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P918. Breast cancer: response to primary chemotherapy and biological parameters (ER, PgR, Ki67)
EuropeanSociety of Mastology Abstracts 335 a mean 4 x 4 ems width, total doses ranged between 26 Gy and 45 Gy, with conventional fractionation (1.8-25 Gy, 5 times/week) in all but 3 cases treated with 3 Gy fractions. Subjective palliative effects was obtained in 75% of evaluable patients. Complete recovery of visual acuity was reported in 1 patient for 15 months. Acute side effects were: conjunctivitis in 1 patient, conjunctival haemorrhage in 1 patient. No late side effects were observed. In our experience a short course of external beam radiation therapy is useful palliative treatment for ocular metastases from breast cancer.
P917. Taxol and fluorouracil as second line chemotherapy for metastatic breast cancer A Fomasiero,C Ghiotto, 0 Daniele, P D’Amanzo, SML Aversa, V Chiarion Sileni, MV Fiorentino Divisione di Onclogia Medica-Azienda Ospendaliera di Padova, Italy A dose finding study was planned for the combination of Paclitaxel (Pcl) and Fluorouracil (Fu) in pretreated breast cancer patients (pts) with metastatic disease (II line chemotherapy). The starting dose was: Fu 400 mg/m* on day 1 and 2, plus Pcl 125 mg/m’ on day 1. After the first triplet of pts had been treated at this dose level, without evident toxicity, other triplets were entered, with progressive increases of the Pcl dose by 25 mg/m’ for each new triplet. At the 250 mg/m2 step, 2 cases of grade 3 neurotoxiciy (WHO scale) appeared. Two other pts were treated at this dose level, without marked side effects. The immediately lower Pcl dose (225 mg/m*) was chosen for an escalation of Fu, which was given to subsequent triplets at 500 and then at 600 mg/m’, No relevant toxicity appeared, but also no relevant increase in efficacy: so we concluded that there was little interest in further increasing the Fu dose. 27 pt have received Pcl + Fu as second line chemotherpy; the maximum “well tolerated” dose is Fu 600 mg/m’ x 2 plus Pcl 225 mg/m* x 1 per course, administered every 3 weeks. A preliminary efficacy evaluation was not among the objectives of the study, but retrospectively, if we account for the 18 pts receiving a dose of Pcl> 200 mg/m’ per course, we have observed 10 objective remission (of which 4 were complete and 6 partial). The overall response rate of this combination in larger trials may be rewarding.
P918. Breast cancer: responseto primary chemotherapy and biological parameters (ER, PgR, Ki67)
M Donadio, E Manzin, C Bumma Department of Medical Oncology, S. Giovanni Antica Sede Hospital, Torino, Italy The administration of primary chemotherapy allows biological studies to value the interactions between cytotoxic drugs and tumor biology. From March 1994 to December 1996, 63 consecutive patients (pts) bearing T2-T4, NO-l, MO primary breast cancer received 3 cycles of either epirubicin 120 mg/m* every 3 weeks (57 pts) or CMF regimen l”, 8” day every 4 weeks (6 pts) as neoadjuvant chemotherapy before surgery. 43 pts were assessed, immediately before chemotherapy, for several bilogical parameters (ER, PgR, Ki 67) using immunohistochemisny on line-needle aspiration biopsy material. Clinical response to treatment was assessed after 3 cycles of chemotherapy. The overall response rate was 28/43 (65.1%). Preliminary results are reported below:
ER pts evaluable CR+PR NC+PD
PgR POS
NEG
POS
NEG
18 77.8% 22.2%
24 54.2% 45.8%
22 72.7% 27.3%
21 57.1% 42.9%
Ki67 LOW
HIGH
18 61.1% 38.9%
21 66.7% 33.3%
This study indicates that it is possible to analyze the relationships between some biological parameters, evaluated by immunohistochemistry on fine needle aspiration biopsies and response to chemotherapy. At this point in time the patients with ER-, PgR- seem to respond to chemotherapy better than those with ER+, PgR+. No differences have been observed in turnouts with a high proliferative activity compared with those with low activity, as estimated from Ki 67 labelling concerning the response to chemotherapy.
P919. Subfractions of prostate specific antigen differ in serum of normal women and women with malignant and benign breast diseases M Giai, R Ponzone,R Roagna,L Sgro, N Biglia, GH Borchert, EP Diamandis,P Sismondi Dept of Gynecological Oncology, University of Turin, Italy and Dept of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada Prostate-specific antigen (PSA) is a 33 kDA serine protease and is currently used as a marker for treating and monitoring patients affected by prostate adenocarcinoma. Until recently, PSA was believed to be produced only by prostatic epithelial cells. We have reported that concentrations t 0.03 ng/mg may also be found in approximately 30% of cytosols from female breast mmours and that patients with PSA-positive tumours have a lower risk of relapse and death in comparison with patients whose tumours are PSA-negative. We studied a total of 826 female sera from patients with breast cancer, benign breast diseases and normal blood donors. PSA was measured with a highly sensitive immunofluorometric procedure which is capable of measuring 1 rig/L of PSA or higher. In 6.5% of healthy women to 16.5% of women with benign breast diseases, the PSA level in the serum was greater than 10 rig/L. Serum samples with more than 20 rig/L of PSA were separated on a high performance liquid chromatography gel filtration column and each fraction was assayed for PSA. Our method allows to separate free PSA and PSA bound to IX, antichymotrypsin (PSA-ACT). Serum PSA subfractions in patients with breast diseases were substantially different from PSA subfractions in serum of healthy females. Free PSA (33 KDa) was the predominant molecular form in seven of 16 breast cancer patients and in 11 of 19 patients with benign breast diseases. In healthy women, free PSA was hardly detectable and was never the predominant molecular form. In the same patients with breast cancer, when the serum was collected post-surgically, free PSA was the predominant molecular form in only three out of 11 patients. The total PSA concentration in the serum was also significantly decreased after surgery. Total serum PSA and PSA molecular forms in female serum correlate with patient age and other clinical and pathological variables. We conclude that the molecular forms of PSA in female serum are substantially different between normal women and women with’either breast cancer or benign breast diseases. The mechanism by which the amounts of free PSA and PSA-ACT are altered in benign and malignant breast diseases is still unknown.
P920. Breast cancer with more than 3 positive nodes: adjuvant epirubicin followed by CMF +/hormonotherapy. Preliminary results A de Matteis, GD’Aiuto, R Thomas,C Longo, P Frezza,
P917. Taxol and fluorouracil as second line chemotherapy for metastatic breast cancer A Fomasiero,C Ghiotto, 0 Daniele, P D’Amanzo, SML Aversa, V Chiarion Sileni, MV Fiorentino Divisione di Onclogia Medica-Azienda Ospendaliera di Padova, Italy A dose finding study was planned for the combination of Paclitaxel (Pcl) and Fluorouracil (Fu) in pretreated breast cancer patients (pts) with metastatic disease (II line chemotherapy). The starting dose was: Fu 400 mg/m* on day 1 and 2, plus Pcl 125 mg/m’ on day 1. After the first triplet of pts had been treated at this dose level, without evident toxicity, other triplets were entered, with progressive increases of the Pcl dose by 25 mg/m’ for each new triplet. At the 250 mg/m2 step, 2 cases of grade 3 neurotoxiciy (WHO scale) appeared. Two other pts were treated at this dose level, without marked side effects. The immediately lower Pcl dose (225 mg/m*) was chosen for an escalation of Fu, which was given to subsequent triplets at 500 and then at 600 mg/m’, No relevant toxicity appeared, but also no relevant increase in efficacy: so we concluded that there was little interest in further increasing the Fu dose. 27 pt have received Pcl + Fu as second line chemotherpy; the maximum “well tolerated” dose is Fu 600 mg/m’ x 2 plus Pcl 225 mg/m* x 1 per course, administered every 3 weeks. A preliminary efficacy evaluation was not among the objectives of the study, but retrospectively, if we account for the 18 pts receiving a dose of Pcl> 200 mg/m’ per course, we have observed 10 objective remission (of which 4 were complete and 6 partial). The overall response rate of this combination in larger trials may be rewarding.
P918. Breast cancer: responseto primary chemotherapy and biological parameters (ER, PgR, Ki67)
M Donadio, E Manzin, C Bumma Department of Medical Oncology, S. Giovanni Antica Sede Hospital, Torino, Italy The administration of primary chemotherapy allows biological studies to value the interactions between cytotoxic drugs and tumor biology. From March 1994 to December 1996, 63 consecutive patients (pts) bearing T2-T4, NO-l, MO primary breast cancer received 3 cycles of either epirubicin 120 mg/m* every 3 weeks (57 pts) or CMF regimen l”, 8” day every 4 weeks (6 pts) as neoadjuvant chemotherapy before surgery. 43 pts were assessed, immediately before chemotherapy, for several bilogical parameters (ER, PgR, Ki 67) using immunohistochemisny on line-needle aspiration biopsy material. Clinical response to treatment was assessed after 3 cycles of chemotherapy. The overall response rate was 28/43 (65.1%). Preliminary results are reported below:
ER pts evaluable CR+PR NC+PD
PgR POS
NEG
POS
NEG
18 77.8% 22.2%
24 54.2% 45.8%
22 72.7% 27.3%
21 57.1% 42.9%
Ki67 LOW
HIGH
18 61.1% 38.9%
21 66.7% 33.3%
This study indicates that it is possible to analyze the relationships between some biological parameters, evaluated by immunohistochemistry on fine needle aspiration biopsies and response to chemotherapy. At this point in time the patients with ER-, PgR- seem to respond to chemotherapy better than those with ER+, PgR+. No differences have been observed in turnouts with a high proliferative activity compared with those with low activity, as estimated from Ki 67 labelling concerning the response to chemotherapy.
P919. Subfractions of prostate specific antigen differ in serum of normal women and women with malignant and benign breast diseases M Giai, R Ponzone,R Roagna,L Sgro, N Biglia, GH Borchert, EP Diamandis,P Sismondi Dept of Gynecological Oncology, University of Turin, Italy and Dept of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada Prostate-specific antigen (PSA) is a 33 kDA serine protease and is currently used as a marker for treating and monitoring patients affected by prostate adenocarcinoma. Until recently, PSA was believed to be produced only by prostatic epithelial cells. We have reported that concentrations t 0.03 ng/mg may also be found in approximately 30% of cytosols from female breast mmours and that patients with PSA-positive tumours have a lower risk of relapse and death in comparison with patients whose tumours are PSA-negative. We studied a total of 826 female sera from patients with breast cancer, benign breast diseases and normal blood donors. PSA was measured with a highly sensitive immunofluorometric procedure which is capable of measuring 1 rig/L of PSA or higher. In 6.5% of healthy women to 16.5% of women with benign breast diseases, the PSA level in the serum was greater than 10 rig/L. Serum samples with more than 20 rig/L of PSA were separated on a high performance liquid chromatography gel filtration column and each fraction was assayed for PSA. Our method allows to separate free PSA and PSA bound to IX, antichymotrypsin (PSA-ACT). Serum PSA subfractions in patients with breast diseases were substantially different from PSA subfractions in serum of healthy females. Free PSA (33 KDa) was the predominant molecular form in seven of 16 breast cancer patients and in 11 of 19 patients with benign breast diseases. In healthy women, free PSA was hardly detectable and was never the predominant molecular form. In the same patients with breast cancer, when the serum was collected post-surgically, free PSA was the predominant molecular form in only three out of 11 patients. The total PSA concentration in the serum was also significantly decreased after surgery. Total serum PSA and PSA molecular forms in female serum correlate with patient age and other clinical and pathological variables. We conclude that the molecular forms of PSA in female serum are substantially different between normal women and women with’either breast cancer or benign breast diseases. The mechanism by which the amounts of free PSA and PSA-ACT are altered in benign and malignant breast diseases is still unknown.
P920. Breast cancer with more than 3 positive nodes: adjuvant epirubicin followed by CMF +/hormonotherapy. Preliminary results A de Matteis, GD’Aiuto, R Thomas,C Longo, P Frezza,