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S16 Local and Systemic Treatment of DCIS
Thursday, 27 January 2005
Session 5. Innovations in Local Treatments: Surgery and Radiotherapy
regional or distant recurrence; 2. Monitor for second primary; 3. Maintain ongoing relationship with patient to facilitate communication if symptoms of recurrent disease develop; 4. Assess and treat complications of therapy (i.e. osteoporosis); 5. Encourage compliance with ongoing therapy; 6. Provide psychosocial support and provide advice about health decisions (i.e. pregnancy) that may be influenced by a history of breast cancer. Randomized clinical trials have failed to demonstrate an improvement in patient outcome for more versus less intensive monitoring for systemic recurrence. While it is important to evaluate symptoms that may be suggestive of a systemic recurrence, there is no evidence that the early identification of asymptomatic disease at distant sites will improve survival or quality of life. For this reason, most organizations such as the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) do not recommend any routine imaging studies (apart from breast imaging) as part of follow-up care. The approach may change in the years ahead if new and more effective treatment approaches become available for women with metastatic disease breast cancer.
THURSDAY, 27 JANUARY 2005
14.00-15.30
Session 4. Early Stages of Breast Cancer and DCIS
I
•
Biological Variables and Prognosis of DCIS
M.J. van de Vijver. The Netherlands Cancer Institute, Dept of Pathology,
Amsterdam, The Netherlands Ductal carcinoma in situ (DCIS) is a clonal proliferation of malignant epithelial cells within the ducts and Iobules of the breast. As invasive growth is absent, DCIS will not lead to distant metastases. The main aim of treatment of DCIS is to prevent progression to invasive breast cancer and distant metastasis. The challenge for optimal treatment of DCIS is to provide less aggressive treatment than mastectomy without an increase in progression to invasive breast cancer and most notably, without an increase in distant metastasis and death of breast cancer. The most important options for the management of patients of DCIS are: incisional biopsy; excision of the whole lesion; excision of the who lesion followed by radiotherapy. For all of these management options, hormonal therapy can be considered as additional treatment. It would be of great clinical value if biological variables could be identified that can reliably predict specific questions concerning the expected behaviour of DCIS, most notably: 1) What is the likelihood of local recurrence; how likely is progression to invasive breast cancer? 2) If an invasive tumor develops, what is the likelihood of developing distant metastases? 3) Are the tumor cells responsive for radiotherapy? 4) Are the tumor cells responsive to hormonal therapy? Biological variables, such as genetic alterations and the expression patterns of genes and proteins, play an important role in the development and progression of DCIS, but are not currently used to guide the clinical management of DCIS. It has been found that most genetic alterations that play a role in breast cancer development are already present in DCIS. Most notably, amplification of the HER2 gene and mutations in the p53 gene are found in a large proportion of DCIS. Inactivation of the E-cadherin gene is present in all most all cases of Iobular carcinoma in situ, but never in DCIS. Other genetic mutations have been described but have not yet been characterized in much detail in DCIS. There is a rapid increase in the knowledge on genetic alterations in breast cancer, including DCIS. To assess the potential use of these biological factors for assessing risk of progression to invasive cancer and metastasis, large series of DCIS from patients that have undergone breast conserving treatment of incisional biopsy need to be studied. Thus far, these studies have not been carried out, but will hopefully start
IS~
Sentinel Lymphnodes for Localized DClS?
P. Veronesi 1, M. Intra 1, A.R. Vento 1, P. Naninato 1, P. Caldarella ~, G. Paganelli 2, G. Viale 3 . ~European Institute of Oncology, Department of
Senology, Milano, Italy; 2 European Institute of Oncology, Department of Nuclear Medicine, Milano, Italy; 3 European Institute of Oncology, Department of Pathology, Milano, Italy
Introduction:Ductal carcinoma in situ (DCIS), by definition, cannot give axillary metastases. Axillary dissection is therefore not indicated. The role of sentinel lymph node (SLN) biopsy in the management of DCIS has not yet been established. A 6-13% risk of SLN involvement is reported in the literature. Moreover, very often we cannot exclude before surgery the presence of microinvasion at the definitive histology, even if the diagnosis of DCIS has been conducted via a vacuum assisted biopsy device (Mammotome ®). Aim: The aim of the present study is to assess the role of SLN biopsy in patients with DCIS and attempt to identify guidelines for routine practice in managing such patients. Patients and methods: From January 1998 to December 2003, 482 unselected consecutive patients with pure DCIS of the breast underwent SLN biopsy at the European Institute of Oncology in Milan. Clinical and pathological data were prospectively collected. In all cases of previous surgery or stereotactic biopsy performed elsewhere all pathological slides were reviewed. Cases with microinvasion were excluded from this investigation. Lymphatic mapping was performed using a radiocolloid technique. Most of the patients underwent conservative surgery and removal of the SLN which was sent for conclusive histology. Results: SLN metastases were detected in 9 out of 482 (1.9%) patients with a conclusive diagnosis of pure DCIS without evidence of microinvasion. In seven patients only micrometastasis was detected. Eight patients underwent complete axillary dissection. In none of these patients did we find additional positive lymph nodes. Discussion. Due to the very low prevalence of metastasis, SLN biopsy should not be considered a standard procedure in the treatment of patients with pure DCIS who are candidates for conservative surgery. Very often however we cannot exclude before surgery the presence of microinvasion. In a series of 396 consecutive patients diagnosed with DCIS by means of a vacuum assisted biopsy device (Mammotome ®) at our institution and thus referred to surgery we found 67 (16.9%) infiltranting carcinomas. This risk increased to 26.5% in cases of diffuse or plurifocal microcalcifications while it was only 2.9% in cases of limited clusters of microcalcifications completely excised with Mammotome ®. Conclusions:SLN biopsy is not routinely indicated in patients with pure DCIS. Nevertheless in some clinical settings the SLN biopsy should be recommended and precisely in those settings with patients with diffuse or plurifocal microcalcifications who are candidates for total mastectomy and in patients with extended microcalcifications in whom a vacuum assisted device biopsy (with a diagnosis of DCIS) has left a residual lesion in the breast.
I
S
•
DCIS: Which are its Precursors?
w, Boecker, Germany Abstract not received.
THURSDAY,27 JANUARY2005
16.00-17.30
Session 5. Innovations in Local Treatments: S u r g e r y and Radiotherapy
I
soon.
$7
•
Limiting Breast Surgery to the Proper Minimum
M, Morrow, Fox Chase Cancer Center, Surgica/ Onco/ogy, Phi/ade/phia, PA,
I-~
Local and Systemic Treatment of DCIS
R,E, Mansel, United Kingdom Abstract not received,
United States of America Multiple mature prospective randomized trials have demonstrated that survival rates after breast conserving treatment (BCT) and mastectomy are equal, Experience has demonstrated that contraindications to BCT are uncommon, and that patients can be selected for BCT on the basis of a history, physical exam, and diagnostic mammography with an accuracy of 95% or greater. Although local recurrence rates 10 years after BCT were initially 1520%, they have fallen to less than 10%, and in many cases less than 5%, with improved understanding of patient selection and the routine use of adjuvant systemic therapy. There is great interest in the use of new imaging modalities such as US and MRI in the selection of patients for BCT due to the ability
Session 5. Innovations in Local Treatments: Surgery and Radiotherapy
regional or distant recurrence; 2. Monitor for second primary; 3. Maintain ongoing relationship with patient to facilitate communication if symptoms of recurrent disease develop; 4. Assess and treat complications of therapy (i.e. osteoporosis); 5. Encourage compliance with ongoing therapy; 6. Provide psychosocial support and provide advice about health decisions (i.e. pregnancy) that may be influenced by a history of breast cancer. Randomized clinical trials have failed to demonstrate an improvement in patient outcome for more versus less intensive monitoring for systemic recurrence. While it is important to evaluate symptoms that may be suggestive of a systemic recurrence, there is no evidence that the early identification of asymptomatic disease at distant sites will improve survival or quality of life. For this reason, most organizations such as the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) do not recommend any routine imaging studies (apart from breast imaging) as part of follow-up care. The approach may change in the years ahead if new and more effective treatment approaches become available for women with metastatic disease breast cancer.
THURSDAY, 27 JANUARY 2005
14.00-15.30
Session 4. Early Stages of Breast Cancer and DCIS
I
•
Biological Variables and Prognosis of DCIS
M.J. van de Vijver. The Netherlands Cancer Institute, Dept of Pathology,
Amsterdam, The Netherlands Ductal carcinoma in situ (DCIS) is a clonal proliferation of malignant epithelial cells within the ducts and Iobules of the breast. As invasive growth is absent, DCIS will not lead to distant metastases. The main aim of treatment of DCIS is to prevent progression to invasive breast cancer and distant metastasis. The challenge for optimal treatment of DCIS is to provide less aggressive treatment than mastectomy without an increase in progression to invasive breast cancer and most notably, without an increase in distant metastasis and death of breast cancer. The most important options for the management of patients of DCIS are: incisional biopsy; excision of the whole lesion; excision of the who lesion followed by radiotherapy. For all of these management options, hormonal therapy can be considered as additional treatment. It would be of great clinical value if biological variables could be identified that can reliably predict specific questions concerning the expected behaviour of DCIS, most notably: 1) What is the likelihood of local recurrence; how likely is progression to invasive breast cancer? 2) If an invasive tumor develops, what is the likelihood of developing distant metastases? 3) Are the tumor cells responsive for radiotherapy? 4) Are the tumor cells responsive to hormonal therapy? Biological variables, such as genetic alterations and the expression patterns of genes and proteins, play an important role in the development and progression of DCIS, but are not currently used to guide the clinical management of DCIS. It has been found that most genetic alterations that play a role in breast cancer development are already present in DCIS. Most notably, amplification of the HER2 gene and mutations in the p53 gene are found in a large proportion of DCIS. Inactivation of the E-cadherin gene is present in all most all cases of Iobular carcinoma in situ, but never in DCIS. Other genetic mutations have been described but have not yet been characterized in much detail in DCIS. There is a rapid increase in the knowledge on genetic alterations in breast cancer, including DCIS. To assess the potential use of these biological factors for assessing risk of progression to invasive cancer and metastasis, large series of DCIS from patients that have undergone breast conserving treatment of incisional biopsy need to be studied. Thus far, these studies have not been carried out, but will hopefully start
IS~
Sentinel Lymphnodes for Localized DClS?
P. Veronesi 1, M. Intra 1, A.R. Vento 1, P. Naninato 1, P. Caldarella ~, G. Paganelli 2, G. Viale 3 . ~European Institute of Oncology, Department of
Senology, Milano, Italy; 2 European Institute of Oncology, Department of Nuclear Medicine, Milano, Italy; 3 European Institute of Oncology, Department of Pathology, Milano, Italy
Introduction:Ductal carcinoma in situ (DCIS), by definition, cannot give axillary metastases. Axillary dissection is therefore not indicated. The role of sentinel lymph node (SLN) biopsy in the management of DCIS has not yet been established. A 6-13% risk of SLN involvement is reported in the literature. Moreover, very often we cannot exclude before surgery the presence of microinvasion at the definitive histology, even if the diagnosis of DCIS has been conducted via a vacuum assisted biopsy device (Mammotome ®). Aim: The aim of the present study is to assess the role of SLN biopsy in patients with DCIS and attempt to identify guidelines for routine practice in managing such patients. Patients and methods: From January 1998 to December 2003, 482 unselected consecutive patients with pure DCIS of the breast underwent SLN biopsy at the European Institute of Oncology in Milan. Clinical and pathological data were prospectively collected. In all cases of previous surgery or stereotactic biopsy performed elsewhere all pathological slides were reviewed. Cases with microinvasion were excluded from this investigation. Lymphatic mapping was performed using a radiocolloid technique. Most of the patients underwent conservative surgery and removal of the SLN which was sent for conclusive histology. Results: SLN metastases were detected in 9 out of 482 (1.9%) patients with a conclusive diagnosis of pure DCIS without evidence of microinvasion. In seven patients only micrometastasis was detected. Eight patients underwent complete axillary dissection. In none of these patients did we find additional positive lymph nodes. Discussion. Due to the very low prevalence of metastasis, SLN biopsy should not be considered a standard procedure in the treatment of patients with pure DCIS who are candidates for conservative surgery. Very often however we cannot exclude before surgery the presence of microinvasion. In a series of 396 consecutive patients diagnosed with DCIS by means of a vacuum assisted biopsy device (Mammotome ®) at our institution and thus referred to surgery we found 67 (16.9%) infiltranting carcinomas. This risk increased to 26.5% in cases of diffuse or plurifocal microcalcifications while it was only 2.9% in cases of limited clusters of microcalcifications completely excised with Mammotome ®. Conclusions:SLN biopsy is not routinely indicated in patients with pure DCIS. Nevertheless in some clinical settings the SLN biopsy should be recommended and precisely in those settings with patients with diffuse or plurifocal microcalcifications who are candidates for total mastectomy and in patients with extended microcalcifications in whom a vacuum assisted device biopsy (with a diagnosis of DCIS) has left a residual lesion in the breast.
I
S
•
DCIS: Which are its Precursors?
w, Boecker, Germany Abstract not received.
THURSDAY,27 JANUARY2005
16.00-17.30
Session 5. Innovations in Local Treatments: S u r g e r y and Radiotherapy
I
soon.
$7
•
Limiting Breast Surgery to the Proper Minimum
M, Morrow, Fox Chase Cancer Center, Surgica/ Onco/ogy, Phi/ade/phia, PA,
I-~
Local and Systemic Treatment of DCIS
R,E, Mansel, United Kingdom Abstract not received,
United States of America Multiple mature prospective randomized trials have demonstrated that survival rates after breast conserving treatment (BCT) and mastectomy are equal, Experience has demonstrated that contraindications to BCT are uncommon, and that patients can be selected for BCT on the basis of a history, physical exam, and diagnostic mammography with an accuracy of 95% or greater. Although local recurrence rates 10 years after BCT were initially 1520%, they have fallen to less than 10%, and in many cases less than 5%, with improved understanding of patient selection and the routine use of adjuvant systemic therapy. There is great interest in the use of new imaging modalities such as US and MRI in the selection of patients for BCT due to the ability