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Correlation of histological classification of the in situ component of infiltrating ductal, carcinoma of the breast with grade of tumour, biological features and prognosis
importance. This difference remained significant when adjusted individually for nodal status, tumour size, age and treatment groups. The difference was not found to be significant in patients with tumours < = 3 cm (n = 146: DFS; chi-squared = 0.31, p = 0.58, OS; chi-squared = 0.16, p = 0.69), but highly significant in patients with tumours >3 cm (n = 70:DFS; chisquared = 9.91, p = 0.0016, OS; chi-squared = 15.74, p = 0.0001). In multivariate analysis LMP group remained significant for both DFS and OS, and was independent from nodal status, tumour size and age. These data suggest that further investigation into the possible mechanisms for the observed survival effect is warranted, and support the need for a prospective study.
64 Correlation of histological classification of the in situ component of infiltrating ductal, carcinoma of the breast with grade of tumour, biological features and prognosis R. R. Millis, 0. T. Lampejo, P. Smith, D. M. Barnes Guy’s Hospital, London, UK and University of Alabama, USA There is, currently, considerable interest in the classicification and biology of pure ductal carcinoma in situ (DCIS). New criteria are being recommended for the histological classification of DCIS but the significance of the subgroups so defined will not be evident until adequate follow-up is available. Another approach is to study the relationship between subtypes of DCIS and associated infiltrating carcinomas. The DCIS component of 214 infiltrating carcinomas was divided into three groups (low, intermediate and high grade) on the basis of histological growth pattern, nuclear differentiation and necrosis. The relationship of these subtypes to grade of infiltrating carcinoma, oncogene expression and prognosis was examined in patients with nine to 13 years follow-up. High grade DCIS was significantly associated with grade III (high grade) infiltrating carcinoma (p < 0.0001) and c-erbB-2 oncoprotein expression (p = 0.0028). Both disease-free survival and overall survival were also significantly related to DCIS subtypes. Patients with tumours containing high grade DCIS fared worst and those with low grade DCIS had an excellent prognosis (p = 0.03), although in a Cox multivariate analysis, this association was lost when grade was included in the model. The association between DCIS subtypes with morphological and biological markers of aggressiveness in associated infiltrating carcinoma and with prognosis suggest that the DCIS classification employed may also be of clinical significance in cases of pure DCIS.
65 Flap recurrence following simple mastectomy:
an audit S. O’Rourke, M. H. Galea, D. Morgan, D. Euhus, S. Pinder, I. 0. Ellis, C. W. Elston, R. W. Blarney. City Hospital, Nottingham UK This retrospective
study determined the clinical significance of local recurrence (LR) after simple mastectomy and node biopsy, without postoperative irradiation or systemic adjuvant therapy for primary operable breast cancer. LR was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. 996 consecutive simple mastectomies with a median followup of 7 years were reviewed. 23% developed LR but half of these were small single lesions, 70 women had multiple discrete lesions and only 21 had diffuse carcinomatous dermal infilitration. LR showed highly significant associations with
tumour grade, nodal stage, and the presence of lympho-vascular invasion (LVI) in the primary tumour. A predictive score comprising these 3 variables has been constructed. Adjuvant irradiation of the flaps is recommended for 24% of mastectomies with high scores; such patients would otherwise have a 39% chance of developing LR by 5 years. Different types of local recurrence have differing chances of responding to local therapy: 13% of single LR, 32% of multiple and 70% of the diffuse type failed to respond to local therapy.
66 Delayed progression of bone metastases with
bisphosphonate therapy: a randomised phase III trial with intravenous Aredia (pamidronate disodium) in breast cancer patients P. F. Conte, J. Latreille, L. Mauriac, L. Koliren, F. Calabresi J. M. Ford S. Chiara Hospital, Pisa, Italy, on behalf of the Aredia Multinational Cooperative Group and Ciba-Geigy, Basel, Switzerland By inhibiting osteoclast-mediated bone destruction treatment with bisphosphonates could delay progression of bone metastases (BM). To test this hypothesis 295 breast cancer patients (pts) with lytic or mixed BM were randomized to receive 3-weekly cycles of intravenous (i.v.) Aredia 45 mg plus standard chemotherapy or chemotherapy alone. 44 centres participated in 7 countries. The primary end-point of the trial was time to progressive disease (PD) in bone on serial X-rays and bone scans. To minimise bias the time to PD in bone was determined by a blinded “extra-mural review” (EMR) of all imaging studies performed during the trial. Secondary end-points included the following complications of BM-pain, analgesic and radiotherapy requirements, pathological fracture and hypercalcaemia. An interim analysis of time to PD in bone has been performed on all data collected until 15.5.92 and is shown in the following table:
No. of pts randomized No. of pts evaluated by EMR No. of pts with PD in bone Median time to PD in bone (days) *(p = 0.05 Wilcoxon test)
Aredia
Control
142 116 67 249*
153 115 75 192*
These interim results indicate that i.v. Aredia progression of BM in breast cancer patients.
can delay
67 Non comparative multi centre open trial in patients with breast cancer and bone metastases to investigate the effect of apd (pamidronate) on bone healing, morbidity bone metabolism C. J. Tyrrell, P. F. Bruning, F. May-Levin, C. Rose, J. M. Ford Plymouth General Hospital, Plymouth, UK, Netherlands Cancer Institute, Amsterdam, Netherlands Institute Gustave Roussy, France Odense Sygehus, Denmark, Ciba-Geigy Pharmaceuticals, Switzerland 69 patients with painful bone metastases from metastatic breast cancer were treated with 60 mg Pamidronate in 250 ml normal saline over 1 h every 2 weeks to a maximum of 13 infusions. Patients were assessed fortnightly for pain, performance status and analgesic intake. Response of bone was assessed on X ray by assessment of sclerosis.
64 Correlation of histological classification of the in situ component of infiltrating ductal, carcinoma of the breast with grade of tumour, biological features and prognosis R. R. Millis, 0. T. Lampejo, P. Smith, D. M. Barnes Guy’s Hospital, London, UK and University of Alabama, USA There is, currently, considerable interest in the classicification and biology of pure ductal carcinoma in situ (DCIS). New criteria are being recommended for the histological classification of DCIS but the significance of the subgroups so defined will not be evident until adequate follow-up is available. Another approach is to study the relationship between subtypes of DCIS and associated infiltrating carcinomas. The DCIS component of 214 infiltrating carcinomas was divided into three groups (low, intermediate and high grade) on the basis of histological growth pattern, nuclear differentiation and necrosis. The relationship of these subtypes to grade of infiltrating carcinoma, oncogene expression and prognosis was examined in patients with nine to 13 years follow-up. High grade DCIS was significantly associated with grade III (high grade) infiltrating carcinoma (p < 0.0001) and c-erbB-2 oncoprotein expression (p = 0.0028). Both disease-free survival and overall survival were also significantly related to DCIS subtypes. Patients with tumours containing high grade DCIS fared worst and those with low grade DCIS had an excellent prognosis (p = 0.03), although in a Cox multivariate analysis, this association was lost when grade was included in the model. The association between DCIS subtypes with morphological and biological markers of aggressiveness in associated infiltrating carcinoma and with prognosis suggest that the DCIS classification employed may also be of clinical significance in cases of pure DCIS.
65 Flap recurrence following simple mastectomy:
an audit S. O’Rourke, M. H. Galea, D. Morgan, D. Euhus, S. Pinder, I. 0. Ellis, C. W. Elston, R. W. Blarney. City Hospital, Nottingham UK This retrospective
study determined the clinical significance of local recurrence (LR) after simple mastectomy and node biopsy, without postoperative irradiation or systemic adjuvant therapy for primary operable breast cancer. LR was defined as a histologically proven lesion in or deep to the mastectomy skin flaps. 996 consecutive simple mastectomies with a median followup of 7 years were reviewed. 23% developed LR but half of these were small single lesions, 70 women had multiple discrete lesions and only 21 had diffuse carcinomatous dermal infilitration. LR showed highly significant associations with
tumour grade, nodal stage, and the presence of lympho-vascular invasion (LVI) in the primary tumour. A predictive score comprising these 3 variables has been constructed. Adjuvant irradiation of the flaps is recommended for 24% of mastectomies with high scores; such patients would otherwise have a 39% chance of developing LR by 5 years. Different types of local recurrence have differing chances of responding to local therapy: 13% of single LR, 32% of multiple and 70% of the diffuse type failed to respond to local therapy.
66 Delayed progression of bone metastases with
bisphosphonate therapy: a randomised phase III trial with intravenous Aredia (pamidronate disodium) in breast cancer patients P. F. Conte, J. Latreille, L. Mauriac, L. Koliren, F. Calabresi J. M. Ford S. Chiara Hospital, Pisa, Italy, on behalf of the Aredia Multinational Cooperative Group and Ciba-Geigy, Basel, Switzerland By inhibiting osteoclast-mediated bone destruction treatment with bisphosphonates could delay progression of bone metastases (BM). To test this hypothesis 295 breast cancer patients (pts) with lytic or mixed BM were randomized to receive 3-weekly cycles of intravenous (i.v.) Aredia 45 mg plus standard chemotherapy or chemotherapy alone. 44 centres participated in 7 countries. The primary end-point of the trial was time to progressive disease (PD) in bone on serial X-rays and bone scans. To minimise bias the time to PD in bone was determined by a blinded “extra-mural review” (EMR) of all imaging studies performed during the trial. Secondary end-points included the following complications of BM-pain, analgesic and radiotherapy requirements, pathological fracture and hypercalcaemia. An interim analysis of time to PD in bone has been performed on all data collected until 15.5.92 and is shown in the following table:
No. of pts randomized No. of pts evaluated by EMR No. of pts with PD in bone Median time to PD in bone (days) *(p = 0.05 Wilcoxon test)
Aredia
Control
142 116 67 249*
153 115 75 192*
These interim results indicate that i.v. Aredia progression of BM in breast cancer patients.
can delay
67 Non comparative multi centre open trial in patients with breast cancer and bone metastases to investigate the effect of apd (pamidronate) on bone healing, morbidity bone metabolism C. J. Tyrrell, P. F. Bruning, F. May-Levin, C. Rose, J. M. Ford Plymouth General Hospital, Plymouth, UK, Netherlands Cancer Institute, Amsterdam, Netherlands Institute Gustave Roussy, France Odense Sygehus, Denmark, Ciba-Geigy Pharmaceuticals, Switzerland 69 patients with painful bone metastases from metastatic breast cancer were treated with 60 mg Pamidronate in 250 ml normal saline over 1 h every 2 weeks to a maximum of 13 infusions. Patients were assessed fortnightly for pain, performance status and analgesic intake. Response of bone was assessed on X ray by assessment of sclerosis.