P929. Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the regional treatment of locally advanced breast cancer

EuropeanSociety of Mastology Abstracts 337 V Tombolini, A Vitturini, M Valeriani, E Banelli Istituto di Radiologia, Universitiz “La Sapienza”, Policlinico Umberto I., Italy The incidence of breast cancer in patients with age over 65 is twice that in younger women. Several authors have reported giving only palliative therapy to elderly patients. 82 women with breast cancer, aged over 70 years were treated at the Institute of Radiology between 1980 and 1986. The mean age was 77 years. 30 (37%) were stage I, 26 (32%) stage II, 18 (22%) stage III, 7 (9%) stage IV. 8 cases had radiotherapy after radical mastectomy. All patients were treated with photons of 4-6 MeV, daily dose 2 Gy, fractionation 5 days per week and total dose of 50 Gy. Five cases discontinued therapy because of erythema for a period no longer than 8 days. 45% of cases also had hormonal therapy. The 5 years overall survival was 83% in stage I, 80% in stage II, 70% in stage III and 15% in stage IV. The incidence of local recurrence was 14%. 3 cases developed bone metastases, 2 lung metastases and one liver metastases. Results of this series demonstrate similar rate of problems in this elderly group to that of younger women having radical radiotherapy and satisfactory survival figures.

P926. Two-phase early detection project in the No. 13 local health unit of the Veneto Region, Italy M Bari, C Milanesi, U Sicari, A Rossato,L Bertoldo, I Vinci, R Manconi, R Segati, G Azzarello, GL Pappagallo, 0 Vinante ULSS No. 13, Veneto Region, Italy A 2-phase early detection project was activated in Mar 1991 at the No. 13 (former No. 17) Local Health Unit of the Veneto Region, Italy. The project was designed to selectively screen women aged 40 to 70 years, by involving both general practioners and hospital specialists (radiologist, pathologist, surgeon, oncologist). 49 of 102 general practioners (48%, covering the 43% of the eligible population) agreed to participate to the project, and 7677 of 9454 (81%) women were called to visit from Mar 1991 to Ott 1992. 6092 (79%) women presented to practioner’s for a history and breast examination. 2310 women (38%) were sent for mammography because of the presence of at least one of the following risk factors: previous breast cancer, positive family history, nulliparity, age at first childbirth > 30, postmenopausal obesity, benign tibrocystic disease. 1075 women (18%) had a positive breast examination. 29 tumors were detected: 7 by mammography in risk positive (clinical negative), 7 in both risk and clinical positive group, 15 in clinical positive (risk negative) women. 21 of 29 (72%) tumors were < 2 cm in diameter (3 pTis, 18 pTl), 17 of which pStage I (59% of tumours). The 2nd phase of the project was conducted from Jan 1993 to Jun 1994, with the participation of only 29 of 49 general practioners who had initially agreed to the programme. 3372 women of 4187 recalled (80%) were examined; 1059 (31%) were sent to mammography and 459 (14%) were sent for hospital assessment. 13 tumours were detected by this phase, 69% of which pT1 and 61% pStage I. After Jun 1994, in the absence of any early detection programme, 22 further tumours were diagnosed within the 6042 women who initially entered the programme (14 of 22 in women previously submitted to mammography); 45% of neoplasms were pT1 and 36% pStage I. The latter findings were comparable to those observed within the 40-70 years female population referred to practioners who initially disagreed to enter the project; 94 tumours were diagnosed in the same period, 53% pTis-pT1 and 35% pStage I.

P927. Analysis of BRCA-1 mutations in families from Southern Italy G Viglietto, P Bruni, I Capasso,MT Vento, E Squame, M D’Aiuto, S Buonagura,M Pizzorusso,G Esposito, G Chiappetta,GD’Aiuto Istituto Nazional dei tumori, Naples, Italy Breast cancer is the most frequent malignant neoplasm in women. Genetic factors appear to contribute to between 5 and 10% of cases. Recent studies have reported that 50% of families with a high incidence of breast cancer have mutations in the BRCA- 1 gene; 30% of familial cases of mammary carcinomas may result from alterations of the BRCA-2 gene and 20% appears to be linked to at least one more gene. The BRCA-1 locus spans 80 Kb of genomic DNA and encodes for a transcript of 7.8 Kb composed of 22 coding exons giving origin to a protein of 1863 amino acids. Several mutations have been reported in all coding exons of the BRCA-1 gene. In particular, the most common mutation found so far is 185AGde1, which has been reported in the Askhenazi Jew population. The aim of the research was to identify constitutional genetic alterations in the gene encoding for BRCA-1 in the components of families with a high incidence of breast cancer. 203 women distributed in 75 families have been included in this study. Clinical criteria for admission was the presence of breast cancer in at least 3 members of the family. Pheripheral blood samples were taken from each woman and genomic DNA was extracted. The 22 coding exons of the BRCA-1 gene have been amplified by PCR (Polynucleotide Chain Reaction) and analysed either by SSCP (single strand conformation polymorphism), direct DNA sequencing of the amplified product, or by use of the PTT (Protein Truncation Test). Here we report preliminary data on 13 families. None of the 13 families analyzed carry the mutation 185AGdel. Conversely, polymorphic mutations were detected in 2 different families in exon 6 and 16, respectively. Finally, a non-polymorphic, l-2 nucleotide insertion was detected by SSCP in exon 12. Sequence analysis is under way to determine the type of mutation.

P929. Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the regional treatment of locally advanced breast cancer JC Doughty, E Kane, TG Cooke, CS McArdle Department of Surgery, Royal Infirmary Glasgow and Department of Surgery, Western Infirmary Edinburgh, UK Regional chemotherapy is one method of treating patients with locally advanced breast cancer. Conventionally it is delivered by surgical implantation of a catheter into the subclavian artery but the less invasive angiographic technique is increasingly being used. There have been many reports of Mitozantrone, Methotrexate and Mitomycin (MMM) administered regionally but we have obtained severe wound breakdown associated with the use of Mitomycin C (MMC). This paper therefore compares the results and the toxicity obtained delivering Mitozantrone and Methotrexate (MM) with and without MMC via angiographically placed catheters in the internal mammary and lateral thoracic arteries. Fifty two patients with a histological diagnosis of locally advanced breast cancer were recruited. Thirty three patients received MMM and seventeen MM. The response rates as defined by WHO criteria were as follows: Number of patients

MMM

MM

Complete response Partial response Stable disease Progressive disease

11 13 8 1

5 8 4 0

338

The Breast

There were no significant differences (x2 test) between the responders and non-respondersin the two groups,however local toxicity was significantly increasedin the patientswho receivedMMM. We conclude that regional chemotherapyusing MM is as effective as MMM in the treatmentof locally advancedbreast cancerand avoids the severelocal skin reactionsassociatedwith MMC.

P930. Supportive care with disodic pamidronate in the treatment of breast cancer metastatic bone lesions P Candido,MT Cattaneo,N Tosca,S Ferrario,A Gambaro,B Orlandini, MA Nosenzc,E Piazza Oncology Department, L. Sacco Hospital, Milan, Italy Disodic Pamidronate(DP) is an effective drug commonly utilized in the treatment of painful osteolytic bone metastasesand in paraneoplastic hypercalcaemia,becauseof its mechanismof action of inhibiting osteoclast osseousresorption. Since January 1994 to December 1996, we have treated 47 pts with symptomatic bone lesions from metastatic breast cancerwith Disodic Pamidronate.The schedulewas: 60 mg.tot. in physiological solution 500 cc. in a three hour intravenousinfusion, every 21 days for 6-12 cycles. Radiotherapywas given to lo/47 pts (21.2%). Objective responsewas evaluatedby adequatecontrol of pain and diseasestabilization documentedwith 99Tcn-osteoscan. Partial responsewas recordedin U/47 pts (PR = 57.4%), apparently unrelatedto tumour histotype or previous radiotherapy.Six pts (12.7%) had no change.ProgressiveDiseasewas documentedin 14/47pts (29.7%). Toxicities related to DP utilization (I”-II” WHO) occurred in 9/47 pts (19.1%): in 4 pts these were gastrointestinalsymptoms, in 3 pts hyperpyrexia and in 2 pts neurologicalsymptoms @araestbesiae). We conclude DP has an effective role in bone metastasesfrom breast cancerand it may also be useful in treatingother osteolytebone metastases and in paraneoplastic hypercalcaemia arising from lung, colorectal, bladderand prostatic cancer.

P.932. Cystic tumors of the breast: a diagnostic and therapeutical problem G Moretto, GP Pollini, E Iellici, R Sandrini,F Pellini, A Molino, F Bonetti, C Prezzi Department of Surgical Sciences, Pathology and Radiology, Ospedale Policlinico B.go Roma, Verona, Italy The finding of cystic breast massesis a relatively frequent event (up to 7-10% of women develop a clinical cyst at sometime during their life), while the finding of an intracystic lesion is rare. If while using mammography and ultrasoundwe detect intracystic lesions, these findings force the operatorto use other tools for his/her investigationsas mammography does not allow one to distinguish betweenan intracystic lesion and a cyst by itself, becauseof the poor differential absorpionof the tissue forming the breast.Even though sonographyis able to distinguish easily the two components(the liquid tram-sonic one, and the solid hypemchoicone) the US characteristicsfor the differential diagnosisbetweenbenign and malignant lesions(edges’feature,structuralhomogeneity),at presenttime in the case of a complex cystic lesion sonographydoes not have high a specificity, so we must use cytology and/or histology. Breast cysts are usually of little significance,there are howeverfour situationsin which a clinically cystic lesion can be associatedwith malignancy:(1) invasion of a carcino-

ma into an areaof cystic disease;(2) cystic degenerationof a high grade malignancy; (3) carcinomaarising in a cyst wall; (4) intracystic papillary carcinoma. It is the authors’opinion that every cyst which bears ambiguous elements such as irregular thickenings of their wall, very thick fluid or fibrotic bridges, should be regardedwith suspicion and studied not just with mammographyor ultrasoundbut with cystic fluid aspiration; the characteristicsof this latter can be by itself an useful index of malignancy. Cytology should be carried out everytime bloodstainedfluid is obtained by cystic aspiration, becausethere is a significant chancethat the lesion could be a neoplasm.The presenceof a residual mass after aspiration of the cystic fluid in an elderly patient is strongly indicative of malignancy and thus it must be investigatedwith mammographyand ultrasound. Surgical excision should be performed in every case with positive or either suspect imaging or cytology. The type of surgery performeddependsfrom the type of cystic tumor and its extensionto the surroundingtissue.

P.933. Responseto primary chemotherapyin locally advancedbreast CA: comparative accuracy of MR imaging relative to MX and US ML Grandinetti,FR Ferranti,E Saracca,M Crecco, C Botti, P Vici, M Mattioli. Istituto Regina Elena, Roma, Italy The aim was to evaluatethe comparativeaccuracyof dynamic Magnetic Resonance(MR) imaging relative to mammography(MX) and ultrasound (US) to determinetumour responseand extensionof residualdiseaseafter neoadjuvantchemotherapy. Thirty patientswho were clinically stagedto have T2> 4 cm, T3-4 and/ or NO-l breast cancer were evaluated prior to and after neoadjuvant chemotherapyby MR, physical examination,US and MX. Assesmentof responsedeterminedby the four methodswas compared. Independentinterpretationswithout knowledge of clinical responsewere made by three radiologists. Histological results were analyzed and comparedin 28 patients(two patientshad breastconservation). Overall, 95% of patientsachieveda clinical response(PR, CR). In 60% there was general agreementbetween clinical and radiological results. Histological and clinical results agreedwith MR results in 75% MR was superiorto the other three modalities.MR predictedpathologicalextent of residual cancerafter chemotherapyin 25 of 26 patients (97%) and in one patient identified a controlateraloccult cancer. MR imaging was the more accurateof the three imaging modalities in assessingresponseto neoadjuvantchemotherapy.

P934. Fraction of normal remaining life: a new method for expressingsurvival in cancer JS Vaidya, I Mittra Department of Surgery, University College London, London, UK and Department of Surgery, Tata Memorial Hospital, Bombay, India The plotting of conventionalsurvival curves for cancer,using the interval betweendiagnosisand date of last foilow up or death to denote survival time, ignoresthe patient’s expectedlife spanhad the patient beenhealthy. In human terms, the impact of a projected 10 year survival of a woman diagnosedto have breastcancer(for example)would be different for a 30 year old patient as opposedto a 70 year old. We believe that survival is betterexpressedas a fraction of normal remaininglife spanexpectedat the time of diagnosis.