcinomas. The first two groups have better prognosisand the latter group is reported to have a more aggressiveclinical behaviour. In addition, the majority of basal-like breastcancers are hormone receptors and HER2 negative (triple-negative),and thus cannot be targeted with current tailored therapies(i.e. endocrine and anti-HER2 therapies), but they oftenrespond to conventional neoadjuvant and adjuvant chemotherapyregimes, furthermore their prognosis remains poor.In the same way the quantification of certain genes andtheir weighting according to their impact on predictive value,has been crucial to obtain the so-called predictive genetic test.The diagnostic and therapeutic challenge posed by this newapproach has captured the attention of specialist implied inbreast cancer research(AU)

Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer.

PURPOSE: Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy. PATIENTS AND METHODS: Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m2 followed by docetaxel 75 mg/m2, both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles. RESULTS: Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities. CONCLUSIONS: Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.

Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study.

BACKGROUND: A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients. PATIENTS AND METHODS: Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles). RESULTS: In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64). CONCLUSION: This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.

Retrospective evaluation of toxicity in three different schedules of adjuvant chemotherapy for patients with resected colorectal cancer. TTD Spanish Cooperative Group.

Adjuvant chemotherapy has been established since 1990 as standard treatment for patients with colon cancer stage III (Dukes' C). Chemotherapeutic schemes combining 5-fluorouracil with levamisole or leucovorin have shown significant advantage over surgery alone. Adjuvant trials are being currently implemented to investigate some relevant questions, such as which is the optimal duration of chemotherapy, as well as the possible advantage of levamisol versus leucovorin schedules, and of high-dose versus low-dose leucovorin. While these trials are ongoing, a retrospective evaluation of the toxicity associated with the different chemotherapeutic schemes might be of help when choosing the most appropriate regimen for individual patients not involved in clinical trials. A total of 519 patients subjected to three different schedules of adjuvant chemotherapy between 1993 and 1996, were evaluated for toxicity according to the NCI-CTC criteria. Chemotherapeutic regimens were: 5-fluorouracil plus levamisole (5-Fu+Lev; Moertel schedule), 5-fluorouracil plus low-dose leucovorin (5-Fu+LVLD; NCCTG schedule) and 5-fluorouracil plus high-dose leucovorin (5-Fu+LVHD; IMPACT-modified schedule). 5-Fu+LVLD is significantly more toxic than the other two regimens in terms of neutropenia, mucositis and diarrhea. delay in chemotherapy and dose reduction of 5-fluorouracil were also more frequent in the 5-Fu+LVLD group. However, the percentage of prematurely discontinued treatments was significantly higher in the 5-Fu+Lev group. Information on toxicity of adjuvant chemotherapy for colon cancer may help medical oncologists to choose the most appropriate regimen for individual patients not involved in clinical trials.