Session 3. Breast c’nnc‘rr and the media S5

phasis will be put on excellent prognosis tumour types, like tubular, cribri- form. medullary, mutinous and adenoid cystic carcinomas, and on micropap illary invasive carcinomas and duct carcinomas with extensive central necro- sis or fibrosis, both examples of tumour entities with dismal prognosis.

Another issue characterised by high interobserver variability is the assess- ment of microinvasive carcinomas associated with a predominant intraductal component. To avoid unwarranted surgical and/or adjuvant treatments, the diagnosis of microinvasive carcinomas should rely upon definite morphologi- cal evidences of actual invasion of the stroma by the neoplastic cells. Special care should be given not to overdiagnose as microinvasive tumour nests dis- located within the stroma or even within vessels following needle procedures (fine needle aspiration cytology, core biopsies, etc).

Finally, the implications of peritumoral vascular invasion will be discussed, together with the risk of false-positive sentinel (and nonsentinel) lymph node biopsies, due to the possible (though very uncommon) occurrence within the axillary lymph nodes of ectopic breast tissue, occasionally showing prolifer- ative changes.

Pathologists should take upon themselves the task of assessing prognos- tic and predictive markers in a more standardised fashion, to offer breast carcinoma patients the best choice of adjuvant interventions, avoiding both under- and over-treatments or inappropriate therapeutic options.

u S9 Evaluation of regional lymphnodes: New standards?

Viviana Galimberti. Senology Department, European Institute of Oncology Milan. Italy

Although trials on sentinel node biopsy (SNB) in breast cancer are still on- going, the technique as been widely adopted by surgeons. This is because SNB is considered a staging procedure and not a treatment, and has been shown to stage the axilla at least as accurately as conventional axillary dis- section. Furthermore, when radioactive tracer is used to identify the sentinel node (SN) there is sometimes uptake by a node of the internal mammary chain (IMC) providing an opportunity to further refine staging by biopsying this node. We have found that sampling the IMC nodes, in cases with tumor in the internal quadrants, is a simple procedure and that in about 10% of cases the IMC node is positive leading to stage migration and more targeted treatment.

In order to ensure that examination of a single SN provides an accurate in- dication of axillary status, new histological techniques have been introduced which effectively examine the entire node. This has resulted, not only in an in- creased proportion of positive axillas compared to historical series, but also an increased proportion of cases with only micrometastases (less than or equal to 2 mm) present in the SN. The prognostic significance of this finding is still unclear and we are awaiting the results of a randomized trial (IBCSG 23-01) to answer this question.

We retrospectively examined 981 breast cancer patients, treated from March 1996 to December 2060 who, after a negative finding following SNB. received no further treatment to the axilla. After a median follow-up of 36 months (minimum 24, maximum 73) only two patients in this series have de- veloped overt axillary disease. This is much less than the expected 58 cases of axillary disease based on the assumption that SNB has a false negative rate of about 6%. Since axillary disease generally appears early in follow-up thus extremely low rate of unfavorable axillary events provides reassurance not only on the accuracy but also the safety of SNB and for this reason can be considered the new standard for disease staging in breast cancer.

El Sl 0 Evaluation of bone marrow: Prediction of outcome and response

Stephan Braun’, Florian Vogl*, Wolfgang Janni3, Christian Marth’, Gunter Schlimok4, Klaus Pantels. ’ Univeffiiw Hospital, Dept Ob/Gyn, Innsbruck, Austna; 2 European Academy Bol’ano, Ital& 3 Universi?y Hosp/ta[ Dept. Ob/Gyn, Munich, Germany; 4 Central Hospitat, Dept. Hem/Oncol, Augsburg, Germanx 5 Institute for Tumorbiolog~ Universi?y Hospital, Hamburg, Germany

Metastatic breast cancer rs caused by early and clinically occult spread of tumor cells. Several studies consolidate the view that such hematogenous tumor cell spread represents an important clinical stage within the contin- uum of tumor progression towards distant metastasis. With regard to the malignant nature of such cells emerging evidence from molecular single cell analyses shows that strgmata of malignancy can be found in a large propor- tron of the disseminated tumor cell population. The ongoing debate on the clinrcal impact of bone marrow evaluation for breast cancer patients criticizes the lack of evidence due to the variations of methods and the limited statis- tical power of single studies. Nevertheless, it is being discussed to imple- ment bone marrow evaluation into current tumor risk classification systems. The predominant reason for this is seen in the lack of precision provided

by the established factors currently used for the prediction of patient out- come and response to adjuvant therapy. This is true especially for patients who are staged node-negative, since they require treatment in a significantly lower percentage than that of approximately 90% of patients due to current consensus which is based on age, tumor size, grade and hormone respon- srveness. In addition, the introduction of new targeted treatment strategies, such as adjuvant Herceptin therapy, would require or at least significantly benefit from the availability of a surrogate marker of therapeutic efficacy. Recently, at least 5 matured clinical studies (sufficiently dimensioned study populations, validated immunoassays, meaningful follow-up time), compris- ing approximately 3500 patients and including our own series of almost 1500 patients, provide evidence for the independent prognostic value of the pres- ence of tumor cells in the bone marrow. Besides improved tumor staging, we have pointed to further options of bone marrow evaluation, including patient monitoring during chemotherapeutic and immunologic therapy for the imme- diate assessment of therapeutic efficacy at completion of therapy rather than retrospectively after an extended period of clinical follow-up. At present, we consider bone marrow evaluation a diagnostic tool for improved identification of the individual risk of distant relapse and death among potentially curable breast cancer patients. Due to the lack of consensus for a benchmark tech- nology for tumor cell detection the implementation into tumor classifications is pending, and awaits confirmatory studies (e.g. meta-analyses, more pow- erful validation studies) which are currently underway. Except for promising pilot studies, no data are available to support the immediate use of bone marrow evaluation for treatment monitoring in order to enable the predic- tion of response to adjuvant therapy. Large multi-center trials based upon a validated benchmark methodology, appropriately designed and carried-out by an international cooperate study group are warranted to investigate both improved treatment strategies in patients with tumor cells in bone marrow, and the necessity of adjuvant therapy in those with a negative bone marrow status.

Risk factors, treatment options and follw-up

T. Powles. UK

Abstract not received

THURSDAY, 13 MARCH 2003 11.00-l 2.30

Session 3. Breast cancer and the media

L-J S12 Epidemiology of breast cancer

Jack Cuzick. Cancer Research UKDepatiment of Epidemiology Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Charterhouse Square* London ECIM SEQ, UK

Breast cancer is primarily a disease related to oestrogen exposure. Most of the standard risk factors such as age of menarche, age at first childbirth, parity, and age at menopause are related to oestrogen, and the ability of drugs such as tamoxifen and anastrozole to reduce the incidence of new tu- mours all support this. Further support is provided by the direct association with oral contraceptives and hormone replacement therapy. Also the role of obesity in post menopausal but not premenopausal breast cancer supports this contention. However oestrogen appears to stimulate only oestrogen re- ceptor positive cancers and there is some evidence that these factors are only related to oestrogen receptor positive breast cancer. Other factors such as family history appear to be relevant to both receptor positive and receptor negative tumours. There is much interst as to whether separate aetiologies can be ascribed to these different types of casncers.

These and other factors such as mammographic density will be briefly reviewed and discussed in terms of the type of cancers they engender.

L-! S13 Nutrition and breast cancer

Timothy J. Key. Cancer Research UK Epidemiology Unit, Universiv of Oxford Oxford, UK

The high rates of breast cancer in Western countries have suggested that some features of a Western diet may increase breast cancer risk. Most of the established risk factors for breast cancer are hormonal, and nutri- tion may affect breast cancer risk through changes in hormone metabolism. The only well established diet-related risk factors for breast cancer are obe- sity and alcohol consumption. Obesity increases breast cancer risk in post-