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1 ORAL The characteristics of invasive breast cancer in women who use and do not use hormone replacement therapy in the Million Women Study
S2
Proffered papers: Breast cancer I
PROFFERED PAPERS
Breast cancer I 1
ORAL
The characteristics of invasive breast cancer in women who use and do not use hormone replacement therapy in the Million Women Study T. Gathani, J. Green, G. Reeves, V. Beral. University of Oxford, Cancer Epidemiology Unit, Oxford, United Kingdom Introduction: Postmenopausal women who are current users of hormone replacement therapy are at increased risk of developing breast cancer. The effect of HRT on the subsequent pathological characteristics of the tumours is unclear as data from observational studies and randomised trials do not agree. Methods: A prospective study of 622 postmenopausal women who had all been screened and diagnosed with breast cancer either at screening or in the interval between screening, was carried out within the Million Women Study with information about HRT exposure collected at recruitment via selfreporting questionnaire. HRT users were defined as those women who were either currently using HRT or had stopped HRT use in the year previous to diagnosis. HRT non-users were defined as those women who had never used HRT or have used HRT more than one year previous to diagnosis. Information about the pathological characteristics of invasive breast cancer was collected from hospital pathology record data without knowledge of HRT use. Odds ratios of the invasive tumour characteristics in relation to HRT use were calculated using a multivariate logistic regression equation. Results: Among the 622 women, 305 women were users of HRT and 307 women were non-users. The mean tumour size was significantly higher among the HRT users compared with the non-user group (18.9mm vs 16.6mm, p=0.02). The proportion of tumours with lymphovascular invasion (30% vs 21%, p=0.02) and positive axillary nodes (35% vs 25%, p=0.04) was also significantly higher among the HRT users. However following adjustment for the mode of detection i.e. screen-detection or interval cancer, on multivariate analysis no significantly increased risk of these characteristics was observed, however the risk of a grade 3 tumour was significantly lower in HRT users compared to non-users (odds ratio 0.47; 95% confidence interval 0.26-0.85; p=0.01). Conclusion: Tumours in HRT users compared to non-users are larger and more likely to have spread beyond the breast but these differences are largely explained by differences in the mode of detection with HRT users more likely to be detected with cancer in the interval between screens, as HRT is known to decrease the sensitivity and specificity of mammography. 2
ORAL
Magnetic Resonance Imaging (MRI) in the preoperative assessment of patients with lobular carcinoma of the breast M.C. Kokke 1 , A. Kyriazopoulos 2 , J.C. Wissing 1 , M.B.J.M. Korst 2 , M.J.C.M. Rutten 2 , W.A.H. Gelderman 1 , K. Bosscha 1 . 1 Jeroen Bosch Hospital, Department of Surgery, ’s-Hertogenbosch, The Netherlands; 2 Jeroen Bosch Hospital, Department of Radiology, ’s-Hertogenbosch, The Netherlands Purpose: In this study we retrospectively compared findings on preoperative MRI with mammography and ultrasonography in 24 patients with lobular carcinoma and evaluated the effect on the surgical therapy. Introduction: Infiltrating lobular carcinoma is the second most common breast malignancy and represents 7-15% of all invasive breast cancers. The diagnosis is however not without difficulties. Lobular carcinoma shows a diffuse growth pattern of cellular infiltration, including linear file arrangement and a lack of desmoplastic reaction, necrosis or calcification. These typical histological characteristics may account for the existing imaging difficulties. Methods: Two radiologists retrospectively reviewed all imaging modalities. They noted tumour size and localization as well as suspicion of multifocal or multicentric disease. The information on the therapeutic strategy was retrieved from the patients’ files. The size and extent of the tumour on MRI was used to plan the definite surgical treatment.
Results: A change in therapeutic strategy was obtained in 12 out of 24 patients. In 4 patients MRI showed a lager tumour size than was measured on clinical examination, mammography and ultrasound. In 6 patients a change in the therapeutic plan was made because of a multifocal tumour, which was suggested at MRI. Two patients had a change in surgical strategy because the tumour was diffusely spread towards the skin. Conclusion: In this series the initial surgical procedure was changed in 12 out of 24 patients with invasive lobular carcinoma because of additional findings on MRI. Therefore MRI should be a standard preoperative procedure in every patient with a lobular carcinoma. 3
ORAL
Prognostic value of Mib-1 proliferation index in breast cancer. A prospective study on 669 patients A. Neri, D. Marrelli, E. Pinto, A. De Stefano, F. Mariani, C. Pedrazzani, S. Caruso, G. De Marco, T. Cioppa, F. Roviello. Surgical Oncology, Human Pathology and Oncology, Siena, Italy Background: Cell proliferation has an important role as an indicator of biological aggressiveness in breast cancer. Although not considered an obligatory marker, Mib-1 proliferation index is frequently measured in breast cancer patients as a static marker of proliferative activity. The purpose of our study was to prospectively analyze the prognostic value of the Mib-1 proliferation index in a series of 669 consecutive patients operated on for invasive breast cancer at the Surgical Oncology Section of the Department of Human Pathology and Oncology, University of Siena, Italy. Methods: Mib-1 labeling index was evaluated by immunohistochemistry, its association with conventional clinico-pathological factors was analysed by univariate analysis and logistic regression and its prognostic impact was evaluated by multivariate analysis. Results: Tumors were considered expressing an high Mib-1 index when >20% of cells counted were stained. A high Mib-1 proliferation index was expressed in 330 cases (49.3%), and resulted significantly related to high tumor grade, tumor size, absence of progesteron receptors and p53 expression. With a median follow-up of 65 months, an independent negative prognostic impact on disease free survival (DFS) was observed for presence of LVI, high Mib-1 index, tumor size, absence of estrogen receptors and number of involved axillary lymphnodes. Independent prognostic factors for overall survival (OS) included tumor size (p<0.05), high Mib-1 index (p<0.05), absence of estrogen receptors (p<0.05) and number of metastatic axillary lymphnodes (p<0.001). Conclusions: These data may indicate that expression of high values of Mib-1 labeling index is a marker of breast cancers with high proliferative activity. The independent prognostic value of Mib-1 index either for DFS and OS supports its use as a marker of tumors with high biological aggressiveness. As a consequence, determination of Mib-1 index may be particularly useful in the clinical setting allowing to identify, together with other established prognostic factors, subsets of patients with high risk of relapse. 4
ORAL
Achieving breast conservation with 1 mm pathological tumour free margin M. Khan 1 , R. Ganga 1 , P. Mansour 2 , S. Meehan 1 , S. Jmor 1 . 1 Southport and Ormskirk Hospitals NHS Trust, Breast Surgery, Southport, United Kingdom; 2 Southport and Ormskirk Hospitals NHS Trust, Pathology, Southport, United Kingdom Introduction: Margin status is a significant risk factor for residual tumour burden after breast conservation therapy (BCT). The aim of this study was to assess the risk factors for incomplete breast cancer excision and local recurrence with 1mm tumour free margin. Patients and Methods: Retrospective review of 203 patients with 206 breast cancers who underwent BCT from January 2000 to December 2003 at a single specialist unit. All the patients with pathological margin <1mm underwent further surgery until clear margins were obtained. The probability of residual tumour was evaluated with respect to tumour size, tumour grade, histological subtype, extent of the tumour free margin and lymph node metastasis. Local recurrence was assessed in relation to margin status.
Proffered papers: Breast cancer I
PROFFERED PAPERS
Breast cancer I 1
ORAL
The characteristics of invasive breast cancer in women who use and do not use hormone replacement therapy in the Million Women Study T. Gathani, J. Green, G. Reeves, V. Beral. University of Oxford, Cancer Epidemiology Unit, Oxford, United Kingdom Introduction: Postmenopausal women who are current users of hormone replacement therapy are at increased risk of developing breast cancer. The effect of HRT on the subsequent pathological characteristics of the tumours is unclear as data from observational studies and randomised trials do not agree. Methods: A prospective study of 622 postmenopausal women who had all been screened and diagnosed with breast cancer either at screening or in the interval between screening, was carried out within the Million Women Study with information about HRT exposure collected at recruitment via selfreporting questionnaire. HRT users were defined as those women who were either currently using HRT or had stopped HRT use in the year previous to diagnosis. HRT non-users were defined as those women who had never used HRT or have used HRT more than one year previous to diagnosis. Information about the pathological characteristics of invasive breast cancer was collected from hospital pathology record data without knowledge of HRT use. Odds ratios of the invasive tumour characteristics in relation to HRT use were calculated using a multivariate logistic regression equation. Results: Among the 622 women, 305 women were users of HRT and 307 women were non-users. The mean tumour size was significantly higher among the HRT users compared with the non-user group (18.9mm vs 16.6mm, p=0.02). The proportion of tumours with lymphovascular invasion (30% vs 21%, p=0.02) and positive axillary nodes (35% vs 25%, p=0.04) was also significantly higher among the HRT users. However following adjustment for the mode of detection i.e. screen-detection or interval cancer, on multivariate analysis no significantly increased risk of these characteristics was observed, however the risk of a grade 3 tumour was significantly lower in HRT users compared to non-users (odds ratio 0.47; 95% confidence interval 0.26-0.85; p=0.01). Conclusion: Tumours in HRT users compared to non-users are larger and more likely to have spread beyond the breast but these differences are largely explained by differences in the mode of detection with HRT users more likely to be detected with cancer in the interval between screens, as HRT is known to decrease the sensitivity and specificity of mammography. 2
ORAL
Magnetic Resonance Imaging (MRI) in the preoperative assessment of patients with lobular carcinoma of the breast M.C. Kokke 1 , A. Kyriazopoulos 2 , J.C. Wissing 1 , M.B.J.M. Korst 2 , M.J.C.M. Rutten 2 , W.A.H. Gelderman 1 , K. Bosscha 1 . 1 Jeroen Bosch Hospital, Department of Surgery, ’s-Hertogenbosch, The Netherlands; 2 Jeroen Bosch Hospital, Department of Radiology, ’s-Hertogenbosch, The Netherlands Purpose: In this study we retrospectively compared findings on preoperative MRI with mammography and ultrasonography in 24 patients with lobular carcinoma and evaluated the effect on the surgical therapy. Introduction: Infiltrating lobular carcinoma is the second most common breast malignancy and represents 7-15% of all invasive breast cancers. The diagnosis is however not without difficulties. Lobular carcinoma shows a diffuse growth pattern of cellular infiltration, including linear file arrangement and a lack of desmoplastic reaction, necrosis or calcification. These typical histological characteristics may account for the existing imaging difficulties. Methods: Two radiologists retrospectively reviewed all imaging modalities. They noted tumour size and localization as well as suspicion of multifocal or multicentric disease. The information on the therapeutic strategy was retrieved from the patients’ files. The size and extent of the tumour on MRI was used to plan the definite surgical treatment.
Results: A change in therapeutic strategy was obtained in 12 out of 24 patients. In 4 patients MRI showed a lager tumour size than was measured on clinical examination, mammography and ultrasound. In 6 patients a change in the therapeutic plan was made because of a multifocal tumour, which was suggested at MRI. Two patients had a change in surgical strategy because the tumour was diffusely spread towards the skin. Conclusion: In this series the initial surgical procedure was changed in 12 out of 24 patients with invasive lobular carcinoma because of additional findings on MRI. Therefore MRI should be a standard preoperative procedure in every patient with a lobular carcinoma. 3
ORAL
Prognostic value of Mib-1 proliferation index in breast cancer. A prospective study on 669 patients A. Neri, D. Marrelli, E. Pinto, A. De Stefano, F. Mariani, C. Pedrazzani, S. Caruso, G. De Marco, T. Cioppa, F. Roviello. Surgical Oncology, Human Pathology and Oncology, Siena, Italy Background: Cell proliferation has an important role as an indicator of biological aggressiveness in breast cancer. Although not considered an obligatory marker, Mib-1 proliferation index is frequently measured in breast cancer patients as a static marker of proliferative activity. The purpose of our study was to prospectively analyze the prognostic value of the Mib-1 proliferation index in a series of 669 consecutive patients operated on for invasive breast cancer at the Surgical Oncology Section of the Department of Human Pathology and Oncology, University of Siena, Italy. Methods: Mib-1 labeling index was evaluated by immunohistochemistry, its association with conventional clinico-pathological factors was analysed by univariate analysis and logistic regression and its prognostic impact was evaluated by multivariate analysis. Results: Tumors were considered expressing an high Mib-1 index when >20% of cells counted were stained. A high Mib-1 proliferation index was expressed in 330 cases (49.3%), and resulted significantly related to high tumor grade, tumor size, absence of progesteron receptors and p53 expression. With a median follow-up of 65 months, an independent negative prognostic impact on disease free survival (DFS) was observed for presence of LVI, high Mib-1 index, tumor size, absence of estrogen receptors and number of involved axillary lymphnodes. Independent prognostic factors for overall survival (OS) included tumor size (p<0.05), high Mib-1 index (p<0.05), absence of estrogen receptors (p<0.05) and number of metastatic axillary lymphnodes (p<0.001). Conclusions: These data may indicate that expression of high values of Mib-1 labeling index is a marker of breast cancers with high proliferative activity. The independent prognostic value of Mib-1 index either for DFS and OS supports its use as a marker of tumors with high biological aggressiveness. As a consequence, determination of Mib-1 index may be particularly useful in the clinical setting allowing to identify, together with other established prognostic factors, subsets of patients with high risk of relapse. 4
ORAL
Achieving breast conservation with 1 mm pathological tumour free margin M. Khan 1 , R. Ganga 1 , P. Mansour 2 , S. Meehan 1 , S. Jmor 1 . 1 Southport and Ormskirk Hospitals NHS Trust, Breast Surgery, Southport, United Kingdom; 2 Southport and Ormskirk Hospitals NHS Trust, Pathology, Southport, United Kingdom Introduction: Margin status is a significant risk factor for residual tumour burden after breast conservation therapy (BCT). The aim of this study was to assess the risk factors for incomplete breast cancer excision and local recurrence with 1mm tumour free margin. Patients and Methods: Retrospective review of 203 patients with 206 breast cancers who underwent BCT from January 2000 to December 2003 at a single specialist unit. All the patients with pathological margin <1mm underwent further surgery until clear margins were obtained. The probability of residual tumour was evaluated with respect to tumour size, tumour grade, histological subtype, extent of the tumour free margin and lymph node metastasis. Local recurrence was assessed in relation to margin status.